The Chlamydia Pneumoniae Handbook

The Chlamydia Pneumoniae Handbook

Purposes of this Handbook

This "Handbook" is an attempt to organize and pull together information on Chlamydia pneumoniae, it's impact on human diseases, and it's treatment via combined antibiotic protocols into a more easily accessible, organized and up to date format. Some of the material has already been posted on www.cpnhelp.org website and is simply linked here in a more organized way. Some of the material in this handbook is new and represents the most current, state of the art information on Cpn, CAP, and the various supplements which have been found helpful in clinical experience. We will endeavor to update and expand the Cpn Handbook as new information becomes available.

Important Disclaimer: Read This Before Using the Cpn Handbook-

The information anywhere in the Cpn Handbook, and on www.cpnhelp.org, should not be considered medical advice, not complete, nor should it be relied on or interpreted to suggest a course of treatment for any individual. This information is for research and knowledge purposes only, and it should not be used in place of a visit, call, consultation or the advice of your physician or other qualified health care provider.

Any application or implementation of information in the Cpn Handbook, and on www.cpnhelp.org is considered at the readers own risk. The reader/user of information in the Cpn Handbook, and on www.cpnhelp.org agrees not to hold liable the providers of the www.cpnhelp.org for any use or misuse of the information provided. The providers of the Cpnhelp.org site are not medical physicians and the information here is not medical advice. Should you have any health care-related questions, please call or see your physician or other qualified health care provider promptly.

Printing the Handbook

Consider printing out the whole Handbook for yourself or your doctor, here's a trick:

  1. At the bottom of this page of the Cpn Handbook click the "print friendly" link. You should get a document of 50+ pages to appear.
  2. You can directly print or save as pdf file and print from your own computer.
  3. The only thing which doesn't come out right is the Table of Contents. Trick: Go to that page from the Handbook left sidebar link (you only see this once the Handbook is selected) and then at the bottom go to the "print friendly" link (not the "alternative" line) and it should appear.
  4. Print it out or save as pdf file and add to your handbook copies.

 Of course, you can print out individual selections of the Handbook by going to that specific page and using the 'print friendly' link at the bottom of the page.

Date your copies, and check back to make sure you have the most current edition as we are adding to it and editing frequently. 

Under Construction:

This is the starting page for a collaborative effort to pull together the information gathered about Cpn: research, it's implication in various diseases, the arguments about it's legitimacy, its treatment via combination antibiotic protocol, and frequently asked questions about all this. Ahem! Quite a run-on sentence.

The handbook will be organized from existing pages, as well as from new and updated material. It's a work in progress so... stay tuned!

Jim K Tue, 2006-01-24 16:29

Introduction to Chlamydia Pneumoniae (Cpn)

Introduction to Chlamydia Pneumoniae (Cpn)

Introduction to Chlamydia Pneumoniae (Cpn)

Chlamydia Pneumoniae (Cpn) is a tiny bacterium which is most often noted for causing a form of pneumonia. Up until the 1970's it was not even isolated and was mistaken for a virus (its discovery is an interesting story and can be found here: http://www.washington.edu/research/pathbreakers/1989a.html).

It was not until 1989 that J. Thomas Grayston and his associates named it as a separate species of the Chlamydiae. Cpn is very difficult to culture and so, without modern lab techniques, also to study. It is an intracellular bacterium, which means that it invades the body cells, and it is an obligate parasite, which means that it cannot supply it's own energy source and so takes over the energy machinery of the body cells it invades, depleting them and leaving the host cell less functional.

 

Cpn has been implicated in a wide variety of diseases and is seen by some researchers as a causal factor in particular disease such as  Multiple sclerosis , Chronic fatigue , Asthma , Rheumatoid Arthritis (RA) , Fibromyalgia , Chronic refractory sinusitis , Cardiac disease , Interstitial cystitis  , Prostatitis, Alzheimer's disease Crohn's disease , Inflammatory bowel disease and others

Below: a diagram of the Cpn life cycle from http://herkules.oulu.fi/isbn9514269853/html/x467.html (which is also an excellent text on Cpn biology and treatment).

 Cpn Life Cycle

 

What makes Chlamydia Pneumoniae (Cpn) especially troublesome?

    * While it may start as a respiratory infection, Cpn can be carried to other parts of the body and infect many other tissues, including nerve tissue, the brain, muscles, kidneys, liver, prostate, the lining of blood vessels and even your immune cells (macrophages and monocytes). Thus a wide array of problems can be caused by this single bug.
    * The standard single antibiotic courses (two weeks monotherapy) which doctors typically used only kill Cpn in one of its three life phases, leaving other live forms of Cpn bacteria which are in other stages to renew infection. This is what creates persistence and relapse in Cpn and it's related diseases.
    * Cpn contains at least two endotoxins (toxic chemicals) which cause tissue damage and inflammation, chronic immune activation and toxic load in your body. Killing the Cpn releases large amounts of these endotoxins, called a die-off reaction, making treatment uncomfortable.
    * Cpn infects inside your cells and parasitically steals energy from your own body cells in order to replicate. The cells and organs it effects become less and less functional over time as Cpn load increases in them.
    * The only way to cure it is to take a combination of antibiotics (see Combination Antibiotic Protocols), to kill it in all of its life phases so nothing is left behind to re-infect. This can take a long time depending on the load of Cpn in your system, the organs infected and other variables. Typical courses of 1-3 years are not unusual.

Next:
The Basics Page
provides answers your basic questions about Cpn and the Combined Antibiotic Protocols used to treat it.

Cpn Simple the simplest summary of we could think of, and might be a good beginning for those of us a bit brain fogged or just plain overwhelmed by the whole thing? 

Jim K Fri, 2006-02-03 18:48

Advice to Non-Medical Newcomers

Advice to Non-Medical Newcomers

Why are you here?  The reason is the same for all of us.  Either you or someone you care for is sick, so you're looking for something, anything to help.  Maybe it's MS, CFS, ME, FM, Lupus, Alzheimer's, unrelenting fatigue, pain and inflammation, or something else.  You might  be desperate because you're up against a wall built of words like incurable, untreatable, and of unknown origin.  Perhaps a cutting-edge medication has been tried and failed.  With the media full of news about medical breakthroughs, you're frustrated that a meaningful treatment has not been found for your illness.  You're thinking that surely the answer lies somewhere out there in the vast body of knowledge that makes up modern medicine...someone just hasn't connected the dots yet.  You surf the internet and find websites offering support and education on the illness. You read articles about research and new treatments.  Much of it is written in medical-ese, and you may feel overwhelmed, even handicapped in your ability to milk the meaning out of the information you find.

I am a caregiver and care advocate for my husband who has a degenerative illness.  I have no medical background and I'm cyber-challenged.  If, like me, you're stubborn enough to keep struggling with all those research and treatment articles, and if you can make any sense out of them, a bigger picture emerges.  When you step back to assess the various bits of information collectively, you will find a gaping hole.  Something huge is missing.  The problem is that most of the current research and emerging treatments focus on "tinkering" with the disease process, not on addressing the root cause of the disease.  Why is that?

Things they forgot:  Entertain some what ifs with me.  What if research into the disease had been underway for several decades?  What if, in those early days, research efforts were concentrated on finding a microbe as the villain?  After all, the immune systems of the people afflicted with the disease seemed to be attacking something that shouldn't have been there.  What if, after no infectious agent was found, the research community embraced the theory that the body sometimes goes nuts and attacks itself via a defective immune system?  What if this interesting autoimmune concept led researchers into some limited success in developing drugs that "tinker" with the immune system to some benefit for some of the afflicted some of the time?  Limited success is better than no success.  What if herd-mentality caused a stampede of researchers in one direction?  What if, in the meantime, there had been advances in microscopy and lab techniques that might have enabled those early researchers to find what they had been looking for?  What if the majority of the research/medical community had somehow lost track that the model of autoimmunity was an unproven theory, and they had comfortably incorporated it into their thinking and efforts as though it were a given fact?  What if new technology applied to old ideas could result in the hope of treating the disease at its core rather than just "tinkering" with the disease process?

My husband's illness has been rubber-stamped as autoimmune.  Like you, I was searching, and like you, I am a relative newcomer to this website.  Most of the material on cpnhelp.org is very understandable, but you will eventually run into unfamiliar medical terms and processes.  Advice from other users, resource tips gleaned from their blogs, and my own experience have helped me develop a system for digesting the cpnhelp.org material and for understanding the medical-ese I encounter elsewhere on the internet as I investigate my husband's illness.  I'm offering you a shortcut.  Please let me help you in your quest to get the most out of this website, lits linked websites, other websites you are already visiting, and those you will visit in the future (especially those research articles).

THE SYSTEM:

Once over lightly - Follow the advice on the Homepage by reading Cpn Simple and The Basics Page in the Cpn Handbook...go back to the Handbook and skim through the sections concerning treatment just to know what's there.  Be sure to read the disclaimer and privacy statement.

Prepare to go deeper - Very simple, free, not much time, and so worth the effort.

  • If you think you might want to try my system, print it and keep it handy.
  • Build a small foundation of knowledge and understanding.  I can't emphasize enough how helpful this is.  After you do it, you'll want to revisit those research articles that were so befuddling.

Read the entire Homepage again.

Read the Handbook.

  • Read it all the way through or click on the topics in the Table of Contents found on the left side of the screen to read specific information.
  • Use the glossary on the left side of the screen (you may need to use the up/down slide bar to locate it).
  • Some terms in the Handbook will be marked with a highlighted " i  " at the end.  Click on the " i " for a definition or a comment about that term.
  • For terms not found in the glossary, minimize the active cpnhelp.org page by clicking its identifying tab in the bar at the bottom of the screen.  Then go to medterms.com, wikipedia, or even howstuffworks.com (it's good, but has its limits).  You will discover other resources to use for the same purpose.
  • After reading the definition(s) on the other websites, minimize the resource page(s).  Keep these resources at the ready in the bottom bar to pop up for future use.  Then click the appropriate bottom bar tab to restore the cpnhelp.org page.
  • You may want to print the entire Handbook for portable reading.  Follow the printing instructions on the introduction page, especially the part about The Table of Contents.  A printed copy of the glossary is a good take-along aid as well.

Visit other cpnhelp.org resources by clicking the tabs found at the top of the screen.  The Patient Stories are sure to be a favorite resource.

Find out what the website users are blogging about by clicking recent posts on the left side of the screen.  If you spot a blogger that may be of interest because you suspect you have an illness in common, click on that user's highlighted name.  This will take you to a window where you can track other comments made by that user.

Navigate your way to the older posts; they are still new to you.

Search for a specific topic in the Search slots located in the upper right and lower left sides of the screen.

Check out what's happening on the right side of the screen.  Click around here and there and you'll soon become an expert navigator.  You will eventually want to participate, or perhaps you will want to go where only a user can go.  Welcome aboard, it's time to REGISTER!

 

 

 

 

cypriane Sun, 2006-06-04 23:18

Cpn Simple

Cpn Simple

 

Cpn Simple- The shortest explanation we could think of!

  • Cpn has been clearly proven to have persistence in the body despite “standard” antibiotic treatment (two weeks of a single antibiotic).
  • Cpn has been implicated in a wide variety of diseases (see bottom of this page).
  • Blood tests and cultures are not reliable indicators of whether Cpn is part of your disease.
  • If you have any of the diseases in which Cpn has been implicated, it may be worth trying an “empirical” (based on symptoms alone) combination antibiotic protocol (Link).
  • Most doctors are not familiar with this, and you will have to present a rational and evidence based case to them for prescription of the appropriate antibiotics through information such as on this site.

Is this right for you? 

 

Four indicators can be used to help you determine if an empirical test of the full combination antibiotic protocol is useful for you. You should be on it for for a minimum of 6 months to a year. The first three suggest that you have Cpn and you should continue this treatment.
1. You experience distinct reactions to the antibiotics indicative of Cpn die-off (see Reactions to Treatment link).
2. You have improvement of disease symptoms.
3. You have noticeable halting of symptom progression.
4. Nothing at all and decide this isn’t for you.

Killing Cpn In Different Phases

Diagram from David Wheldon (http://www.davidwheldon.co.uk/killing.jpg) used by permission. 

Phases of the Cpn bacteria and what agents effect those phases:

EB’s- Elementary Body What are they? EB’s are spore-like forms which are infectious and metabolize minimally (aren’t using nutrients, replicating, exchanging with the environment, etc.). They are tough, tiny and reside in the intercellular tissues (outside of actual body cells). What do they do? EB’s attach to your body’s cells and invade them. Since there can be more EB’s than can get into cells, EB’s build up in local tissues causing inflammation and immune response.

What kills them? They are killed by amoxicillin, which is transformed to penicilamine in your own body, and destroys the bonds which hold the EB cell wall together. An amino acid NAC (N-acetyl cysteine) also is used for this purpose. What happens? When you kill them, they release toxin into the tissues in which they have built up, and you get inflammation and pain there, which can last for days or weeks afterwards before you feel relief of symptoms. Most people taking NAC report a period of flu-like feeling of malaise, achyness, nunning nose, perhaps coughling.

RB's- Reticulate Body What are they? Once an EB enters a host cell it transforms into a form which can replicate new EB's which is called a Reticulate Body or RB. The RB has no energy source of it's own for this, so it must steal energy (ATP) from the host cell, leaving the host cell weakened and less functional. The RB also inhibits the natural cell death of the host cell so that it can survive while it replicates. After the production of many new EB's the host cell bursts and dies, spreading the infectious new EB's into the surrounding tissue.RB's are inhibited in replicating by various antibiotics such as doxycycline, azithromycin, roxythromycin and others, and subject to this will convert into the Cryptic (and nonreplicating) form where they can be killed by metronidazole. RB's are prevented from forming by rifamcin.

Cryptic form
What are they? When RB’s face an environment which threatens their survival inside a cell (lack of food, antibiotic attack, etc) they can transform into a “Cryptic” form which stays inside the cell, but is in hibernation, so to speak. What do they do? In this form it is not vulnerable to regular antibiotics and can reside there until conditions change, then become an RB again and start to replicate and reinfect with EB’s. What kills them? Flagyl (metronidazole) or Tinactin (tinidazole) are used to kill the cryptic forms of Cpn. Nitrofurantoin, an old urinary tract infection drug, also has antichalmydial effect in this phase. These drugs can be hard to tolerate for various reasons, and so are commonly “pulsed” by taking a course for 5 days every 3-4 weeks, rather than taken continuously. Some protocols may eventually have one of these drugs taken continuously for some period as the patient can tolerate. Patients may experience fatigue, nausea, bowel upset, deep joint achyness and muscle pain as the cryptic orgnanisms are killed and the immune system engages in clean up.


Much of the discomfort from treating Cpn is a combination of the organism's endotxin itself, and the inflammation caused by your own immune system (cytokine) reactions to that.

SUMMARY

Amoxicillan and NAC kills the infectious spore-like EB forms which build up in the tissues.

Rifamcin kills EB’s transforming to RB’s in a vulnerable enzyme transformation phase.

Doxycycline and either Rozithromycin or Azithromycin, are used in combination to interfere with the RB’s ability to replicate. Two are used which work on different proteins to minimize creating resistance.

Five days a month of metronidazole or tinidazole (added to the first two continuous antibiotics) targets the cryptic formi, to kill the bacteria outright.

Supplements are recommended to help counter the impact of Cpn on the body, and of the inflammatory effect of the die off during treatment.

Treatment can take months to years to completely eradicate Cpn from the body.

What diseases has it been implicated in?
Additionally: chronic obstructive pulmonary disease, uveitis, optic neuritis, radiculitis, nerve deafness, transverse myelitis, sarcoid, myocarditis, pericarditis, culture-negative endocarditis, atheromatous arterial disease, aneurysm, giant-cell (temporal) arteritis, polyarteritis nodosa, Wegener's granuloma, primary sclerosing cholangitis, reactive arthritis, Reiter's syndrome, Behcet's disease, cutaneous vasculitides including pyoderma gangrenosa. Wheldon adds: "Conditions which may suggest the possibility of flare-ups of chronic Chlamydia pneumoniae infection deserving serological investigation include the following — a multiplicity being more strongly suggestive: recurrent sinusitis, recurrent chest infections, chronic fatigue (especially if following a respiratory infection), focal neurological deficits, myalgia, muscle fasciculation's, recurrent episodes of bronchospasm, unexplained pleuritic pain, angina, recurrent arthralgia, unexplained recurrent abdominal pain, unexplained menorrhagia, recurrent fistula-in-ano, recurrent cutaneous vasculitides, achalasia, intestinal dysmotility."
Jim K Wed, 2005-10-12 23:58

Slide Presentation on Cpn from Charles Stratton

Slide Presentation on Cpn from Charles Stratton

Although focused on respiratory disease, this slide show provides and excellent summary of Cpn in general, and why combination antibiotic therapy is so important.

Click This Link for a powerpoint presentation by Charles Stratton on Cpn.

It includes great pictures of the organism at different life phases, and links Cpn various diseases.

Download a .pdf file of the slide show, thanks to Red (!) CLICK HERE
Jim K Sun, 2005-09-11 12:38

The Basics Page

The Basics Page

Hello and Welcome!

This site is focused on treatment of chronic disease like Multiple Sclerosis (MS) Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FMS) an many other diseases with antibiotics. Recent research indicates that Chlamydia Pneumoniae (CPn) plays a role in these diseases.

Here are the basics that make it easier for people new to the site to get going (if your brain isn't ready for even this much right now-- we've all been there-- read Cpn Simple first):

Is this a sexually transmitted disease? No. this is chlamydia pneumoniae, a bacteria that can cause pneumonia. It may soon be called chlamydiophilia (meaning in the family of).

Is chlamydia pneumoniae (CPn) rare?

No it is a common cause of respiratory illness, but it has an interesting and abnormal way of existing because it can change forms and inhabit the very cells of your body. It can go into your monocytes (a blood cell), your macrophages (an immune cell), microglia (a brain cell that causes immune reaction) endothelial cells (blood vessels) and others and actually take over.  We say then it has parasitized the cell. Your cell can't do the work it was meant to do now because it's busy supporting the CPn, all the energy of the cell going to make energy for the CPn and it using that energy to make new CPn cells.  For all intents and purposes, your cell is no longer a functional cell and cannot do what it was designed to do.

How does it spread?

From person to person when in the respiratory tract it is spread by droplets; in a cough for example. The form that goes from one to another is the elementary body (EB), a tough, little tiny bacteria. It may actually cause pneumonia in the respiratory tract. In some cases once inside, the EB will look for a home (cell) to parasitize so it can have an energy source. Once inside the cell the EB turns into a reticular body (RB) which can produce new infective cells (EB's) that can find and parasitize other cells. Gradually the cells of your body lose the ability to do what they were meant to do. They are now supporting CPn lifecycle and not taking care of your lifecycle. If it's a monocyte that's infected for example, it is now a factory for EB's not a functional monocyte.  We say then the CPn has parasitized the cell.

Click here for a detailed explanation of of Cpn

Why doesn't my immune system kill it?

This is a complex question. It depends on where the infection is and how advanced it is and what cells have been infected. People who get CPn as a form of pneumonia and do have an active immune response to the bacteria in that instance, though as a form of pneumonia it is mild. Often it is referred to as "walking pneumonia" because people, while ill, are not prostrate with it. Since most people get CPn in their lifetime and get over it as evidenced by rising titers to the bacteria, we can assume that most of the time the immune response is effective enough to for all intents and purposes "get over it."

In some people however, perhaps because of their genetic makeup or some other factor, the bacteria is carried in blood or immune system cells In this case it "goes underground" and infects the tissues far from the origin of the lungs. Key to this discussion is that your immune system cells are some of the ones that now have these nasty little bacteria hiding in them, so where the immune system goes, the CPn goes too and over time may render the immune cells less effective.

Second, the germ is INSIDE the cells. Your immune system can't see them in there. Your immune system "sees" what is "you" and what is "foreign" by looking at the proteins on the outside of the cell wall. The outside of this cell is you. For all your system knows, it is a friendly cell, so your immune system is quiet and unexcited. Meanwhile the stealthy pathogen is hiding, slipping into the cells and taking over one cell at a time, and one cell at a time they are now CPn factories not whatever they were meant to be.

While in some cases CPn is a fairly "benign" germ under certain conditions such as when it is attacked by antibiotics or "starved" it becomes cryptic or shuts down so it can't be harmed or detected. When cryptic it is so quiet and hidden in the body, your body does not really notice it. It then becomes active at some later time causing a "new" infection, perhaps in new parts of the body.

Changing forms of Cpn

This bacteria diabolically can change from any form, EB, RB, Cryptic or persistent, to any other form based on the environment. It will choose the form least affected by whatever is threatening it! If you take an antibiotic, let's say for a bladder infection, the CPn will hide in a non replicating and non metabolizing form until the threat is over and your internal environment is less hostile. Virtually all people will have rising titers to CPn over their lifetime, meaning they have been exposed and make antibodies to it from the occasional experience with it as a respiratory pathogen, but also perhaps because they harbor this cryptic form which later "wakes up" and then subsides or is treated. But as a cryptic pathogen we know little about it. It is just emerging as a known cause of disease. The Centers for Disease Control list it as an Emerging Pathogen in atherosclerosis. See the slides to see pictures of these germs in the cells.here

Why do steroids help MS then? This question was asked to Dr Wheldon and Dr A. The answer is found here

Why is it true that your doctor does not tell you about this?

This is new understanding and it's not well defined yet. For example why is it cryptic in some people? We are not certain at all. The CPn was first seen in 1965 and was identified as the cause of an outbreak of pneumonia in the early 80's. Before that time we had no research or concept about bacteria with lifecycles that included changing forms from one to another and hiding inside the cells of your body. Bacteria were seen as one form either a cocci, or a spirochete, or a rod and you were given one antibiotic and it would go away. Everyone who was trained in medicine was taught this and spent long hours studying these facts.

Now, research on CPn indicates it plays a role in several chronic diseases by using these peculiar and not well understood ways of being in the body. We have to go back to the books and learn a whole new kind of bacterial science where germs evade and hide from our treatments in ways that seem impossible or outlandish based on prior learning and understanding. New knowledge takes time to filter into the mainstream because physicians spend so many years studying biochemistry and microbiology that they feel like experts. This is so different that it sounds "wrong". Also some other research seems to find it is not a factor in chronic illness, which gives the individual physician a sense this is too new to act on yet.

For example, some research in CPn in multiple sclerosis (MS) does not find an increased incidence of CPn in the nervous system in people with MS while other research does find CPn DNA in the nervous system of people with MS. This creates doubt in the minds of physicians and a sense that we need to wait for more definitive research before acting. And finally, medicine is extremely slow to change paradigms.

We have a superb example of this in helicobacter pylori, a bacteria, in peptic ulcer disease. This bacteria was discovered in 1982 by Barry Marshall. He produced a large amount of good research on h. pylori causing peptic ulcers that went largely ignored. Why? Because "everyone knew" that bacteria could not survive in the stomach (wrong) and he literally had to swallow the bacteria himself and prove that it then caused him an ulcer. When he healed it with antibiotics others to finally accepted his research. It's very difficult to get medicine in general to accept new science, even if it's absolutely correct.

I bet you're thinking that everyone gets antibiotics for ulcers these days, but you'd be wrong. Up to 9 out of 10 ulcers can be healed by treating with appropriate antibiotics for 2 weeks. Yet today, 23 years after the discovery that ulcers are caused by bacteria, not lifestyle or stress, over 50% of ulcers are STILL treated with proton pump inhibitors (medicines that decrease stomach acid)or other palliative measures that do not kill the bacteria, which also may play a role in gastric cancer. This link is to the American Centers for Disease Control detailing these facts HERE There is a serious "blind spot" in medicine about potential infectious causes of chronic disease. Clearly, even a proven fact can still be ignored by doctors.

Why does research say it's not a factor sometimes?

The fact of the matter is that CPn in cryptic form, that means in the cells in an unmetabolizing and non relicating form, is hard to detect. It's virtually impossible to detect without extremely complicated procedures and even in the infectious form it is hard to detect with sensitive DNA (PCR, below) tests, let alone less sensitive antibody tests. You cannot just see if the person is making antibodies to the bacteria as you would in other infections and as mentioned above, people have rising titers (rising numbers of antibodies) to CPn over their lifetimes as most all of us are exposed repeatedly.

Instead of checking for antibodies a newer advanced kind of technique must be done called polymerase chain reaction (PCR) to see if CPn is in the tissue. This technique uses small amounts of DNA to detect the presence of the bacteria, not the old method of just screening the blood to see if you have antibodies to CPn.

The trouble with this is that just like our understanding of CPn is growing so is our understanding about how to detect it. Labs are developing ways of finding and testing for the DNA fragments, however this is still early days. Some labs use one part of the DNA for detection; others use another. This accounts for discrepancy in results as it has not yet been agreed upon by everyone that one lab's approach is the clear winner for accuracy.

It appears at this time that the Vanderbilt University test is the best at detecting the DNA via PCR. They have doccumented that they have concordance with split samples. In other words, samples tested as positive are positive and negatives are negative in a second test done at another lab. VU finds CPn in the majority of MS cases.

Another reason we have confusion about whether CPn is in chronic disease or not is some research almost inexplicably seems to be set to NOT find it. For example, just testing the antibody titers of people with MS or CFS or FM and people who have no chronic disease is sure to result in no difference between the groups since this is a common bacteria we all will be exposed to over our lives. Yet we still see some "research" doing exactly this; saying that the titers were the same in both the chronic illness group and the normal group and reaching a conclusion that CPn plays no role in the disease. This is silly! The question is not have you been exposed to CPn and do you have a high titer, the question is whether it is an active infection and or whether it has gone cryptic in your particular case. There is no consensus yet as to how to determine that all important question. However evidence is emerging, and in some areas it's substantial (as it is in the area of atherosclerosis) that CPn is the cause of chronic illness. The CDC lists CPn as an emerging pathogen in the cause of atherosclerosis.

What is empirical treatment for Cpn?

If you are tested as positive for Cpn either through antigen or PCR testing, then you clearly know you need to treat it. In that case, know that the standard two week course of a single antibiotic may be inadequate to kill the Cpn in some of it’s life-phases, and re-infection can occur unless a combination antibiotic protocol such as the Vanderbilt or Wheldon protocols, is followed. But if you have any of the diseases in which Cpn has been implicated (see list on Home page), it may be worth doing an “empirical” (based on symptoms) course of a combination antibiotic protocol even if your tests for Cpn are negative or uncertain. The antibiotics used are not considered harmful, even for long courses. If you have Cpn involved in your disorder and try this protocol you will likely experience the following: an inflammatory reaction or worsening of some of your symptoms (caused by the bacteria dying and releasing it’s toxin in larger amounts), followed by a gradual improvement in your disease symptoms. Reactions to treatment can range from mild, if your load of Cpn is not great, to very strong and uncomfortable. In the latter case, you have to go very slowly to get to full dose of the protocol. Similarly, improvements in your condition depend on how long you have been infected, and what your total load of Cpn is, and how much permanent damage it might have created to your body.

Why are there so many antibiotics?

CPn exists in your body in several different forms. The first is the elementary body. It is small hard and is not actively replicating or metabolizing. It is "looking" for a cell to adhere to and be absorbed by. At this stage amoxicillin can force the EB into the cells.

Once inside a cell, the EB goes through a transformation becoming metabolically active and replicating. To make this transformation, proteins are used and reassembled to cause the change. It grows huge compared to it's EB size and when the transformation is complete, it takes over the cell's energy system, robbing all the energy for it's own purposes. At this point the tetracycline antibiotics block one of the proteins used in the transformation process (that's how antibiotics work; by blocking proteins used to replicate) so the EB is stuck halfway transformed to an RB (replicating body).

Now, one of the problems we have with antibiotics in general is that bacteria are very crafty and they have "learned" to resist different antibiotics by replicating using different pathways than before so the blocked protein is no longer needed. This is what we mean by resistance. A certain bacteria is no longer stopped by a certain antibiotic from replicating. The concern about CPn resistence can be stopped in it's tracks by adding a macrolide antibiotic such as rifampin, azithromycin or roxithromycin in addition to tetracyclines because it blocks protein synthesis in a second part of it's pathway. It is effectively impossible for CPn to develop resistance with this double whammy.

Both the tetracyclines and the macrolides are considered bacteriostatic. They do not kill germs outright, but stop replication so your body can clean up and win the battle without a growing bacterial population to deal with. In the case of CPn however, the EB is stuck halfway converted. It is not able to take over the cell's energy system, so it's on it's own. It has some rudimentary ability to survive on it's own in this anaerobic (without oxygen) state, but not much. As a result a number of the CPn germs will die causing an endotoxin reaction (see below) even though at this stage you are only taking bacteriostatic drugs.

However a good number of the bacteria will survive even though many die under the stress of living stuck halfway between EB and RB, reducing the overall bacterial load by a good margin. This brings us to flagyl (metronidazole). This antibiotic kills the CPn outright, causing for some people a big reaction to the endotoxin, depending on how extensive the bacterial load still is for them as they begin it's use. For this reason, many people wait a number of months after starting the bacteriostatics before taking their first dose of flagyl. Then, they may take flagyl for only one dose the first time they take it, then wait for the body to recover a bit before dosing again. Pulsing the flagyl kills off some germs,  then gives the body and tissues reacting to the released LPS a rest.

The Wheldon regimen recommends using the flagyl for 5 days once every three weeks while continuing to take the other antibiotics. Effectively the CPn is stuck by the bacteriostatic agents waiting to be killed by your next flagyl pulse, though some die simply waiting. The VU protocol recommends flagyl without rest in between and amoxicillin to force the EB's into the cells where they can be killed by the flagyl. This can result in a fairly vigorous LPS reaction (below). Dr A stated in his interview he has no probelm with people pulsing flagyl if they wish to do so.

What is endotoxin and how is that related to "herxheimer"?  

Endotoxin is a lipopolysaccharide (LPS), the protein that is on the outside of every gram negative bacteria.  A gram negative bacteria is one that does not take gram stain.  LPS is very immunogenic meaning it causes a brisk reaction by the immune system to it's presence.  When gram negtive bacteria die, either naturally or by antibiotic, the resulting load of LPS floating around is toxic to the person. "Toxic shock syndrome" is a reaction to LPS in a gram negative bacteria.  The kinds of reactions to LPS vary a bit depending on the bacteria in question, some being more toxic than others.  CPn LPS is not very toxic as far as LPS goes, though it does cause a noticable reaction, it's not threatening as other LPS can be. 

Syphilis as another gram negative bacteria.  When antibiotics were first applied to this dread disease, the patients got markedly worse as the LPS built up in thier systems.  This was named for the doctors that described it as "Jarisch Herxheimer Reactions".  It has been specualted that the phrase "you have to get worse before you get better" came from this phenomenon.  Today the term herxheimer or herx has been in common usage to mean any reaction to a gram negative bacteria.  I have even heard of people using the phrase in relation to the die off of candida after appropriate anti-yeast drugs have been taken.

What diseases has it been implicated in?
  • Multiple sclerosis
  • Chronic fatigue
  • Asthma
  • Arthritis
  • Fibromyalgia
  • Chronic refractory sinusitis
  • Cardiac disease
  • Interstitial cystitis 
  • Prostatitis
  • Crohn's disease
  • Inflammatory bowel disease
  • Alzheimer's disease
  • Additionally: chronic obstructive pulmonary disease, uveitis, optic neuritis, radiculitis, nerve deafness, transverse myelitis, sarcoid, myocarditis, pericarditis, culture-negative endocarditis, atheromatous arterial disease, aneurysm, giant-cell (temporal) arteritis, polyarteritis nodosa, Wegener's granuloma, primary sclerosing cholangitis, reactive arthritis, Reiter's syndrome, Behcet's disease, cutaneous vasculitides including pyoderma gangrenosa. Wheldon adds: "Conditions which may suggest the possibility of flare-ups of chronic Chlamydia pneumoniae infection deserving serological investigation include the following — a multiplicity being more strongly suggestive: recurrent sinusitis, recurrent chest infections, chronic fatigue (especially if following a respiratory infection), focal neurological deficits, myalgia, muscle fasciculation's, recurrent episodes of bronchospasm, unexplained pleuritic pain, angina, recurrent arthralgia, unexplained recurrent abdominal pain, unexplained menorrhagia, recurrent fistula-in-ano, recurrent cutaneous vasculitides, achalasia, intestinal dysmotility."
    mrhodes40 Wed, 2005-09-14 14:49

    Chlamydia Pneumoniae in Human Disease

    Chlamydia Pneumoniae in Human Disease

    These links present this topic best:

    *The pdf of Charles Stratton's review of Cpn in Chronic Disease : http://www.cpnhelp.org/pdfs/ChronicDisease.pdf

    A detailed review of Cpn in chronic diseases at: http://www.chlamydiae.com/Chlamydophila_pneumoniae_introbk.asp

    Crossing the Barriers http://www.cpnhelp.org/?q=node/35

    We will have separate pages eventually which discuss specific Cpn in diseases eventually. For now you can find these reference links as starter points.

    Multiple Sclerosis-

    David Wheldon't site http://www.davidwheldon.co.uk/ms-treatment.html

    and the following links from Marie's excellent compilation on our Research page:

     

    CPn and Cardiovascular Issues

    We have so many links to cardiovascular issues that these are now found on their own page here. Please do read this material even if you are here for something other than cardiovascular problems! While you may be on this site for MS, CFS or FMS, it is the cardiovascular research that has all the depth and impressive volume about CPn and how it causes human disease that makes the picture truly clear. Don't make the mistake of thinking this is some new idea or that it has only a few studies just because it is relatively unknown in one field. This is as significant to human disease as understanding staphylococcus, only we are talking in this case about chlamydia pneumoniae. Information about the germ applies and transfers from one field to the next: the important thing is to understand the pathogen.

    CPn and Arthritis:

    -Antibiotic treatment of arthritis Osteoarthritis when treated with doxycycline has significantly reduced joint space narrowing 40% better than controls.

    Persisitant CPn and Arthritis Great paper overviews the concept of CPn and C. trachomatis as causitive agents in arthritis.

    CPn and Respiratory disease:

    Mechanisms of chlamydiophilia mediated GM-CSF release in HUman Bronchial cellsHow does CPn tirgger inflammatoin in lung tissue? this attempts to pinpoint the answer

    Serum IgG and IgA antibodies to CPn in EmphysemaThis article indicates that serology is positive in emphysema and that clinical course and worsening is tied to CPn status

    Asthma and CPn. Explains interaction of patient immune system with the CPn. Technical.

    -Cpn in recurrent respiratory infections This work with children with recurrent respiratory infections indicates that treating for cryptic bacteria improves outcomes. Treatment was prolonged due to the nature of cryptic, or "atypical" bacteria.

    Chlamydia Pneumoniae and COPD This reserach indicates that acute exacerbations of COPD re associated with CPn.

    -Cpn in asthma This research indicates that cryptic bacteria play a role in asthma. Outcomes were improved by adding abx.

    CPn and other diseases:

     

    Behcets may be CPn related. A disease traditionally thought to be autoimmune is found to have significant titers of CPn.

    -Cpn in prostate pathology This research found CPn in prostates with pathology. It even offers the theory that patholgy from hypertrophy to cancer represents different stages of infection. -Chlamydia Pneumoniae in Interstitial Cystitis Is IC a mystery disease or is it a bacteria? This paper outlines the results of research investigating this.

    Interstitial cystitis and CPn Link out to paper on this subject.

    -Chlamydia pneumoniae in the Alzheimer's brain varies with APOE genotype The APOE genotype apparently interacts with CPn in alzheimers patients carrying that genotype. This suggests an interesting theory: that a bacteria is not the same in every person in terms of effects but rather an interaction between genes and bugs results in the pathology an individual experiences. This is a whole new understanding of how we interact with our environment.

     

    Jim K Sat, 2006-02-04 11:44

    How Chlamydia Pneumoniae Causes Such a Plethora of Diseases

    How Chlamydia Pneumoniae Causes Such a Plethora of Diseases

    The following is a condensation of a slightly longer post which can be found at this link.

    Jim K

    Dr. Charles Stratton's Current Thinking on How Chlamydia Pneumoniae (Cpn) Infection Causes Specific Diseases

     

    Dr. Stratton has been observing the emerging literature and research on Cpn, as well as the clinical trials of new anti-chlamydial agents (see footnotes at bottom of this page). His unique and expert microbiological perspective on Cpn helps to shed some light on how such a singular organism can engender such multiple and varied clinical diseases.

    These observations inform Dr. Stratton’s current thinking about the course and pattern of Cpn infection. I’ve attempted to diagram this below to give the reader a feel for the sequence and locus of Cpn in the body, as well as the resulting disease picture. WHile these should be termed theoretical speculations, his theoretical speculations are based on his considerable research, his expertise in microbiology, and his varied clinical experience in treating numerous Cpn infections in a variety of diseases. The picture he describes makes much clearer the multiple pathways and illnesses caused by Cpn, as well as the challenges in treating it.

     Initial Infectious Entry-

    The initial entry into the body for Cpn infection is through the respiratory system. Studies have demonstrated that Cpn crosses from the lungs into the blood stream via infecting macrophages, the first response immune cells which are trying to combat the respiratory infection.

     

    These circulating infected macrophages both produce EB’s, the infectious spores of Cpn, directly into the blood stream where they attach to and are carried by red blood cells throughout the body (see the picture on our home page), and are taken up by the natural filter organs of the body where they infect those organs with Cpn.

     

    The Inflammatory Trigger:

    Stage is now set for focal diseases: any source of inflammation attracts infected macrophages and white cells as well as EB carrying red cells as part of the body’s natural repair process. Cpn then transfers from damaged macrophages via EB’s and sets up shop in inflamed areas.

     

    At this point in the infection cycle, the type and locus of the Cpn infection then determines which disease will result and manifest symptomatically (the following is meant for example only, and is not intended to be a complete or exhaustive list):

     

     

    Where specialists, and patients, tend to look at a particular disease as the problem, the microbiological perspective Dr. Stratton brings sees the problem as one of a systemically based infection.

     

    Dr. Stratton now posits that the primary infection in Cpn is of the immune system: immune cells & bone marrow.

    • It is this which, in part, causes such difficulty in getting rid of Cpn.
    • It also causes continuous reinfection if the full spectrum of Cpn infection is untreated.
    • It also lowers the body’s ability to cope with other bacterial and viral infections.
    • This, in turn, fosters further sources of inflammation, and even has the potential (through immuno-incompetence) to compromise the body’s ability to fight cancer and other diseases.

     

    It also answers some common questions that arise in Cpn Combined Antibiotic Protocol (CAP) treatment.

     

    Why do viruses and cold sores “surface” during CAP treatment?

    This could be due to apoptosis (cell death) of infected immune cells and resulting neutropenia which temporarily lowers your immune response until these cells are replaced. Hence latent but suppressed viruses and fungi emerge as immune cells, which previously held them in check, die.

     

    Why is aggressive or rapid treatment of Cpn potentially dangerous?

    In addition to the misery of massive endotoxin release from killing Cpn, and related cytokine (inflammatory) responses of pain and brain fog, massive kill of Cpn infected cells in the body could potentially cause crashing white counts and potential organ dysfunction or even organ failure (E.G.. liver failure) as large scale apoptosis of infected immune and organ cells occurs. As there is no quantitative measure of infectious load, and no way other than symptoms to know which organs are significantly infected, it behooves physicians treating Cpn to start gradually until some measure of the patient’s response indicates how quickly one can “ramp up” to full treatment. This also suggests that highly potent anti-chlamydial agents such as Rifabutin are not the best first-line treatment, even though they appear to be more effective at killing Cpn more quickly. Once the load has been brought down through gradual introduction of the regular CAP, then a cautious trial of such other agents can be considered.

     

    Dr. Stratton has been paying close attention to reports of drug trials of Rifabutin, a very potent new anti-chlamydial. Even healthy young volunteers showed lowered white cells and liver problems during the Pfizer trials.

     

    Given that Dr. Lee Stewart’s findings that 20-25% of young, healthy blood donors were found to be  flow cytometry positive for Cpn, Dr. Stratton believes that these effects could be not so much side effects of Rifabutin, as it has been currently viewed, but rather a main effect of the drug, that of killing Cpn and resulting death of previously infected cells.

     

    In other words, since Cpn infection is ubiquitous and often sub-clinical, and “side” effects from potent antichlamydial agents in so-called “healthy” volunteers are actually main effects--- the subjects were not healthy after all, just not clinically ill.

     

    Multi-year treatment process-

    Treating Cpn is a multi-year treatment process because of it’s potential to be widespread throughout in body organs, the vascular system, and immune system, as well as it’s toxicity in treatment (from endotoxins, porphyrins, inflammatory and cellular apoptosis). The more body systems involved, the longer and more difficult it is to treat, both in terms of tolerance of treatment from endotoxins, porphyria and apoptosis, as well as being able to get to all the tissues involved, which have differentials in terms of how antibiotics may concentrate in them. Cpn cells also have active pumps which try to lower concentrations of noxious substances (like antibiotics) which also have to be overcome.

     

    How long treatment will take depends, of course, on the degree of infection, amount of bacterial load, severity of infection and number of organs involved, and so on. We don’t have any quantitative measures of infection currently. A good clinician, knowledgeable about the conditions which Cpn can cause, may be able to make an educated guess as to how many organ systems are involved on the basis of history and symptoms. Dr. Stratton sees the degree of reaction to NAC as a useful rough indicator of EB load—the more you react to it the more EB’s you have built up. He also sees the length of time one has been infected (when symptoms may have started) as a rough indicator of the length of treatment (note: one can only guess at this, as we may have initiated Cpn infection from what seemed a mild respiratory infection many years ago, and did not demonstrate serious problems such as MS until years later).

     

    Dr. Stratton’s rule is “Go as fast as you can but no faster,” i.e. as rapidly as your own particular condition can tolerate given the above factors.

     

    He sees that towards the latter phase of treatment, when one is no longer responding with significant reactions to metronidazole pulses, doing a course of 2 weeks on Flagyl and 2 weeks off while continuing with dual antibiotics, is a useful process to clear remaining tissues. When this is tolerated without significant side effects, a cautious trial of Zithromax and Rifabutin as a final test of Cpn clearance could be tried under careful supervision (watching for plummeting white cells and liver toxicity). At this point one should have cleared organs sufficiently that any apoptosis from the potency of Rifabutin would likely be easily tolerated.

     



    Footnotes: Specific observations

     

    Dr. Stratton has paid particular attention to findings by Dr. Stewart that supposedly young, healthy blood donors are showing positive cultures and flow cytometry for Cpn. Her study showed a number of very important findings with implications for our understanding of Cpn transmission and proliferation in the body.

     

    The first is that approximately 25% of buffy coat samples (a buffy coat is the WBC— white blood cell— portion of spun blood) were culture positive for Cpn. This is not an antigen test, but means that Cpn could actually be cultured or grown in the lab from 25% of white blood cell samples. This means infectious Elementary Bodies are circulating in the blood stream.

     

    The second significant finding in Dr. Stewart’s study, was that approximately 25% of WBC’s were seen by Flow Cytometry to have intracellular Cpn. The work of Yamaguchi, demonstrating messenger RNA from peripheral blood mononuclear cells, suggests that these intracellular Cpn found by Stewart are viable. Thus, we know that viable Cpn in WBCs and infectious Cpn elementary bodies circulate in the blood stream and can go anywhere blood goes and can infect any tissue. I will go into why Dr. Stratton sees this finding as so important in a bit.

     

    Dr. Stratton also notes that, in her study, this 25% of donors infected with viable Cpn, both intracellular and free EB’s, occurred in so-called “young healthy blood donors.” That is, while they were culture-positive for Cpn, they have no disease symptoms and were considered to be a “normal” control sample. Dr. Stratton links this finding to reports from the Pfizer drug trials for Rifabutin, a highly potent anti-chlamydial. In the drug trials for Rifabutin there were some cases of liver failure and also of plummeting white blood cell counts in “healthy” volunteer subjects. This has been interpreted in some places as a potential side effect of the medication.

     

    From Dr. Stratton’s perspective on the biology of Cpn, and utilizing the evidence from Stewart, Yamaguchi and others, if 25% of “healthy” volunteers are in fact infected with Cpn, including potentially liver and immune system (white cells) cells as important sites of infection (see explanation below), then a highly potent anti-chlamydial agent will kill many Cpn in parasitized cells. This could initiate large-scale apoptosis (natural cell death) of those body cells that have been inhibited from apoptosis by the Cpn which previously infected them.

     

    Let me say that again, a little differently. We know that Cpn inhibits apoptosis of its host cell so that the host cell stays alive and the infecting Cpn survives. If you kill the Cpn invader, the host cell is no longer being prevented from it’s natural death and replacement cycle. And If you kill a bunch of Cpn all at once, you have a bunch of your body or organ cells dying all at once, and it takes time for them to be cleared by the immune system and then replaced by the natural cell replacement process. It is this, on a more gradual scale, which David Wheldon has noted makes for continuing die-off like symptoms after a Flagyl pulse has been completed.

     

    So, if a whole bunch of liver cells undergo apoptosis at once then liver failure or liver problems could occur. Similarly, if a whole bunch of immune cells undergo apoptosis then, then macrophages and white cells die and severe neutropenia (lowered white count) could occur. From Dr. Stratton’s perspective, these reports may not be a side effect of the Rifabutin, i.e. an unintended effect of a medication, but rather could be due to it’s main effect—killing Cpn.

     

     

    Jim K

     

    Related References-

     

     

    Prevalence of viable Chlamydia pneumoniae in peripheral blood mononuclear cells of healthy blood donors.

    Yamaguchi H, Yamada M, Uruma T, Kanamori M, Goto H, Yamamoto Y, Kamiya S.

    Transfusion. 2004 Jul;44(7):1072-8. 

     

    Department of Infectious Disease, Division of Microbiology, and the Department of 1st Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.

     

    BACKGROUND: Demonstration of viable Chlamydia (Chlamydophila) pneumoniae in peripheral blood mononuclear cells (PBMNCs) is essential to understand the involvement of C. pneumoniae in atherosclerosis. Nevertheless, the prevalence of viable C. pneumoniae in the blood of healthy donors has not yet been studied. STUDY DESIGN AND METHODS: The presence of C. pneumoniae transcript in PBMNCs from blood of healthy human donors was assessed by real-time reverse transcription-polymerase chain reaction (RT-PCR) with primers for C. pneumoniae 16S rRNA, which is more sensitive than genomic-DNA-based analysis, and by the use of staining with fluorescein isothiocyanate-conjugated chlamydia monoclonal antibody (MoAb). RESULTS: Thirteen of 70 donors (18.5%) showed the presence of bacterial transcript in cultured PBMNCs. The prevalence of bacterial detection and bacterial numbers was significantly increased in PBMNC cultures incubated with cycloheximide. Immunostaining of PBMNCs with antichlamydial MoAb also revealed the presence of bacterial antigen in the PBMNCs judged as positive. Nevertheless, cultivation of C. pneumoniae from all PCR-positive donors was unsuccessful. There was no signifi-cant correlation between the presence of chlamydia and either sex or current smoking habits. A possible age variation, however, in the presence of chlamydia in blood of healthy donors was suggested by the results obtained. CONCLUSION: The bacterial transcripts in PBMNCs obtained from healthy donors were detected by the RT-PCR method. Viable C. pneumoniae may be present in healthy human PBMNCs.

     

    Detection of Chlamydia in the peripheral blood cells of normal donors using in vitro culture, immunofluorescence microscopy and flow cytometry techniques

    BMC Infectious Diseases 2006, 6:23     doi:10.1186/1471-2334-6-23

    Frances Cirino (fcirino@microbio.umass.edu)

    Wilmore C. Webley

    Nancy L. Croteau (Nancy.Croteau@umassmed.edu)

    Chester Andrzejewski Jr. (chester.andrzejewski@bhs.org)

    Elizabeth S. Stuart (esstuart@microbio.umass.edu)

     

    Eur J Haematol. 2005 Jan;74(1):77-83.

    Detection of Chlamydophila pneumoniae in the bone marrow of two patients with unexplained chronic anaemia.

    Nebe CT, Rother M, Brechtel I, Costina V, Neumaier M, Zentgraf H, Bocker U, Meyer TF, Szczepek AJ.

    Central Laboratory, University Hospital Mannheim, Mannheim, Germany. thomas.nebe@ikc.ma.uni-heidelberg.de

    Anaemia of chronic disease (ACD) is a common finding involving iron deficiency and signs of inflammation. Here, we report on two patients with ACD where a persistent infection with Chlamydophila (Chlamydia) pneumoniae (CP) was detected in bone marrow (BM) biopsies. Infection was suspected by routine cytology and confirmed by immunofluorescence, electron microscopy, polymerase chain reaction (PCR) including different primer sets and laboratories and sequencing of the PCR product. This is a first report of chlamydial presence in the BM of anaemic patients. The cases are presented because persistent chlamydial infection may contribute more frequently to chronic refractory anaemia than previously suspected.

     

    Tolerance and Pharmacokinetic Interactions of Rifabutin

    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,

    0066-4804/01/$04.000 DOI: 10.1128/AAC.45.5.1572–1577.2001May 2001, p. 1572–1577 Vol. 45, No. 5

    Copyright © 2001, American Society for Microbiology. All Rights Reserved.

    and Azithromycin

    RICHARD HAFNER,1* JAMES BETHEL,2 HAROLD C. STANDIFORD,3 STEPHEN FOLLANSBEE,4

    DAVID L. COHN,5 RONALD E. POLK,6 LARRY MOLE,7 RALPH RAASCH,8 PRINCY KUMAR,9

    DAVID MUSHATT,10 AND GEORGE DRUSANO11 FOR THE DATRI 001B STUDY GROUP†

    This multicenter study evaluated the tolerance and potential pharmacokinetic interactions between azithromycin and rifabutin in volunteers with or without human immunodeficiency virus infection. Daily dosing with the combination of azithromycin and rifabutin was poorly tolerated, primarily because of gastrointestinal symptoms and neutropenia. No significant pharmacokinetic interactions were found between these drugs.

     

    Severe neutropenia among healthy volunteers

    given rifabutin in clinical trials

    CLINICAL PHARMACOLOGY & THERAPEUTICS DECEMBER 2003 591

    Glen Apseloff, MD

    The Ohio State University

    College of Medicine and Public Health

    Columbus, Ohio

    CLINICAL PHARMACOLOGY & THERAPEUTICS

    Letters to the Editor DECEMBER 2003, p. 592

     

     

    Comparison of azithromycin and clarithromycin in their interactions with rifabutin in healthy volunteers.

    J Clin Pharmacol. 1998 Sep;38(9):830-5

    Apseloff G, Foulds G, LaBoy-Goral L, Willavize S, Vincent J.

     

    Department of Pharmacology, The Ohio State University College of Medicine, Columbus 43210-1239, USA.

     

    A 14-day, randomized, open, phase I clinical trial was designed to examine possible pharmacokinetic interactions between rifabutin and two other antibiotics, azithromycin and clarithromycin, used in the treatment of Mycobacterium avium complex infections. Thirty healthy male and female volunteers were divided into five groups of six participants each: 18 received 300 mg/day of rifabutin, 12 in combination with therapeutic doses of either azithromycin or clarithromycin; the remaining 12 received azithromycin or clarithromycin alone. On day 10 the study was terminated because of adverse events, including severe neutropenia. Fourteen participants who received rifabutin developed neutropenia, including all 12 participants who received azithromycin or clarithromycin concomitantly. Analyses of serum revealed no apparent pharmacokinetic interaction between azithromycin and rifabutin. However, the mean concentrations of rifabutin and 25-O-desacetyl-rifabutin (an active metabolite) in participants who received clarithromycin and rifabutin concomitantly were more than 400% and 3,700%, respectively, of concentrations in those who received rifabutin alone. Physicians should be aware that recommended prophylactic doses of rifabutin may be associated with severe neutropenia within 2 weeks after initiation of therapy, and all patients receiving rifabutin, especially with clarithromycin, should be monitored carefully for neutropenia.

     

    Jim K Sun, 2006-12-24 23:31

    Chlamydia Pneumoniae in CFS/ME & Fibromyalgia

    Chlamydia Pneumoniae in CFS/ME & Fibromyalgia


    Chronic Fatigue Syndrome, Fibromyalgia & Chlamydia Pneumoniae[1]

    Introduction

    (Note: the original page for this became non-functional for some reason. This copy is identical except for some minor text layout details)

    Chronic Fatigue Syndrome (CFS), also called Chronic Fatigue Immunodeficiency Disorder (CFIDS), or called Myalgic Encephalomyelitis (ME) in Great Britain. CFS affects 1 million Americans, with "tens of millions" more who have a fatigue condition that doesn't meet the strict criteria for Chronic Fatigue Syndrome.[2] According to the Center for Disease Control (CDC), which considers CFS an accepted medical condition,[3] there is no officially known cause or cure for CFS or for the related, and often co-occurring, condition of Fibromyalgia Syndrome (FMS).[4]

    Despite the CDC's affirmation, the syndrome and its diagnosis is still considered controversial even in this day and age. Some doctors continue to insist that Chronic Fatigue Syndrome is not a "real" disease entity. It may be rather a surprise to it's sufferers when, naively seeking medical assistance, they find that their doctor doesn't believe that their symptoms are from a "real disease" or merits medical treatment. That there is no known "test" for Chronic Fatigue Syndrome that can conclusively demonstrate its existence is one of the difficulties here.

    Perhaps another difficulty is that medical practitioners are socialized to believe that feelings of their own helplessness are a sign of personal failure. A solution to this psychological conundrum is to blame the patient by "psychologizing" the problem i.e. "It's in your head." Fortunately, acceptance of the legitimacy of the disease has increased in recent years, even if conventional medical treatment for it continues to have little to offer of help.

    As the causal factors of CFS are considered unknown, conventional medical treatment for it and for Fibromyalgia Syndrome are all palliative (symptomatic) in nature: antidepressants for mood and pain associated with it, medications for sleep, stimulants for the fatigue, behavioral strategies, and so on. These can help make life bearable but don't fundamentally change the condition. [5]
    Disease Syndromes: more common than you think -

    Chronic Fatigue Syndrome is often disparaged as being a "syndrome," merely a collection of symptoms, not a disease i.e. a causal entity. Of course, a critique applying to one syndrome should apply to them all, yes? A syndrome is a collection of signs and symptoms (Sign= something you can measure; Symptom= patient reports) that appear to have diagnostic consistency. A syndrome tells you nothing per se about the cause of the problem. Many different causes, and sometimes more than one cause at the same time, can result in a syndrome. Interestingly, the diagnosis of "Pneumonia," just like Chronic Fatigue Syndrome, is actually a syndrome, though it is not referred to as "Pneumonia Syndrome." The diagnosing "pneumonia" does not tell you what is causing it, which can be variously viral, bacterial, food aspiration and so on.

    Similarly, diagnosing Chronic Fatigue Syndrome doesn't tell you about possible causes until further investigation is done. There could be a variety and/or combination of potential causes. There are examples of modern, multi-factorial and case-individualized approaches to CFS/FMS that go far beyond conventional medical ignorance about CFS. These combine both symptomatic treatment and search for possible causal contributors for each specific patient.[6]

    The various causal factors being looked into are amply discussed elsewhere and can be found in any web search. One of the proposed causal mechanisms for at least a sub-set of Chronic Fatigue Syndrome is that of bacterial or viral infection. Especially "occult infections" i.e. those organisms that are either typically overlooked, difficult to test for, or tend to evade the immune system[7]. Within this causal possibility are infectious organisms such as Chlamydia pneumoniae.

    My purpose here will be to present the information that argues for the involvement of Chlamydia pneumoniae in at least a sub-set of Chronic Fatigue Syndrome and Fibromyalgia Syndrome patients. I will outline how Chlamydia pneumoniae's known biology and impact on the body could explain some of the characteristic symptoms and signs of Chronic Fatigue Syndrome.

    At the outset it should be said that Chlamydia pneumoniae is not the only infectious agent that has implicated in Chronic Fatigue Syndrome/Fibromyalgia Syndrome. We certainly don't know if it is involved in all, a subset or merely a co-condition of such cases. But there is good reason to look further at this particular organism's involvement. Most of the argument discounting Cpn's involvement in CFS/FMS has been based on ignorance and poor understanding about the organism itself and the difficulties of testing and treatment for it. This is an attempt at trying to correct this ignorance, and place Chlamydia pneumoniae more clearly in the realm of possible sources for these devastating conditions.

    The Early Vanderbilt Work: Chlamydia pneumoniae in Chronic Fatigue Syndrome-
    The Incomplete Research-

    There is some published work linking Chlamydia pneumoniae to Chronic Fatigue Syndrome/Fibromyalgia Syndrome in medical research journals.[8] But perhaps the most important research in this regard never reached publication. This article is the first thorough description in a public information setting.

    The original initial work at Vanderbilt by Dr. Charles Stratton and his lab on Chlamydia pneumoniae in human disease was actually not first directed at Multiple Sclerosis, as is more commonly believed, but looked Chlamydia pneumoniae in Chronic Fatigue Syndrome. The first grant monies received by Dr. Stratton for Chlamydia pneumoniae research, using the highly sensitive tests they had developed, was from Massachusetts Chronic Fatigue Foundation in the mid to late 1990's.

    Dr. Stratton was asked to test blood samples submitted by the well-known Chronic Fatigue Syndrome physicians Cheney, Peterson & Bell to explore the possible involvement of Chlamydia pneumoniae in their Chronic Fatigue Syndrome patients. As I understand it, the grant was given to these doctors, and the determination of patients was by their own diagnostic selection. This research was never published, for reasons that will be explained later. The lack of publication and follow through of this work may be one of the great tragedies in a long line of them in the history of Chronic Fatigue Syndrome. Many patients may have suffered needlessly from this disease because the strong link between CFS and Cpn has remained largely unknown.
    A remarkable finding:

    In this research Dr.'s Cheney, Peterson & Bell sent blood samples from their own Chronic Fatigue Syndrome patients to Dr. Stratton's Vanderbilt Chlamydia pneumoniae lab for testing. According to Dr. Stratton, they tested 100's if not 1000's of such blood samples. These were tested using both ELISA-based serologic methods and PCR testing using the tests developed by Stratton, et al. at the Vanderbilt Chlamydia Research Laboratory. Dr. Stratton's lab found that the majority (almost 100%) of Chronic Fatigue Syndrome patients were PCR positive for Chlamydia pneumoniae in blood samples.

    That the selected patient group of Chronic Fatigue Syndrome patients had almost 100% positive PCR tests for Chlamydia pneumoniae (actual proteins, which means actual presence of the bacterial particles not only an antigen response which could be remnant from prior infection) is an extraordinary finding. Further, the majority also had either elevated IgM or IgG antibodies to Chlamydia pneumoniae major outer membrane protein cross-confirming the PCR based findings.

    Of course this in-of-itself does not mean Cpn is the cause of CFS. The presence of Chlamydia pneumoniae could be due to some third factor that is part of Chronic Fatigue Syndrome (such as immuno-suppression, etc). But such high of a correlation with one specific organism outweighs every other or biological finding to date in CFS research. No other single variable in the CFS literature even comes close to being found in near 100% of CFS patients. Now, there are some unknowns here, especially the criterian used to select those patient samples sent to Vanderbilt. This remains unknown as of this writing.

    The first research problem:

    They also discovered that many of the randomly selected "healthy controls" were also Cpn PCR positive. This would tend to call into question the tests themselves, i.e. suggesting that the tests are generating false positives. So, they tested a random sample of blood donors to have a larger pool of healthy controls from which to get a baseline comparison for the study's original control group. They found that, of "healthy blood donors" about 20% were Chlamydia pneumoniae positive! This percentage was higher than expected at the time, as it was not yet understood how ubiquitous Cpn is.

    However, it turns out that this matches the figures of Cpn found in recent research with healthy, young blood donors.[9] That these earlier Vanderbilt studies found the percentage of Chlamydia pneumoniae occurring in healthy donors replicating the current accepted findings (which range from 18-25%) lends credence to the accuracy and sensitivity of the tests used to study this original Chronic Fatigue Syndrome sample. In other words, post hoc data suggests that their finding of an incidence of Cpn in healthy "controls" was an accurate one, not an artifact from an inaccurate test.

    The next problem- treatment:

    The obvious next step was to try courses of antibiotics known to be antichlamydial and see if reduction of PCR signal for Cpn correlated with reduction in CFS symptoms. This was done by the by Dr.'s Cheney, Peterson & Bell with a sample of their patients. It turned out that no single antibiotic agent eradicated the Chlamydia pneumoniae PCR signal. So, Dr. Stratton's lab, having laboriously developed the PCR susceptibility tests (described quite elegantly in the patent materials which can be found linked elsewhere in this website) now had to use them to discover which agents or combinations of agents were required to eradicate Cpn completely, such that no PCR signal was evident in blood samples. This is called "sensitivity testing."

    This was a greater challenge than most of us would think. Along the way to infecting mice and cell cultures with Cpn and looking for effective combinations of antibiotics, they discovered that the available laboratory mice and commercial cell cultures widely assumed by scientists to be "clean," and thus proper starting points for introducing new variables, were themselves often infected with Chlamydia pneumoniae. This could seriously skew the interpretation of their tests. So Dr. Stratton's lab had to first develop methods to clear the cell cultures of Chlamydia pneumoniae and prove such clearance using their sensitive PCR testing. This is a remarkable bit of science here. Their finding that common biological laboratory materials are contaminated with Cpn appears also to be relatively unknown.

    From all of this they managed to find that only certain combinations of antibiotic agents (described elsewhere in this website) would completely eradicate Chlamydia pneumoniae from tissue cultures and laboratory mice, as indicated by clearance of Cpn PCR signal. No single antibiotic treatment, nor any series of antibiotics one at a time, was able to eradicate Cpn. Now that they had the combination antibiotic protocol (CAP) protocol, they could test the impact of eradicating Cpn on the resulting CFS symptoms, and then confirm whether patients were actually clear of Cpn from the blood testing.

    And another thing…

    As in all research, there is always another problem ahead. This time the problem was with the reactions to the clinical treatment itself being tried by Dr.'s Cheney, Peterson & Bell, as well as by Dr. Stratton with his own Chronic Fatigue Syndrome patients. The treatment was indeed working to kill Cpn, but the toxicity of the Cpn kill was causing existing symptoms to worsen significantly. The dropout rate using the combination antibiotic protocol (CAP) for Chronic Fatigue Syndrome was very high. Many patients were unable to see it through to the endpoint of the whole of the treatment process—where PCR signal was absent for Cpn. As Dr. Stratton put it to me in an interview, "The cure appeared worse than the disease." It was difficult for the treating physicians to keep patients on the protocol long enough to begin to see significant symptomatic improvement. This was due to two major difficulties.

    Die-off reactions- When combinations were used the die-off reactions from this potent mix could be as bad, or worse, than the Chronic Fatigue Syndrome itself. Little was yet known about how to support patients through these reactions, or what exactly their nature was.
    Length of treatment- Moreover, the length of treatment of Cpn with these combination antibiotic protocols for Chronic Fatigue Syndrome was very long. It was difficult to get patients to "stay the course" without extraordinary support, or dedication on the part of both the patient and the physician.

    It was quite a challenge for the Chronic Fatigue Syndrome physicians, including Dr. Stratton, to know how to manage these responses and how to support their patients to hang in with a treatment that seemed to have little short term gain.[10] Of those patients (a small number) who Dr. Stratton treated personally and who continued after the end of the study through the full course of protocol there was, says Dr. Stratton, "100% improvement of symptoms."

    Why did the eradication of Chlamydia pneumoniae cause such reaction in CFS patients? People treated for actual pneumonia caused by Cpn (community acquired pneumonia) don't appear to have severe reactions to their antibiotics after all.

    First, the combination antibiotic protocol (CAP) was far more effective than a single antibiotic used in standard treatment of Cpn pneumonia because it attacked all of the phases of the Cpn life cycle. A single antibiotic only kills Cpn in one of it's life phases. The symptoms of CFS disease are related to Cpn's toxic and inflammatory impact on the body. The more you kill at once, the more these reactions.

    Secondly, CFS patients appear to have built up a very high load of Cpn, spread through a large variety of tissues: the bone marrow, the connective tissue, the liver, the spleen, the vascular system, heart, and so on. When you have a highly toxic organism being killed in large numbers, in a wide variety of tissues, you have more severity of reactions.

    Additionally, the overall Chlamydia pneumoniae bacterial load appears to be one of the big determining factors in the length of the therapy needed. The higher the load, the longer the therapy required.

    Implied in this also is...

    * The longer one has had the disease,
    * The more organ systems affected,
    * The less resilient the patient from age, additional illnesses, etc.,

    ...The longer and more challenging is the treatment required.

    As a group, patients with Chronic Fatigue Syndrome/Fibromyalgia Syndrome appear to have higher Chlamydia pneumoniae loads in more different organs and tissues, compared to say MS patients, making treatment with the CAP more challenging, longer, and creating a significant dropout rate as it took longer to see the beneficial results versus the immediate term die-off reactions. But further research into this very promising but challenging treatment process was halted before questions about how to improve the treatment process could be answered.

    Research is halted-

    At about this point in the research, word was getting out in the medical community that they were testing blood samples from Chronic Fatigue Syndrome patients. There ensued a deluge of protest from medical colleagues who objected to research with Chronic Fatigue Syndrome being conducted at Vanderbilt. According to Dr. Stratton, the objections were "quite heated."

    Why would microbiological research, as hard-science an aspect of the medicine as one could imagine, stir such heated outrage?

    At that time, the late 1990's the diagnosis of Chronic Fatigue Syndrome was hugely controversial. Even more than it is today. Despite having a CDC case definition, a significant number of physicians believed that Chronic Fatigue Syndrome did not exist as a real medical entity or diagnosis. They believed that it was a false, catchall "syndrome," essentially representing psychiatric problems. Therefore it was not considered a legitimate area of serious scientific medical research.

    The expressed concern was that the reputation of Vanderbilt University, and by extension the protesting physicians who were associated with Vanderbilt, would be sullied by sponsoring work such a medical "non-entity" and be seen as fostering specious science. This kind of reaction was not just reflective of physicians only associated with Vanderbilt of course. In general at this time, scientists or institutions associated with any kind of Chronic Fatigue Syndrome research were seen as incompetents, and were often made pariahs to conventional medicine. CFS research was often a career ender for career scientists. The reactions from potential publication journals at this time were similar. Please remember that this was only 10 or 12 years ago, and these attitudes still exist today in medicine.

    At about this time the grant money for this study ran out. As Dr. Stratton was serving only as the testing laboratory, he did not have access to the patient data himself to have adequate controls over patient selection and the like to make for publishable results. Vanderbilt itself did not have a CFS clinic to draw from.

    As Dr. Stratton's expertise was in Chlamydia, not in CFS, he turned his research interests towards an area of research on Cpn with less diagnostic controversy, and where Vanderbilt did have it's own disease based clinic. Dr. Stratton and his colleagues, spearheaded by Dr. Siram in neurology, shifted the focus of their research to Multiple Sclerosis. This was done in part to have a widely accepted, "legitimate" nosological (diagnostic) entity for research. As an accepted neurological disease, no one could call MS a psychological problem. As many of us know, this research has turned out to be almost as controversial, although for different reasons than the CFS study.

    While one might wonder at Dr. Stratton's penchant for seeking controversy, the reality is that any research that cuts across accepted conventional viewpoints in medicine is likely to face rejection and derision. Anyone who knows Dr. Stratton would know that controversy is not at all a motivator in picking his research areas, Chlamydia is the motivator. Dr. David Wheldon, a colleague and friend of Dr. Stratton's, noted Dr. Stratton's avoidance of the limelight by saying that he "Tends to hide his considerable light under a bushel."

    There are probably other factors operating here as well. Any treatment process requiring a combination of three to four antibiotics for a very long period of time is anathema to most conventionally trained MD's. Most physicians have only the rudiments of microbiology in their training, and no basis to understand the complexities of treating multiple life-phase infectious agents.

    As well, the development of antibiotic resistant strains of bacteria has created a kind of phobia about the long term use of antibiotics amongst most practicing MD's. This attitude is even more true for the use of multiple antibiotics at the same time. It is ironic that physicians who see nothing wrong in pumping patients full of multiple chemotoxic agents for cancer treatment will balk at the suggestion of far less harmful multiple antibiotic agents, calling it "polypharmacy." Ironically too, it is actually the use of multiple antibiotics in the CAP for Chlamydia pneumoniae that truly minimizes the chance of developing bacterial resistance, while repeated courses of single antibiotics, the "conventional medical" approach, creates much higher risk for developing bacterial resistance.

    At any rate, these very interesting findings were never pursued. We still don't know what percentage of CFS patients are PCR positive for Chlamydia pneumoniae, and exactly how much Cpn is the origin of symptoms in this disease syndrome. What we do know is that those of us who have diagnosed CFS/FMS and have positive blood tests for Cpn have benefited, slowly, gradually, but significantly in many of our symptoms from the CAP for Cpn based on Dr. Stratton's work. This improvement is true as well for a number of CFS/FMS patients who, while not testing positive for Cpn using standard tests that are not as sensitive as those used by Dr. Stratton's lab, have evidenced typical die-off reactions to the CAP antibiotics, suggesting Cpn infection. Is it the case for all CFS/FMS? No one knows.

    Chlamydial persistence and antibiotic response-

    Cpn has some unique characteristics which make it both an adaptive parasite, and difficult to eradicate. While over the years, some clinicians treating Chronic Fatigue Syndrome/Fibromyalgia Syndrome patients have tried the use of monotherapy (single) antibiotics with the notion that there might be an occult (hidden) bacterial infection involved in the disease, response by patients has been inconsistent. Some CFS/FMS patients may even have found their own symptoms temporarily improving when on incidental antibiotic treatment, say for ear infections and the like, but improvements not lasting.

    That informal clinical experimenting with antibiotics in CFS/FMS has not resulted in much useful direction of treatment or research has to do with the unique biology and characteristics of Cpn. As these unique characteristics apparently are only known by microbiologists, and little understood by treating physicians, treatment of CFS/FMS with antibiotics has yielded conflicting results. Curiously, this ignorance of important microbiological facts about Cpn (and other infectious organisms) appears to extend to medical Infectious Disease specialists, whose knowledge of microbiology appears shockingly limited, and have not intelligently pursued the possibility of occult infection in these disorders.

    Antibiotics in CFS/FMS have resulted in the whole range of responses:

    * No improvement—leading to the assumption that no bacterial presence is involved.
    * Improvements followed by a return of symptoms after the antibiotic is withdrawn. Since long-term use of antibiotics is discouraged, with the fear of creating resistance, further treatment is often discouraged.
    * Symptoms worsening—leading to the assumption that they are having toxic or allergic effects, and leading to halting antibiotic treatment.

    If, in fact, Cpn causes even a subset of CFS/FMS, the lack of consistency to antibiotic treatment has to be explained. This inconsistency becomes understandable if you know some key features about the biology of Chlamydia pneumoniae.

    No improvement- the antibiotics used may not be effective antichlamydials. Thus a "trial of antibiotics" using the incorrect agent would be expected to yield negative results in the disease symptoms. The sensitivity tests done by Stratton, et al demonstrated clearly that a number of commonly held "high power" antibiotics are not effective against Chlamydia pneumoniae.
    Temporary improvement- One of the great scientific puzzles about Chlamydia pneumoniae has been its ability to persist and reinfect, even treatment by antibiotics. It does this, and evades the immune system and threats such as starvation, by its ability to switch forms and survive in a different life phase that not affected by the particular threat.

    There are three known phases or forms of Cpn:

    1. The infectious, spore-like Elementary Body (EB): only killed by cysteine reducing agents like N-acetyl-cysteine and amoxicillin
    2. Once the EB invades a host cell it converts to the replicating Reticulate Body (RB)- only antibiotics that interfere with replication, such as protein synthase inhibitors doxycycline or azithromycin, affect it.
    3. Finally, Cpn can survive those drugs by converting to the low metabolizing "cryptic" form, which Dr. Stratton's research found is only killed by metronidazole family drugs.

    Thus two weeks, or even two years of a single antibiotic may improve symptoms by suppressing one form of Chlamydia pneumoniae, but symptoms recur as soon as the antibiotic is withdrawn.

    * Worsening- Killing Chlamydia pneumoniae liberates significant amounts of bacterial endotoxins which cause widespread cytokine reactions, including inflammation, pain, depression, low energy and so on. These are precisely the symptoms of Chronic Fatigue Syndrome/Fibromyalgia Syndrome itself. In addition, Stratton's work found that Chlamydia pneumoniae causes a condition of secondary porphyria[11] that engenders further misery and suffering. Reports of strong reactions to antibiotics, and particularly to metronidazole, have lead the treating clinicians to misinterpret these reactions as allergy or drug reactions, and to prematurely withdraw the agent. The reality is that it is these bacterial toxins which are a great part of what causes the symptoms in CFS/FMS, and there is no way to kill Cpn without dumping these toxins into the system and feeling worse. The only question is how to pace it, and what measures can be taken to make it more tolerable.

    Chronic Fatigue Syndrome/Fibromyalgia Syndrome Symptoms & Chlamydia pneumoniae

    When we look at the common symptoms of Chronic Fatigue Syndrome and Fibromyalgia how might they be explained by what we know about Chlamydia pneumoniae biology and infection? In this section I will present a list of the major symptoms and look at how chlamydial biology and our own bodily response to this might generate these often puzzling symptoms.

    Features of Chlamydia pneumoniae (Cpn) and Cpn infection:

    Multi-Organ Infection- Cpn crosses from the respiratory system and can infect multiple organ systems including the nervous system, liver, heart, bone marrow, immune cells, skin, and so on.

    Intracellular Energy Parasite- Cpn reproduces by entering the host cell of your body tissue and stealing the ATP energy molecules that your cells function with.

    Secondary porphyria- Depletion of host cell ATP by Chlamydia pneumoniae means that your cells don't have enough energy to complete their normal biochemical reactions. One of these, the production of heme, requires lots of ATP to come to completion. ATP depletion results in incomplete heme production and a build up of the incomplete byproducts called porphyrins. Porphyrins are neurotoxic and have numerous deleterious effects on the nervous system including anxiety, depression, bowel and digestive disturbance, and interference with sleep, rapid pulse, and even psychosis.

    Chlamydial Endotoxins- Chlamydia pneumoniae contains a number of endotoxins in it's structure, such as LPS and HSP-60. These endotoxins cause widespread inflammation (cytokine cascades) and a host of other metabolic disturbances. These are released chronically in small amounts in Chlamydial pneumoniae infection and in large amounts when Cpn cells are killed.

    Cytokine cascades- Cytokine responses (inflammatory immune reactions) are rampant in Chlamydia pneumoniae infection from a number of sources: to Cpn endotoxins; to the bacterial envelopes left behind by dead Chlamydia pneumoniae bacteria in tissue cause a variety of inflammatory reactions; and even the death of neighboring non-infected healthy cells.[12]

    Antibodies to vitamin B-12- B-12 is an important co-factor in a number of energy and detoxification processes in the body. One of the unique findings of Dr. Stratton's group was that antibodies to vitamin B-12 develop in many Chlamydia pneumoniae infected patients. This means that normal blood levels of this vitamin are insufficient as it is bound to antibodies and useless to body functions affecting energy production and detoxification (methylization).

    With these in mind, let's look at how these, and other factors about Cpn, might explain some of the otherwise mysterious symptoms of Chronic Fatigue Syndrome and Fibromyalgia.
    General, unrelieved fatigue-

    * This is the most characteristic feature of CFS and, other than pain, of FMS.
    * ATP depletion from Chlamydia pneumoniae parasitism simply leaves less energy available for body functions.
    * Fatigue is a main symptom of porphyria.
    * Cardiac infection: Cpn infects the cardiac system, and is a major culprit being investigated as a source of cardiac disease. Parasitization of cardiac muscle by Chlamydia pneumoniae would reduce heart efficiency and contribute significantly to fatigue. A recent paper found evidence of Cpn throughout myocardium, the heart muscle wall. These infected muscles would presumably be functioning at lower efficiency because of ATP depletion, resulting in a chronic cardiac insufficiency. This is consistent with findings of cardiac insufficiency in CFS patients (see Peckerman)." [13] [14]
    * Cytokine cascade in CFS[15]- the typical malaise and fatigue of a cold or flu is caused by the flood of cytokines that are generated in the innate immune response. Chlamydia pneumoniae infection tends to stimulate a chronic innate immune response and this chronic cytokine cascade is an additional source possible in CFS fatigue. This has been called "sickness behavior" i.e. the behavioral responses to an immune cascade. (See "Cytokine dysregulation, inflammation and well-being" in references).

    Tender axillary or cervical lymph nodes

    One of the main routes by which Cpn is carried through the body is the lymphatic system via infected immune cells. Chlamydia pneumoniae infected lymphocytes and/or infection of the lymphatic system itself would easily account for this clinical finding in CFS.[16][17] These lymph nodes in particular drain the upper respiratory system (sinuses, throat, etc), and these areas are a major entry point for Cpn into the body via sinus infection, laryngitis, and so on.
    Immune deficiency[18]

    * Chlamydia pneumoniae can infect bone marrow[19]that is where our immune cells (macrophages, monocytes, neutrophils) are produced. Infected bone marrow will produce infected and thus poorly functioning immune cells resulting in a low-grade immunodeficiency.
    * Co-infections resulting from poor immune functioning from opportunistic organisms- viruses, bacteria, mycoplasms, fungi & yeasts and such- are more likely gain a foothold. These further confuse the clinical picture as to what is cause and what is effect or co-factor, and add to further immune burden and further reduced immune function. The more organisms the immune system (already infected itself) has to deal with, the less resources available for any one thing.

    Cardiac insufficiency-

    Cardiac insufficiency has been identified in CFS patients as a significant correlate to symptom severity[20], so much so that Dr. Paul Cheney (yes, the same one who participated in the CFS/CPN study) has focused on this as his cause celebre for CFS recently.[21] As we have noted, Cpn is parasitic and steals ATP, the energy molecule, from the infected host cell to subvert it for it's own replication process. Heart muscle is one of the most ATP demanding cells. Cpn infection of heart muscle as discussed previously is likely to result in reduced heart efficiency, explaining the results of the Peckerman study and giving a causal element to Dr. Cheney's observations of cardiac dysfunction in CFS. Why Dr. Cheney has ignored the earlier work he participated in, which implicates an organism that is becoming well known for its involvement in cardiac disease, is a real curiosity.

    Exercise intolerance and post-exertional fatigue-

    * Cardiac insufficiency: see cardiac infection comments previously noted. Impaired performance on treadmill commonly noted in CFS/FMS could be similarly explained by this as well as other factors.
    * Muscle and general ATP depletion- Chlamydia pneumoniae is an ATP parasite in infected cells, leaving of this energy molecule for host cells. In a broad based Chlamydia pneumoniae infection stores of ATP would be generally depleted, such that high output exercise would leave a significant ATP deficit in some systems such as the muscular system.
    * Porphyrins- Porphyrin load increases after exercise or exertion because ATP stores, already in short supply because of Cpn parasitism, are used up at rapid rate by muscle activity. This makes even less ATP available for heme production resulting in incomplete heme and its byproducts, porphyrins. An inadequate supply of ATP means that only the amount of exercise up to the ATP limit at that particular moment can be tolerated. The increased porphyrin byproducts result in post-exertional fatigue and long recover time. This is the "over-exert one day, payback for three days" report common to many CFS patients.

    Gastrointestinal problems

    * CFS and FMS patients often have concomitant gastrointestinal problems, ranging from Irritable Bowel Syndrome, poor nutrient absorption, and other problems.
    * Cpn infects endothelial tissues, as it's preferred home, including the endothelial tissues of the gut. Some of the micrographs of Cpn infected cells which can be viewed on this website are of stained intestinal endothelial tissues.[22]
    * Porphyria is notorious for causing chronic gut distress: nausea, intestinal cramping, etc. Chlamydia pneumoniae infection of gut endothelial tissue.
    * Gut co-infections from fungi, bacterial, or yeast resulting from general immunosuppression, or specific Cpn infected gut-immune system will further add to gastrointestinal problems.

    Sleep disorder

    * Porphyrins block GABA receptors, a main cause of anxiety and agitation in porphyria, and likely to interfere with sleep.
    * Melatonin serves a number of functions that are related to protecting cells from oxidation[23] as well as binding inflammatory endotoxins[24] and activating immune functions[25]. Melatonin depletion from it being used up for antioxidant and other metabolic purposes resulting from Cpn infection could result in inadequate amounts left for neurotransmitter production and it's influence on inducing sleep.
    * Hypothalamic infection and disturbance by Chlamydia pneumoniae could be a contributing factor.
    * Cytokine disturbance of sleep regulation.[26]

    Anxiety & depression

    * Porphyrins- noted previously for causing anxiety, depression even psychosis.
    * Depletion of melatonin noted above causes depletion of serotonin in the brain. Inadequate serotonin results in depression, as well as increased pain sensitivity.
    * Cytokine depression- cytokines are clearly linked to causing depressive symptoms.[27]

    Endocrine disturbance (thyroid, periods, etc.)

    * Infection of endocrine gland cells: thyroid, pancreas islet cells, pituitary, pineal, etc.
    * Glucose disturbance- Chlamydia pneumoniae, steals ATP that requires the host cell to absorb and metabolize more glucose. This disturbs glucose homeostasis. "Hypoglycemic" symptoms (must have food now, worsening of inflammatory and porphyric symptoms when get depleted of glucose or during fasting, etc) are common in CFS/FMS and are quite notable in those suffering from disseminated Chlamydia pneumoniae infection. Anecdotally, Chlamydia pneumoniae patients on the CAP report significant lessening of these episodes of these hypoglycemic symptoms over the course of treatment.

    Headaches

    * Porphyrins- one of the neurotoxic effects of porphyrins is headaches.
    * Vascular disturbance direct and indirect- Cpn infects the vascular system leading to high blood pressure (from rigidified vascular walls), headaches, inflammation of blood vessels (including those in the brain), etc.
    * Sympathetic nervous system over activation from chronic upregulated innate immune response caused by infection.[28]

    "Sickness behavior"

    Mentioned earlier, sickness behaviors are the innate, the behavioral responses to cytokines that have been stimulated by infection: feeling lousy, withdrawal, depression, movement avoidance, and energy conserving, etc. [29]
    Cognitive Dysfunction (Brain Fog)-

    This is one of the most frustrating features of CFS/FMS, and one with little explanation in the domain, despite it being one of the most life-impacting symptoms for the sufferer. Cpn infection explains this very wel.

    * Secondary porphyria induced by it and the impact of porphyrins on brain functioning.
    * Cerebral inflammation from circulating cytokines.
    * Brain infection
    * Endotoxins.

    Fibromyalgia Symptoms[30]

    All of the above plus...
    Musculoskeletal pain and inflammation

    * Soft tissue infection by Chlamydia pneumoniae and subsequent inflammation
    * Fibromyalgia Syndrome often starts after injury/accident. In the normal response to tissue repair, injured and inflamed areas attract macrophages. Chlamydia pneumoniae infected macrophages can leave Chlamydia pneumoniae behind in injured/inflamed area. Infection then becomes progressive gradually spreading from that area. As generalized inflammation increases (from free circulating cytokines) these sites are further infected by parasitized macrophages drawn to increasingly inflamed sites, etc. http://www.cpnhelp.org/how_chlamydia_pneumoniae_
    * Porphyrins blocking GABA receptors will also lowers pain tolerance.
    * Generalized cytokine load causes broad based "feels lousy all over."

    The case for Cpn in CFS does not prove that Cpn is always the causal element. As a syndrome, Chronic Fatigue may originate from a variety of causal factors, and these could be different for different patients. But in a disease where modern medicine has had no curative treatment to offer, it is clearly a causal factor worth looking into. Even with negative blood tests for Cpn, an empirical trial of the CAP for Cpn is worth exploring.

    In future articles I hope to discuss some of the potential complexities of treating Cpn in CFS/FMS patients with the Combination Antibiotic Protocol, and some considerations that make treating this different from other Cpn related diseases.

    References

    [1] My deep appreciation to Dr. Charles Stratton for his review and consultation in formulating this article. Beyond that, my tender deepest respect to him for bravery under fire.

    My thanks also to Marie Rhodes, for saving me some grammatical embarrassments!

    [2] http://www.cdc.gov/cfs/cfsbasicfacts.htm#prevalence
    [3] CDC Diagnostic Symptoms-

    1. Unexplained, persistent fatigue that is not due to ongoing exertion, is not substantially relieved by rest, is of new onset (not lifelong) and results in a significant reduction in previous levels of activity.

    2. Four or more of the following symptoms are present for six months or more: .

    • Impaired memory or concentration

    • Postexertional malaise (extreme, prolonged exhaustion and exacerbation of symptoms following physical or mental exertion)

    • Unrefreshing sleep

    • Muscle pain

    • Multi-joint pain without swelling or redness adults

    • Headaches of a new type or severity

    • Sore throat that’s frequent or recurring

    • Tender cervical or axillary lymph nodes
    Other Commonly Observed Symptoms in CFS

    The frequencies of occurrence of these symptoms vary from 20% to 50% among CFS patients. … include abdominal pain, alcohol intolerance, bloating, chest pain, chronic cough, diarrhea, dizziness, dry eyes or mouth, earaches, irregular heartbeat, jaw pain, morning stiffness, nausea, night sweats, psychological problems (depression, irritability, anxiety, panic attacks), shortness of breath, skin sensations, tingling sensations, and weight loss.

    [4] Estimated by the American College of Rheumatology to effect 6 million Americans.

    [5] A popular palliative intervention with “cutting edge” conventional practitioners is Cognitive Behavioral Therapy (CBT). I’m a psychologist by profession and should be fond of my profession’s contributions to a challenging disease. But my personal and professionally informed commentary on the value of CBT as a CFS/FMS treatment is not high. As applied to the condition of Chronic Fatigue Syndrome, CBT may be likened teaching someone to how to become more relaxed and organized while one is standing upon a sinking ship. Thus, metaphorically, CBT teaches one how to adjust their viewpoint as the horizon tilts; how to stop worrying about the water lapping at their feet, how to counter the emotional responses of impending doom, how to relax so their stress doesn’t add water to the already sinking ship, and so on. Like my stubborn friends here at www.cpnhelp.org dealing with Multiple Sclerosis who were often told there’s nothing that can be done but “get comfortable with your disease,” finding comfort in my decline has never been personally attractive to me as a solution.

    Some studies have found CBT “effective” in reducing CFS symptom severity. This makes CBT much beloved by conventional physicians as it, a) Is legitimized by scientific research, b) they feel at least they have something to offer these “difficult-to-help-patients,” and c) CBT still fits comfortably with the continuing vague suspicion that CFS isn’t really a disease at all but is really “all in their head” after all. I have not spoken a single CFS patient, and I have communicated with many, who has found that CBT did anything of significance for them in terms of their disease. This said, CBT does teach highly valuable relaxation, stress management and cognitive strategy skills. These are useful in a disorder highly impacted by stress and which is very cognitively disorganizing. However like all palliative measures, CBT is only helpful at managing the disease, and in this it is not even profoundly so.

    See http://www.meresearch.org.uk/research/reviews/cbt.html for further discussion.

    [6] Effective Treatment Of Chronic Fatigue Syndrome (CFIDS) & Fibromyalgia (FMS) - A Randomized, Double-Blind, Placebo-Controlled, Intent To Treat Study

    Teitelbaum J.*1, Bird B., Greenfield R.*1, Weiss A.*1, Muenz L.*2, Gould L.*3

    [* Annapolis Research Center For Effective FMS/CFIDS Therapies; 466 Forelands Rd., Annapolis, MD 21401; 1) Anne Arundel Medical Center, Annapolis, MD; 2) Gaithersburg, MD; 3) USDA, Beltsville, MD]

    Journal Of Chronic Fatigue Syndrome Volume 8, Issue 2 - 2001

    Background: Hypothalamic dysfunction has been suggested in Fibromyalgia (FMS) and Chronic Fatigue Syndrome (CFS). This dysfunction may result in disordered sleep, subclinical hormonal deficiencies, and immunologic changes. Our previously published open trial showed that patients usually improve by using a protocol which treats all the above processes simultaneously. The current study examines this protocol using a randomized, double-blind design with an intent-to-treat analysis.

    Methods: 72 FMS patients (38 active: 34 placebo; 69 also met CFS criteria) received all active or all placebo therapies as a unified intervention. Patients were treated, as indicated by symptoms and/or lab testing, for: (1) subclinical thyroid, gonadal, and/or adrenal insufficiency, (2) disordered sleep, (3) suspected Neurally Mediated Hypotension (NMH), (4) opportunistic infections, and (5) suspected nutritional deficiencies.

    Results: At the final visit, 16 active patients were “much better,” 14 “better,” 2 “same,” 0 “worse,” and 1 “much worse” vs. 3, 9,11, 6, and 4 in the placebo group (p < .0001, Cochran-Mantel-Haenszel trend test). Significant improvement in the FMS Impact Questionnaire (FIQ) scores (decreasing from 54.8 to 33.2 vs. 51.4 to 47.7) and Analog scores (improving from 176.1 to 310.3 vs. 177.1 to 211.9) (both with p < .0001 by random effects regression), and Tender Point Index (TPI) (31.7 to 15.5 vs. 35.0 to 32.3, p < .0001 by baseline adjusted linear model) were seen. Long term follow-up (mean 1.9 years) of the active group showed continuing and increasing improvement over time, despite patients being able to discontinue most treatments.

    Conclusions: Significantly greater benefits were seen in the active group than in the placebo group for all primary outcomes. Using an integrated treatment approach, effective treatment is now available for FMS/CFS.

    Article link here

    [7] The immune system, atherosclerosis and persisting infection

    http://www.cpnhelp.org/?q=node/129

    [8]

    Article link here

    Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms.

    Nicolson GL, Gan R, Haier J.

    Clin Infect Dis. 1999 Aug;29(2):452-3.

    Chronic Chlamydia pneumoniae infection: a treatable cause of chronic fatigue syndrome.

    Chia JK, Chia LY.

    Torrance Memorial Medical Center, California, USA.

    J Infect Dis. 1992 Jan;165(1):184.

    [9] Detection of Chlamydia in the peripheral blood cells of normal donors using in vitro culture, immunofluorescence microscopy and flow cytometry techniques

    BMC Infectious Diseases 2006, 6:23 doi:10.1186/1471-2334-6-23

    Frances Cirino, Wilmore C. Webley, Nancy L. Croteau, Chester Andrzejewski Jr.,Elizabeth S. Stuart (esstuart@microbio.umass.edu)

    Transfusion. 2004 Jul;44(7):1072-8.

    Prevalence of viable Chlamydia pneumoniae in peripheral blood mononuclear cells of healthy blood donors.

    Yamaguchi H, Yamada M, Uruma T, Kanamori M, Goto H, Yamamoto Y, Kamiya S.

    Department of Infectious Disease, Division of Microbiology, Kyorin University School of Medicine, Tokyo, Japan. hiroyuki@sahs.med.osaka-u.ac.jp

    …”Thirteen of 70 donors (18.5%) showed the presence of bacterial transcript in cultured PBMNCs. …CONCLUSION: The bacterial transcripts in PBMNCs obtained from healthy donors were detected by the RT-PCR method. Viable C. pneumoniae may be present in healthy human PBMNCs…”

    [10] Note- One of the things Dr. Stratton said to me shortly after I started www.cpnhelp.org was that this kind of thing was one of the missing elements in the treatment process: some kind of on-going support community that could help patients through the challenges and confusions of being on a difficult protocol.

    [11] As far as I know Dr. Stratton’s group are the only ones to have found the link between Chlamydia pneumoniae infection and secondary porphyria. It remains unpublished in the scientific literature and so virtually unknown to most medical practitioners.

    [12] http://www.cpnhelp.org/?q=cell_death_and_inflammati

    [13] Article link here

    : Am J Pathol. 2007 Jan;170(1):33-42.

    Persistent Chlamydia pneumoniae infection of cardiomyocytes is correlated with fatal myocardial infarction.

    * Spagnoli LG, Pucci S, Bonanno E, Cassone A, Sesti F, Ciervo A, Mauriello A.

    Cattedra di Anatomia ed Istologia Patologica, Dipartimento di Biopatologia e Diagnostica per Immagini, Universita di Roma Tor Vergata, Via Montpellier 1, Rome, Italy. spagnoli@uniroma2.it

    Acute myocardial infarction (AMI) associated with unfavorable prognosis is likely to be the consequence of a diffuse active chronic inflammatory process that destabilizes the whole coronary tree and myocardium, suggesting a possible common causal agent underlying both conditions. The main objective of this study was to investigate whether Chlamydia pneumoniae (CP) infection occurred beyond the coronary plaques, namely in the myocardium of individuals who died of AMI. The presence of CP cell wall antigen (OMP-2) and CP-HSP60 was investigated in the myocardium and coronary plaques of 10 AMI and 10 age-matched control patients by immunohistochemistry, electron microscopy, and molecular biology. OMP-2 antigens were found in the unaffected myocardium of 9 of 10 AMI patients. Conversely, only 1 of 10 control patients exhibited a positive staining for CP. Moreover, OMP-2 and CP-HSP60 were detected in the whole coronary tree. CP presence was strongly associated with a T-cell inflammatory infiltrate. Our results suggest that CP may underlie both coronary and myocardial vulnerabilities in patients who died of AMI and corroborate the notion that CP may act by reducing cardiac reserves, thus worsening the ischemic burden of myocardium.

    [14] Additional cardiac findings in CFS consistent with cardiac infection by Chlamydia pneumoniae—

    From: Causes of death among patients with chronic fatigue syndrome.

    Journal: Health Care Women Int. 2006 Aug;27(7):615-26.

    Authors: Jason LA, Corradi K, Gress S, Williams S,

    Torres-Harding S.

    Affiliation: DePaul University, Chicago, Illinois, USA.

    NLM Citation: PMID: 16844674

    “… in response to postural stress, 81% of patients with CFS, but none of controls, experienced ejection fraction decreases (suggesting left ventricular dysfunction in the heart) and those with more severe symptoms had greater decreases (Peckerman, Chemitiganti, et al., 2003).

    Patients with CFS might have lower cardiac output, and the resulting low flow circulatory state could make it difficult for patients to meet the demands of everyday activity, and it could also lead to fatigue and other symptoms (Peckerman, LaManca, et al., 2003)…”

    [15] Annals of the New York Academy of Sciences 933:185-200 (2001)

    © 2001 New York Academy of Sciences

    Cytokines and Chronic Fatigue Syndrome

    Roberto Patarcaa

    E. M. Papper Laboratory of Clinical Immunology, Department of Medicine, University of Miami School of Medicine, Miami, Florida 33101, USA

    Address for correspondence: E. M. Papper Laboratory of Clinical Immunology, Department of Medicine (R-42), University of Miami School of Medicine, P.O. Box 016960, Miami, FL 33101.

    http://www.annalsonline.org/cgi/content/abstract/933/1/185

    [16] Vestn Ross Akad Med Nauk. 2005;(2):17-22.

    The immune system, atherosclerosis and persisting infection

    Pigarevskii PV, Mal'tseva SV, Seliverstova VG.

    Article Link here

    [17] Eur Respir J. 2004 Apr;23(4):506-10.

    Phagocytes transmit Chlamydia pneumoniae from the lungs to the vasculature.

    Gieffers J, van Zandbergen G, Rupp J, Sayk F, Kruger S, Ehlers S, Solbach W, Maass M.

    Institute for Medical Microbiology and Hygiene, University of Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany. jens.gieffers@hygiene.ukl.mu-luebeck.de

    Chlamydia pneumoniae, a major cause of community-acquired pneumonia, primarily infects the respiratory tract. Chronic infection of nonrespiratory sites, such as the vascular wall, the brain or blood monocytes, requires evasion from the lungs and spreading via the bloodstream. The cell types involved in dissemination are insufficiently characterised. In this study, New Zealand White rabbits were infected intratracheally with C. pneumoniae, and lung manifestation and systemic dissemination were monitored by polymerase chain reaction and immunohistochemistry. Infection of the lungs was characterised by an early phase dominated by granulocytes and a late phase dominated by alveolar macrophages (AM). Granulocytes, AM and alveolar epithelial cells acted as host cells for chlamydiae, which remained detectable for up to 8 weeks. AM transported the pathogen to the peribronchiolar lymphatic tissue, and subsequently C. pneumoniae entered the spleen and the aorta via dissemination by peripheral blood monocytes. In conclusion, Chlamydia pneumoniae-infected alveolar macrophages transmigrate through the mucosal barrier, and give the pathogen access to the lymphatic system and the systemic circulation. Infected peripheral blood monocytes are the vector system within the bloodstream and transmit the infection to the vascular wall. This is the first description of granulocytes acting as a reservoir for Chlamydia pneumoniae early in infection.

    Article link here

    [18] From: Causes of death among patients with chronic fatigue syndrome.

    Journal: Health Care Women Int. 2006 Aug;27(7):615-26.

    Authors: Jason LA, Corradi K, Gress S, Williams S,

    Torres-Harding S.

    Affiliation: DePaul University, Chicago, Illinois, USA.

    NLM Citation: PMID: 16844674

    People with CFS appear to have two basic problems with immune function: immune activitation as demonstrated by elevations of activated T lymphocytes, including cytotoxic T cells and elevations of circulating cytokines; and poor cellular function, with low natural killer cell cytotoxicity and frequent immunoglobulin deficiencies (most often IgG1 and IgG3; Patarca-Montero, Mark, Fletcher, & Klimas, 2000).

    For example, Antoni, Fletcher, Weiss, Maher, Siegel, and Klimas, (2003) found that patients with low natural killer cell activity (NKCA) and a state of overactivation of lymphocyte subsets (e.g., CD2+CD26+% activation markers) had the greatest fatigue intensity and greatest fatigue-related impairments in emotional and mental functioning. It seems that the Th2 cytokines are dominant over the Th1 cytokines.

    In addition, Suhadolnik and colleagues (1997) found a novel low-molecular-weight (37 kDa) binding protein in a subset of individuals with CFS who are severely disabled by their disease. A European team (De Meirleir et al., 2000) has also found increased levels of 80 kDa and 37 kDa RNase L in patients with CFS. The ratio of this 37 kDa protein to the normal 80 kDa protein was high in 72% of patients with CFS but only in 1% of the healthy controls and in none of the depression and fibromyalgia control patients.

    [19] Eur J Haematol. 2005 Jan;74(1):77-83.

    Detection of Chlamydophila pneumoniae in the bone marrow of two patients with unexplained chronic anaemia.

    Nebe CT, Rother M, Brechtel I, Costina V, Neumaier M, Zentgraf H, Bocker U, Meyer TF, Szczepek AJ.

    Central Laboratory, University Hospital Mannheim, Mannheim, Germany. thomas.nebe@ikc.ma.uni-heidelberg.de

    Anaemia of chronic disease (ACD) is a common finding involving iron deficiency and signs of inflammation. Here, we report on two patients with ACD where a persistent infection with Chlamydophila (Chlamydia) pneumoniae (CP) was detected in bone marrow (BM) biopsies. Infection was suspected by routine cytology and confirmed by immunofluorescence, electron microscopy, polymerase chain reaction (PCR) including different primer sets and laboratories and sequencing of the PCR product. This is a first report of chlamydial presence in the BM of anaemic patients. The cases are presented because persistent chlamydial infection may contribute more frequently to chronic refractory anaemia than previously suspected.

    [20] Am J Med Sci. 2003 Aug;326(2):55-60.Click here to read Links

    Abnormal impedance cardiography predicts symptom severity in chronic fatigue syndrome.

    Peckerman A, LaManca JJ, Dahl KA, Chemitiganti R, Qureishi B, Natelson BH.

    Department of Neurosciences, CFS Cooperative Research Center, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA. apeckerm@njneuromed.org

    BACKGROUND: Findings indicative of a problem with circulation have been reported in patients with chronic fatigue syndrome (CFS). We examined this possibility by measuring the patient's cardiac output and assessing its relation to presenting symptoms. METHODS: Impedance cardiography and symptom data were collected from 38 patients with CFS grouped into cases with severe (n = 18) and less severe (n = 20) illness and compared with those from 27 matched, sedentary control subjects. RESULTS: The patients with severe CFS had significantly lower stroke volume and cardiac output than the controls and less ill patients. Postexertional fatigue and flu-like symptoms of infection differentiated the patients with severe CFS from those with less severe CFS (88.5% concordance) and were predictive (R2 = 0.46, P < 0.0002) of lower cardiac output. In contrast, neuropsychiatric symptoms showed no specific association with cardiac output. CONCLUSIONS: These results provide a preliminary indication of reduced circulation in patients with severe CFS. Further research is needed to confirm this finding and to define its clinical implications and pathogenetic mechanisms.

    Article Link Here

    [21] http://www.cfids-cab.org/MESA/Lerner.html

    [22] http://www.cpnhelp.org/cpn_in_gi_tract_tissue_1

    http://www.cpnhelp.org/cpn_in_gi_tract_tissue_2

    http://www.cpnhelp.org/cpn_in_gi_tract_tissue_3

    [23] Recent Patents on Endocrine, Metabolic & Immune Drug Discovery 2007, 1, 63-82 63

    Melatonin as Antioxidant Under Pathological Processes

    Cristina Tomás-Zapico*, Ana Coto-Montes1

    Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain

    http://www.bentham.org/emi/samples/emi1-1/Tom%E1s-Zapico.pdf

    [24] Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents

    endotoxemia in lipopolysaccharide-induced multiple organ dysfunction syndrome in rats

    ELENA CRESPO,* MANUEL MACI´AS,* DAVID POZO,† GERMAINE ESCAMES,*

    MIGUEL MARTI´N,* FRANCISCO VIVES,* JUAN M. GUERRERO,† AND

    DARI´O ACUN˜ A-CASTROVIEJO*,1

    www.fasebj.org/cgi/reprint/13/12/1537.pdf

    [25] J Immunol. 1994 Sep 15;153(6):2671-80.

    Activation of human monocytes by the pineal hormone melatonin.

    Morrey KM, McLachlan JA, Serkin CD, Bakouche O.

    Department of Molecular Pharmacology and Biologic Chemistry, Northwestern University Medical School, Chicago, IL 60611.

    To determine the effects of the pineal hormone melatonin on human monocytes, human monocytes were activated by different concentrations of melatonin. Above the activation threshold of 5 x 10(-11) M, melatonin was able to induce the cytotoxicity of human monocytes, the secretion of IL-1, and the production of reactive oxygen intermediates. Melatonin and LPS seemed to have a synergistic effect on human monocyte activation. Indeed, below their respective monocyte activation threshold (5 x 10(-11) M and 0.625 ng/ml), melatonin (10(-12) M) in association with LPS (0.2 ng/ml) was able to induce cytotoxicity, IL-1 secretion, and reactive oxygen intermediates production. Melatonin alone at 10(-12) M or LPS alone at 0.2 ng/ml did not activate monocytes. Furthermore, melatonin was able to prime the monocytes for a subsequent activation by LPS. When monocytes were activated by LPS (0.25 ng/ml) at the time that they were plated and then activated by melatonin (10(-12) M) 8 h later, no IL-1 secretion and no cytotoxicity were detected. However, when the cells were first activated by melatonin (10(-12) M), and then 8 h later by LPS (0.25 ng/ml), IL-1 secretion and monocyte cytotoxicity were observed. Above its monocyte activation threshold, melatonin induces both cell-associated IL-1 alpha and IL-1 beta activities. Below this activation threshold, i.e., at 10(-12) M, melatonin does not induce the cell-associated IL-1 alpha and IL-1 beta activities, but does induce the mRNA for both IL-1 (alpha and beta). It seems that melatonin activates monocytes through protein kinase C. These data suggest that melatonin activates monocytes and induces their cytotoxic properties, along with the IL-1 secretion.
    Article link here

    Annals of the New York Academy of Sciences

    Volume 933 THE ROLE OF NEURAL PLASTICITY IN CHEMICAL INTOLERANCE Page 211 - March 2001

    Annals of the New York Academy of Sciences 933 (1), 211–221.

    The Role of Cytokines in Physiological Sleep Regulation

    * James M. Kruegera et al

    Article link here

    [27] “…cytokine treatment causes serotonin depletion. They hypothesized that cytokines suppress serotonin by activating the enzyme indoleamine-2,3-dioxygenase (IDO) that catabolizes tryptophan. Dr. Dantzer explained that in the brain, IDO prevents tryptophan from being turned into serotonin, which causes decreased levels of serotonin and leads to the symptoms of depression.”

    Dr. Dantzer pointed out that his current research is built on a concept that he had ignored a few years ago, which is the fact that the brain is representing what is going on in the body—“what we already knew for quite a long time, but in terms of inflammation, and it is doing that with the same molecules as the ones that are promoting inflammation at the periphery. If you have an inflammatory response in your body, it will be represented in the brain with exactly the same molecules that in your body are responsible for inflammation. This normally is responsible for what we call sickness behavior—why you feel sick and behave in a sick way when you are ill.”

    http://www.neuropsychiatryreviews.com/sep04/sep04_npr_inflammatory.html

    [28] Migraine: A Chronic Sympathetic Nervous System Disorder

    Stephen J. Peroutka

    http://www.medscape.com/viewarticle/466937_1

    [29]Illness, cytokines, and depression.

    Ann N Y Acad Sci. 2000;917:478-87.

    Yirmiya R, Pollak Y, Morag M, Reichenberg A, Barak O, Avitsur R, Shavit Y, Ovadia H, Weidenfeld J, Morag A, Newman ME, Pollmacher T.

    Department of Psychology, Hebrew University, Hadassah Hospital, Jerusalem, Israel. msrazy@mscc.huji.ac.il

    Various medical conditions that involve activation of the immune system are associated with psychological and neuroendocrine changes that resemble the characteristics of depression. In this review we present our recent studies, designed to investigate the relationship between the behavioral effects of immune activation and depressive symptomatology. In the first set of experiments, we used a double-blind prospective design to investigate the psychological consequences of illness in two models: (1) vaccination of teenage girls with live attenuated rubella virus, and (2) lipopolysaccharide (LPS) administration in healthy male volunteers. In the rubella study, we demonstrated that, compared to control group subjects and to their own baseline, a subgroup of vulnerable individuals (girls from low socioeconomic status) showed a significant virus-induced increase in depressed mood up to 10 weeks after vaccination. In an ongoing study on the effects of LPS, we demonstrated significant LPS-induced elevation in the levels of depression and anxiety as well as memory deficits. These psychological effects were highly correlated with the levels of LPS-induced cytokine secretion. In parallel experiments, we demonstrated in rodents that immune activation with various acute and chronic immune challenges induces a depressive-like syndrome, characterized by anhedonia, anorexia, body weight loss, and reduced locomotor, exploratory, and social behavior. Chronic treatment with antidepressants (imipramine or fluoxetine) attenuated many of the behavioral effects of LPS, as well as LPS-induced changes in body temperature, adrenocortical activation, hypothalamic serotonin release, and the expression of splenic TNF-alpha mRNA. Taken together, these findings suggest that cytokines are involved in the etiology and symptomatology of illness-associated depression.

    Neuroimmunomodulation. 2005;12(5):255-69.

    Cytokine dysregulation, inflammation and well-being.

    * Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP.

    Division of Rheumatology, Immunology and Allergy, Georgetown University Medical Center, Washington, D.C., USA.

    Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1 versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic 'overshooting' with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-alpha and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the 'systemic anti-inflammatory feedback' and/or 'hyperactivity' of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases. Copyright (c) 2005 S. Karger AG, Basel

    [30] In 1990, the American College of Rheumatology, the official body of doctors who treat arthritis and related conditions, finally legitimized fibromyalgia in the medical community by presenting its criteria for diagnosing it. It is diagnosed when the you display the following symptoms:

    A history of widespread pain (pain on both sides of the body and above and below the waist) that is present for at least three months

    Pain in at least 11 of 18 tender-point sites.

    http://www.arthritis.org/conditions/DiseaseCenter/Fibromyalgia/fibromya…

    An excellent review of infectious issues in Fibromyalgia can be found at:

    Fibromyalgia- is there an infectious connection?

    http://www.roadback.org/index.cfm/fuseaction/education.display/display_…

    <!--break-->

    Jim K Sat, 2007-12-29 18:53

    Chlamydia pneumoniae and Rosacea: A potential link?

    Chlamydia pneumoniae and Rosacea: A potential link?

     

    While the exact pathology of rosacea is not completely understood or widely agreed upon, recent studies suggest that chronic inflammation likely plays a role in many of the symptoms associated with this disease.

     

    Background

    Rosacea is a chronic disorder of still unknown cause that affects an estimated 14 million Americans.1 Rosacea often initially presents itself with transient flushing and redness of the cheeks, nose, forehead and chin, but it may also involve other areas of the body, including the ears, neck, and chest. With time the transient flushing becomes more frequent, the transient redness tends to become more persistent, and papules, pustules, and visible blood vessels called telangiectasias may also appear. Facial swelling, or edema, also often accompanies rosacea, as do burning or stinging sensations of the affected areas. In addition, many people with rosacea often also have the concomitant chronically irritated eye and eyelid symptoms of ocular rosacea and blepharitis.2

    The exact pathology of rosacea is not completely understood or widely agreed upon, but recent studies suggest that chronic inflammation likely plays a role in many of the symptoms associated with this disease. And the chronic inflammation and blood vessel involvement in this disorder may well point to involvement of gram-negative bacteria, or more particularly their endotoxins, which have been shown to elicit similar response upon entry into the bloodstream.

    While several gram-negative bacteria, including H. pylori and B. oleronius (found in Demodex folliculorum) have been associated with rosacea in the past, they have not been shown to enter the bloodstream, and thus they are unlikely to play anything more than a secondary role in the disease. Chlamydia pneumoniae, however, has been associated with rosacea in one small study, and studies in other inflammatory diseases in which it is being studied closely indicate that it is quite capable entering and persisting in the bloodstream, as well as producing the type of chronic inflammatory response that has been associated with rosacea. This evidence suggests the potential for C. pneumoniae's involvement in rosacea, at least secondarily.

     

    Evidence

    Although the exact pathology of rosacea is still unknown, recent studies suggest that chronic inflammation likely plays a role in many of the symptoms associated with the disease. Supporting the role for chronic inflammation is the host of elevated proinflammatory cytokines (TNF-a, IL-1B), matrix metalloproteinases (MMP-1, MMP-3, and MMP-9), nitric oxide (NO), and reactive oxygen species (ROS) that have been associated with rosacea in recent studies.3 Rosacea has been associated with elevated vascular endothelial growth factor (VEGF) in recent studies as well.4

    It is important to note that the discovery of these elevated inflammatory mediators in rosacea may suggest important clues to an underlying disease etiology when comparing them as a whole to other known pathologies. And indeed, the elevated cytokines, MMPs, VEGF, NO and ROS associated with rosacea, match closely with the known pathology of early gram-negative sepsis, an infection of the bloodstream caused by toxin-producing bacteria.5

    In fact, endotoxins, or rather lipopolysaccharides (LPS), portions of the outer membrane of gram-negative bacteria, are widely known to induce a variety of inflammatory responses, ranging from mild to severe inflammation (and death), depending on the virulence of the bacteria endotoxins themselves.6 Recent studies suggest as well that vascular endothelial growth factor (VEGF) itself may actually be a key biomarker for sepsis.7

    While gram-negative bacteria such as H. pylori and even B. oleronius (found in Demodex folliculorum) have been associated with rosacea in past studies, since these bacteria have not been shown to enter the bloodstream, one would not expect them to produce pathology similar to early sepsis.8 So looking at other inflammatory diseases for clues relating to associated gram-negative bacteria, one such pathogen, Chlamydia pneumoniae, stands out for its association with many inflammatory diseases, including Atherosclerosis, Multiple Sclerosis, Asthma, Alzheimer's and other inflammatory disorders.9

    Interestingly, one small study has linked C. pneumoniae with rosacea directly, detecting serum antibodies of C. pneumoniae in 8 of 10 patients with rosacea and detecting C. pneumoniae specimens in 4 of 10 cheek biopsy.10 Other studies suggest that infection with C. pneumoniae can lead to pustular rashes (acute generalized exanthematous pustulosis) and increased VEGF production, as in the case with wet age-related macular degeneration.11,12 These of course are most likely caused as by-products of the chronic inflammation associated with this pathogen, but I point them out since papule and pustule rashes and increased VEGF production are symptoms of rosacea.

    Persistent C. pneumoniae infection of epithelial cells has been shown to produce chronic blood vessel inflammation, resulting in production of a host of cytokines and growth factors such as those found in rosacea as well as promoting a "foci of inflammatory responses in addition to promoting cellular proliferation, tissue remodeling and healing processes".13 And additional studies suggest that chlamydiae, while classified as gram-negative bacteria due to their outer LPS coating, are actually a distinct group of eubacteria, with a unique multi-form, intracellular and extracellular development cycle, allowing them to change between forms and promote the persistent infection that may lead to chronic inflammatory disease.14

    Another clue potentially linking rosacea with C. pneumoniae involves recent studies in the anti-microbial peptides, cathelicidins, and their activity in rosacea. These recent studies have identified unusually high levels of kallikrein activated cathelicidins in rosacea and suggest that these two substances may be in part responsible for producing the papules and pustules associated with rosacea as well as in promoting the angiogenesis associated with the disease.15,16,17 Some additional studies have shown too that C. pneumoniae seems to invoke unusually high levels of cathelicidin activity and that endotoxins in general activate the kallikrein-kinin system.18,19 Intriguingly, still other studies suggest that cathelicidins seem to be ineffective in clearing C. pneumoniae infection.20 Potentially this is due to C. pneumoniae's ability to revert between forms, effectively evading the immune response. If this were correct then a C. pneumoniae infection, with the resulting ineffective yet elevated levels of activated cathelicidins, could indeed explain the unusual cathelicidin activity found in rosacea.

    Dr. Charles Stratton, MD, at Vanderbilt University, in a recent interview, 21 summarized his observations of some of the emerging research on C. pneumoniae. He noted how C. pneumoniae crosses from the lungs to the bloodstream via infected macrophages. The spore-like Elementary Bodies (EB's) then circulate in the bloodstream to infect other organs throughout the body, including the liver, bone marrow, spleen, kidneys and skin.21 Potentially this might explain how C. pneumoniae, whose initial entry into the body is via the respiratory system, might arrive in the skin to cause rosacea. This may explain too the discovery of C. pneumoniae in cheek biopsy of rosacea as in the study discussed above.

     

    Conclusion

    In summary, Chlamydia pneumoniae may be involved at least secondarily in the etiology of rosacea. C. pneumoniae is a persistent, gram-negative bacteria known to enter and exist in the epithelial cells of the bloodstream, and it is known to produce the type of chronic inflammation that can be found in rosacea. Studies suggest C. pneumoniae may be involved with the etiology of many other inflammatory diseases, and intriguingly, a small study suggests a potential link with rosacea itself. Combined, this evidence would suggest more study related to C. pneumoniae's potential involvement in rosacea is necessary.

     

     

    References

    1. National Rosacea Society. Information for Patients: If You Have Rosacea, You're Not Alone. Rosacea.org.

    2. National Rosacea Society. Information for Patients: All About Rosacea. Rosacea.org.

    3. Bikowski, Joseph. Examining Inflammation as a Common Factor in Theories of Rosacea Pathophysiology. RosaceaToday.com.

    4. Smith JR, Lanier VB, Braziel RM, Falkenhagen KM,White C, Rosenbaum JT. Expression of vascular endothelial growth factor and its receptors in rosacea. Br J Ophthalmol. 2007 Feb;91(2):226-9.

    5. Institute for Inflammation Research, Rigshospitalet Univ Hosp, Copenhagen. Diagram: Early events in sepsis. Inet.uni2.dk.

    6. Todar, Kenneth. Online Book of Bacteriology: Mechanisms of Bacterial Pathogenicity: Endotoxins. Textbookofbacteriology.net.

    7. Prescott, Bonnie. New Study Finds Key Role For VEGF In Onset Of Sepsis. Medical News Today. 21 May 2006.

    8. Rebora, A. The management of rosacea. Am J Clin Dermatol. 2002;3(7):489-96.

    9. Stratton, Charles W. Association of Chlamydia pneumoniae with Chronic Human Diseases. Antimicrobics and Infectious Diseases Newsletter. 2000 July; 18(7).

    10. Fernandez-Obregon A and Patton DL. The Role of Chlamydia pneumoniae in the Etiology of Acne Rosacea: Response to Oral Use of Azithromycin. Cutis. 2007 Feb;79(2):163-7.

    11. Manzano S, Guggisberg D, Hammann C, Laubscher B. Acute generalized exanthematous pustulosis: first case associated with a Chlamydia pneumoniae infection. Arch Pediatr. 2006 Sep;13(9):1230-2. Epub 2006 Aug 17.

    12. Leach, Mary E. Chlamydia pneumoniae present in eyes with 'wet' age-related macular degeneration. Medical News Today. 13 Nov 2005.

    13. Blasi F, Centanni S, Allegra L. Chlamydia pneumoniae: crossing the barriers? Eur Respir J 2004; 23:499-500.

    14. Hogan Richard J, Mathews Sarah A, Mukhopadhyay Sanghamitra, Summersgill James T, Timms, Peter. Chlamydial Persistence: beyond the Biphasic Paradigm. Infection and Immunity, April 2004, p. 1843-1855, Vol. 72, No. 4.

    15. National Rosacea Society. Is Rosacea Like an Allergy?, Rosacea.org. Aug 2006.

    16. Koczulla Rembert, von Degenfeld Georges, Kupatt Christian, Krotz Florian, Zahler Stefan, Gloe Torsten, Issbr¸cker Katja, Unterberger Pia, Zaiou Mohamed, Lebherz Corinna, Karl Alexander, Raake Philip, Pfosser Achim, Boekstegers Peter, Welsch Ulrich, Hiemstra Pieter S, Vogelmeier Claus, Gallo Richard L, Clauss Matthias, Bals Robert. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest. 2003 June 1; 111(11): 1665–1672.

    17. Nizet Victor, Gallo Richard L. Cathelicidins and Innate Defense Against Invasive Bacterial Infection. Scand J Infect Dis. 2003; 35: 670-676.

    18. Edfeldt K, Agerberth B, Rottenberg ME, Gudmundsson GH, Wang XB, Mandal K, Xu Q, Yan ZQ. Involvement of the antimicrobial peptide LL-37 in human atherosclerosis. Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1551-7. Epub 2006 Apr 27.

    19. DeLa Cadena Raul A, Suffredini Anthony F, Page Jimmy D, Pixley Robin A, Kaufman Nathan, Parrillo Joseph E, Colman Robert W. Activation of the Kallikrein-Kinin System after Endotoxin Administration to Normal Human Volunteers. J Amer Soc Hematology. 1993; 81(12), 3313-3317.

    20. Donati Manuela, Di Leo Korinne, Benincasa Monica, Cavrini Francesca, Accardo Silvia, Moroni Allessandra, Gennaro Renato, Cevenini Roberto. Activity of Cathelicidin Peptides against Chlamydia spp. Antimicrobial Agents and Chemotherapy, March 2005, 49(3), 1201-1202.

    21. Jim K. Recent Observations by Dr. Charles Stratton on Chlamydia Pneumoniae (Cpn) Infection. Cpnhelp.org. Aug 2006.

     

     

    Red Thu, 2007-03-01 08:45

    Chlamydia pneumoniae in Chronic Fatigue Syndrome and Fibromyalgia

    Chlamydia pneumoniae in Chronic Fatigue Syndrome and Fibromyalgia

    This page is broken. The article can be found here: http://www.cpnhelp.org/chlamydia_pneumoniae_in_0

    Chronic Fatigue Syndrome, Fibromyalgia & Chlamydia Pneumoniae[1]

    Introduction

    Chronic Fatigue Syndrome (CFS), also called Chronic Fatigue Immunodeficiency Disorder (CFIDS), or called Myalgic Encephalomyelitis (ME) in Great Britain. CFS affects 1 million Americans, with "tens of millions" more who have a fatigue condition that doesn't meet the strict criteria for Chronic Fatigue Syndrome.[2] According to the Center for Disease Control (CDC), which considers CFS an accepted medical condition,[3] there is no officially known cause or cure for CFS or for the related, and often co-occurring, condition of Fibromyalgia Syndrome (FMS).[4]

    Despite the CDC's affirmation, the syndrome and its diagnosis is still considered controversial even in this day and age. Some doctors continue to insist that Chronic Fatigue Syndrome is not a "real" disease entity. It may be rather a surprise to it's sufferers when, naively seeking medical assistance, they find that their doctor doesn't believe that their symptoms are from a "real disease" or merits medical treatment. That there is no known "test" for Chronic Fatigue Syndrome that can conclusively demonstrate its existence is one of the difficulties here.

    Perhaps another difficulty is that medical practitioners are socialized to believe that feelings of their own helplessness are a sign of personal failure. A solution to this psychological conundrum is to blame the patient by "psychologizing" the problem i.e. "It's in your head." Fortunately, acceptance of the legitimacy of the disease has increased in recent years, even if conventional medical treatment for it continues to have little to offer of help.

    As the causal factors of CFS are considered unknown, conventional medical treatment for it and for Fibromyalgia Syndrome are all palliative (symptomatic) in nature: antidepressants for mood and pain associated with it, medications for sleep, stimulants for the fatigue, behavioral strategies, and so on. These can help make life bearable but don't fundamentally change the condition. [5]

    Disease Syndromes: more common than you think -

    Chronic Fatigue Syndrome is often disparaged as being a "syndrome," merely a collection of symptoms, not a disease i.e. a causal entity. Of course, a critique applying to one syndrome should apply to them all, yes? A syndrome is a collection of signs and symptoms (Sign= something you can measure; Symptom= patient reports) that appear to have diagnostic consistency. A syndrome tells you nothing per se about the cause of the problem. Many different causes, and sometimes more than one cause at the same time, can result in a syndrome. Interestingly, the diagnosis of "Pneumonia," just like Chronic Fatigue Syndrome, is actually a syndrome, though it is not referred to as "Pneumonia Syndrome." The diagnosing "pneumonia" does not tell you what is causing it, which can be variously viral, bacterial, food aspiration and so on.

    Similarly, diagnosing Chronic Fatigue Syndrome doesn't tell you about possible causes until further investigation is done. There could be a variety and/or combination of potential causes. There are examples of modern, multi-factorial and case-individualized approaches to CFS/FMS that go far beyond conventional medical ignorance about CFS. These combine both symptomatic treatment and search for possible causal contributors for each specific patient.[6]

    The various causal factors being looked into are amply discussed elsewhere and can be found in any web search. One of the proposed causal mechanisms for at least a sub-set of Chronic Fatigue Syndrome is that of bacterial or viral infection. Especially "occult infections" i.e. those organisms that are either typically overlooked, difficult to test for, or tend to evade the immune system[7]. Within this causal possibility are infectious organisms such as Chlamydia pneumoniae.

    My purpose here will be to present the information that argues for the involvement of Chlamydia pneumoniae in at least a sub-set of Chronic Fatigue Syndrome and Fibromyalgia Syndrome patients. I will outline how Chlamydia pneumoniae's known biology and impact on the body could explain some of the characteristic symptoms and signs of Chronic Fatigue Syndrome.

    At the outset it should be said that Chlamydia pneumoniae is not the only infectious agent that has implicated in Chronic Fatigue Syndrome/Fibromyalgia Syndrome. We certainly don't know if it is involved in all, a subset or merely a co-condition of such cases. But there is good reason to look further at this particular organism's involvement. Most of the argument discounting Cpn's involvement in CFS/FMS has been based on ignorance and poor understanding about the organism itself and the difficulties of testing and treatment for it. This is an attempt at trying to correct this ignorance, and place Chlamydia pneumoniae more clearly in the realm of possible sources for these devastating conditions.

    The Early Vanderbilt Work: Chlamydia pneumoniae in Chronic Fatigue Syndrome-

    The Incomplete Research-

    There is some published work linking Chlamydia pneumoniae to Chronic Fatigue Syndrome/Fibromyalgia Syndrome in medical research journals.[8] But perhaps the most important research in this regard never reached publication. This article is the first thorough description in a public information setting.

    The original initial work at Vanderbilt by Dr. Charles Stratton and his lab on Chlamydia pneumoniae in human disease was actually not first directed at Multiple Sclerosis, as is more commonly believed, but looked Chlamydia pneumoniae in Chronic Fatigue Syndrome. The first grant monies received by Dr. Stratton for Chlamydia pneumoniae research, using the highly sensitive tests they had developed, was from Massachusetts Chronic Fatigue Foundation in the mid to late 1990's.

    Dr. Stratton was asked to test blood samples submitted by the well-known Chronic Fatigue Syndrome physicians Cheney, Peterson & Bell to explore the possible involvement of Chlamydia pneumoniae in their Chronic Fatigue Syndrome patients. As I understand it, the grant was given to these doctors, and the determination of patients was by their own diagnostic selection. This research was never published, for reasons that will be explained later. The lack of publication and follow through of this work may be one of the great tragedies in a long line of them in the history of Chronic Fatigue Syndrome. Many patients may have suffered needlessly from this disease because the strong link between CFS and Cpn has remained largely unknown.

    A remarkable finding:

    In this research Dr.'s Cheney, Peterson & Bell sent blood samples from their own Chronic Fatigue Syndrome patients to Dr. Stratton's Vanderbilt Chlamydia pneumoniae lab for testing. According to Dr. Stratton, they tested 100's if not 1000's of such blood samples. These were tested using both ELISA-based serologic methods and PCR testing using the tests developed by Stratton, et al. at the Vanderbilt Chlamydia Research Laboratory. Dr. Stratton's lab found that the majority (almost 100%) of Chronic Fatigue Syndrome patients were PCR positive for Chlamydia pneumoniae in blood samples.

    That the selected patient group of Chronic Fatigue Syndrome patients had almost 100% positive PCR tests for Chlamydia pneumoniae (actual proteins, which means actual presence of the bacterial particles not only an antigen response which could be remnant from prior infection) is an extraordinary finding. Further, the majority also had either elevated IgM or IgG antibodies to Chlamydia pneumoniae major outer membrane protein cross-confirming the PCR based findings.

    Of course this in-of-itself does not mean Cpn is the cause of CFS. The presence of Chlamydia pneumoniae could be due to some third factor that is part of Chronic Fatigue Syndrome (such as immuno-suppression, etc). But such high of a correlation with one specific organism outweighs every other or biological finding to date in CFS research. No other single variable in the CFS literature even comes close to being found in near 100% of CFS patients. Now, there are some unknowns here, especially the criterian used to select those patient samples sent to Vanderbilt. This remains unknown as of this writing.

    The first research problem:

    They also discovered that many of the randomly selected "healthy controls" were also Cpn PCR positive. This would tend to call into question the tests themselves, i.e. suggesting that the tests are generating false positives. So, they tested a random sample of blood donors to have a larger pool of healthy controls from which to get a baseline comparison for the study's original control group. They found that, of "healthy blood donors" about 20% were Chlamydia pneumoniae positive! This percentage was higher than expected at the time, as it was not yet understood how ubiquitous Cpn is.

    However, it turns out that this matches the figures of Cpn found in recent research with healthy, young blood donors.[9] That these earlier Vanderbilt studies found the percentage of Chlamydia pneumoniae occurring in healthy donors replicating the current accepted findings (which range from 18-25%) lends credence to the accuracy and sensitivity of the tests used to study this original Chronic Fatigue Syndrome sample. In other words, post hoc data suggests that their finding of an incidence of Cpn in healthy "controls" was an accurate one, not an artifact from an inaccurate test.

    The next problem- treatment:

    The obvious next step was to try courses of antibiotics known to be antichlamydial and see if reduction of PCR signal for Cpn correlated with reduction in CFS symptoms. This was done by the by Dr.'s Cheney, Peterson & Bell with a sample of their patients. It turned out that no single antibiotic agent eradicated the Chlamydia pneumoniae PCR signal. So, Dr. Stratton's lab, having laboriously developed the PCR susceptibility tests (described quite elegantly in the patent materials which can be found linked elsewhere in this website) now had to use them to discover which agents or combinations of agents were required to eradicate Cpn completely, such that no PCR signal was evident in blood samples. This is called "sensitivity testing."

    This was a greater challenge than most of us would think. Along the way to infecting mice and cell cultures with Cpn and looking for effective combinations of antibiotics, they discovered that the available laboratory mice and commercial cell cultures widely assumed by scientists to be "clean," and thus proper starting points for introducing new variables, were themselves often infected with Chlamydia pneumoniae. This could seriously skew the interpretation of their tests. So Dr. Stratton's lab had to first develop methods to clear the cell cultures of Chlamydia pneumoniae and prove such clearance using their sensitive PCR testing. This is a remarkable bit of science here. Their finding that common biological laboratory materials are contaminated with Cpn appears also to be relatively unknown.

    From all of this they managed to find that only certain combinations of antibiotic agents (described elsewhere in this website) would completely eradicate Chlamydia pneumoniae from tissue cultures and laboratory mice, as indicated by clearance of Cpn PCR signal. No single antibiotic treatment, nor any series of antibiotics one at a time, was able to eradicate Cpn. Now that they had the combination antibiotic protocol (CAP) protocol, they could test the impact of eradicating Cpn on the resulting CFS symptoms, and then confirm whether patients were actually clear of Cpn from the blood testing.

    And another thing…

    As in all research, there is always another problem ahead. This time the problem was with the reactions to the clinical treatment itself being tried by Dr.'s Cheney, Peterson & Bell, as well as by Dr. Stratton with his own Chronic Fatigue Syndrome patients. The treatment was indeed working to kill Cpn, but the toxicity of the Cpn kill was causing existing symptoms to worsen significantly. The dropout rate using the combination antibiotic protocol (CAP) for Chronic Fatigue Syndrome was very high. Many patients were unable to see it through to the endpoint of the whole of the treatment process—where PCR signal was absent for Cpn. As Dr. Stratton put it to me in an interview, "The cure appeared worse than the disease." It was difficult for the treating physicians to keep patients on the protocol long enough to begin to see significant symptomatic improvement. This was due to two major difficulties.

    • Die-off reactions- When combinations were used the die-off reactions from this potent mix could be as bad, or worse, than the Chronic Fatigue Syndrome itself. Little was yet known about how to support patients through these reactions, or what exactly their nature was.

    • Length of treatment- Moreover, the length of treatment of Cpn with these combination antibiotic protocols for Chronic Fatigue Syndrome was very long. It was difficult to get patients to "stay the course" without extraordinary support, or dedication on the part of both the patient and the physician.

    It was quite a challenge for the Chronic Fatigue Syndrome physicians, including Dr. Stratton, to know how to manage these responses and how to support their patients to hang in with a treatment that seemed to have little short term gain.[10] Of those patients (a small number) who Dr. Stratton treated personally and who continued after the end of the study through the full course of protocol there was, says Dr. Stratton, "100% improvement of symptoms."

    Why did the eradication of Chlamydia pneumoniae cause such reaction in CFS patients? People treated for actual pneumonia caused by Cpn (community acquired pneumonia) don't appear to have severe reactions to their antibiotics after all.

    First, the combination antibiotic protocol (CAP) was far more effective than a single antibiotic used in standard treatment of Cpn pneumonia because it attacked all of the phases of the Cpn life cycle. A single antibiotic only kills Cpn in one of it's life phases. The symptoms of CFS disease are related to Cpn's toxic and inflammatory impact on the body. The more you kill at once, the more these reactions.

    Secondly, CFS patients appear to have built up a very high load of Cpn, spread through a large variety of tissues: the bone marrow, the connective tissue, the liver, the spleen, the vascular system, heart, and so on. When you have a highly toxic organism being killed in large numbers, in a wide variety of tissues, you have more severity of reactions.

    Additionally, the overall Chlamydia pneumoniae bacterial load appears to be one of the big determining factors in the length of the therapy needed. The higher the load, the longer the therapy required.

    Implied in this also is...

    • The longer one has had the disease,
    • The more organ systems affected,
    • The less resilient the patient from age, additional illnesses, etc.,

    ...The longer and more challenging is the treatment required.

    As a group, patients with Chronic Fatigue Syndrome/Fibromyalgia Syndrome appear to have higher Chlamydia pneumoniae loads in more different organs and tissues, compared to say MS patients, making treatment with the CAP more challenging, longer, and creating a significant dropout rate as it took longer to see the beneficial results versus the immediate term die-off reactions. But further research into this very promising but challenging treatment process was halted before questions about how to improve the treatment process could be answered.

    Research is halted-

    At about this point in the research, word was getting out in the medical community that they were testing blood samples from Chronic Fatigue Syndrome patients. There ensued a deluge of protest from medical colleagues who objected to research with Chronic Fatigue Syndrome being conducted at Vanderbilt. According to Dr. Stratton, the objections were "quite heated."

    Why would microbiological research, as hard-science an aspect of the medicine as one could imagine, stir such heated outrage?

    At that time, the late 1990's the diagnosis of Chronic Fatigue Syndrome was hugely controversial. Even more than it is today. Despite having a CDC case definition, a significant number of physicians believed that Chronic Fatigue Syndrome did not exist as a real medical entity or diagnosis. They believed that it was a false, catchall "syndrome," essentially representing psychiatric problems. Therefore it was not considered a legitimate area of serious scientific medical research.

    The expressed concern was that the reputation of Vanderbilt University, and by extension the protesting physicians who were associated with Vanderbilt, would be sullied by sponsoring work such a medical "non-entity" and be seen as fostering specious science. This kind of reaction was not just reflective of physicians only associated with Vanderbilt of course. In general at this time, scientists or institutions associated with any kind of Chronic Fatigue Syndrome research were seen as incompetents, and were often made pariahs to conventional medicine. CFS research was often a career ender for career scientists. The reactions from potential publication journals at this time were similar. Please remember that this was only 10 or 12 years ago, and these attitudes still exist today in medicine.

    At about this time the grant money for this study ran out. As Dr. Stratton was serving only as the testing laboratory, he did not have access to the patient data himself to have adequate controls over patient selection and the like to make for publishable results. Vanderbilt itself did not have a CFS clinic to draw from.

    As Dr. Stratton's expertise was in Chlamydia, not in CFS, he turned his research interests towards an area of research on Cpn with less diagnostic controversy, and where Vanderbilt did have it's own disease based clinic. Dr. Stratton and his colleagues, spearheaded by Dr. Siram in neurology, shifted the focus of their research to Multiple Sclerosis. This was done in part to have a widely accepted, "legitimate" nosological (diagnostic) entity for research. As an accepted neurological disease, no one could call MS a psychological problem. As many of us know, this research has turned out to be almost as controversial, although for different reasons than the CFS study.

    While one might wonder at Dr. Stratton's penchant for seeking controversy, the reality is that any research that cuts across accepted conventional viewpoints in medicine is likely to face rejection and derision. Anyone who knows Dr. Stratton would know that controversy is not at all a motivator in picking his research areas, Chlamydia is the motivator. Dr. David Wheldon, a colleague and friend of Dr. Stratton's, noted Dr. Stratton's avoidance of the limelight by saying that he "Tends to hide his considerable light under a bushel."

    There are probably other factors operating here as well. Any treatment process requiring a combination of three to four antibiotics for a very long period of time is anathema to most conventionally trained MD's. Most physicians have only the rudiments of microbiology in their training, and no basis to understand the complexities of treating multiple life-phase infectious agents.

    As well, the development of antibiotic resistant strains of bacteria has created a kind of phobia about the long term use of antibiotics amongst most practicing MD's. This attitude is even more true for the use of multiple antibiotics at the same time. It is ironic that physicians who see nothing wrong in pumping patients full of multiple chemotoxic agents for cancer treatment will balk at the suggestion of far less harmful multiple antibiotic agents, calling it "polypharmacy." Ironically too, it is actually the use of multiple antibiotics in the CAP for Chlamydia pneumoniae that truly minimizes the chance of developing bacterial resistance, while repeated courses of single antibiotics, the "conventional medical" approach, creates much higher risk for developing bacterial resistance.

    At any rate, these very interesting findings were never pursued. We still don't know what percentage of CFS patients are PCR positive for Chlamydia pneumoniae, and exactly how much Cpn is the origin of symptoms in this disease syndrome. What we do know is that those of us who have diagnosed CFS/FMS and have positive blood tests for Cpn have benefited, slowly, gradually, but significantly in many of our symptoms from the CAP for Cpn based on Dr. Stratton's work. This improvement is true as well for a number of CFS/FMS patients who, while not testing positive for Cpn using standard tests that are not as sensitive as those used by Dr. Stratton's lab, have evidenced typical die-off reactions to the CAP antibiotics, suggesting Cpn infection. Is it the case for all CFS/FMS? No one knows.

    Chlamydial persistence and antibiotic response-

    Cpn has some unique characteristics which make it both an adaptive parasite, and difficult to eradicate. While over the years, some clinicians treating Chronic Fatigue Syndrome/Fibromyalgia Syndrome patients have tried the use of monotherapy (single) antibiotics with the notion that there might be an occult (hidden) bacterial infection involved in the disease, response by patients has been inconsistent. Some CFS/FMS patients may even have found their own symptoms temporarily improving when on incidental antibiotic treatment, say for ear infections and the like, but improvements not lasting.

    That informal clinical experimenting with antibiotics in CFS/FMS has not resulted in much useful direction of treatment or research has to do with the unique biology and characteristics of Cpn. As these unique characteristics apparently are only known by microbiologists, and little understood by treating physicians, treatment of CFS/FMS with antibiotics has yielded conflicting results. Curiously, this ignorance of important microbiological facts about Cpn (and other infectious organisms) appears to extend to medical Infectious Disease specialists, whose knowledge of microbiology appears shockingly limited, and have not intelligently pursued the possibility of occult infection in these disorders.

    Antibiotics in CFS/FMS have resulted in the whole range of responses:

    • No improvement—leading to the assumption that no bacterial presence is involved.
    • Improvements followed by a return of symptoms after the antibiotic is withdrawn. Since long-term use of antibiotics is discouraged, with the fear of creating resistance, further treatment is often discouraged.
    • Symptoms worsening—leading to the assumption that they are having toxic or allergic effects, and leading to halting antibiotic treatment.

    If, in fact, Cpn causes even a subset of CFS/FMS, the lack of consistency to antibiotic treatment has to be explained. This inconsistency becomes understandable if you know some key features about the biology of Chlamydia pneumoniae.

    • No improvement- the antibiotics used may not be effective antichlamydials. Thus a "trial of antibiotics" using the incorrect agent would be expected to yield negative results in the disease symptoms. The sensitivity tests done by Stratton, et al demonstrated clearly that a number of commonly held "high power" antibiotics are not effective against Chlamydia pneumoniae.
    • Temporary improvement- One of the great scientific puzzles about Chlamydia pneumoniae has been its ability to persist and reinfect, even treatment by antibiotics. It does this, and evades the immune system and threats such as starvation, by its ability to switch forms and survive in a different life phase that not affected by the particular threat.

    There are three known phases or forms of Cpn:

    1. The infectious, spore-like Elementary Body (EB): only killed by cysteine reducing agents like N-acetyl-cysteine and amoxicillin
    2. Once the EB invades a host cell it converts to the replicating Reticulate Body (RB)- only antibiotics that interfere with replication, such as protein synthase inhibitors doxycycline or azithromycin, affect it.
    3. Finally, Cpn can survive those drugs by converting to the low metabolizing "cryptic" form, which Dr. Stratton's research found is only killed by metronidazole family drugs.

    Thus two weeks, or even two years of a single antibiotic may improve symptoms by suppressing one form of Chlamydia pneumoniae, but symptoms recur as soon as the antibiotic is withdrawn.

    • Worsening- Killing Chlamydia pneumoniae liberates significant amounts of bacterial endotoxins which cause widespread cytokine reactions, including inflammation, pain, depression, low energy and so on. These are precisely the symptoms of Chronic Fatigue Syndrome/Fibromyalgia Syndrome itself. In addition, Stratton's work found that Chlamydia pneumoniae causes a condition of secondary porphyria[11] that engenders further misery and suffering. Reports of strong reactions to antibiotics, and particularly to metronidazole, have lead the treating clinicians to misinterpret these reactions as allergy or drug reactions, and to prematurely withdraw the agent. The reality is that it is these bacterial toxins which are a great part of what causes the symptoms in CFS/FMS, and there is no way to kill Cpn without dumping these toxins into the system and feeling worse. The only question is how to pace it, and what measures can be taken to make it more tolerable.

    Chronic Fatigue Syndrome/Fibromyalgia Syndrome Symptoms & Chlamydia pneumoniae

    When we look at the common symptoms of Chronic Fatigue Syndrome and Fibromyalgia how might they be explained by what we know about Chlamydia pneumoniae biology and infection? In this section I will present a list of the major symptoms and look at how chlamydial biology and our own bodily response to this might generate these often puzzling symptoms.

    Features of Chlamydia pneumoniae (Cpn) and Cpn infection:

    Multi-Organ Infection- Cpn crosses from the respiratory system and can infect multiple organ systems including the nervous system, liver, heart, bone marrow, immune cells, skin, and so on.

    Intracellular Energy Parasite- Cpn reproduces by entering the host cell of your body tissue and stealing the ATP energy molecules that your cells function with.

    Secondary porphyria- Depletion of host cell ATP by Chlamydia pneumoniae means that your cells don't have enough energy to complete their normal biochemical reactions. One of these, the production of heme, requires lots of ATP to come to completion. ATP depletion results in incomplete heme production and a build up of the incomplete byproducts called porphyrins. Porphyrins are neurotoxic and have numerous deleterious effects on the nervous system including anxiety, depression, bowel and digestive disturbance, and interference with sleep, rapid pulse, and even psychosis.

    Chlamydial Endotoxins- Chlamydia pneumoniae contains a number of endotoxins in it's structure, such as LPS and HSP-60. These endotoxins cause widespread inflammation (cytokine cascades) and a host of other metabolic disturbances. These are released chronically in small amounts in Chlamydial pneumoniae infection and in large amounts when Cpn cells are killed.

    Cytokine cascades- Cytokine responses (inflammatory immune reactions) are rampant in Chlamydia pneumoniae infection from a number of sources: to Cpn endotoxins; to the bacterial envelopes left behind by dead Chlamydia pneumoniae bacteria in tissue cause a variety of inflammatory reactions; and even the death of neighboring non-infected healthy cells.[12]

    Antibodies to vitamin B-12- B-12 is an important co-factor in a number of energy and detoxification processes in the body. One of the unique findings of Dr. Stratton's group was that antibodies to vitamin B-12 develop in many Chlamydia pneumoniae infected patients. This means that normal blood levels of this vitamin are insufficient as it is bound to antibodies and useless to body functions affecting energy production and detoxification (methylization).

    With these in mind, let's look at how these, and other factors about Cpn, might explain some of the otherwise mysterious symptoms of Chronic Fatigue Syndrome and Fibromyalgia.

    General, unrelieved fatigue-

    • This is the most characteristic feature of CFS and, other than pain, of FMS.
    • ATP depletion from Chlamydia pneumoniae parasitism simply leaves less energy available for body functions.
    • Fatigue is a main symptom of porphyria.
    • Cardiac infection: Cpn infects the cardiac system, and is a major culprit being investigated as a source of cardiac disease. Parasitization of cardiac muscle by Chlamydia pneumoniae would reduce heart efficiency and contribute significantly to fatigue. A recent paper found evidence of Cpn throughout myocardium, the heart muscle wall. These infected muscles would presumably be functioning at lower efficiency because of ATP depletion, resulting in a chronic cardiac insufficiency. This is consistent with findings of cardiac insufficiency in CFS patients (see Peckerman)." [13] [14]
    • Cytokine cascade in CFS[15]- the typical malaise and fatigue of a cold or flu is caused by the flood of cytokines that are generated in the innate immune response. Chlamydia pneumoniae infection tends to stimulate a chronic innate immune response and this chronic cytokine cascade is an additional source possible in CFS fatigue. This has been called "sickness behavior" i.e. the behavioral responses to an immune cascade. (See "Cytokine dysregulation, inflammation and well-being" in references).

    Tender axillary or cervical lymph nodes

    One of the main routes by which Cpn is carried through the body is the lymphatic system via infected immune cells. Chlamydia pneumoniae infected lymphocytes and/or infection of the lymphatic system itself would easily account for this clinical finding in CFS.[16][17] These lymph nodes in particular drain the upper respiratory system (sinuses, throat, etc), and these areas are a major entry point for Cpn into the body via sinus infection, laryngitis, and so on.

    Immune deficiency[18]

    • Chlamydia pneumoniae can infect bone marrow[19]that is where our immune cells (macrophages, monocytes, neutrophils) are produced. Infected bone marrow will produce infected and thus poorly functioning immune cells resulting in a low-grade immunodeficiency.
    • Co-infections resulting from poor immune functioning from opportunistic organisms- viruses, bacteria, mycoplasms, fungi & yeasts and such- are more likely gain a foothold. These further confuse the clinical picture as to what is cause and what is effect or co-factor, and add to further immune burden and further reduced immune function. The more organisms the immune system (already infected itself) has to deal with, the less resources available for any one thing.

    Cardiac insufficiency-

    Cardiac insufficiency has been identified in CFS patients as a significant correlate to symptom severity[20], so much so that Dr. Paul Cheney (yes, the same one who participated in the CFS/CPN study) has focused on this as his cause celebre for CFS recently.[21] As we have noted, Cpn is parasitic and steals ATP, the energy molecule, from the infected host cell to subvert it for it's own replication process. Heart muscle is one of the most ATP demanding cells. Cpn infection of heart muscle as discussed previously is likely to result in reduced heart efficiency, explaining the results of the Peckerman study and giving a causal element to Dr. Cheney's observations of cardiac dysfunction in CFS. Why Dr. Cheney has ignored the earlier work he participated in, which implicates an organism that is becoming well known for its involvement in cardiac disease, is a real curiosity.

    Exercise intolerance and post-exertional fatigue-

    • Cardiac insufficiency: see cardiac infection comments previously noted. Impaired performance on treadmill commonly noted in CFS/FMS could be similarly explained by this as well as other factors.
    • Muscle and general ATP depletion- Chlamydia pneumoniae is an ATP parasite in infected cells, leaving of this energy molecule for host cells. In a broad based Chlamydia pneumoniae infection stores of ATP would be generally depleted, such that high output exercise would leave a significant ATP deficit in some systems such as the muscular system.
    • Porphyrins- Porphyrin load increases after exercise or exertion because ATP stores, already in short supply because of Cpn parasitism, are used up at rapid rate by muscle activity. This makes even less ATP available for heme production resulting in incomplete heme and its byproducts, porphyrins. An inadequate supply of ATP means that only the amount of exercise up to the ATP limit at that particular moment can be tolerated. The increased porphyrin byproducts result in post-exertional fatigue and long recover time. This is the "over-exert one day, payback for three days" report common to many CFS patients.

    Gastrointestinal problems

    • CFS and FMS patients often have concomitant gastrointestinal problems, ranging from Irritable Bowel Syndrome, poor nutrient absorption, and other problems.
    • Cpn infects endothelial tissues, as it's preferred home, including the endothelial tissues of the gut. Some of the micrographs of Cpn infected cells which can be viewed on this website are of stained intestinal endothelial tissues.[22]
    • Porphyria is notorious for causing chronic gut distress: nausea, intestinal cramping, etc. Chlamydia pneumoniae infection of gut endothelial tissue.
    • Gut co-infections from fungi, bacterial, or yeast resulting from general immunosuppression, or specific Cpn infected gut-immune system will further add to gastrointestinal problems.

    Sleep disorder

    • Porphyrins block GABA receptors, a main cause of anxiety and agitation in porphyria, and likely to interfere with sleep.
    • Melatonin serves a number of functions that are related to protecting cells from oxidation[23] as well as binding inflammatory endotoxins[24] and activating immune functions[25]. Melatonin depletion from it being used up for antioxidant and other metabolic purposes resulting from Cpn infection could result in inadequate amounts left for neurotransmitter production and it's influence on inducing sleep.
    • Hypothalamic infection and disturbance by Chlamydia pneumoniae could be a contributing factor.
    • Cytokine disturbance of sleep regulation.[26]

    Anxiety & depression

    • Porphyrins- noted previously for causing anxiety, depression even psychosis.
    • Depletion of melatonin noted above causes depletion of serotonin in the brain. Inadequate serotonin results in depression, as well as increased pain sensitivity.
    • Cytokine depression- cytokines are clearly linked to causing depressive symptoms.[27]

    Endocrine disturbance (thyroid, periods, etc.)

    • Infection of endocrine gland cells: thyroid, pancreas islet cells, pituitary, pineal, etc.
    • Glucose disturbance- Chlamydia pneumoniae, steals ATP that requires the host cell to absorb and metabolize more glucose. This disturbs glucose homeostasis. "Hypoglycemic" symptoms (must have food now, worsening of inflammatory and porphyric symptoms when get depleted of glucose or during fasting, etc) are common in CFS/FMS and are quite notable in those suffering from disseminated Chlamydia pneumoniae infection. Anecdotally, Chlamydia pneumoniae patients on the CAP report significant lessening of these episodes of these hypoglycemic symptoms over the course of treatment.

    Headaches

    • Porphyrins- one of the neurotoxic effects of porphyrins is headaches.
    • Vascular disturbance direct and indirect- Cpn infects the vascular system leading to high blood pressure (from rigidified vascular walls), headaches, inflammation of blood vessels (including those in the brain), etc.
    • Sympathetic nervous system over activation from chronic upregulated innate immune response caused by infection.[28]

    "Sickness behavior"

    Mentioned earlier, sickness behaviors are the innate, the behavioral responses to cytokines that have been stimulated by infection: feeling lousy, withdrawal, depression, movement avoidance, and energy conserving, etc. [29]

    Cognitive Dysfunction (Brain Fog)-

    This is one of the most frustrating features of CFS/FMS, and one with little explanation in the domain, despite it being one of the most life-impacting symptoms for the sufferer. Cpn infection explains this very wel.

    • Secondary porphyria induced by it and the impact of porphyrins on brain functioning.
    • Cerebral inflammation from circulating cytokines.
    • Brain infection
    • Endotoxins.

    Fibromyalgia Symptoms[30]

    All of the above plus...

    Musculoskeletal pain and inflammation

    • Soft tissue infection by Chlamydia pneumoniae and subsequent inflammation
    • Fibromyalgia Syndrome often starts after injury/accident. In the normal response to tissue repair, injured and inflamed areas attract macrophages. Chlamydia pneumoniae infected macrophages can leave Chlamydia pneumoniae behind in injured/inflamed area. Infection then becomes progressive gradually spreading from that area. As generalized inflammation increases (from free circulating cytokines) these sites are further infected by parasitized macrophages drawn to increasingly inflamed sites, etc. http://www.cpnhelp.org/how_chlamydia_pneumoniae_
    • Porphyrins blocking GABA receptors will also lowers pain tolerance.
    • Generalized cytokine load causes broad based "feels lousy all over."

    The case for Cpn in CFS does not prove that Cpn is always the causal element. As a syndrome, Chronic Fatigue may originate from a variety of causal factors, and these could be different for different patients. But in a disease where modern medicine has had no curative treatment to offer, it is clearly a causal factor worth looking into. Even with negative blood tests for Cpn, an empirical trial of the CAP for Cpn is worth exploring.

    In future articles I hope to discuss some of the potential complexities of treating Cpn in CFS/FMS patients with the Combination Antibiotic Protocol, and some considerations that make treating this different from other Cpn related diseases.

    References



    [1] My deep appreciation to Dr. Charles Stratton for his review and consultation in formulating this article. Beyond that, my tender deepest respect to him for bravery under fire.

    My thanks also to Marie Rhodes, for saving me some grammatical embarrassments!

    [3] CDC Diagnostic Symptoms-

    1. Unexplained, persistent fatigue that is not due to ongoing exertion, is not substantially relieved by rest, is of new onset (not lifelong) and results in a significant reduction in previous levels of activity.

    2. Four or more of the following symptoms are present for six months or more: .

    • Impaired memory or concentration

    • Postexertional malaise (extreme, prolonged exhaustion and exacerbation of symptoms following physical or mental exertion)

    • Unrefreshing sleep

    • Muscle pain

    • Multi-joint pain without swelling or redness adults

    • Headaches of a new type or severity

    • Sore throat that’s frequent or recurring

    • Tender cervical or axillary lymph nodes

    Other Commonly Observed Symptoms in CFS

    The frequencies of occurrence of these symptoms vary from 20% to 50% among CFS patients. … include abdominal pain, alcohol intolerance, bloating, chest pain, chronic cough, diarrhea, dizziness, dry eyes or mouth, earaches, irregular heartbeat, jaw pain, morning stiffness, nausea, night sweats, psychological problems (depression, irritability, anxiety, panic attacks), shortness of breath, skin sensations, tingling sensations, and weight loss.

    [4] Estimated by the American College of Rheumatology to effect 6 million Americans.

    [5] A popular palliative intervention with “cutting edge” conventional practitioners is Cognitive Behavioral Therapy (CBT). I’m a psychologist by profession and should be fond of my profession’s contributions to a challenging disease. But my personal and professionally informed commentary on the value of CBT as a CFS/FMS treatment is not high. As applied to the condition of Chronic Fatigue Syndrome, CBT may be likened teaching someone to how to become more relaxed and organized while one is standing upon a sinking ship. Thus, metaphorically, CBT teaches one how to adjust their viewpoint as the horizon tilts; how to stop worrying about the water lapping at their feet, how to counter the emotional responses of impending doom, how to relax so their stress doesn’t add water to the already sinking ship, and so on. Like my stubborn friends here at www.cpnhelp.org dealing with Multiple Sclerosis who were often told there’s nothing that can be done but “get comfortable with your disease,” finding comfort in my decline has never been personally attractive to me as a solution.

    Some studies have found CBT “effective” in reducing CFS symptom severity. This makes CBT much beloved by conventional physicians as it, a) Is legitimized by scientific research, b) they feel at least they have something to offer these “difficult-to-help-patients,” and c) CBT still fits comfortably with the continuing vague suspicion that CFS isn’t really a disease at all but is really “all in their head” after all. I have not spoken a single CFS patient, and I have communicated with many, who has found that CBT did anything of significance for them in terms of their disease. This said, CBT does teach highly valuable relaxation, stress management and cognitive strategy skills. These are useful in a disorder highly impacted by stress and which is very cognitively disorganizing. However like all palliative measures, CBT is only helpful at managing the disease, and in this it is not even profoundly so.

    See http://www.meresearch.org.uk/research/reviews/cbt.html for further discussion.

    [6] Effective Treatment Of Chronic Fatigue Syndrome (CFIDS) & Fibromyalgia (FMS) - A Randomized, Double-Blind, Placebo-Controlled, Intent To Treat Study

    Teitelbaum J.*1, Bird B., Greenfield R.*1, Weiss A.*1, Muenz L.*2, Gould L.*3

    [* Annapolis Research Center For Effective FMS/CFIDS Therapies; 466 Forelands Rd., Annapolis, MD 21401; 1) Anne Arundel Medical Center, Annapolis, MD; 2) Gaithersburg, MD; 3) USDA, Beltsville, MD]

    Journal Of Chronic Fatigue Syndrome Volume 8, Issue 2 - 2001

    Background: Hypothalamic dysfunction has been suggested in Fibromyalgia (FMS) and Chronic Fatigue Syndrome (CFS). This dysfunction may result in disordered sleep, subclinical hormonal deficiencies, and immunologic changes. Our previously published open trial showed that patients usually improve by using a protocol which treats all the above processes simultaneously. The current study examines this protocol using a randomized, double-blind design with an intent-to-treat analysis.

    Methods: 72 FMS patients (38 active: 34 placebo; 69 also met CFS criteria) received all active or all placebo therapies as a unified intervention. Patients were treated, as indicated by symptoms and/or lab testing, for: (1) subclinical thyroid, gonadal, and/or adrenal insufficiency, (2) disordered sleep, (3) suspected Neurally Mediated Hypotension (NMH), (4) opportunistic infections, and (5) suspected nutritional deficiencies.

    Results: At the final visit, 16 active patients were “much better,” 14 “better,” 2 “same,” 0 “worse,” and 1 “much worse” vs. 3, 9,11, 6, and 4 in the placebo group (p < .0001, Cochran-Mantel-Haenszel trend test). Significant improvement in the FMS Impact Questionnaire (FIQ) scores (decreasing from 54.8 to 33.2 vs. 51.4 to 47.7) and Analog scores (improving from 176.1 to 310.3 vs. 177.1 to 211.9) (both with p < .0001 by random effects regression), and Tender Point Index (TPI) (31.7 to 15.5 vs. 35.0 to 32.3, p < .0001 by baseline adjusted linear model) were seen. Long term follow-up (mean 1.9 years) of the active group showed continuing and increasing improvement over time, despite patients being able to discontinue most treatments.

    Conclusions: Significantly greater benefits were seen in the active group than in the placebo group for all primary outcomes. Using an integrated treatment approach, effective treatment is now available for FMS/CFS.

    Article link here

    [7] The immune system, atherosclerosis and persisting infection

    http://www.cpnhelp.org/?q=node/129

    [8]

    Article link here

    Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms.

    Nicolson GL, Gan R, Haier J.

    Clin Infect Dis. 1999 Aug;29(2):452-3.

    Chronic Chlamydia pneumoniae infection: a treatable cause of chronic fatigue syndrome.

    Chia JK, Chia LY.

    Torrance Memorial Medical Center, California, USA.

    J Infect Dis. 1992 Jan;165(1):184.

    [9] Detection of Chlamydia in the peripheral blood cells of normal donors using in vitro culture, immunofluorescence microscopy and flow cytometry techniques

    BMC Infectious Diseases 2006, 6:23 doi:10.1186/1471-2334-6-23

    Frances Cirino, Wilmore C. Webley, Nancy L. Croteau, Chester Andrzejewski Jr.,Elizabeth S. Stuart (esstuart@microbio.umass.edu)

    Transfusion. 2004 Jul;44(7):1072-8.

    Prevalence of viable Chlamydia pneumoniae in peripheral blood mononuclear cells of healthy blood donors.

    Yamaguchi H, Yamada M, Uruma T, Kanamori M, Goto H, Yamamoto Y, Kamiya S.

    Department of Infectious Disease, Division of Microbiology, Kyorin University School of Medicine, Tokyo, Japan. hiroyuki@sahs.med.osaka-u.ac.jp

    …”Thirteen of 70 donors (18.5%) showed the presence of bacterial transcript in cultured PBMNCs. …CONCLUSION: The bacterial transcripts in PBMNCs obtained from healthy donors were detected by the RT-PCR method. Viable C. pneumoniae may be present in healthy human PBMNCs…”

    [10] Note- One of the things Dr. Stratton said to me shortly after I started www.cpnhelp.org was that this kind of thing was one of the missing elements in the treatment process: some kind of on-going support community that could help patients through the challenges and confusions of being on a difficult protocol.

    [11] As far as I know Dr. Stratton’s group are the only ones to have found the link between Chlamydia pneumoniae infection and secondary porphyria. It remains unpublished in the scientific literature and so virtually unknown to most medical practitioners.

    [13] Article link here

    : Am J Pathol. 2007 Jan;170(1):33-42.

    Persistent Chlamydia pneumoniae infection of cardiomyocytes is correlated with fatal myocardial infarction.

    * Spagnoli LG, Pucci S, Bonanno E, Cassone A, Sesti F, Ciervo A, Mauriello A.

    Cattedra di Anatomia ed Istologia Patologica, Dipartimento di Biopatologia e Diagnostica per Immagini, Universita di Roma Tor Vergata, Via Montpellier 1, Rome, Italy. spagnoli@uniroma2.it

    Acute myocardial infarction (AMI) associated with unfavorable prognosis is likely to be the consequence of a diffuse active chronic inflammatory process that destabilizes the whole coronary tree and myocardium, suggesting a possible common causal agent underlying both conditions. The main objective of this study was to investigate whether Chlamydia pneumoniae (CP) infection occurred beyond the coronary plaques, namely in the myocardium of individuals who died of AMI. The presence of CP cell wall antigen (OMP-2) and CP-HSP60 was investigated in the myocardium and coronary plaques of 10 AMI and 10 age-matched control patients by immunohistochemistry, electron microscopy, and molecular biology. OMP-2 antigens were found in the unaffected myocardium of 9 of 10 AMI patients. Conversely, only 1 of 10 control patients exhibited a positive staining for CP. Moreover, OMP-2 and CP-HSP60 were detected in the whole coronary tree. CP presence was strongly associated with a T-cell inflammatory infiltrate. Our results suggest that CP may underlie both coronary and myocardial vulnerabilities in patients who died of AMI and corroborate the notion that CP may act by reducing cardiac reserves, thus worsening the ischemic burden of myocardium.

    [14] Additional cardiac findings in CFS consistent with cardiac infection by Chlamydia pneumoniae—

    From: Causes of death among patients with chronic fatigue syndrome.

    Journal: Health Care Women Int. 2006 Aug;27(7):615-26.

    Authors: Jason LA, Corradi K, Gress S, Williams S,

    Torres-Harding S.

    Affiliation: DePaul University, Chicago, Illinois, USA.

    NLM Citation: PMID: 16844674

    “… in response to postural stress, 81% of patients with CFS, but none of controls, experienced ejection fraction decreases (suggesting left ventricular dysfunction in the heart) and those with more severe symptoms had greater decreases (Peckerman, Chemitiganti, et al., 2003).

    Patients with CFS might have lower cardiac output, and the resulting low flow circulatory state could make it difficult for patients to meet the demands of everyday activity, and it could also lead to fatigue and other symptoms (Peckerman, LaManca, et al., 2003)…”

    [15] Annals of the New York Academy of Sciences 933:185-200 (2001)

    © 2001 New York Academy of Sciences

    Cytokines and Chronic Fatigue Syndrome

    Roberto Patarcaa

    E. M. Papper Laboratory of Clinical Immunology, Department of Medicine, University of Miami School of Medicine, Miami, Florida 33101, USA

    Address for correspondence: E. M. Papper Laboratory of Clinical Immunology, Department of Medicine (R-42), University of Miami School of Medicine, P.O. Box 016960, Miami, FL 33101.

    http://www.annalsonline.org/cgi/content/abstract/933/1/185

    [16] Vestn Ross Akad Med Nauk. 2005;(2):17-22.

    The immune system, atherosclerosis and persisting infection

    Pigarevskii PV, Mal'tseva SV, Seliverstova VG.

    Article Link here

    [17] Eur Respir J. 2004 Apr;23(4):506-10.

    Phagocytes transmit Chlamydia pneumoniae from the lungs to the vasculature.

    Gieffers J, van Zandbergen G, Rupp J, Sayk F, Kruger S, Ehlers S, Solbach W, Maass M.

    Institute for Medical Microbiology and Hygiene, University of Lubeck, Ratzeburger Allee 160, 23538 Lubeck, Germany. jens.gieffers@hygiene.ukl.mu-luebeck.de

    Chlamydia pneumoniae, a major cause of community-acquired pneumonia, primarily infects the respiratory tract. Chronic infection of nonrespiratory sites, such as the vascular wall, the brain or blood monocytes, requires evasion from the lungs and spreading via the bloodstream. The cell types involved in dissemination are insufficiently characterised. In this study, New Zealand White rabbits were infected intratracheally with C. pneumoniae, and lung manifestation and systemic dissemination were monitored by polymerase chain reaction and immunohistochemistry. Infection of the lungs was characterised by an early phase dominated by granulocytes and a late phase dominated by alveolar macrophages (AM). Granulocytes, AM and alveolar epithelial cells acted as host cells for chlamydiae, which remained detectable for up to 8 weeks. AM transported the pathogen to the peribronchiolar lymphatic tissue, and subsequently C. pneumoniae entered the spleen and the aorta via dissemination by peripheral blood monocytes. In conclusion, Chlamydia pneumoniae-infected alveolar macrophages transmigrate through the mucosal barrier, and give the pathogen access to the lymphatic system and the systemic circulation. Infected peripheral blood monocytes are the vector system within the bloodstream and transmit the infection to the vascular wall. This is the first description of granulocytes acting as a reservoir for Chlamydia pneumoniae early in infection.

    Article link here

    [18] From: Causes of death among patients with chronic fatigue syndrome.

    Journal: Health Care Women Int. 2006 Aug;27(7):615-26.

    Authors: Jason LA, Corradi K, Gress S, Williams S,

    Torres-Harding S.

    Affiliation: DePaul University, Chicago, Illinois, USA.

    NLM Citation: PMID: 16844674

    People with CFS appear to have two basic problems with immune function: immune activitation as demonstrated by elevations of activated T lymphocytes, including cytotoxic T cells and elevations of circulating cytokines; and poor cellular function, with low natural killer cell cytotoxicity and frequent immunoglobulin deficiencies (most often IgG1 and IgG3; Patarca-Montero, Mark, Fletcher, & Klimas, 2000).

    For example, Antoni, Fletcher, Weiss, Maher, Siegel, and Klimas, (2003) found that patients with low natural killer cell activity (NKCA) and a state of overactivation of lymphocyte subsets (e.g., CD2+CD26+% activation markers) had the greatest fatigue intensity and greatest fatigue-related impairments in emotional and mental functioning. It seems that the Th2 cytokines are dominant over the Th1 cytokines.

    In addition, Suhadolnik and colleagues (1997) found a novel low-molecular-weight (37 kDa) binding protein in a subset of individuals with CFS who are severely disabled by their disease. A European team (De Meirleir et al., 2000) has also found increased levels of 80 kDa and 37 kDa RNase L in patients with CFS. The ratio of this 37 kDa protein to the normal 80 kDa protein was high in 72% of patients with CFS but only in 1% of the healthy controls and in none of the depression and fibromyalgia control patients.

    [19] Eur J Haematol. 2005 Jan;74(1):77-83.

    Detection of Chlamydophila pneumoniae in the bone marrow of two patients with unexplained chronic anaemia.

    Nebe CT, Rother M, Brechtel I, Costina V, Neumaier M, Zentgraf H, Bocker U, Meyer TF, Szczepek AJ.

    Central Laboratory, University Hospital Mannheim, Mannheim, Germany. thomas.nebe@ikc.ma.uni-heidelberg.de

    Anaemia of chronic disease (ACD) is a common finding involving iron deficiency and signs of inflammation. Here, we report on two patients with ACD where a persistent infection with Chlamydophila (Chlamydia) pneumoniae (CP) was detected in bone marrow (BM) biopsies. Infection was suspected by routine cytology and confirmed by immunofluorescence, electron microscopy, polymerase chain reaction (PCR) including different primer sets and laboratories and sequencing of the PCR product. This is a first report of chlamydial presence in the BM of anaemic patients. The cases are presented because persistent chlamydial infection may contribute more frequently to chronic refractory anaemia than previously suspected.

    [20] Am J Med Sci. 2003 Aug;326(2):55-60.Click here to read Links

    Abnormal impedance cardiography predicts symptom severity in chronic fatigue syndrome.

    Peckerman A, LaManca JJ, Dahl KA, Chemitiganti R, Qureishi B, Natelson BH.

    Department of Neurosciences, CFS Cooperative Research Center, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA. apeckerm@njneuromed.org

    BACKGROUND: Findings indicative of a problem with circulation have been reported in patients with chronic fatigue syndrome (CFS). We examined this possibility by measuring the patient's cardiac output and assessing its relation to presenting symptoms. METHODS: Impedance cardiography and symptom data were collected from 38 patients with CFS grouped into cases with severe (n = 18) and less severe (n = 20) illness and compared with those from 27 matched, sedentary control subjects. RESULTS: The patients with severe CFS had significantly lower stroke volume and cardiac output than the controls and less ill patients. Postexertional fatigue and flu-like symptoms of infection differentiated the patients with severe CFS from those with less severe CFS (88.5% concordance) and were predictive (R2 = 0.46, P < 0.0002) of lower cardiac output. In contrast, neuropsychiatric symptoms showed no specific association with cardiac output. CONCLUSIONS: These results provide a preliminary indication of reduced circulation in patients with severe CFS. Further research is needed to confirm this finding and to define its clinical implications and pathogenetic mechanisms.

    Article Link Here

    [23] Recent Patents on Endocrine, Metabolic & Immune Drug Discovery 2007, 1, 63-82 63

    Melatonin as Antioxidant Under Pathological Processes

    Cristina Tomás-Zapico*, Ana Coto-Montes1

    Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain

    http://www.bentham.org/emi/samples/emi1-1/Tom%E1s-Zapico.pdf

    [24] Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents

    endotoxemia in lipopolysaccharide-induced multiple organ dysfunction syndrome in rats

    ELENA CRESPO,* MANUEL MACI´AS,* DAVID POZO,† GERMAINE ESCAMES,*

    MIGUEL MARTI´N,* FRANCISCO VIVES,* JUAN M. GUERRERO,† AND

    DARI´O ACUN˜ A-CASTROVIEJO*,1

    www.fasebj.org/cgi/reprint/13/12/1537.pdf

    [25] J Immunol. 1994 Sep 15;153(6):2671-80.

    Activation of human monocytes by the pineal hormone melatonin.

    Morrey KM, McLachlan JA, Serkin CD, Bakouche O.

    Department of Molecular Pharmacology and Biologic Chemistry, Northwestern University Medical School, Chicago, IL 60611.

    To determine the effects of the pineal hormone melatonin on human monocytes, human monocytes were activated by different concentrations of melatonin. Above the activation threshold of 5 x 10(-11) M, melatonin was able to induce the cytotoxicity of human monocytes, the secretion of IL-1, and the production of reactive oxygen intermediates. Melatonin and LPS seemed to have a synergistic effect on human monocyte activation. Indeed, below their respective monocyte activation threshold (5 x 10(-11) M and 0.625 ng/ml), melatonin (10(-12) M) in association with LPS (0.2 ng/ml) was able to induce cytotoxicity, IL-1 secretion, and reactive oxygen intermediates production. Melatonin alone at 10(-12) M or LPS alone at 0.2 ng/ml did not activate monocytes. Furthermore, melatonin was able to prime the monocytes for a subsequent activation by LPS. When monocytes were activated by LPS (0.25 ng/ml) at the time that they were plated and then activated by melatonin (10(-12) M) 8 h later, no IL-1 secretion and no cytotoxicity were detected. However, when the cells were first activated by melatonin (10(-12) M), and then 8 h later by LPS (0.25 ng/ml), IL-1 secretion and monocyte cytotoxicity were observed. Above its monocyte activation threshold, melatonin induces both cell-associated IL-1 alpha and IL-1 beta activities. Below this activation threshold, i.e., at 10(-12) M, melatonin does not induce the cell-associated IL-1 alpha and IL-1 beta activities, but does induce the mRNA for both IL-1 (alpha and beta). It seems that melatonin activates monocytes through protein kinase C. These data suggest that melatonin activates monocytes and induces their cytotoxic properties, along with the IL-1 secretion.

    Article link here

    Annals of the New York Academy of Sciences

    Volume 933 THE ROLE OF NEURAL PLASTICITY IN CHEMICAL INTOLERANCE Page 211 - March 2001

    Annals of the New York Academy of Sciences 933 (1), 211–221.

    The Role of Cytokines in Physiological Sleep Regulation

    * James M. Kruegera et al

    Article link here

    [27] “…cytokine treatment causes serotonin depletion. They hypothesized that cytokines suppress serotonin by activating the enzyme indoleamine-2,3-dioxygenase (IDO) that catabolizes tryptophan. Dr. Dantzer explained that in the brain, IDO prevents tryptophan from being turned into serotonin, which causes decreased levels of serotonin and leads to the symptoms of depression.”

    Dr. Dantzer pointed out that his current research is built on a concept that he had ignored a few years ago, which is the fact that the brain is representing what is going on in the body—“what we already knew for quite a long time, but in terms of inflammation, and it is doing that with the same molecules as the ones that are promoting inflammation at the periphery. If you have an inflammatory response in your body, it will be represented in the brain with exactly the same molecules that in your body are responsible for inflammation. This normally is responsible for what we call sickness behavior—why you feel sick and behave in a sick way when you are ill.”

    http://www.neuropsychiatryreviews.com/sep04/sep04_npr_inflammatory.html

    [28] Migraine: A Chronic Sympathetic Nervous System Disorder

    Stephen J. Peroutka

    http://www.medscape.com/viewarticle/466937_1

    [29]Illness, cytokines, and depression.

    Ann N Y Acad Sci. 2000;917:478-87.

    Yirmiya R, Pollak Y, Morag M, Reichenberg A, Barak O, Avitsur R, Shavit Y, Ovadia H, Weidenfeld J, Morag A, Newman ME, Pollmacher T.

    Department of Psychology, Hebrew University, Hadassah Hospital, Jerusalem, Israel. msrazy@mscc.huji.ac.il

    Various medical conditions that involve activation of the immune system are associated with psychological and neuroendocrine changes that resemble the characteristics of depression. In this review we present our recent studies, designed to investigate the relationship between the behavioral effects of immune activation and depressive symptomatology. In the first set of experiments, we used a double-blind prospective design to investigate the psychological consequences of illness in two models: (1) vaccination of teenage girls with live attenuated rubella virus, and (2) lipopolysaccharide (LPS) administration in healthy male volunteers. In the rubella study, we demonstrated that, compared to control group subjects and to their own baseline, a subgroup of vulnerable individuals (girls from low socioeconomic status) showed a significant virus-induced increase in depressed mood up to 10 weeks after vaccination. In an ongoing study on the effects of LPS, we demonstrated significant LPS-induced elevation in the levels of depression and anxiety as well as memory deficits. These psychological effects were highly correlated with the levels of LPS-induced cytokine secretion. In parallel experiments, we demonstrated in rodents that immune activation with various acute and chronic immune challenges induces a depressive-like syndrome, characterized by anhedonia, anorexia, body weight loss, and reduced locomotor, exploratory, and social behavior. Chronic treatment with antidepressants (imipramine or fluoxetine) attenuated many of the behavioral effects of LPS, as well as LPS-induced changes in body temperature, adrenocortical activation, hypothalamic serotonin release, and the expression of splenic TNF-alpha mRNA. Taken together, these findings suggest that cytokines are involved in the etiology and symptomatology of illness-associated depression.

    Neuroimmunomodulation. 2005;12(5):255-69.

    Cytokine dysregulation, inflammation and well-being.

    * Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP.

    Division of Rheumatology, Immunology and Allergy, Georgetown University Medical Center, Washington, D.C., USA.

    Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1 versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic 'overshooting' with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-alpha and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the 'systemic anti-inflammatory feedback' and/or 'hyperactivity' of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases. Copyright (c) 2005 S. Karger AG, Basel

    [30] In 1990, the American College of Rheumatology, the official body of doctors who treat arthritis and related conditions, finally legitimized fibromyalgia in the medical community by presenting its criteria for diagnosing it. It is diagnosed when the you display the following symptoms:

    A history of widespread pain (pain on both sides of the body and above and below the waist) that is present for at least three months

    Pain in at least 11 of 18 tender-point sites.

    http://www.arthritis.org/conditions/DiseaseCenter/Fibromyalgia/fibromyalgia.asp

    An excellent review of infectious issues in Fibromyalgia can be found at:

    Fibromyalgia- is there an infectious connection?

    http://www.roadback.org/index.cfm/fuseaction/education.display/display_id/135.html

    Jim K Wed, 2007-03-14 14:57

    Diseases associated with Cpn: the exhaustive list

    Diseases associated with Cpn: the exhaustive list

    I have culled from Mitchell & Stratton patent #6,884,784 an exhaustive list of diseases where Cpn has been implicated as a possible cause or co-factor (reference: Mitchell & Stratton patent #6,884,784):

    Diseases where an association has been discovered between chronic Chlamydia infection of body fluids and/or tissues with several disease syndromes of previously unknown etiology in humans which respond to unique antichlamydial regimens include:

    Editorial comment: Strong findings from their research. If you have any of these it suggests to me that at least an empirical course of the combination antibiotic therapy is strongly indicated, with or without serology.


    Multiple Sclerosis (MS)
    Rheumatoid Arthritis (RA)
    Inflammatory Bowel Disease (IBD)
    Interstitial Cystitis (IC)
    Fibromyalgia (FM)
    Autonomic nervous dysfunction (AND neural-mediated hypotension);
    Pyoderma Gangrenosum (PG)
    Chronic Fatigue (CF) and Chronic Fatigue Syndrome (CFS).

    Diseases where Cpn load has been associated where measured, and where treatment can create improvement in the primary condition:

    Chronic hepatitis
    Systemic lupus erythematosus
    Arthritis
    Thyroidosis
    Scleroderma
    Diabetes mellitus
    Graves' disease
    Beschet's disease and
    Graft versus host disease (graft rejection).

    Diseases where Cpn may be associated as a secondary or primary factor:

    Editorial Comment: The diseases from here on have been associated with Cpn. At minimum it seems to suggest that at least serology  for Cpn should be explored, or where there are other diagnostic indicators of Cpn an empirical course of the combination protocol should be looked at.

    Sepsis syndrome
    Cachexia
    Circulatory collapse and shock resulting from acute or chronic bacterial infection
    Acute and chronic parasitic and/or infectious diseases from bacterial
    Viral or fungal sources such as a HIV, AIDS (including symptoms of cachexia, autoimmune disorders, AIDS dementia complex and infections) can be treated as well as Wegners Granulomatosis.

    Various inflammatory diseases, there are certain features of the inflammatory process that are generally agreed to be characteristic. These include fenestration of the microvasculature, leakage of the elements of blood into the interstitial spaces, and migration of leukocytes into the inflamed tissue. On a macroscopic level, this is usually accompanied by the familiar clinical signs of erythema, edema, tenderness (hyperalgesia), and pain. Inflammatory diseases, such as chronic inflammatory pathologies and vascular inflammatory pathologies, including:
    Chronic inflammatory pathologies such as aneurysms
    Hemorrhoids
    Sarcoidosis
    Chronic inflammatory bowel disease
    Ulcerative colitis
    Crohn's disease and vascular inflammatory pathologies
    Disseminated intravascular coagulation
    Atherosclerosis
    Kawasaki's pathology
    Coronary artery disease
    Hypertension
    Stroke
    Asthma
    Chronic hepatitis
    Multiple sclerosis
    Peripheral neuropathy
    Chronic or recurrent sore throat
    Laryngitis
    Tracheobronchitis
    Chronic vascular headaches (including migraines
    Cluster headaches and tension headaches) and pneumonia when demonstrated to be pathogenically related to Chlamydia infection.

    Treatable disorders when associated with Chlamydia infection also include but are not limited to Neurodegenerative diseases including
    Demyelinating diseasessuch as multiple sclerosis and acute transverse myelitis;
    Extrapyramidal and cerebellar disorders such as lesions of the corticospinal system;
    Disorders of the basal ganglia or cerebellar disorders;
    Hyperkinetic movement disorders such as Huntington's Chorea and senile chorea;
    Drug-induced movement disorders such as those induced by drugs which block CNS dopamine receptors;
    Hypokinetic movement disorders
    such as Parkinson's disease;
    Progressive supranucleo palsy;
    Cerebellar and Spinocerebellar Disorders such as astructural lesions of the cerebellum;
    Spinocerebellar degenerations (spinal ataxia)
    Friedreich's ataxia
    Cerebellar cortical degenerations
    Multiple systems degenerations (MencelDejerine-Thomas
    Shi-Drager and Machado Joseph)); and systemic disorders (Refsum's disease
    Abetalipoprotemia, ataxia telangiectasia and mitochondrial multi-system disorder);
    Demyelinating core disorders such as:
    Multiple sclerosis
    Acute transverse myelitis;
    Disorders of the motor unit such as neurogenic muscular atrophies (anterior horn cell degeneration) such as
    Amyotrophic lateral sclerosis
    Infantile spinal muscular atrophy and juvenile spinal muscular atrophy);
    Alzheimer's disease;
    Down's Syndrome in middle age;
    Diffuse Lewy body disease; Senile Dementia of Lewy body type;
    Wernicke-Korsakoff syndrome;
    Chronic alcoholism;
    Creutzfeldt-Jakob disease;
    Subacute sclerosing panencephalitis
    Hallerrorden-Spatz disease; and
    Dementia pugilistica

    Malignant pathologies involving tumors or other malignancies such as:
    Leukemias (acute chronic myelocytic
    chronic lymphocytic and/or myelodyspastic syndrome);
    Lymphomas (Hodgkin's and non-Hodgkin's lymphomas such as malignant lymphomas (Burkitt's lymphoma or Mycosis fungoides));
    Carcinomas (such as colon carcinoma) and metastases thereof;
    Cancer-related angiogenesis;
    Infantile hemangiomas;
    Alcohol-induced hepatitis.
    Ocular neovascularization
    Psoriasis
    Duodenal ulcers
    Angiogenesis of the female reproductive tract
    can also be treated when demonstrated by the diagnostic procedures described herein to be associated with Chlamydial infection.

    An immunocompromised individual is generally defined as a person who exhibits an attenuated or reduced ability to mount a normal cellular or humoral defense to challenge by infectious agents
    e.g., viruses, bacterial, fungi and protozoa. Persons considered immunocompromised include malnourished patients, patients undergoing surgery and bone narrow transplants, patients undergoing chemotherapy or radiotherapy, neutropenic patients, HIV-infected patients, trauma patients, burn patients, patients with chronic or resistant infections such as those resulting from myeloodysplastic syndrome, and the elderly, all of who may have weakened immune systems. A protein malnourished individual is generally defined as a person who has a serum albumin level of less than about 3.2 grams per deciliter (g/dl) and/or unintentional weight loss greater than 10% of usual body weight.

    The course of therapy, serological results and clinical improvements from compassionate antichlamydial therapy in patients diagnosed with the diseases indicated were observed and are reported in Example 5. The data provides evidence to establish that treatment of Chlamydia infection results in the serological and physical improvement of a disease state in the patient undergoing combination therapy. These observations were consistent among a variety of different diseases which fall within a generalized disease class.

    Other Diseases of Unknown Etiology with New Evidence for a Chlamydia pneumoniae Etiology

    Both C. trachomatis and C. psittaci exhibit a protean disease complex dependent on different serovars. One known basis for this diversity to date is the amino acid sequence of the MOMP. FIG. 1 shows a sequence alignment of various Chlamydia MOMPs. Note that the size and sequence are relatively homologous except for the four variable regions that are responsible for the serovar (serotype) basis of classification. Further, it has been discovered that C. pneumoniae infects blood vessel endothelial cells from which EBs are released in the blood stream. In addition, macrophages are known targets for C. pneumoniae and may serve as reservoirs and provide an additional mechanism of transmission. C. pneumoniae is thus able to spread throughout the human body, establishing infection in multiple sites and in multiple organ systems. Infected sites may exist for an extended period without inducing symptoms that are noticed by the patient or by an examining physician. Sequence variability of MOMPs or other chlamydial antigens may provide a basis for organ specificity while other chlamydial proteins, such as the 60K and 70K heat shock proteins or LPS, may influence immune response.

    C. psittaci and C. pecorum are known to cause a host of infections in economically significant animals. Thus, the teachings of this invention are relevant to animals. Throughout this application and for purposes of this invention, "patient" is intended to embrace both humans and animals. Virtually all rabbits and mice tested to date have PCR signals for C. pneumoniae. They can be used as appropriate animal models for treatment using specific combination antibiotics to improve therapy. (Banks et al., Ameri. J. of Obstetrics and Gynecology 138(7Pt2):952-956 (1980)); (Moazed et al., Am. J. Pathol. 148(2):667-676 (1996)); (Masson et al., Antimicrob. Agents Chemother. 39(9):1959-1964 (1995)); (Patton et al., Antimicrob. Agents Chemother. 37(1):8-13 (1993)); (Stephens et al., Infect. Immun. 35(2):680-684 (1982)); and (Fong et al., J. Clin. Microbiol. 35(1):48-52 (1997)).

    Coupled with these developments are the recently developed rabbit models of coronary artery disease, where rabbits exposed to C. pneumoniae subsequently develop arterial plaques similar to humans (Fong et al., J. Clin. Microbiol. 35:48-52 (1997)). Most recently, a study at St. George's Hospital in London found that roughly 3⁄4 of 213 heart attach victims have significant levels of antibodies to C. pneumoniae antibody and that those that have such antibodies achieve significantly lower rates of further adverse cardiac events when treated with antibiotics (Gupta et al., Circulation 95:404-407 (1997)). Taken together, these three pieces of evidence (the bacteria found in diseased tissue, inoculation with the bacteria causes diseases, and treating for the bacteria mitigates disease) make a case for a causal connection.

    Jim K Sun, 2006-01-22 08:41

    Multiple Sclerosis and the CPn model

    Multiple Sclerosis and the CPn model

    Multiple sclerosis is a disease of the central nervous system thought by most to be autoimmune because it is clear that the nervous tissue is being damaged and that also the immune system is present at the actual lesion location. Efforts to find a germ that the immune system is attacking have fallen flat with conflicting and inconclusive results. We propose here that MS may be caused by chlamydia pneumoniae (CPn). In this book page I will outline the various findings in research on MS and also findings on CPn highlighting similarites.

    While it is very interesting material, the reader must understand that this is a theoretical model and I am coming at it with this point of view, "If CPn causes MS what does this research mean?" I do have a bias as I begin. But I offer this to you, the reader: Everyone has a bias, I am just stating mine up front. The pharmaceutical company that is making a drug to suppress your immune system comes at the issue from a bias that MS is autoimmune, even though this is not proven but a model. So, we will start there.....

    MS:Is it autoimmune?

    Most of the medical community thinks MS is autoimmune because every damaged area in the MS brain has immune system cells present. Or do they? In 2004, Prineas and Barnett rocked the MS world with their paper "Relapsing and remitting multiple sclerosis: pathology of a newly forming lesion" found HERE

    As you can see in that paper, and I was lucky enough to read the whole citation, the notion that the immune system comes in and damages the nerves is seriously questioned. Essentially these authors found that in autopsied brain tissue, the brain had the lesions that they expected with immune system cells present, but these tissue samples ALSO had NEW lesions in which the nerve had died, but the immune system had not yet gotten there to clean the area up and remove the dead tissue. How can the immune system have caused the injury if the injury occurs before it arrived? If we understand that immunity includes cleaning up dead cells and unwanted tissue, we see there is a very good reason for the immune system to be present in the brain if a nerve has died from some other cause.
    In fact this is a very logical reason for the immune system to be present because we already know that the immune system works this way naturally, this is what it is designed to do. All other theories from molecular mimicry to autoimmunity require that the body made a mistake and began attacking itself.

    This work is supported by review of the issue written by Chaudhuri and referenced on pubmed HERE I have been fortunate enough read this paper (the link I provide here has a "blank", you'd have to subscribe to read it) and this author is adament that MS is not autoimmune,. In an earlier paper he said;

    "Multiple sclerosis (MS) is a common, disabling neurological condition whose pathogenesis is not clearly understood. Although current treatment recommendations assume an immunopathogenic disease mechanism, MS may not be an autoimmune disorder. Long-term immunological therapy for MS is in our view an untested approach, guided by uncritical acceptance of data from drug trials. We do not believe that there is convincing evidence that any of these immune-based treatments prevents long-term disease progression, or has much effect on common disabilities such as fatigue, pain, depression and cognitive impairment. The recent recommendations of the National Institute of Clinical Excellence did not address important issues regarding disease modification, management of paroxysmal symptoms and the likely therapeutic candidates for future treatment trials. We discuss treatment options for MS beyond the NICE guidelines" (Chaudhuri 2005) reference HERE.

    A recent work by Dr Sriram of Vanderbilt University published in the Annals of Neurology and referenced HERE indicates that MS is utterly different on a cellular level than EAE which is a pure autoimmune disease. There are different cytokine upregulations and a cellular immune different profile altogether, which is a critical issue because the therapies generated by looking at what impacts EAE are geared to alter these cytokines. He contends that the constant reliance on this model as a "good model" of MS and through which all treatments are brought to us limits research understandings about what MS really is. In essence we are treating EAE not MS when we bring new protocols and strategies to market via this method. It is interesting to note that EAE is curable and it has been so for decades via the same medications that do not actually help people with MS.

    HERE
    is yet another abstract indicating that anti-inflammatory approaches may be misdirected in MS. Importantly, these authors say that even the newer immune suppressing approaches, while they do result in a large decreases in MRI activity, do not result in an improvement in disabiilty long term. Quote;

    "Suppressing relapses by disease-modifying agents does not dramatically influence the progression of irreversible disability. Interferons beta reduce the relapse rate by 30% and conventional MRI activity by more than 50%. In spite of this effect on inflammation, the effect on disability is only marginal and possibly relapse-reduction-dependent. Administration of Campath-1H to patients with very active disease in terms of frequency of relapses, accumulation of disability and MRI activity, results in a profound, prolonged lymphopenia and the suppression of clinical and MRI activity, but in spite of this, clinical disability and cerebral atrophy still progress. The same experience has been reported with cladribine and autologous haematopoietic stem cell transplantation..." copied verbatim
    The paper suggests that neuro regeneration and protection should be the main focus of MS strategies, not simply reducing inflammation. It also raises an important question for medicine in general in regards to currently available therapies, namely exactly what does reduction in inflammation accomplish for the MS patient and at what cost?

    So here I have presented the idea that MS is not autoimmune and offered research that caused me to form that opinion. So, If MS is not autoimmune but instead a disease in which the nerves die for some reason then the immune system comes in to clean up the debris just as it is supposed to, what bacteria or virus is to blame?

    The infective model of MS

    The infective model of MS is the notion that MS is caused by a virus or bacteria. While numerous attempts have been made to isolate the infective organism, unfortunately no one organism has been consistently tied to MS. Several of the possibiities are human herpes 6 (roseola), epstein barr virus (mono or glandular fever), and pleomorphic bacteria like chlamydia pneumoniae, borrelia, and mycoplasma. While there are articles outlining some people finding and isolating each of these things in the MS brain, others do not find the same organism. Here in these pages we are presenting the idea of CPn as the possible infective organism but it may be that the kinds of changes we see in CPn could be common to changes seen in other bacterial infections like persistant borreliosis and potentially even viral causes. The body often uses the same strategies to do multiple things as in, for example, creating a fever in both viral and bacterial infections of many kinds. We are investigating CPn specifically here as the theoretical cause of MS because Vanderbilt University research finds CPn in higher numbers in the CFS of people with MS. Additionally, there is a lot of general research on CPn indicating it is causing a variety of chronic illnesses because it has the ability to change forms and invade the cells themselves including especially immune cells, nerve cells, vessel walls, lung tissue, and blood cells. For example, CPn is considered an emerging pathogen in atherosclerosis. See the CDC link HERE It is also implicated in asthma, and some authorities such as Margaret Hammerschlag MD of the CDC are now saying that asthma, long thought to be a chronic illness of unknown pathology which has decades of research looking at genetics and other putative factors as causal, is in fact probably a chronic infection with CPn. When discussing MS specifically, it is less clear at this point although there is a lot of circumstantial evidence for CPn possibly playing a role as well as the research done at VU finding it directly.

    The first people to produce work that shows CPn in the MS brain were at Vanderbilt University Sriram, Stratton and Mitchell. The first paper is here. This paper is the whole citation, and it is an incredible privilege to have this paper available to us. This was reprinted on CPnhelp.org with permission. In essence, the upshot of this article is that using their techniques, the team at VU found evidence of CPn in the vast majority of MS patients. It is important to note that the team used PCR analysis, CSF immunoglobin IgG reactivity with CPn antigens and culture to evaluate the presence of CPn in these MS brains. People who produce work counter to this frequently offer a single test ie "we cultured the CSF for CPn and found none." Such "opposing" research simply does not have the authority that the original work did due to the lack of diligence. We will investigate this specific issue in depth in the next page about the debate.

    Other researchers all over the world have also found CPn in MS brains. A list of some of these follows:

    HERE is a paper by Contini C, et al titled "Cerebrospinal fluid molecular demonstration of Chlamydia pneumoniae DNA is associated to clinical and brain magnetic resonance imaging activity in a subset of patients with relapsing-remitting multiple sclerosis". This paper found that CPn was associated with MS more often if the disease was active on MRI and if RRMS. Again this author used several detection methods. But in this paper they also found CPn in people with other neurological diseases as well, suggesting it may be able to cause several problems. This might be compared to e.coli causing a bladder infection, urethritis, or nephritis. All are urinary tract infections with slightly different locations and problems.

    HERE is a link to an abstract by Dong-Si T, et al titled "Increased prevalence of and gene transcription by Chlamydia pneumoniae in cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis". This author again found that other neurological diseases also had increased CPn, but that in MS patinets there was increased gene trascription of CPn indicating it may be more active for them.

    HERE is a link to an abstract by Sotgiu s, et al titled "Chlamydia pneumoniae in the cerebrospinal fluid of patients with multiple sclerosis and neurological controls.". This author found CPn in the MS patients only, as different from others.

    HERE is a paper by Fainardi E, Et al titled "Intrathecal production of Chlamydia pneumoniae-specific high-affinity antibodies is significantly associated to a subset of multiple sclerosis patients with progressive forms" in which an association between CPn and MS was found. The conclusion was "These findings confirm that the presence of a humoral immune response to C. pneumoniae within the central nervous system (CNS) is not selectively restricted to MS, but is shared by several inflammatory neurological conditions. In addition, our results suggest that an intrathecal production of C. pneumoniae-specific high-affinity IgG can occur in a subset of patients with MS progressive forms in which a C. pneumoniae brain chronic persistent infection may play an important pathogenetic role."

    This is a sample of the work that found CPn in MS. To read more simply click one of the links and enter "multiple sclerosis chlamaydia pneumoniae" in the search box on pubmed. You'll get a whole list. Of interest note that this work is done all over the world and a considerable amount of it is done by infectious disease specialists and pathologists, not necessarily neurologists. There is other work, of course, that did not find it since this is how science works to advance understanding. For the best review of the debate on the potential for CPn to be the causitive organism in MS is found in David Wheldon's site. There is a greater number and a more in depth evaluation of studies there. HERE. The question "how do we evaluate these controversial findings?" is tackled on the Great Debate page.

    mrhodes40 Thu, 2006-03-02 12:32

    Cpn in MS: Over Easy

    Cpn in MS: Over Easy

    Why could Cpn affect MS sufferers so much?
    There may be more than one explanation…

    The answer could lie in a person’s genes.  

    Amongst our genetic code we all have instructions for T-cells.   These are a group of white blood cells, part of the body's immune system, that defend against infection.    Whilst these T cells are necessary for us to fight infection if they run unchecked they can cause damage to the Central Nervous System (CNS) by damaging the nerve fibres.   In MS patients it is possible that the cells  that stop some T cells from being over efficient are not working properly.

    For a more comprehensive explanation please visit
    http://www.msneighborhood.com/content/in_the_news/archive_2248.aspx

     

    Or in the Blood-Brain Barrier

    The brain is an especially sensitive area of the body which is protected by the Blood Brain Barrier (BBB) basically a very fine meshed sieve.   Unlike the kitchen variety it is selective of what can go through.   It will only allow what it needs to pass through the BBB but some infections get in under cover of other cells, a bit like a Trojan horse.   The idea here is that Cpn has infected the brain and the BBB opens up enough to allow the body’s immune system to come and fight the infection and remove the debris.   In the process the very sensitive brain could be damaged by the clean up operation.

    For a more comprehensive explanation please visit
    www.cpnhelp.org/?q=the_brain_and_pathogenic_

     
    Or it could be a combination of factors, such as a BBB which does not work quite as it should and an immune systems that over-reacts.   There are many other possibilities, including infection by viruses or bacteria and many others are unknown.

     

    How Cpn could affect MS patients

    Cpn is a common organism (a bacterium) which can affect many parts of the body without causing too many problems if it decides to settle in areas that are not particularly sensitive.  

    Many people will have sinusitis, or a dry cough, or dry skin, or what feels like an upset tummy and carry on regardless of these small discomforts.  

    But if the bacteria infect the brain then, over a period of years, the symptoms recognised as MS may surface.   Often this first shows up as eye problems, maybe some numbness which goes away after a couple of weeks, but gradually the symptoms can become more severe and end up disabling the sufferer.

    One possible reason for this is that Cpn is a slow growing organism and it could be many years before the infection is bad enough to cause the immune system to react to it so severely as to result in disablement.

     

    For a more comprehensive explanation please visit
    http://www.cpnhelp.org/?q=multiple_sclerosis_and_th

    www.cpnhelp.org/pdfs/Cp-MSAssoc.pdf

     

     

    Michèle Tue, 2006-04-25 06:53

    Limitations of the Model

    Limitations of the Model

    Hello, if you have come to this page you are probably investigating this protocol and you are looking for as much information as possible. This page is not here to discourage people but to be honest in offering a more balanced picture, though I am stating up front that I am biased towards this model.

    Every approach has limitations. In the field of MS, even the traditional approaches have one: the autoimmune model remains unproven. Even so many pharmaceutical companies and doctors treat based on this model anyway. In a situation where something must be done for the patient or you may watch them slip away, this may be fine. But one of the biggest complaints I have against the traditional approach is the lack of honesty about this limitation and the unwillingness to discuss it with you, the person who needs treatment.

    We want you to understand that the CPn/MS model has limitations as well in the interests of full disclosure and healthy scientific self-examination. These arguments may be mostly of interest to the scientifically minded and should not discourage anyone from considering this approach. But we believe you should know the scientific realities as part of your considerations. It is not a sure bet, partly because it has not been done with hundreds of MS patients so that statistics and clarity about who should be treated this way and who should not are not known. It appears clear from cases reporting here that some people experience changes dramatic enough to change EDSS scores and cause some reversal of lost function. The limitations on this page also apply generally to treatment with CAP for other diseases as well.

    If you have read all the other pages in this section of the handbook on MS; Multiple Sclerosis and the CPn Model, Smoking Guns, Cellular Similarities between CPn and MS, The Great Debate and The Brain on Pathogenic treatment, you are well versed in the model we use here as a guide for treatment. It is a very good model with many reasons to think CPn is possibly the cause of MS. The question then becomes is it possible that there are any limitations to this model? Is it possible that it could be incorrect?

    It is possible and this is where the limitations are.

    1. It is not known if all people with MS have this kind of MS or not.

    Pneumonia can be caused by a virus, a bacteria, a chemical, or even smoke inhalation. Obviously, if someone had viral pneumonia, antibiotics, which treat bacteria, would only play a supportive role in healing by preventing any bacteria from taking advantage of the already inflamed tissue and becoming a secondary issue. The actual cause of the pneumonia in that case would need to heal on its own, or possibly be treated by using antivirals.

    In the same way, more than one trigger might be cause MS. If this is true, there will be some people for whom treatment works perfectly and others for whom it does not and there is no way to know ahead of time which group you would be in.

    2. There is no standard lab test and no standard primer used in the MS/CPn research.

    This means that many researchers use in house tests-- tests that they developed themselves. Obviously every standard test at one time was someone's in house test so this is not a criticism in and of itself, but it does mean that the research from one worker to another is not necessarily looking at the same thing. It also means that other acknowledged CPn experts in the field do not necessarily agree that "x" researcher using his in house test and who says CPn is there actually was testing for CPn.

    Margaret Hammerschlag MD who is a CPn researcher says the VU work was looking at and amplifying human genetic material not CPn. VU says the supposed "clean" primers MH used to make that determination from the lab supply were themselves infected with CPn, so it was CPn they were finding not human. Other labs in other places using OTHER tests also said CPn was present in MS patients, and still others said no CPn in MS. The fact the VU team has been working on this specific issue (rather than CPn in general) for over 10 years gives them added credibility in my mind, but the fact remains that this is unresolved and there is no agreement as to how to detect cryptic CPn.

    In regards to MS and the possibility that CPn is the root cause, this means that the research looking at that issue is not necessarily authoritative and the findings must be considered "preliminary". This is true for BOTH sides of the debate, those who find it AND those who do not.

    This ties in to the first issue as well since it means that we can't know who to treat and who not to treat. If we had a generally accepted lab test for cryptic CPn that issue would be solved. Another route for proving that CPn causes MS is if researchers use autopsied MS brain tissue and look directly and specifically for CPn in lesions.

    Until there is a test that is universally considered reliable for cryptic CPn infection, we are in a place of assessing the model for its circumstantial support. There is a large body of research on how CPn behaves in the body and about the difficulties finding it in cryptic states, which seem to fit nicely with MS. The model makes sense on many levels, but it remains unproven at this time.

    3. It is possible that CPn is a bystander, a secondary infection that moves in to the MS brain potentially making the "real" cause of MS more complicated than simply a bacterial cause.

    This might be compared to a person with cystic fibrosis, who has very thick secretions in the lungs due to this genetic defect, getting a bacterial pneumonia in addition to the primary disease process. The bacterial process has sinister implications for the person compromised in that way. Treating the bacteria will allow them to return to being relatively stable, but the underlying disease process is still there. It should be noted though that it is always best to treat secondary infections; one does not ignore them and they can be more problematic than the original disease process.

    4. It is also possible that the real cause is a combination of infective organisms, such as viral and bacterial. If such were true, it is possible that antivirals might be needed. It is also possible that these co pathogens would not be an issue in most patients and as their immune system recovers they would be completely cleared of such secondary infections, while some other patients with more advanced secondary infections might need antivirals as well to get a complete cure. These copathogens are known to be present in CPn infection but it is not known for certain when they might need to be addressed and when they can be ignored.

    5. In the lab it is possible for CPn infected mice to develop secondary autoimmune disease through epitope spreading. In other words, the body attacks the CPn but in its effort to clear the infection it also accidentally makes antibodies that are self-reactive. It is possible that CPn causes MS but that a secondary autoimmune process is also in play. If such were true, it is possible ridding the person of the infection and addressing the autoimmunity as well would best facilitate treatment. On the other hand, rheumatic fever, which is an autoimmune disease secondary to a germ (strep), is self-limiting once the germ is gone so even if CPn autoimmunity were an issue it may not be something that needs treatment.

    I have been told by my neurologist that only about 10% of people with MS actually have myelin active antibodies in their blood that can be treated with the new treatment in development in which they filter your blood and extract the myelin active antibodies, radiate them, and reinject them as a vaccine so your body destroys those antibodies (this treatment is called "Tovaxin"). Is it possible that 10% of people infected with CPn develop autoimmunity? Such things are unknown, but certainly could complicate the picture and the eventual "best" treatment.

    The actual facts of how MS develops and what co factors are in play is unknown. The theory that CPn causes MS is plausible and very compelling, but it is possible some of these other co factors will be understood as more people are treated this way or as more research comes out.

    Treating Empirically has some limitations also.

    1. There is no reliable test for cryptic infection. However, empirical treatment is problematic because it may be hard to know when you have enough objective improvement to know it is working for you. In terms of MS, some of your symptoms may be caused by axonal degeneration and permanent scarring which may not go away without regeneration of some kind; it is hard to know what "I still have a weak leg" means in relation to CAPs treatment. It may be that some people with disease of shorter duration recover function with EDSS scores lowering, while others with more longstanding disability may "only" stop progressing. However it should be noted that the brain is much more plastic than used to be thought and it is likely some level of regeneration is possible if the disease process is stopped (just as people who've had strokes can recover more function with aggressive rehabilitation than anyone ever thought before recent research proved it was possible). If you do not have noticeable or dramatic exacerbations it might also be some time before you know you have stopped progressing, or if you have stopped. This can be devilishly frustrating.

    2. It is possible that reactions to the antibiotics do not mean that a CPn brain infection is present. There could be other bugs, even normal intestinal bacteria, causing some systemic reaction to antibiotics. It is also possible that you are reacting to CPn in your body, but none of it has passed through the blood brain barrier and thus none is in your brain. If this were so, one could "react" to antibiotic treatment but the real MS process would go on unhindered.

    3. It is also possible that the antibiotics themselves ameliorate the disease process in a way not related to their antibiotic activity. There is a fair amount of reserch on minocin, a tetracycline antibiotic closely related to doxycycline, which suggests it helps MS by altering the immune system and dampening it a little thus reducing lesion loads and exacerbations. If you are a person who believes the CPn model, you might see that relief as an antibiotic effect instead of any immune system modulation. However, one cannot determine cause by results so such positive outcomes do not prove either theory.

    4. It is possible the adjuncts to treatment, the supplements, have an ameliorating effect on symptoms all by themselves. Many people who start the adjuncts first report that they already feel better before they have begun taking antibiotics. It is possible that a combination of supplements and amelioration of symptoms by the anti-inflammatory effects of antibiotics combine to create some apparent improvement independent of any antibacterial activity.

    5. The protocols here are based on current research and are still evolving as new material comes out. Even if the MS/CPn model is proven it is possible the eventual protocol will include elements not now known, or that co factors will be understood and addressed in a way not now imagined.

    What IS a "proven" approach?

    If a person is given a pill filled with sugar, a placebo, and believes it will help, about 35% of the time it will actually help them. Their belief activates their healing in some way we do not thoroughly understand. It is more than just "thinking" they are doing better-- they really do better.

    The CRAB drugs are all considered "proven" meaning that they have been given in blinded trials to larger groups of MS patients and shown to be marginally better than placebo. For more on this and why I used the word "marginal", please look at the objective Cochrane reviews of these drugs on Pubmed.

    MS is a disease of unknown origin. It is often stated as being autoimmune, but that is actually an unproven theory. For autoimmiunity to be proven, it would need to be shown that a specific part of the immune system is different consistently in MS patients and that inducing this precise difference in other animals, preferably primates, results in a relapsing remitting neurodegenerative disease that eventually becomes progressive identical to MS. After decades of looking, no such trigger has been uncovered.

    In light of the unknown trigger for MS what drug manufacturers can do for us now is to treat based on the generally accepted "best" theory for MS, do a trial, and see if they actually get any positive results with their drug. These trials result in "proven" therapies even though the cause of MS is still unknown: they do not prove the theory that MS is autoimmune, they only show that the approach used helps in some unknown way. These are relatively expensive trials and are undertaken for promising therapies likely to recover the cost of the trial. This is just a simple business reality, not a conspiracy.

    It is extremely unlikely that CAPs will be trialed in the way described above to see if it helps patients with MS. The drugs are long off patent so they cannot generate the profits necessary to make it possible to recoup the expense.

    Our best hope is for someone in academic research to look for and find CPn in MS lesions by preserving a donated MS brain properly and staining the samples near lesions correctly to see inclusions. This would result in a proven association with MS. However, even if such were discovered tomorrow it would likely be a long time before there was a universally accepted and proven antibiotic regimen for patients (although IMHO the VU protocol is the most likely due to the extensive research they have done).

    As an illustrative example, it has been known for years that atherosclerotic lesions have CPn in them, yet the medical literature continues to debate whether or not it is a secondary infection or causative, whether or not intermittent mono therapy antibiotics reduce second heart attacks, whether it has triggered a secondary autoimmune attack on the blood vessels, and whether it is even possible to get rid of cryptic CPn infections. I have not yet seen anything remotely resembling a CAPs protocol being tested on atherosclerosis patients. During these years of debate on the issue, dozens of patent medicines to treat cholesterol have come out and patients needing some kind of treatment today are offered these new drugs because nothing related to CPn and atherosclerosis is proven. During these years also heart disease remains the leading cause of death. Once again we see drugs go to trials based on the most generally accepted theory, in this case that cholesterol causes atherosclerosis. This offers proprietary targets (cholesterol is a viable target for drugs) and when the created patented drug works better than placebo in reducing cholesterol, the drug is approved for use in patients. However, if CPn causes atherosclerosis, there will never be a cure by reducing cholesterol.

    With a few exceptions, science moves very slowly with a lot of back and forth research before final conclusions are drawn and everyone agrees on one fact as a generally accepted principle to guide treatment. This process is greatly enhanced when a commercially viable product is the agent in question, and there is not one for CPn.

    No one can or should make any promises to you about how you will do on CAPs, there are unknowns as described in this page. What I can tell you is that some people, though not all, have had verified reductions in EDSS scores using this approach and that if CPn causes MS then this is the best hope you have for a cure.

    With all these limitations duly noted, there are good reasons to initiate a CAP for Cpn despite these scientific uncertainties. In many cases there are really no good approved treatments for the individual person. Additionally, CAP protocols do not conflict with other approved treatments so it is certainly possible to do both. CAPs are also low risk and low cost, and if you are a person who engaged in Empirical treatment and reacted to the NAC, the antibiotics, or the protocol in general you know you are dealing with some kind of bacterial load, the eradication of which cannot help but improve your system.

    Addendum: In a thread started to discuss this Limitations page found HERE Dr aWheldon made a comment on this page that lends adds more food for thought and I have pasted it below. The link to the thread is worthwhile reading also.

    Dr Wheldons's comment on this page:
    I always look forward to Marie's posts; this one is an analysis of the limitations in the viewpoint that C. pneumoniae has a role in Multiple Sclerosis. It is impartial and thorough. I read it carefully and with great interest, and recommend others to read it also.

    As I read it I found myself pondering the manner in which medicine is practised. It is often not very rational. I recall, as a medical student, standing in a women's ward in a big mental hospital which had been built in the 30's in beautiful countryside. It was a consultant ward round; we had almost finished. We came to one very perplexing woman who was behaving very bizarrely. Her symptoms fitted no psychiatric stereotype. The consultant clearly didn't know what to do. Two psychiatric social workers were having a private but rather loud discussion about tatting in the background. The sister was keeping her thoughts to herself. The registrar was quietly doing isometric exercises. 'Tell you what,' said the registrar, suddenly, and rather impertinently. The consultant looked at him. 'Have you a suggestion?' he asked. 'Yes,' said the registrar, smilingly. 'Let's give ECT[1] a whirl.'

    I've never forgotten that phrase: 'let's give ECT a whirl.' Give it a whirl! What an odd way to recommend a much-argued treatment, and yet how refreshingly honest! There is a deadly comicality about it. The main thing about recommending something on a hunch is never to forget that it is on a hunch. When Sarah was falling through the EDSS numbers, the diagnosis made, the Internet searched, the original Vanderbilt paper discovered, the objections by Hammerschlag discovered also, I must confess that I didn't weigh all the evidence scientifically. I did a brief risk analysis (aggressive SPMS: deadly - doxycycline: one of the most harmless antibiotics available) and started. It was a hunch that maybe the Vanderbilt workers were right and that the entire neurological Home Fleet was wrong. (This was in 2003.) I remember reading an interview with Hammerschlag in which she said ". . . this study shows that it's much too soon to put MS patients on antibiotics for Chlamydia pneumoniae." And as I read these uninspired words that risk analysis went through my head. Other people's risk analyses came to mind, too: the risk that if MS has an infective input (as seems likely from the epidemiological data, even if one does not stipulate a pathogen) the administration of a T-cell immobilizing antibody may be clinically rather unwise. Hippocrates was surely right when he said: 'first, do no harm.' Many times, as a doctor, I have to make recommendations on poor or inadequate information. One has to admit to making assumptions. Often one can only say, 'If I were in your place I would take this road.'

    So Marie is quite right: there is a weight of evidence on either side of the equation, and it's wise that we admit this, even if positive evidence carries more weight than negative evidence. We are still in the opening pages of the story. But I have a hunch that in 20 years' time the idea that C. pneumoniae infection is a key factor in the multifactorial illness MS will be mainstream.

    [1]ECT - Electro-convulsive Therapy.

    -D W

    mrhodes40 Tue, 2007-05-15 15:58

    Smoking Guns, Cellular similarities between CPn cellular reactions and MS

    Smoking Guns, Cellular similarities between CPn cellular reactions and MS

    MS has been well studied for the last several decades. As a result there are volumes of knowledge about what happens inside the brain of an MS patient, though we are still very unclear on the cause. Any potential "cause" of MS has to fit with the known body of evidence for MS. Interestingly enough there are some similarities between MS on the cellular level and CPn infection and this page will explore that.

    As we begin I'd like you to understand that CPn is relatively newly discovered (the 1980's) and new findings are coming out every week in this field. It is also a very different germ in that it behaves in ways that seem "wrong" based on what is "known" about germs. For example, we tend to think of resistence as occuring when a bacteria is exposed to an antibiotic then finds a way to still replicate in the presence of that antibiotic, thus remaining an active infection that we can culture. We do not recognize the kind of resistence that CPn is now proven to be capable of: exposed to an antibiotic it can become persistent, essentially going into hibernation and thus invisible and unaffected by the antibiotic, only to reactivate as soon as the threat of the antibiotic is gone. See THIS PAGE ON PERSISTENCE. Though technical this paper is a wonderful review of the available research on the subject. CPn is an evolutionary coup de gras.

    As backgroud for this page, bear with me as I do a quick overview of the CPn lifecycle because it is pertinent to our discussion. CPn is an obligate (it has to) intracellular ( lives inside of another cell) organsim of eukaryotic cells (cells with a nucleus). It is parasitic in nature meaning it converts the cell's energy mechanisms (mitochondria)for its own uses and leaves the host cell essentially nonfunctional for its original purpose. The elementary body (EB), a tiny hard cell with barbs on it which allow it hook on to potential host cells, is the infective form of CPn. Once contacted, EB's are carried in the blood floating around looking for a cell to hook into and parasitize. As a CPn EB sticks itself to a cell, it is included, or pulled in, to the cell in a sort of tiny bubble. There, it converts to a reticulate body (RB) which does several things. First, it grows larger by about 2 times and takes over the mitochondria. All the energy the cell can now produce is used to feed the RB which now begins metabolizing and replicating, making new EBs which will look for another new cell to infect. In order to escape detection and death, the CPn covers it's inclusion a lipid bilayer. It also turns off apoptosis in order to increase the life of the cell so its home is safe. At the same time, having an infection in the cell makes it vulnerable to death as the toxic by products of the CPn lifecycle are pushed out of the CPn inclusion and into the cytoplasm of the host cell.

    Please also note that CPn was first thought to be a virus because it behaves like one: it floats around and invades your cells themselves, living off of the host cell and unable to metabolize and replicate on its own. Further research showed that it has almost all the usual cellular machinery that bacteria
    have. With its own machinery, and a bacterial-size genome (not the tiny gene sequences that viruses have), it can play more tricks than viruses can play. For example, it can convert freely back and forth between these different forms, it can detect "threats" to its survival like antibiotics or gamma interferon, and then go persistent or hibernate in a non metabolic state wherein it is immune to the abx. The article on persistnce above is very good on this subject.

    So let's begin noticing the cellular similarities with a well known concern in MS: The fact that nitric oxide (NO) is high. An example of MS research on this can be found HERE This particular abstract was chosen for two reasons. First it shows that researchers believe that NO is part of the problem in MS, and this fact is so well established that I can't find a reference that establishes it.

    So in MS the upregulation of NO is an accepted problem. Frequently we see research focused on potential strategies to reduce the NO and thus spare the nerves. But might that high NO indicate that CPn is present? In this abstract HERE we have the authors showing that the body upregulates NO on purpose to defeat CPn. The organism cannot multiply in the presence of NO. This is the way the body kills unwanted villains like bacteria and viruses, with oxidative metabolites that are harmful to them, then the other immune cells like phagocytes can come in and clean up the debris. Interestingly enough, it is gamma interferon that is responsible for signalling this upregulation(and gamma interferon will come up again later). HERE we have second paper in which cells that can make NO and cells that could not were compared. The NO sufficient cells were regulatory for CPn as we might expect. This is just two of the studies on this subject.

    Point two from the abstract on NO in MS above was that LPS was the agent that the researchers used to damage the oligodendrocytes so that they could study the effect of NO in the MS brain. What is LPS? Lipopolysaccharide is the fragment of the outer cell of a gram negative bacteria. LPS is very toxic to cells in general, and very immunogenic causing a brisk reaction of the immune system, and here we see it is used to induce damage typical of MS damage to oligodendrocytes. LPS comes from a gram negative bacteria like CPn when it dies. This is a very important bit of circumstantial evidence for CPn causing MS. Clearly if CPn, which is a gram negative bacteria, was in the brain and died there would be oligodendrocyte damage similar to MS due to the presence of the LPS fragments released.

    Lets go deeper into this subject with THIS paper which discusses the microglial activation in the CNS by LPS. This paper shows that it is the microglia specifically that must respond to LPS damage of the nerves, and it also says plainly that LPS causes " injury to oligodendrocytes and myelin as occurs in periventricular leukomalacia and multiple sclerosis", a direct replication of the information above. This work also says the oligodendrocyte precursor cells were damaged by the LPS. Since OPC's are another known concern in MS, LPS damage to brain tissue is a good match for MS damage. Also, note that microglial activation opens the BBB and allows peripheral immune cells like B-cells and T-cells in to the area to aid in cleanup.

    HERE is an abstract and link to an older paper that discusses the activation of microglia in the CNS in MS and EAE. This supports both the idea that microglial activation is normal in infection, as well as presenting the notion that microglial activation is the damaging feature of MS. These authors suggest that if we could turn off the microglial activation, the MS brain could be spared. But obviously if the brain is responding to pathogen by turning on microglia to fight the germ, ridding the brain of that pathogen "turns off" microglial activation, and it does this without leaving the brain open to opportunistic infections like PML. It leaves your brain's pathogen surveillance system intact.

    Another well known fact in MS is that there is upregulation of cox 2 prostaglandins which are inflammatory.HERE is one paper showing that this is true in MS. HERE is another, this one also tying it in to the oligodendrocytes, which when injured send out the Cox 2 signal which results in caspase 3 activation and death. The speculated conclusion of this paper is that it is the cox 2 that causes MS oligodendrocyte damage. It supposedly does this by cox 2 upregulating by itself (autoimmune theory) and thus starting the cascade we call MS.

    HERE is a paper that shows that cox 2 is upregulated by the body on purpose in CPn infection. Actually, cox 2 upregulation can be inferred from the previous discussion on the LPS damage because it is stated that damaged oligodendrocytes will send out this chemical signal. Once again we see natural, expected immune reactions to infection occuring that mirror the known cellular/chemical profile in MS.

    I mentioned gamma interferon above. In early studies (the 1970's) of the interferon drugs, pwMS got rapidly worse when taking gamma interferon. Yet we just showed that gamma interferon regulates CPn growth by being responsible for upregulating NO. Isn't this opposing the CPn theory? In fact in those early trials the patients given gamma interferon had myalgia, fevers, and arthralgia, and while gamma interferon itself may have caused this directly, this triad of symptoms is also common to endotoxin reaction. No patient of the seven who had worsening had residual symptoms and every patient had a flare up of symptoms already known to them, suggesting pseudoflare (common in fevers, and familiar to people using the CPn protocols here as an endotoxin reaction)not a true exacerbation which would be involvement of a new area of the brain. The reference for this information is HERE titled "Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis." by Sriram S and Steiner I in the Annals of Neurology Dec 2005. You have to get the whole citation to read the material about the gamma interferon I mention as it is not discussed in the abstract. Might it be true these people had transient worsening due to endotoxin as the gamma interferon via nitric oxide and tryptophan depletion killed some of the CPn load? It is unusual for people to have worsening with no residual deficits. This author also mentions that gamma globulin results in an upregulation of gamma interferon without exacerbation in MS ptients. Circumstantial but possibly important information supporting the idea that gamma interferon may not be the profoundly negative influence it was thought to be.

    Tryptophan is of interest in MS also and has a role in CPn regulation. In the Eur J Neurol. 2005 Aug;12(8):625-31 there was a paper titled "Interferon-beta affects the tryptophan metabolism in multiple sclerosis patients" authored by Amirkhani A, et al found HERE In this work it is clear that the tryptophan pathway is altered in MS and that beta interferon plays a role in mediating this. But in CPn the body, again via the gamma interferon pathway, catabolizes tryptophan in order to deny this amino acid to the CPn which needs it to replicate. See this HERE from our own archives. So tryptophan is altered in MS, but it is altered by the body in response to CPn also. Tryptophan is important because it is necessarly for making melatonin and serotonin in the brain, two important neurotransmitters associated with mood and immune function. Without adequate amounts a person is prone to depression and poor sleep, both known problems in MS.

    Speaking of beta interferon, it also hampers CPn apparently. HERE is a citation titled "Role of Interferon-Stimulated Gene Factor 3 and Beta Interferon in HLA Class I Enhancement in Synovial Fibroblasts upon Infection with Chlamydia trachomatis " by Jürgen Rödel, et al. Perhaps the modest improvement seen with beta interferon use in people with MS could be related to this mechanism.

    Many features of MS are actually known features of EAE with the authors ASSUMING that MS has this same feature. For example, caspase 3 is a regulator of apoptosis (organized cell death) and is seen to be upregulated in EAE. There has been speculation that caspase 3 itself may be at fault in MS, the logic being that if there was extra caspase 3 floating around it would mistakenly kill off perfectly good nerves and thus cause MS. While we do see CNS cells dying, they also would die from being infected and as discussed above, this will result in caspase 3 activation secondary to cox 2 activation caused by LPS. And all of this would cause the body to respond to the area with inflammation and immune cells to clean up the dead tissue. So it is not necessarily true that caspase 3 activation is secondary to anything other than natural response to pathogen. The Prineas and Barnett paper cited earlier also looked at caspase3 in the areas of apoptotic nerve cells. They found very little.

    And here we have this PDF file which is a review of the pathology of the MS lesion found HERE Note that the author of the review of the pathology of an MS lesion draws a very clear parallel between the MS brain and viral infection, saying the cellular immunopathology is the same while also noting that EAE is not the same as MS. This again supports and repeats the information offered on the page "MS and the CPn Model" which establishes that there is significant research showing MS is not autoimmune. Additionally, remember that CPn is very similar to viruses because it is an intracellular organism. Once again we have support for the notion that MS is not autoimmune and a clue that the cytokine profile we see in MS is indistinguishable from a natural reaction to a pathogen, and here on this page we are showing research that directly ties the same cytokines to CPn.

    Another angle to MS which is considered an autoimmune clue which people frequently point out is that MS has been shown to have various upregulated genes. Doesn't that prove that pwMS have a problem gene that causes this abherrent reaction? Well, no it does not. The average person thinks a gene is like your eye color- it is what it is and it cannot be different. But genes turn on and off all the time and this is called upregulation and down regulation, and they do this in reaction to the environment. HERE is an abstract that outlines a couple of kinds of gene upregulation in response to CPn infection. In this case the macrophages (an immune system cell) have upregulated some genes and down regulated others.

    In another example of genetic changes, HERE is a paper that shows how CPn itself changes and upregulates a whole bunch of its genes in persistent states vs acute infection, this giving it the flexibility to do the many things it is capable of doing and making it so difficult a pathogen to eliminate.

    In order to be fair it is obvious that some genes such as your HLA type impacts the way your body responds to germs. It is possible that some people with some genetic profiles respond to CPn in such a way that persistence is more likely in that individual. It would be narrow to assume that a genetic type could cause autoimmunity, but not that it could cause an atypical reaction to a bacteria.

    So this page is focused on the fact that many known features of MS are also known physiological reactions to CPn infection, remembering that infections of many kinds likely have a similar if not identical profile. This is not unexpected as it has been amply pointed out by many authors that MS resembles, on a cellular level, a reaction to an infective process. The fly in the ointment has been the inability to culture anything consistently, though the known fact that CPn is possibly unculturable in the persistent state might easily account for the "we found it" and the "we tried to replicate their work and did not find it" back and forth nature of the MS/CPn research to date.

    It is interesting to note that while CPn is known to live in human cells, is known to cause cellular inflammatory reactions to that cellular infection, is known to cause immune reactions and cellular death and that it is very hard (and some say impossible)to culture and complicated to kill in persistent state, we still have people who debate whether or not it is a "problem" suggesting perhaps CPn's presence is innocuous for human beings. And we also have people seeing cell death, immune response and inflammation, and who are unable culture any germs at the site continue to insist that this immune response has to be the body attacking itself for no good reason (autoimmunity)seemingly oblivious to the possibility of an intracellular infection like CPn and ignoring the limitations of current ability to find these bacteria.

    At this point in time it is not proven one way or the other. We really need a test every competant researcher can do which shows the presence of CPn in MS brains to get to that level of understanding. This is all circumstantial evidence for the presence of CPn in MS brains. But also note there is nothing that is excludes the possibility of it either and the evidence indicates that if CPn WERE in a brain it would: upregulate NO, cause oligodendrocyte damage via LPS identical to MS damage, cause the cox 2 prostaglandin to be made which would signal caspase 3 and apoptosis, would damage the nerves and cause death, would cause microglial activation, would catabolize tryptophan. Since this profile of changes mirrors MS, we have a smoking gun in CPn for being involved in MS.

    This is speculative and based on currently available research which may not be all inclusive, or which may not apply to you directly. It is posted here for informational and purposes. This page may be added to or revised as new material comes up......

    mrhodes40 Fri, 2006-03-03 12:28

    The Brain and Pathogenic Treatment

    The Brain and Pathogenic Treatment

    The brain. For many the final frontier of medicine, it's fragile tissues the seat of the mind and in many ways, the very heart of personality and who we are.

    What is known about this privileged area of the body is that healing is limited and things that on other parts of the body would be minor issues in the brain become devastating and life altering. A simple extavasation of blood, which in an arm is a mere bruise or hematoma, in the brain becomes a hemmorhagic stroke, the person forever altered and changed by this mere physical accident.

    Why is that? Why is a minor issue on the periphery a major life changing event in the brain? Why does it not heal as does the arm? The answer lies in how the brain is set up.

    The brain is a privileged area of the body. It separated from the rest of the body by the blood brain barrier which is a special different kind of endotheluim than is present in the rest of the vascular system. The BBB has very, very tight bonds between the cells and thus is very selective and allows only very specific things that the brain needs in, and keeps out other things that flow freely through the rest of the body, out. Among the things not permitted in are the immune cells of the peripheral system, like t cells, b cells, macrophages etc.

    Because of this protection from the rest of the body, the brain has its own immune cells called microglia. Microglia are essentially very similar to monocytes and macrophages in other peripheral areas of the body, except that they have very specialized abilities. The microgia can send a chemical signal to the BBB to open up and allow t-cells, b-cells, monocytes and macrophages to enter if they need help cleaning up a problem inside the brain. This makes sense! How else can the "garbage" be taken out of the brain! There are well known situations that allow BBB to be opened by the microglia, for example infections, particularly any that involve the microglial cells themselves such as HIV, cytomegalovirus, the herpes viruses, and any situation in which cells inside the BBB died or were injured. It is known in vitro that CPn can invade microglia, so we might make an assumption that should that happen the BBB would be opened to clean up the area.

    Microglia live in a quiet resting state termed "ramified" Ramified microglia are not activated and are easy to see in a microscope as different from the activated form which is "amoeboid", and so it is the ameboid form we see in activated microglia and it is ameboid activated microglia we see in MS lesions. It has been this fact that has led researchers to believe that the microglia are to blame for MS damage, assuming that the microglia activated mistakenly and "attacked" the nerves causing them to die. This has been presumed to be the initial event in MS and a considerable amount of research has been focused on how we can turn off the microglia in MS patients. Activated microglia express many immune factors such as interleukins and toll like receptors, many of which are also targets for therapeutic intervention by novel pharmaceuticals. However, it was the detection of ramified (not activated)microglia and no peripheral immune cells in the presence of apoptotic, dying oligodendrocytes in Prineas and Barnett's paper that indicated the nerves had died THEN the microglia and finally the peripheral immune system were recruited to the area. This stunning finding proposes a completely new idea as to why the microglia are activated and ameboid in MS: given how microglia react to cell death it would have been their normal healthy job to open the BBB and allow t-cells b-cells and whatever else in to clean up the apoptotic mess.

    Interestingly enough any activation of the immune system, either inside the brain via microglia or outside in the body by other macrophages, monocytes etc, results in profound changes in the area being repaired by the immune cells themselves. The chemical environment of the area is altered and many different genes are upregulated, cytokines respond, fluid filled with these immune factors rushes to the area and oxidative damage results secondary to all this activity. Much of this in the body outside of the CNS is no big deal, it repairs as "good as new", but this is not true of the brain. The brain, in the presence of these oxidative and otherwise toxic but necessary factors in response to pathogens, is damaged by all this immune activity. The brain literally can't tolerate normal immune responses.

    Thus it is true that in the case of an infection of the brain part of the damage comes from the act of the body responding to the pathogen itself rather than any damage directly caused by that pathogen.

    Why is this important to understand for us here? For several reasons which fall into the arena of my humble opinion based on my understanding of the brain. In terms of using the CAPs there is good justification for going slowly on treatment and not inspiring too large a response at one time. Your brain can only heal so much at once, and it must do that with it's limited resources. It is easy to overwhelm the brain's capacity to supply antioxidants and nutrients needed to repair. Therefore it's probably true that a pulse of flagyl that is small as outlined in the protocols is better than large ongoing doses for long periods of time unrelieved by healing time. It may be fine for CFS patients whose infection is not in the brain to take flagyl continuously as muscle heals in ways the delicate brain can not, but the MS patient is likely to need time to repair in between.

    Another reason it is important to understand is that it offers a good reason for the apparent improvements in MS patients taking immunesuppressive therapies if you accept the model of CPn as causitive for MS. CPn is a slow infection, it invades slowly and does not harm it's host very much. What's a cell here and there being used by CPn? Well if it's a brain cell you DO miss it, and more as more are invaded and lost. But if the cell with CPn in it dies, either because you were taking a flagyl pulse or because it simply died from being infected as it will in the MS patient unaware of CPn, you get acute reaction and response by the immune system as described above, resulting in even more damage to an area. Therefore, if you knock out the immune system you will seemingly get better, at least for a while, because the cytokines and other immune factors are shut off.

    We can understand this if we look at it this way. If you have a cold how do you know you are invaded by a virus? Your nose is plugged up, mucous runs and you feel tired. Every one of those symptoms is caused by your immune activity NOT by the virus. If you take a steroid, thus knocking out the immune system, you will feel better immediately. But the virus then without being "checked" by immunity will get the upper hand leaving you sicker than ever in a day or so. People with HIV who have their immune systems knocked out by HIV will have this happen. They get very serious infections we do not get...and they do not have the symptoms normal people do, all because the immune system is not active. A cold virus is a quick pathogen so we can understand how it reacts to steroids and immune suppression because we see the connection clearly, in a slow virus or bacteria however the connection is not so clear.

    Persistent CPn however is a slow pathogen, so the timeline for all this is years not days when we are talking about possible CPn and the brain. But the cold virus example plainly shows how a patient can seem better simply because of immune suppression. What if an MS patient is given steroids, for example during an exacerbation of MS, and MS is actually an infection, exacerbations being another time when immune activity is clearly causing symptoms? I have often heard people say that MS cannot be an infection because immunosuppression works. Really? Do steroids cure people of MS?

    The long term studies on steroid use for MS are disappointing. Though people given steroids seem better than those given placebo when evaluated within a week or two of treatment, at 6 months the "gain" is gone and there is no statistical difference between treated and untreated people. Steroids do not impact the disease although in the short term they impact the symptoms.

    Other immunosuppressive therapies have not had great success to date either. Most seem to help a little bit for a while, then the gains drop off with time often eventually leaving the person at a few years time functionally equal to the untreated person, in some cases in spite of the fact they remain profoundly impacted by the treatment drug. The newest drugs have no long term time frames to discuss, but read the available research carefully for yourself. If they have gains right away does it remain just as good or get even better after a couple of years? or do the gains drop off so people seem to be much better than placebo in early comparisons but in later comparisons the treated group is maybe only slightly better than the placebo group? These are important questions for the MS patient to know the answers to.

    If the problem is autoimmunity then aggressively knocking out the immune system ought to result in an improvement that gets better and better as time goes on should it not? Now that the brain is relieved of this relentless attack from the immune system, should it not get better and stay better and improve even more with time? Yet time and time again the most promising therapies which prove profound decreases in lesion activity (inflammation is actually what is seen on MRI) do not result in stopped disability. In my mind, it is a concern if people have profoundly impacted immunity but after a few years are nearly in the same boat as the placebo treated persons. This suggests to me the "cause of MS" whatever it is was not stopped but that the immune system was prevented from causing secondary damage in it's efforts to heal. If there were a slow bacteria in the brain this is exactly what would be seen with immunosuppression because the bacteria would continue to slowly invade the cells but the immune system is held at bay, reducing any secondary damage from immune sustem activity yet allowing the slow infection to invade more cells to the point that impairment results anyway. This is exactly like giving steroids to a person with a cold to me, only in slow infections timelines are years long compared to the "cold" model.

    Who knows what the patient thus treated will be like at later years. Will the thing that causes MS, maybe CPn, get the upper hand and will the patient go downhill faster than ever later? People with immunosuppression are at risk for cancer and infection since immunity is grossly impaired, will they succomb to such issues? And if the treated people are much better than the placebo treated group in early comparisons but in later comparisons the treated and the placebo group are only a little different did the treated patient gain anything? Since most of us will live for decades, is this temporary gain worthwhile considering the cost? These things must be evaluated carefully by the patient. Ask questions about this of your doctor and get all the answers you can. You have a right to know what is known about the treatment you are considering. You have a right to know the limitations of the treatment you are being offered including what is not known about it. In the end it is you who lives with the decision and it's results.

    There may be good reasons to take abx even if CPn is NOT at fault in MS. Minocin, a tetracycline drug similar to doxycycline, has been shown to have neuroprotective and antiinflammatory aspects to it. It is being tested in conjunction with a traditional medication as an "add on" combination therapy. They will compare the combination of traditional/minocin in this test to the traditional alone, but unfortunately there is not a treatment arm with just the minocin. This is sad. Perhaps the minocin with it's antiinflammatory properties all by itself would be as effective as the combined drugs, who could know without testing this? But this obviously not in the interest of the company who is running the trial, that company being the traditional medicine. They have no interest in abx as a stand alone therapy and it would bode poorly for their drug if the minocin won out as the best therapy since it is off patent. At any rate, there is no way of knowing or guessing how much of an effect this neuroprotection and antiinflammatory action is as such quantification of this property of the minocin has not been undertaken. It might be large or insignificant, but what I can tell you is that when people like S. Sriram at Vanderbilt University Neurology Center tested people using abx and published positive results, others who did not believe this could possibly work immediately said it was these "immune modulating properties" of the drug that caused the improvement, not the antibiotic aspects of it. Interestingly enough I bet that no one ever said to you "Well, we know that abx have these protective properties how about before we give you these immunosuppressives we try that to see if it helps..."?

    It makes you wonder why there is objection to anyone trying antibiotics.

    Cpn as the cause of MS is theoretical at this point and not proven. Most of the traditional medical communnity thinks MS is autoimmune. There is evidence that points the other way though and these pages explore these possibilities for informational puposes.

    Deciding to use an experimental and unproven protocol is a decision you must make under guidance and advice of your doctor, based on your particular situation. Some people with very benign disease may want to use traditionals and wait for science to find a more certain answer. Some with more advanced disease may be at a point that for some reason they do not want or are not a candidate for the drugs available (heart disease runs in my family, I have made a personal decision not to use Novantrone, though I know some who think it was helpful for them). Some may even have tried the traditional medicines for MS and found them ineffective and they are thus without good options. These people may be interested in investigating this experimental approach. The VU released the information about the protocol they were using experimentally for just such compassionate purposes, and our pages here are for support of people doing just that. If you are in one of these situations and you decide with your doctor it makes sense for you in this site you will find others trying this approach as well as others who have had success with this approach already.

    mrhodes40 Sat, 2006-03-11 19:30

    The great MS debate Do we find CPn?

    The great MS debate Do we find CPn?

    One of the biggest issues in the question of whether or not CPn is present in MS brains is the publication of work that finds no CPn in MS. It puts us in the uncomfortable position of saying that we choose to think that this researcher is correct and that one is incorrect. Since few of us are lab experts, such discernment may be based on bias and not facts. Yet there may be some very good reasons to find the work that says CPn is not in MS brains is biased itself.

    To look at this chronologically we start with the Vanderbilt University (VU) work found here. This paper is the whole citation. In that original work the team at VU found that pwMS (people with MS)were more likely to have CPn detected by PCR in the brain.

    A top chlamydia expert, Margaret Hammerschlag MD, found the theory intriguing and conducted her own experiments in her labs. They found no CPn in any sample. The abstract may be found HERE

    Following that work, Dr Sriram came out and said it is very difficult to find in the brain and that it was not surprising htey did not find it. What follows is taken from HERE (note: this paper was overall negative about the MS/CPn connection. It is an older paper talking about what was known at that time)

    Quote from that paper:" Sriram responded by saying, "The fact that they can't find it in the brain is not surprising at all" because of difficulties his group had finding C. pneumoniae after injecting it into the brains of mice. "We know we put the bug there," he said. "But we're having difficulty finding out exactly what the conditions are to extract it from brain tissue. I don't know why."

    To help settle the dispute, Sriram agreed to participate in a blinded study with three other teams. All received spinal fluid from patients with MS and controls, sent by Michael Kaufman, MD, of the MS Center of the Carolinas Medical Center in Charlotte, NC. The results, presented at the 2000 meeting of the American Neurology Association, further isolate the Vanderbilt team, who found C. pneumoniae DNA in 22 (73%) of 30 MS cases and in 5 (23%) of 22 controls. The other teams, at Johns Hopkins, the Centers for Disease Control and Prevention, and Umeå University, detected no traces of the organism.

    Hammerschlag said the mass of evidence points to contamination or a lack of experience with delicate screening tests on the part of Sriram and his colleagues. "All of his work is being published in neurology journals, and they just kind of accept the methods. None of it would get published in microbiology journals," she said" end quote

    This is very important. Please do note that in the teams other than VU they found no CPn. None. There have been many published papers since then by many experts all over the world finding CPn in brain samples of MS and other neurological diseases. It is peculiar that in this particular test they found absolutely none at all. But this was a long time ago as science goes and techniques have advanced since then, so the various researchers finding CPn since then may well be using much better techniques.

    Let's note the VU findings in this interesting contest between labs. VU found CPn in 22 of 30 of the MS patients and in only 5 of 22 of controls. If Sriram contaminated his samples how did he manage, in a blinded sample, to contaminate primarily his MS samples? Why not contaminate most samples if his work is sloppy? Or even finding it in all of them?

    It seems to me personally it would be very difficult, and statistically improbable to contaminate mainly the MS samples in a blinded study of that nature. Adding to the evidence that the VU laboratory test for CPn in CFS is finding real CPn in MS is the fact that the numbers of positive samples discovered were very similar to his previously stated numbers of positive MS samples. The VU team seems to find CPn in about 60-95% of MS CSF (multiple sclerosis cerebrospinal fluid).

    Another comment in that article which points out the human side of research is in the final line of the quoted piece as it shows the opinion of one researcher stated as if it were fact. It is not exactly "scientific" but opinion, and peevish at that, to state that the neurology journals are somehow naive in what they accept and that the VU protocol "would never be published in microbiology journals". In fact, the VU lab protocol was published in a laboratory journal two years later HERE

    And in another paper HERE we have the VU team and a team of researchers at the University of South Florida using split samples to compare results with one another. "Split samples", which were also used in the first lab contest above, means they send half any given sample to lab A and half to lab B and see if they get similar results. (Some few samples were too small to split, and VU got all of those samples resulting in the odd numbers)

    In this comparison between USF and VU they both found positive samples of CPn in the MS brains using different CPn tests, confirming that it is possible to culture CPn in MS brains. The conclusion of the paper was quote "In clinically definite MS patients, the VUMC and USF detection rates were 72 and 61%, respectively, and in patients with monosymptomatic MS, the VUMC and USF detection rates were 41 and 54%, respectively. The PCR signal was positive for 7% of the OND controls at VUMC and for 16% at USF. These studies confirm our previous reports concerning the high prevalence of C. pneumoniae in the CSF of MS patients. The presence of C. pneumoniae in patients with monosymptomatic MS would also suggest that infection with the organism occurs early in the course of the disease." end quote

    What we have here is a batch of evidence that indicates the VU approach is fairly effective at finding CPn in MS CSF, that at USF they also have the ability to find this, and the fact that these labs used split samples indicates that there is some concordance. In comment Sriram has been quoted as saying that the problem with the other contests where others found no CPn is that the other labs use formalin preserved brain samples, which ruins the possibility of detecting CPn. According to VU, the lab must use frozen tissue to find the CPn in these samples. USF also uses frozen samples, though they use their own unique test. This is the kind of technical detail that makes the difference, but takes time to prove the value of conclusively so everyone "knows" we must use frozen samples. Clearly in the Hammerschlag lab it is not considered important to use frozen samples.

    Dr Hammerschlag is still convinced that MS has nothing to do with CPn though. As recently as 2005 she was asked to comment on some work being published by VU connecting CPn to MS and once again she talked about the 2000 lab contest in which her labs found no CPn. This comment was titled "The role of chlamydia pneumoniae in multiple sclerosis:real or fictitious? She remains adamant that the original work in which no CPn was found remains unchallenged, apparently rejecting the work of so many in the interveneing years in spite of the fact that various researchers all over the world have found at least some CPn in brain samples of many kinds. She seems very confident of her test results in which she found on CPn in MS CSF samples.

    Interestingly enough though, Dr Hammerschlag herself has since authored a paper which in and of itself may offer support for the CPn theoretical model of MS causation. In this most recent work she states that we cannot culture persistent infection as it is undetectable. Now this is interesting, if a persistent infection is undetectable using currently available lab techniques, then what does it mean if you do a CPn test and it's negative? We know that CPn even in it's persistent state can cause inflammation (see smoking guns next page) so if that is true and you have an inflammatory disease of unknown etiology how can you say conclusively it is not CPn simply because you had a negative test if your own research says that persistent infections produce negative tests? It might be more accurate for her to say I do not agree with the VU methods, but I do not know if MS is related to CPn. The opinion paper indicating that we cannot culture persistent infections that she wrote is found HERE

    If you read it carefully, you will see she is saying that while CPn might cause chronic illness like atherosclerosis and asthma, we can't design good studies since we can't test to know if eradication of CPn occurred. She suggests that without lab work to tell you if the patient got better from eradication of the germ, you can't know why the patient got better and your study is meaningless. From a purely scientific standpoint this is correct. But we are not lab experiments as individuals, and should this be applied to patients in general, it denies that the physician is a diagnostician who has been trained to evaluate people and their physical status based on a variety of findings, not just lab work. It would be naive to imagine labwork is flawless and perfect or the the MD is helpless without it to make clinical decisions. Good grief, if this were so why see an MD at all? Why not just see the lab tech, they're the ones who do the tests!

    I would again like to mention the human side of science. Science has a certain inertia. People at this level and of this stature begin to get locked in to certain points of view for a variety of reasons. Not least is that once you publish a notable finding, you may be granted funding by interested organizations to do more of the same research. This leads you to work again along the same lines and after some time goes by you have a considerable paper trail clearly placing you on one side of the scientific debate. And you really believe your point of view, witness the absolute tanacity of the autoimmune model of MS in light of the research indicating it appears that autoimmunity does not explain the facts. It is difficult for someone who has done a lot of work on an issue to go back and say, "Oh, by the way, all this work I did before was wrong the other guy was right". You could be forced into that eventually, but it will not happen without a lot of weight on the other side to pull you over. Furthermore, the sheer numbers of people on that autoimmune side of the debate means there is a real sense that "most of us are over here and of course we are right, everybody thinks so...." It might help to recognize that Freud and Jung had a lifelong debate as did Einstein and several of his compatriots. Eventually some other finding may clarify a key issue making it possible to finally see what was missed before so everything falls into place. In this debate about CPn nd MS that would be something like a conclusive photo that shows CPn in the key structures of the MS brain. For example, if someone develops a way to see CPn inclusions in oligodendrocytes and we have an unmistakeable picture of such in an MS brain, maybe in a client that also cultured negative for CPn using traditional methods, we'd have extremely persuasive material wouldn't we? We do not have anything like that now however.

    At this point in time there is still considerable debate over this issue. If we had Dr Hammerschlag here she would undoubtedly discuss the technical details of this work in ways I cannot. I am not a chlamydial lab expert. But then again, Dr. Sriram is a neurologist and the director for VU's Multiple sclerosis center. He is teamed up with Dr. Stratton a microbiologist (like MH), and Dr Mitchell an MD PhD pathologist, and they have studied this material and they have made it their business to say this IS happpening in MS and have published extensively on the subject. I am not swayed to believe that Dr Hammerschlag is correct and that the VU team is off base.

    So what about other researchers beyond MH and VU? Well, if you go on pubmed and put "multiple sclerosis chlamydia pneumoniae" in the search box you will get a whole list of this kind of work done all over the world by othe people. Some will support the idea, some will not. This is the way science goes, it is a back and forth process until eventually something conclusive and reproducible is put forth. As you read the research, these are the questions to keep in mind;

    If a study suggests that there were no people with CPn in the brain, what tests did they use to establish that? Often we see something like the VU study which utilized several highly technical and detailed methods on CSF samples to establish that CPn was there being "countered" with a study that used a single test, sometimes even a blood test.

    Or sometimes the author finds not one single case of CPn in the tissue, and you wonder, considering how often other people find it even in seemingly healthy people, how does this author find none at all?

    Or sometimes we lay people cannot judge without a tip from someone inside the study, as in the case where the formalin fixed samples were used. To find that out you might need to read comments or editorials in later issues of the publishing journal.

    And finally, we have the notion that persistent CPn cannot be cultured at all. If you accept this might be a possibility then testing and it's positivity becomes a somewhat moot point, the germaine issue then being who will develop a test that will find persistent CPn, and importantly, has VU done it already?

    So now we come full circle to where I began this page, we are in the uncomfortable position of saying I believe this researcher and not that one, and this question becomes vitally important to us if we are in the unenviable position of suffering from MS and having no results from traditional treatment. Dare we try this treatment in spite of it's not being fully proven and in light of the fact there are some people vehemently stating it is incorrect?

    I offer this and this is entirely my personal opinion: The talented and highly qualified team at VU who have published several peer reviewed papers on the subject claiming that CPn is present in at least a subset of MS patients has been focused on this specific issue now for 9 years. That's 9 years of refining their PCR techniques, 9 years of making the tests more robust and redoing tests to remove doubt, 9 years of watching the few people they've treated experimentally with antibiotics get some level of improvement (which is documented) and 9 years of focus. From this multifaceted effort they say it appears to be there in at least a subset of patients. 9 years is long enough for an MD to become a specialist in a couple of disciplines. In my book I find it impossible to imagine the VU team is not utterly expert at this by now, and more expert than any other researcher because of their focus. Add to that the fact that USF gets similar results using a different test, and that some others all over the world are also weighing in on this side of the debate and we have a good weight of evidence agreeing that CPn appears to be there in MS in at least a subset of patients.

    Considering the fact that this would be treated with currently available antibiotics and it is clear that these drugs are not patent drugs and therefore not going to make anyone anywhere any money, there is no commercial interest here in manipulating the data at all, which is always a concern with commercial patent drug research. I can find no reason for the people at VU to be anything but honest in their work; it appears legitimate even if still not widely accepted yet. We will hope for some large blinded studies down the road that will make it clear to every one the exact extent of CPn incidence in MS and or some interesting other data that clarifies the issue. Another important point related to the fact CPn is treated with antibiotics is that there is no interest on the part of any drug firm to rush to VU with a large grant to further the research either. This is the reality of our commercial research system. It might be worth noting that the year before Barry Marshall proved beyond a shadow of a doubt that h.pylori caused almost all ulcers, he was still correct, even though few agreed with him. A physician I know of made the comment that "CPn could be neurology's h. pylori". The original resistence to the idea on the part of doctors who treated ulcers with surgery and bland diets and who mocked the idea of h pylori causing ulcers are not unlike the neurolosits who reject Cpn/MS idea.

    So that is the debate as it pertains to multiple sclerosis. I did not talk about PCR specifically or other issues about the labwork. For that please consult the other book pages.

    So if we accept that labwork is not in 100% consensus about how to culture CPn in the CSF of the MS patient, nor is it even clear that persistent infection CAN be cultured, is there other circumstantial evidence that supports the theoretical model that CPn plays a role in MS? The next page is smoking guns and it talks about this issue...and I'd like to say for the person who has been into MS research for a long time, it is there that the correlations uncannily begin to fall into place, although once again we are talking about an idea, not a scientifically proven fact at this point.

    mrhodes40 Fri, 2006-03-03 11:58

    The Remarkable Effects of a CAP for Chlamydia Pneumoniae on High Blood Pressure

    The Remarkable Effects of a CAP for Chlamydia Pneumoniae on High Blood Pressure

    One of the remarkable things we have been finding from users of a Combined Antibiotic Protocol is a distinct lowering of blood pressure, even normalizing serious hypertension without other blood pressure medications. This was first noted and observed by David Wheldon in reporting his own treatment of Cpn for cardiovascular issues. As blood pressure readings are easy to gather as hard data, and pre-CAP pressures can be collected from one's own doctor's records, one of our members has been gathering this data into an ongoing survey.

    See for yourself at the link below. The charts are quite something to see, especially as high blood pressure is often very difficult to treat and stabilize.

    Ron's Blood Pressure Survey Link 

    Jim K Sun, 2006-05-21 16:55

    Viruses as cause or co-factors: Viral Henchmen in disease

    Viruses as cause or co-factors: Viral Henchmen in disease

    The question of viral causes or co-factors comes up often, as most of the diseases for which one might use the CAP to treat for Chlamydia pneumoniae have research which has found viral components as well.

    David Wheldon tackles this question on his web site, with his usual clarity of discussion and so well founded in his ready grasp of the scientific literature. Click the link below for his web page:

    David Wheldon on "Viral Henchmen"

     

     

     

    Jim K Mon, 2006-08-07 07:18

    Why your doctor has such resistance to infection as a source to chronic disease?

    Why your doctor has such resistance to infection as a source to chronic disease?

    Under Construction

    Eventually we hope to have more detailed discussions of:

    • The causal vs co-factor question.
    • A brief look at the arguments which refute Cpn as a causal factor (such as the cardiac findings that two weeks of zithro doesn’t prevent future heart attacks) and the counter arguments (e.g. that two weeks of zithro is a ridiculous treatment given persistencei). This should be done at least for cardiac, ms, arthritis.
    • How methodological differences between studies and logical confusion cause premature rejection (maybe premature expostulation!) of emerging findings.

    In the mean time, an two excellent comments on this topic

    An excerpt here from David Wheldon's book review of "The Potbelly Syndrome" where David describes some of the difficulty doctors have looking for occult infections, and a page on his website where he discusses the difficulty doctors have going against what has been so ingrained in them in training.

    Excerpt from http://www.cpnhelp.org/?q=book_review

    And for years people have looked for infections in these chronic illnesses without success. It is forty years since Chl pneumoniae was discovered, and, as the author says, hospital consultants do, by and large, have little understanding of this organism. I can vouch for this. I was speaking to a colleague, a consultant medical microbiologist, who politely asked me my interest within the subject. 'The treatment of chronic infections with Chl pneumoniae.' 'Oh, I never see infections with that!' To which the answer is 'You don't look.' Charles Strattoni, a medical microbiologist at Vanderbilt University, and a member of the team who first discovered the presence - by culture as well as the detection of specific gene-sequences - of Chl pneumoniae in the CSF of people with MSi, believes that method is all important, with fastidious attention to detail and, in the case of culture, repeated centrifugation and prolonged incubation. Doctors are inclined to show undue credulity when it comes to negative laboratory findings. Saying 'we didn't find it so it's not there' is, after all, not that much different from saying 'you claim there is a needle in that haystack; I've spent a whole ten minutes looking for it without finding it so it's not there.'

     

    David Wheldon's "The Curate's Egg" http://www.davidwheldon.co.uk/peer-review.html

    For those not anglophiles, the phrase means:

    "Something bad that is called good out of politeness or timidity."

    Origin

    The origin of the phrase, the George du Maurier cartoon - "True Humility", printed in the magazine Punch, 9th November 1895, gives fuller insight into its meaning, which relies to some extent on an appreciation of irony.

     

    The Curate's Egg
    TRUE HUMILITY. Right Reverend Host. “I’m afraid you’ve got a bad Egg, Mr. Jones!” The Curate. “Oh no, my Lord, I assure you! Parts of it are excellect!

     

    Jim K Sat, 2006-02-04 12:40

    Short letter to a doctor

    Short letter to a doctor

                Your name

    Your address

    Date

    __________________, MD

    Street address

    City, State, Zip code

    Phone number

     

    Dr. _______,

     

    I appreciate your willingness to consider supervising me on a Combined Antibiotic Protocol to treat my (………………….), as an expression of a persistent Chlamydia Pneumoniae (Cpn) infection.   I understand that this protocol is not conventional, and as with any medication, some negative effects could occur, however, there is compelling evidence to suggest that Cpn may be implicated in my condition.

     

    There is also evidence suggesting that lab tests to detect a Cpn infection are not definitive and somewhat limited.  These lab tests are most accurate in showing positive results in the event of a current infection.  Chronic infections may not produce positive lab results due to the obligate intracellular nature of the reticulate body and cryptic life stage of persistent Cpn.   Cryptic Cpn will convert back to reticulate bodies when conditions are favorable for its replication and further infection in the body.

     

    The specific protocol I am asking you to supervise was created to eradicate a Cpn infection but may eradicate other bacterial infections as well.  Proof or identification of a specific infection is not my ultimate objective.  I would like to try this treatment empirically to see if I can halt the progression of my condition.  A document is enclosed which outlines an example of the protocol and basic information about the Cpn lifecycle and the specific aspects needed for its successful treatment.  

     

    Because of these specific circumstances surrounding the life cycle of this bacteria, stopping and starting short courses of a single antibiotic will promote bacterial resistance rendering the antibiotics ineffective.  Using antibiotics in combination has the added advantage of a synergetic effect on the bacterium that inhibits the development of resistance and renders them more effective.   A key point in the successful treatment of this obligate intracellular bacterial infection is that the duration of treatment should be sufficient to eradicate all of the life phases.

     

    I am hoping you will be willing to supervise my progress and provide oversight and treatment for any related concerns as we co-operate to improve my health. 

     

    I can provide you with contact details for the doctors who have been responsible for the research into Cpn and the development of this protocol, should you want to consult them.

    • In the USA, Dr Charles Stratton, MD, of Vanderbilt University
    • In the UK Dr. David Wheldon, MD, consultant microbiologist.

     

    Thank you again for your willingness to consider helping me in trialing this therapy for Cpn.   I hope that we can engage in a co-operative relationship with the aim of improving my health.

     

    Sincerely,

    Michèle Sat, 2008-05-31 08:52

    Strategies for Finding a Doctor

    Strategies for Finding a Doctor

    At this time, we do not have a list of physicians who prescribe a long term combined antibiotic protocol (CAP), and our policy is to maintain the public anonymity of those CAP doctors who have not made themselves public. Please do not e-mail requests for a list or a referral on the "feedback" link. We offer the following strategies and considerations, though, to help you find a doctor to treat you on the protocol.

    One strategy is to try the doctors you already know. For this angle, you should prepare yourself. Understand that the doctor might be unfamiliar with the concept. It’s a plus if the doctor senses that you have a firm grasp of the concept yourself. Here’s a little "cheat sheet" on the critical points:

    1. Chlamydia pneumoniae (Cpn) is also known by its newer name of Chlamydophila pneumoniae.  It is an intracellular pathogen, that is, the infection is inside your cells.

    2. Cpn has three main life cycle phases:

    • The elementary bodies (EBs) – seed-like or spore-like phase that spreads the infection.
    • The reticulate bodies (RBs) - this is the active and reproducing phase.
    • The cryptic bodies (CBs) – relatively inert "hibernating" phase.

    3. Chlamydia pneumoniae is persistent. The reticulate form is the phase that attracts the most attention from your immune system and, ultimately, its presence is the trigger that results in most of the "collateral damage" heaped on the surrounding tissues by the immune response. Threatened by bacteriostatic antibiotics, it can convert to the cryptic form to protect itself. When the threat is gone, it converts back to the reticulate form and continues to reproduce and spark the damage.

    4. Only a long term combined antibiotic protocol effectively and safely kills Cpn in all three phases.

    5. It is necessary that the protocol be a long, gradual kill-off of Cpn in order to avoid too much apoptosis (natural cell death) at once. Natural cell death and replacement is an ongoing process occurring in the bodies of everyone, well and unwell alike. Cpn has developed the ability to keep host cells alive for an artificially long time. When Cpn is killed inside the host cell, the "immortalizing" effect goes away, and the host cell dies as it should have done already. If the whole arsenal, that is the full complement of the combined antibiotics, were hurled at the Cpn population from the beginning of the treatment, too many host cells would die at one time…this could cause organ failure. The protocol employs a gradual ramping-up of the antibiotics which brings about a gradual winnowing-down of the Cpn population. This approach makes the protocol comparatively safe.

    6. Cpn infects immune system cells themselves. As more ineffectual immune cells die-off and get replaced with non-infected cells, the immune system progressively improves and behaves more normally.

    7. A steady pattern of consistent improvement should not be expected. A pattern of ups and downs, two steps forward/one step back is more likely.

    Your doctor may have specific medical concerns---make sure you understand the gravity of the concerns and how the protocol addresses them. These are the main concerns:

    1. Development of bacterial resistance~~~The combination of the antibiotics in the protocol prevents this by attacking Cpn in more than just one way. Here is a helpful article by Dr. Charles Strattoni of Vanderbilt University on the subject.

    2. Potential damage to the liver and other organs~~~The recommended supplements and the gradual approach of the protocol help to prevent damage. Monitoring through appropriate blood testing is recommended.

    3. The potential consequences of gut flora disruption~~~The recommended supplements include antifungals and multi-strain probiotics to forestall these potentialities:

    • Overgrowth of Candida (yeast) and other fungi. 
    • Overgrowth of Clostridium dificile and other harmful bacteria. C. dificile is a particularly nasty bug that can cause diarrhea to the point of dangerous dehydration~~~The multi-strain probiotic should include Saccharomyces boulardii which is especially helpful in controlling the C. dificile population.

    4. Secondary porphyria may be a symptom that is already happening if your liver is infected with Cpn. Antibiotic treatment may exacerbate this problem~~~Avoiding red meats and trans-fat consumption and increasing complex carbohydrate consumption are helpful. Another method of control is taking glucose tablets before eating. For more severe cases, propanolol and other medications are discussed on the website.

    5. Bacterial die-off reactions are no walk in the park. This is caused by the release of endotoxins from the Cpn that have been killed~~~The symptoms are manageable. Some of the most effective ways to limit these reactions are by supplementing extra vitamin C and activated charcoal, using vitamin C flushes, taking Epsom salts baths, and drinking plenty of water. Maintaining bowel regularity is helpful, as a quicker elimination of the endotoxins from the gut lessens their reabsorption.

    Bring documentation to the appointment, but don’t shove too much paper in your doctor’s face at once:

    1. A letter similar to the sample letter in the Cpn Handbook. It should reflect that you understand the concept of the CAP; the risks; the responsibility you accept in proactively taking measures to forestall the risks; and the responsibility you bear in seeking help to manage those potentialities in the event they should arise and warrant medical attention.

    2. A copy of the Cpn Handbook bound in a notebook for later reference.

    3. Tuck some supporting research articles into the notebook pocket.  Those with MS would do well to include the critical sections from Dr. David Wheldon's website.  Your doctor may appreciate his concise protocol presentation.

    4. The opinion of an uninvolved physician can be found here.

    Don’t discuss this subject with the doctor, but do understand that there is an element of risk for the doctor in treating you with a CAP. Weigh the possible benefit of long term CAP treatment against continued use of other treatments and progression of your illness. Decide if you are willing to sign a waiver for the doctor and be prepared to make that offer if you are committed to pursuing a CAP treatment. Receiving this treatment requires that you be an informed patient and accept a degree of responsibility beyond what your previous medical experiences might have required. Incorporate this new way of thinking into your pursuit of effective treatment.

    You might consider doctors other than those who specialize in your illness like your primary care physician: a general practitioner or internist. You may find that an osteopath or an MD with alternative medicine leanings is more receptive to a CAP.

    Try a "Lyme literate" doctor who is already familiar with long term antibiotic treatments.

    Another approach is to seek a doctor who is already treating one of our site users. Make a personal blog entry asking for help with a title that includes your location and illness. Be flexible and willing to travel a distance that you can manage.

    One site user, Ken H, was successful in using a truly unique approach: target an assembled group of doctors and see who’s game.

    Best wishes and Godspeed to you.

    cypriane Thu, 2007-03-29 16:51

    Additional ideas for finding a doctor

    Additional ideas for finding a doctor

    Some additional strategies that people have used:

    • Try to find a doctor in your area that treats Fibromyalgia; there's a list at http://www.co-cure.org/Good-Doc.htm Fibromyalgia just recently became "respectable," so they may be more accustomed to working on diseases that require non-standard handling.
    • In the U.S.: Call a compounding pharmacy in your area. Doctors who use compounding pharmacies may be less tied to off-the-shelf treatment options.
    • Doctors who specialize in treating allergies are accustomed to treating patients on an individual basis for protracted periods -- the rhythm of a CAP may be less unfamiliar to them.
    paron Tue, 2007-04-10 17:03

    Treatment Information for Doctors

    Treatment Information for Doctors

    Information for doctors

    Treating Cpn.

    Chlamidophila Pneumoniae (Cpn – formerly known as Chlamydia Pneumoniae) is an obligate intracellular pathogen which has three life phases. This makes it particularly difficult to diagnose and treat. The only phase of the organism easily identified in blood samples is the Elementary Body phase. The Reticulate Body phase and the Cryptic phase are more difficult to identify as the organism resides within the cell, preventing apoptosis and having the ability to take advantage of suitable conditions for reproduction and further spreading infection. The problem is compounded by the fact that macrophages are often themselves infected and transport the bacterium to new sites in the body.

     

    Cpn, being a vascular disease has been implicated in a wide range of conditions ranging from Asthma to Vasculitis, and including Alzheimer’s, Arthritis, Atherosclerosis, CFS, Fibromyalgia, Hashimoto’s Thyroiditis, MS, Sinusitis etc and displaying a myriad of symptoms.

     

    A simple course of antibiotics will not address the problem; thus a Combined Antibiotic Protocol along the line of the protocol used to treat TB is necessary, and as for TB the treatment is likely to take months and years rather than days and weeks.

     

    Doctors and scientists led by Dr C Stratton at Vanderbilt University researched the action of a number of antibiotics on Cpn and together with Dr D Wheldon (a British consultant microbiologist) formulated the following protocol:

     

    Antibiotic

    Dosage

    When taken

    Notes

    Doxycycline

    100mg

    QD

    Take this alone until well tolerated.

    Azithromycin or Roxithromycin

    250mg

    150mg

    Mon, Wed, Fri

    BID (everyday)

    Add either one or the other of these to 100mg doxycycline

    Doxycycline

    100mg

    BID

    When both the above are well tolerated add another 100mg of doxycycline

    Metronidazole pulse, also called Flagyl.

     

     

    An alternative is Tinidazole

    400mg or 500mg depending on dose available in your country.

    500mg

    TID

     

     

     

    BID

    When the first two antibiotics are well tolerated start pulsing the third. For one day every three to four weeks initially. Increase the number of days per pulse gradually to five days.

     

     

    The dying bacteria produce endotoxins and may cause secondary porphyria which can make patients quite unwell so, initially, it is important to pace the treatment. Metronidazole or Tinidazole are only taken for 5 days in each three or four week cycle to allow the patient to recover from die off effects.

     

    This is only one of several solutions to the treatment of Cpn, but possibly the easiest to administrate and follow. There are other protocols that can be prescribed after the initial period of treatment. For more information on the research that has been done, patients’ experiences and the other protocols please visit: www.cpnhelp.org. This site also provides support for patients and publishes updated information on research and new protocols.

    Michèle Sat, 2008-05-31 09:01

    What to bring to your doctor to educate about Cpn and the protocols

    What to bring to your doctor to educate about Cpn and the protocols

    Select out the most relevant sections of the Handbook, as well as a couple of the research sources, so your doc has the medical rationale but isn't overwhelmed with info. 

    If this is for MS, start with the main page materials from David Wheldon's site.

    Add selected material from the Cpn Handbook from these:

    • Multiple Sclerosis and the CPn model
    • Cpn in MS: Over Easy
    • Smoking Guns, Cellular similarities between CPn cellular reactions and MS
    • The Brain and Pathogenic Treatment
    • The great MS debate Do we find CPn?

    Then these, add specific articles on your particular disease from the research pages:

    • Cpn Simple
    • Possibly selected slides from Stratton Slide presentation
    • The Basics Page
    • Some Answers to Concerns About Long-Term Antibiotics
    • Diagnosis Issues
    • Initial and Following Blood Tests in CAP's Treatment
    • Stratton/Vanderbilt Protocol Update: February 2006
    • Dr. Stratton Answers Some Questions

    Two or three supporting articles I would add from (be selective to fit your doc) our Physicians Page:

    • Association of CPn with Chronic Human Diseases Article in Antimicrobials and infectious diseases
    • Chlamydia pneumoniae infection in circulating monocytes is refractory to antibiotic treatment
    • Interview With Expert close to Vanderbilt on the protocol
    • Chlamydia Pneumonia pathogenesis
    • The pathogeneisis of Chlamydial species Article in Antimicrobials and Infectious Diseases
    • The cellular Pardigm of chlamydial pathogenesis
    • The Pathogenesis of systemic chlamydial infection: the theoretical considerations of host cell energy depletion and it's metabolic consequences Article in Antimicrobials and Infectious Diseases

    Print the pdfs from these (worth printing in color):

    Chronic bacterial infections: living with unwanted guests

    Potential Role of Infections in Chronic Inflammatory Diseases If this link doesn't work, try: http://www.asm.org/asm/files/ccLibraryFiles/Filename/000000001887/znw01105000529.pdf

    If your doc needs more detail I would go right to the Mitchell Stratton patent materials and print the whole thing as it describes all the detailed lab work.

    Even better, Dr. Stratton has been generous about phone consults with doctors interested in using the protocol. Look up his number on the Vanderbilt U website and give to your doctor. It's the best thing if doc to doc they can talk to the worlds expert on this. 

    I would hold off all the other materials until you had a decision about treatment, as these are additional rather than supporting the "Why do a CAP" question. 

    Also from the handbook:

    • A sample letter to local doctor to convince of abx treatment-- modify it for CFS, and mostly for yourself. Rewrite and give to your doc with the packet if you think it would be helpful. 

     

    Jim K Thu, 2006-06-15 07:27

    Isolation and Support in Long-Term Illness

    Isolation and Support in Long-Term Illness

    The rejecting attitudes of many doctors, family members, friends, marital partners and others to long-term or "untreatable" illnesses such as MS, Lupus, CFIDS, Fibromyalgia are a common experience for sufferers. Many people say that simply finding this web-site, and people who take them seriously and believe them, is one of the great moments of healing for them. There is so much to say about this topic and the reasons for these attitudes. I'm a psychologist, and understand the social and psychological dynamics which enter into such poor treatment of the ill by the "well." Understanding helps, but I am still subject to the hurt and blame, and I too need the support of others who take me seriously and can share their difficulties and triumphs.

    The following thread has a long and heartfelt discussion of this, with many examples of the ways people have been rejected and mistreated by those who should support them most, family members. It is titled "Isolation," but I assure you that you will not feel alone as you read it. I recommend it as highly therapeutic.

    Isolation

    Jim K Thu, 2006-09-14 02:18

    Some Answers to Concerns About Long-Term Antibiotics

    Some Answers to Concerns About Long-Term Antibiotics

    Answers to Concerns About Long-Term Antibiotics

    Many doctors, and patients, raise concerns about the long-term effects or side effects of antibiotics, and are frightened of the CAP’s because of this. Doctors, especially, need a little support for going against the grain of their training.

    On the issue of side effects-
    As I noted in a ThisIsMs post, the side effects of MS are devastating disability and death. Kinda puts a scale on things, doesn’t it? Similarly:

    • The side effects of Chronic Fatigue and Fibromyalgia are minimally functional existence, depression, unrelenting pain.
    • The side effects of Rheumatoid Arthritis are unrelenting pain and encroaching disability and dysfunction.
    • The side effects of Alzheimer’s Disease are… well, you get the picture.


    The side effects of the antibiotics commonly used in CAP’s for Cpn are intestinal upset from killing bowel flora, nausea if not taken with food, and some idiosyncratic effects for different people. All of these are transient, and mild or can be handled with counter agents (such as supplementing bowel flora in between antibiotic dosages).

    The main side effects patients with Cpn have are actually die-off reactions from Cpn bacterial kill. Patients who do not have Cpn (or other significantly endotoxic bacteria) will not have these typical die-off reactions to Cpn. These, then, are not “side effects” but actually main effects.

    Long term antibiotic use is harmful- Many antibiotics, especially the tetracycline family such as the doxycycline used in most CAP’s or minocycline, have been used long term (i.e. for years) without harmful effects. They have been used this way as immunomodulators, in low dose protocols (such as for arthritis) and at regular doses for acne.

    Flagyl/Tinidazole are potentially carcinogenic-
    Studies of carcinogenic effects are done on rats with huge doses not used in humans, and are taken continuously to produce these effects. This is another good reason why these medications are pulsed in the CAP's rather than taken continuously. Note: Cpn left to proliferate in tissues is potentially carcinogenic as well.

    Doesn’t long term use of antibiotics create bacterial resistance?

    The use of two anti-replication antibiotics which work on different proteins in the replication process (e.g. doxycycline and azithromycin combo) is done specifically to minimize the possibility of resistance. Taking NAC to kill the infectious Elementary Body stage of the Cpn organism and Flagyl/Tinidazole further minimizes resistance because, as Dr. Charles Stratton noted in an article by this name, “Dead Bugs Don’t Mutate.” Additionally, these antibiotics are not the ones used to treat the dire acute disorders where potential resistance could bbe fatal such as acute septicaemia, acute meningitis etc. So any potential resistance is unlikely to influence treatment of such emergency disorders.

    Won’t antibiotics cause yeast infections?
    If you don’t supplement regularly with probiotic flora you can get intestinal Candida imbalance (dysbiosis). Supplementation, plus appropriate use of antifungals for existing infections (nystatin, diflucan, oregano oil, etc.) will prevent this.

    On a related note: Cpn can infect the bowel quite significantly. Dr. David Wheldon has observed, "The resolution of fungal infections is quite remarkable. I've seen people with long-term dermatomycoses (unresponsive to antifungals) which have paradoxically resolved with Cpn treatment." Many of us with what we thought was chronic yeast infection noticed that after a month or two on antibiotics our “yeast problem” resolved quite a bit. The problem was, in fact, that bowel Cpn was the more central problem, and as it resolved so did other bowel problems. Resolving bowel Cpn also enhances the bowel immune system, since Cpn can infect immune cells. Additionally, the secondary porphyria can cause bowel and stomach problems that resolve as the Cpn infection causing the porphyria resolves.

    To summarize-
    You can reinforce with your doctor:
    That the “side effects” of otherwise untreatable diseases are much more significant than the side effects of these common antibiotics.
    That these antibiotics were especially chosen to have minimal long term effects,
    That they are used long-term for other diseases simply as immune modulators,
    That the more toxic ones (e.g. Flagyl) are used in pulses minimizing their harm potential,
    That the dual abx prevents resistance from arising in long term use,
    That the gut flora effects can be readily balanced by probiotic flora supplements and by anti=yeast medications (e.g. nystatin, diflucan) or herbs.
    That the use of NAC instead of amoxicillin not only further protects gut flora, but protects the liver as well.
     

    Jim K Tue, 2006-02-14 21:41

    Development of antibiotic resistance in Chlamydia pneumoniae

    D W

    I'm quite frequently asked whether the development of antimicrobial resistance in C. pneumoniae is likely, particularly when starting with one antibiotic or when adding metronidazole intermittently. To be honest I think the emergence of antibiotic resistance is unlikely, given that the organism in not actively replicating while in the cryptic form. I've put a new page on my website which discusses this: http://www.davidwheldon.co.uk/resistance.html Do forward comments and criticisms.

    (Editor's note: I've attached this post to the Handbook as-is so that readers may see Dr. Wheldon's article directly on his site through the provided link as well as the discussion here at www.cpnhelp.org . That way readers will have access to the most up-to-date version should he edit it on his site. Jim K) 

    Thank you darling: easily understood, so should put many people's minds at rest.  I'll go and add it to ThisisMS..............SarahAn Itinerary in Light and Shadow   Completed Stratton/Wheldon regime for aggressive secondary progressive MS in June 2007, after four years, three of which intermittent.   Still slowly improving and no exacerbation since starting. EDSS was 7, now 2, less on a good day.
    Completed Stratton/Wheldon regime for aggressive secondary progressive MS in June 2007, after four years, three of which intermittent.   Still improving bit by bit and no relapses since finishing treatment.
    Red

    Thanks as always DW, for the very easy to read and understand explanation.

    One thing I've been kind of confused by recently is discussion about few EBs in chronic infections. I've always thought that the RBs were pumping them out in spades, even in chronic infections.

    So, assuming that chronic infections are behind diseases like CFS, MS, Asthma, etc, how did Cpn infect the local tissues? Is it likely mostly by this transmigration of the RB from the blood monocytes?

    I always thought that Cpn infected blood monocytes showed up in the area, possibly due to some injury, etc and started producing tons of EBs that infected the local tissues.

    Could you explain this area a bit further for the extremely curious?

    Thanks again...

    On Combined Antibiotic Protocol for Cpn in Rosacea 01/06 - 07/07, On Vit D3 + NAC since 07/07 and daily FIR Sauna since 08/07

    Treatment for Rosacea

    • CAP:  01/06-07/07
    • High-Dose Vit D3, NAC:  07/07-11/08
    • Intermtnt CAP, HDose Vit D3:  11/08-01/09
    • HDose Vit D3, Mg, Zn: 01/09-

    Thank-you very much as I can take this into my next appointment as it is seems this is my doctors main concern. On Wheldon protocol for MS since April, 2006.  doxy 200 mgs daily, zithromax 250 mgs 3x/ week , Flagyl Pulses start end Sept., LDN 2004. Gad-enhanced MRI of brain and spine shows NO NEW DISEASE ACTIVITY and one lesion diminishing in size on 9/30.

    5oo mgs Ceftin 2 x/day, 500 mgs Zithromax, 500 mgs 2 x tini pulses,100 mg diflucan, 4.5 ldn; Wheldon protocol for MS April, 2006 to May 2008. 2008 MRI shows NO NEW DISEASE ACTIVITY, 2012 MRI no new disease activity.

    D W

    Hi, Wiggy, I'm glad to be of help: I hope you're successful. Hi, Red - EBs are turned out in vast numbers in acute infection, and seed themselves throughout the body. However, as host defences are mounted, the organism goes into a different mode, relying wholly on host ATP and producing few EBs. (One of the reasons why there is so much argument about C. pneumoniae and MS is that few EBs find their way into the CSF and may even be intermittent.) So, early spread is by seeding with EBs; in chronic infection the spread is much more likely to be transmigration from cell to cell and the stimulation of infected host cells to divide (interestingly, other intracellular pathogens can do this.) You can see this in atheroma: it starts off in childhood as fatty streaks involving the endothelial layer. Later on, these expand, foam cells appear and the structure becomes disorganised, with increased and rather choatic smooth muscle. On doing an autopsy on someone with bad arteriopathy you find that most of the atheromatous lesions are of the same age (and quite ancient: calcification is common.) You tend not to find 'young' and 'old' lesions in the same person. I had always wondered why this was; it was this early 'seeded' appearance which made my path teacher, Oliver Cromwell Lloyd (his real name) suspect infection when everyone else was looking at cholesterol. (Gosh, you have got me thinking about O. C. Lloyd, now. He was a spelaeologist, a cave diver, a musician, a specialist in skin pathology, an archeologist and a Punch and Judy Professor. (All children's entertainers who run a Punch and Judy show are called 'Professor'. O. C. Lloyd's Punch and Judy was very traditional, with no pandering to political correctness. Each and every character who encountered Punch was grimly despatched, meeting a grisly fate usually connected with his trade. For instance, when Punch is sentenced to death he ascends the scaffold where Jack the Hangman is waiting. Punch affects not to understand the principle of the thing, and asks Jack to demonstrate. Jack puts his own head through the noose, and Punch pulls the other end of the rope, shouting 'That's the way to do it!' in his rasping voice - his voice being produced by a schwazzle, an artificial vocal cord held between tongue and palate.) D W - [Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding metronidazole. No medication now; just supplements and IR sauna. Morning BP typically 110/75]
    D W - [Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding metronidazole. No medication now. Morning BP typically 110/75]
    Red

    Ah, the old light bulb finally switched on with this explanation DW.   Thanks!

    And your path teacher, O.C. Lloyd appears to have been quite an amazing character, with extremely varied interests.    I imagine he must have given some very interesting lectures!

    Thanks again... 

    On Combined Antibiotic Protocol for Cpn in Rosacea 01/06 - 07/07, On Vit D3 + NAC since 07/07 and daily FIR Sauna since 08/07

    Treatment for Rosacea

    • CAP:  01/06-07/07
    • High-Dose Vit D3, NAC:  07/07-11/08
    • Intermtnt CAP, HDose Vit D3:  11/08-01/09
    • HDose Vit D3, Mg, Zn: 01/09-

    Thank you David, I have bookmarked this for the information of those who might require it in the future.   I'm of the trusting follower type so I have not had a moment's worry about following the protocol, but I know others do.

    Michele (UK) GFA: Wheldon CAP 1st May 2006. Daily Doxy, Azi MWF, metro pulse. Zoo keeper for Ella, RRMS, At worse EDSS 9, 3 months later 7 now 5.5 Wheldon CAP 16th March 2006

    Michèle (UK) GFA: Wheldon CAP 1st May 2006. Daily Doxy, Azi MWF, metro pulse.

     David- Thanks for this cogent and accessible explanation. I think the proper accolade on your side of the water is "Brilliant!"

    Many people approaching the CAP, especially physicians, have concerns about this issue but don't have enough grasp of the particulars. The dictum of "antibiotic overuse creates resistance" is a useful rule of thumb for busy doctors in their practices, but doesn't say enough about how resistance is formed and in what kind of usage to give the intellect something to reason out the problem with a particular organism or protocol. I'll add this page right to the Handbook with your link intact so that users can always have access to the most up to date version, along with whatever commentary and discussion takes place here.

    CAP for Chlamydia pneumonia since 11/04. 25yrs CFS & FMS- Currently: 200 Doxycycline, 500mg MWF Azithromycin, Tini pulses.

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Thank you, David, for the explanation. I knew that the resistance was unlikely, but like others, I pictured the dynamics of the infection very differently. Barbara Multiple sclerosis, on the intrmittent Wheldon protocol since March 2006, EDSS 0 for over 4 years

    Cured of multiple sclerosis, stopped the Wheldon's protocol in Nov,2008. Use only LDN.

    DW           

    Thanks for the explanation of resistance and how/when it can emerge.  I've wondered about it myself from time to time.  This raises the question about the recent outbreak of resistent staph infections which seem to becoming increasingly common.  Is this a case of the bacteria being resistant to one antibiotic or is it more complex than that?

    Also, in your page you mentioned that production of infectious EBs in the chronic stage to be rare.  That surprises me, I think that most would have expected the opposite.  Why would it be rare, wouldn't there be more RBs pumping out EBs in that stage?

    all my best

    John

    RRMS/EDSS was 4.5, now 4.??? on Wheldon Protocol (nac, doxycycline, azithromycin, metronidazole) since 04/12/2006. Added Rifampin 2x150mg/daily on 08/19/2007

    best, John

    RRMS/EDSS was 4.5, 5, 6, 6.5, 6.9999, 6.5 on Wheldon/Stratton Protocol beginning 04/12/2006
    nac 4x600 mg/day
    doxycycline 2x100mg/day
    azithromycin 3x250mg/day MWF
    metronidazole 3x400mg/day then 3x500mg/day

    David,

    I have a more specific question relating to your post that has been really worrying me for awhile, and I wonder if you would be willing share your opinion or wisdom with regards to the following:  Can cycling any of the first two antibiotics (not flagyl or any other abx added later) increase the probability of the development of resistance or of a poorer treatment outcome? 

     My doctor is fine with giving the abx, but is of the opinion that abx have inherent dangers, kind of like chemotherapy does.  He also said that he has read that cycling abx does not increase resistance.  Therefore, he started giving me doxy and Biaxin in a cycle of 3 days off and 2 days on, and after 5 weeks I am supposed to take 2 weeks off abx.  I am on NAC all the time. 

    I did this for about 6 weeks, but then, of my own accord, I went on abx straight for a month because I was afraid of being off abx so frequently.  I was afraid cycling might promote resistance AND even more so, I was afraid that if I didn't keep a steady or high enough amount of abx in my system, the treatment wouldn't be effective.  

    On the other hand, I am wondering if one can take occasional time off from abx (for reasons such as yeast or extreme diarrhea or a short illness, or just to give the body a short break) without worrying that might have screwed up the treatment.  Is it ever beneficial to take a short break, and if so, when?

    Anybody, please feel free to give me your ideas, but I am mostly very much looking for strong evidence/research/statistics or experienced opinions that will definitely help me make a good judgement call on this.  As I'm sure you would all agree, deciding how to carry out this treatment and whether to depart, in even any small way, from the standard treatment protocol (or how to make mild adjustments) can be a very serious and scary task.  

    On the other hand, I don't want to ignore my doctor's advice without really having a good reason for it.  My doctor has been instrumental in helping me find this treatment and he is quite knowledgeable in general, so I don't want to brush off his opinions or ideas.  On the other hand, I know that even the best doctors sometimes find their long held opinions changing on occasion, and my doctor is always willing to rethink something and make a change.  I just need to arm myself with more facts so that I can feel comfortable that I am making the right decision and feel that I can discuss this with him in an intelligent fashion, and right now I am not armed with that information.  My doctor's view is so unique that I'm just not sure where to find information to either confirm it or intelligently question it.

    I am very afraid of making a huge mistake in my treatment, yet I am not exactly sure what to do.  I would greatly appreciate any insight that you might be able to provide me.

    Reve' 

    Memphis,TN - FM, IBS, rhinitis, depres ~20 yrs. CF, intestine, bladder, pelvic inflam., red itchy skin, anxiety ~5 yrs. CPn titer 1:256.  CAP 6-07 Current NAC 2400 mg; doxy 100 mg x 2 and Biaxin 250 mg with 3 days on 2 off cycle and holiday wks 6,7

    Memphis,TN - FMS, IBS, rhinitis, depres (~20 yrs) CFS, intestine, bladder, pelvic inflam., red itchy skin, anxiety (~5 yrs). CPn titer 1:256.  CAP 6-07 Current NAC 2400mg; doxy 100mg x2, Biaxin 500mg x2, supplements, 1st pulse Flagy

    Reve, coming from someone who has had to quit the abx twice now for a number of months due to liver enzymes . I can tell you that stopping for any length of time just sets you back that much further . Every time you start again you go through symptoms that occured in the beginning. I had hypertention, dizzy spells, muscle fasculations,gaul bladder pain,bowel and bladder troubles to mention a few , all act up again. I dont recommend stopping and starting ! ........chuck treating reiters syndrome, cronic fatigue, heart symptoms, myalgia symptoms, started with doxcycline 200mg and rifampin 300mg in jan 15/05. switched to doxy 200mg and azithromycin 250mg m.w.f in sept 06. after being on abx for two years now doctors dont think I have reiters syndrome
    treating reiters syndrome, cronic fatigue, heart symptoms, myalgia symptoms, started with doxcycline 200mg and rifampin 300mg in jan 15/05. switched to doxy 200mg and azithromycin 250mg m.w.f in sept 06. after being on abx for two years now doctors dont t

    Hi chuck,

    I know your post is seven years old but...

    I was browsing when i saw a reference to Reiter Syndrome. I am 58 and had Reiters when i was 21 - Uvitis, Arthritic swelling, Urethritis - 3 weeks as in patient. No apparent relapses, but have had prostatitis three times and - my reason for finally finding this site - Asthma. Thing is, i always understood reiters to be a classic chlamydial infection; is there any conncetion with Cpn as far as you are aware?

    D W

    Reve,
    I wouldn't intentionally cycle antibiotics as part of a schedule, though sometimes you have to reduce doses because of unpleasant die-off reactions. I've seen some people with MS who have taken intermittent treatment and lost ground.

    John,
    The virtual stopping of the production of EBs in chronic C. pneumoniae infection is due to the organism altering its metabolic strategy (a 'stringent response') as a result of host denial of various important factors. The organism goes into 'tickover' mode, running on the idling jet. There is probably an input from the likely evolutionary history of C. pneumoniae, where chronic infection in man is a dead end. More on this later.

    Red,
    O. C. Lloyd was indeed a most unusual man with very idiosyncratic views. He was not at all amusing in his lectures, but drily informative. He had been a scholar of Classical Greek before reading Medicine, and clearly felt that if you use a word you should know what it means. Medicine is full of Greek and Latin words of which few know the root: OCL would cover the blackboard with Greek symbols to explain the roots of histological words. I recall 'hamartoma' being one such. As an academic he was reputed to be utterly ruthless in the pursuit of what he thought was right. He was much liked by the students, though. His teaching was one of the main reasons I went into pathology. He died in 1985.

    D W - [Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding metronidazole. No medication now; just supplements and IR sauna. Morning BP typically 110/75]

    D W - [Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding metronidazole. No medication now. Morning BP typically 110/75]

    So far, I follow the protocol to the letter.

    Some of my die off symptoms from flagyl pulsing are pretty serious -sudden rage & aggressiveness.  I need to take it slow!

    CFIDS/ME 25yrs, FMS, IBS, EBV, Cpn, (insomnia - melatonin, GABA, tarazadone, temazepam, novocyclopine, allergy formula, 2 gm tryptophan), Natural HRT peri-M, NAC 2.5 gm, 6-07 Doxy 200 mg day pm, Azith 375 mg M/W/Fday, 9-30-07 2nd pulse 1 X 250 mg Metro

    CFIDS/ME, FMS, MCS, IBS, EBV, CMV, Cpn, H1, chronic insomnia, Chronic Lyme, HME, Babesia, Natural HRT-menopause, NAC 2.4 gm,Full CAP 6-2-07, all supplements+Iodorol, Inositol-depression, ultra Chitosan, L lysine Pulse#27 04-19-10 1gm Flagyl/day-5 days<

    Thank you all very much for your input.  David, thank you very much for your answer.  I appreciate it very much.  I will definitely bring this to my doctor's attention at my next appointment.

    Reve' 

    Memphis,TN - FM, IBS, rhinitis, depres ~20 yrs. CF, intestine, bladder, pelvic inflam., red itchy skin, anxiety ~5 yrs. CPn titer 1:256.  CAP 6-07 Current NAC 2400 mg; doxy 100 mg x 2 and Biaxin 250 mg with 3 days on 2 off cycle and holiday wks 6,7

    Memphis,TN - FMS, IBS, rhinitis, depres (~20 yrs) CFS, intestine, bladder, pelvic inflam., red itchy skin, anxiety (~5 yrs). CPn titer 1:256.  CAP 6-07 Current NAC 2400mg; doxy 100mg x2, Biaxin 500mg x2, supplements, 1st pulse Flagy

    Diagnosis Issues

    Diagnosis Issues

    Testing vs diagnosis

    Physicians are enamored of blood tests, as are patients. They seem so clear and unequivocal. But any good doctor knows that blood results do not a diagnosis make. Diagnosis is a complex, multivariate consideration. In the case of infection, serology can contribute significantly to making a diagnosis, but many factors go into whether serology is accurate or not.

    In the case of Chlamydia pnemoniae, there are significant difficulties in obtaining accurate tests. In addition to the accuracy issue, individual's may not respond antigenically. All of this means that having a negative blood test for Cpn does not mean that you don't have Cpn infection. Tests can be inaccurate for the following, and other, reasons:

    • The test may not be sensitive enough. Antigen tests for Cpn are said to be relatively inaccurate. PCR tests are the most sensitive, but dependent on the particular primers used, whether the dna used by the test matches the particular strain of Cpn one has, whether the test used accounts for the type of sample well (blood, sputum, cerebrospinal fluid, etc), the accuracy of the technician (PCR is particularly trickey in a technical sense), and so on.
    • If the infection is predominantly in cryptic phase, there is no serology evident.
    • If the patient's immune system is significantly depleted, they will not show positive antigens for the organism infecting them (they are immuno-incompetant). 

    Since many asymptomatic persons show existing antibodies to Cpn, and many with symptoms show no positive Cpn serology, blood tests are not the last word in diagnosis. Diagnosis requires a physician to put together the whole symptom picture: the suggestive evidence of infectious involvement, serology and other tests, to diagnose and treat a condition.

    Stratton and Wheldon (draft paper) argue that symptomatic suspicion may be enough to warrant an empirical antichlamydial therapy even in the absence of positive serology. Dr. Wheldon's wife, Sarah, is a case in point: worsening symptoms of MS completely reversed and put into remission through use of his protocol, despite no serological indications. Endotoxin reactions to antichlamydial abx's (see below) followed by symptomatic improvement are often taken as a confirmation that the infection exists. The argument, in the absence of serology for Cpn, is that the treatment is low risk.

    Serology is an inadequate indicator of chronic infection (Saikku 1999). It does not indicate the locality of the possible chronic process, and the high frequency of C. pneumoniae antibodies in people makes it difficult to prove an association with a specific disease.
    Tiina Sävykoski nee Huittinen

     

     A sophisticated technical commentary on serology and diagnostic difficulties is provided from:

    http://www.chlamydiae.com/restricted/docs/labtests/diag_serology.asp

    We have already seen that the 'gold standard' micro immunofluorescence (MIF) test is actually not a good test for diagnostic purposes because of its lack of specificity, objectivity, reproducibility and agreed protocol. While expert chlamydiologists might be happy to use the test for comparative epidemiology, most would agree it is quite a different matter to be confident about the meaning of a result in an individual patient. A priori one might expect some of the newer tests with defined antigens to be more specific, but there is little evidence for this at the moment and it is a difficult thing to prove. In studies of the association of antibody to C. pneumoniae with coronary heart disease, the choice of test appears to be very important [Halvorsen et al, 2002; Schumacher et al., 2001]. The newer serological tests based on synthetic or recombinant antigens have largely  been evaluated against the classic MIF as gold standard. It is important to remember that no test can perform better than the selected gold standard and, since MIF is a far from perfect test, it may be that the apparent performance of some of the newer tests is constrained by this choice of gold standard. However further evaluation of these new tests and their application is required before they enter routine diagnostic practice...

    What is the effect of differing antibody and infection kinetics? When individuals acquire a chlamydial infection, there is a lag period before they make an antibody response. Similarly antibody persists for long after an infection is resolved. High or persisting antibody in an individual does not necessarily mean current or persistent infection. [Nor do persisting symptoms]. Persisting or lagging antibody will further confound the positive and negative predictive value of serology. The evidence, such as it is, is that serology and direct evidence of infection are not well correlated [Rabenau et al., 2000]. ...

    ...Bas et al., 2002 tried to determine the most sensitive and specific method of measuring antibody to C. trachomatis in reactive arthritis. A panel of serum samples were chosen from 17 patients with C. trachomatis reactive arthritis and twenty patients with other inflammatory arthritic conditions not involving chlamydiae. Chlamydial IgG, IgM and IgA antibody was measured by immunoblotting, by various enzyme-linked immunosorbent assays using six synthetic peptides or recombinant antigens and microimmunofluorescence. The best association of sensitivity (76%) and specificity (85%) was obtained when IgG and/or IgA reactivity to two species-specific antigens was determined. These antigens were synthetic peptides, derived from species-specific epitopes in the variable domain IV of the major outer membrane protein (Labsystems, Finland) and recombinant polypeptide encoded by open reading frame 3 of the plasmid (pgp3). For the impact of sensitivity and specificity on predictive values see: worked examples. [Comment: This was a good study based on a chronic condition where it might reasonably be expected that specific antibody should be associated with infection. Given that the best that could be achieved using multiple tests was a sensitivity of 76%, (which would not give an impressive negative predictive value) and a specificity of 85% (which would give poor positive predictive value) this reviewer concludes, unlike the authors, that serology has little role to play in the laboratory diagnosis of reactive arthritis]...

    ...Conclusion: There is inadequate scientific justification for making serious clinical decisions about patient management on the basis of chlamydial serology. New generation recombinant or peptide-based tests for antibody to C. trachomatis are likely to be more specific than tests based on whole chlamydial antigens. Where other diagnostic methods are lacking or it is not possible to obtain relevant samples, the new serology tests with their high negative predictive value may be of use for identifying patients in whom it is unlikely that C. trachomatis infection is playing a role. Given that much better methods are available for detecting current chlamydial infection, clinicians are strongly recommended to focus their efforts on seeking direct evidence of chlamydial infection wherever possible, using the best locally available test, preferably one using nucleic acid amplification. Chlamydial serology continues to have a role in research [Moss & Darougar, 2001].

     

    According my recent conversations with Dr. Stratton (2008), he does not consider PCR tests useful for diagnosing Cpn as the primers used can differ from lab to lab and the technique is less standardized and dependent more on operator accuracy. Serology tests have become more accurate and reliable in recent years and would be preferred to PCR tests. Mayo Clinic Lab and Quest Lab both appear to have more reliable tests in the USA. One clinician reported Mayo Clinic Cpn tests as catching about 95% of the Cpn cases in his practice. Many of our members have had Cpn detected through Quest Labs serology tests. Your mileage may vary.
    Jim K Wed, 2006-02-08 20:11

    Secondary Porphyria: what you should know before starting a CAP

    Secondary Porphyria: what you should know before starting a CAP

    Cpn induced secondary porphyria

    Treatment of Chlamydia infection may exacerbate pre-existing genetic porphyria or more likely cause a secondary acute porphyria by making the intracellular Chlamydia more active or by killing infected cells that already are loaded with high porphyrin levels. Some of what is mis-labeled as a “herx” reaction to treatment, is actually an acute porphyria reaction and not a reaction to bacterial endotoxin which is what a true herxheimer reaction is referring to.

    What is Secondary Porphyria? 

     Porphyrias are diseases in which the heme pathway has malfunctioned. They can be genetic or be secondary secondary to another disease process. Part of what is so special about the thoroughness with which Dr. Charles Stratton and his colleagues have studied Chalmydial disease is their discovery that Cpn interferes with the heme pathway, and that many patients with chronic Cpn infections have secondary porphyria to start with, and that this is further exacerbated under treatment. When you understand more about porphyria, it can help you sort out "die-off" as well as chronic symptoms you have, which may be due to heme byproducts-- and how to treat for it.

    Heme is a Fe2+ complex. A number of critical cellular functions rely on it and the biosynthesis of heme occurs in all human cells. Toxic compounds called porphyrinogens are formed in one transitional phase of the heme biosynthesis pathway but under normal circumstances are quickly transformed into heme which is not toxic.

    The porphyrias are consequences of any impairment of the formation of porphyrinogens or in their transformation to heme. Chlamydiae interfere with this step. Porphyrins then accumulate in the cell itself, and then in the extracellular milieu. Within the mitochondrial matrix, the final steps in the biosynthesis of heme are halted. Depletion of host cell energy by the intracellular infection with Chlamydia species causes additional energy-related complications.

    Highly simplified, heme synthesis should look like this:

    Heme precursors >> porphrinogens>> transformation to heme >> increased cellular transport including ATP production.

    Instead, Cpn interferes with this normal process, and this happens:

    Heme precursors >> porphrinogens >> interference with transformation to heme >> build up of unstable heme precursors and porphyrins inside and outside cells >> free radical damage and reduced ATP (energy) synthesis.

    Symptoms of Porphyria- 

    Porphyria may affect the nervous system or the skin.

    When porphyria affects the nervous system, it can cause:

    • chest pain
    • shortness of breath 
    • abdominal pain
    • nausea
    • muscle cramps
    • weakness
    • hallucinations
    • depression
    • anxiety
    • paranoia
    • seizures

    When porphyria affects the skin it can cause:

    • blisters
    • itching
    • swelling
    • sensitivity to the sun (which also can be caused by some antibiotics)
    • purple-red-colored urine

    Stratton's protocol suggests testing for porphyrins prior to treatment, and initiating nutritional and other interventions prior to starting treatment for Cpn to help prevent or limit secondary porphyria.

    "Systemic/chronic chlamydial infections have been noted to have an associated secondary porphyria. Porphyrins, including water-soluble porphyrins (e.g., delta-aminolevulinic acid and porphyrobilinogen) and fat-soluble porphyrins (e.g., coproporphyrin III and protoporphyrin) may produce clinical episodes of porphyria. The presence of such porphyrins in an individual patient with chronic/systemic chlamydial infection can be confirmed pre- and during therapy by appropriate porphyrin tests such as obtaining 24-hour urine and 24-hour stool specimens for porphyrins." (from Stratton & Mitchell's THERAPY OF CHRONIC CHLAMYDIAL INFECTIONS INCLUDING THEIR ASSOCIATED PORPHYRIA AND VITAMIN B12 DEFICIENCY: SEVENTH VERSION

    Two other suggestive indicators of porphyria which don't require the more challenging 24 hour collection of specimens is measuring B-12 deficiency both directly and also from blood elements which are affected by B12 such as serum methyl malonate levels and homocystine levels. However Dr. Stratton notes:

    Homocystine levels are elevated with B12 and folate deficiency, but can be reduced by folate alone. On the other hand, serum methyl malonate levels are elevated in B12 deficiency and are not changed by folate. Therefore, serum methyl malonate levels are the best indicator of B12 deficiency. 

     Another indicator, according to Dr. Stratton, is high hemoglobin and high hematocrit.

    For those already in treatment, to have a rough idea if treatment is overloading them with porphyrigens Dr. Stratton has noted this "Poor Man's Test" of secondary porphyria:

    "Poor Man's" Porphyrin Test According to Chuck Strattoni: If people notice dark urine after taking metronidazolei, have them put their urine in a clear glass container and place it outdoors in the sun for several hours. If the color gets darker (i.e., copper-purple color), then it is due to porphyrins. This is the "poor man's porphyrin test".

     Because secondary porphyria is so common in Cpn infections, Dr. Stratton recommends treating for it almost as a matter of course prior to initiating a CAP's, and continuing treatment for it during the whole process of treatment. This involves:

    Excerpted from: THERAPY OF CHRONIC CHLAMYDIAL INFECTIONS INCLUDING THEIR ASSOCIATED PORPHYRIA AND VITAMIN B12 DEFICIENCY: SEVENTH VERSION

    Charles W. Stratton, MD William M. Mitchell, MD PhD Vanderbilt University School of Medicine Nashville, Tennessee 37232

    IMPORTANT DISCLAIMER Currently there are protocols for appropriate clinical trials for the therapy of a number of different forms of systemic/chronic chlamydial infections being prepared at Vanderbilt. The preliminary suggestions for chlamydial therapy that are contained within this document have been gleaned from early therapy for compassionate reasons and may not represent the final therapy. The use of these suggestions is similarly for compassionate therapy of patients suspected of having a systemic/chronic chlamydial infection.

    Patient education begins with an explanation of the clinical significance of the test results and the potential for associated effects such as porphyria and vitamin B12 deficiency. Additional laboratory tests may be useful in defining the extent of the chlamydial infection and associated metabolic/vitamin disorders. Initial blood work can be obtained for the following tests: 1) CBC, 2) liver function tests, 3) uric acid, and 4) serum iron studies. Other useful tests include: red blood cell ALA dehydratase, red blood cell PBG deaminase, vitamin B-12 level, serum homocysteine level, and serum methymalonate level. A 24-hour urine and stool may be collected for porphyrins. Step 2: Next, the patient is placed on the antiporphyric regimen and vitamin B12 therapy. This is continued throughout the antimicrobial therapy and is an important component as it minimizes cellular damage and facilitates cellular repair. Step 3: Following initiation of the antiporphyric regimen, the first antimicrobial agent is started.

    I. THERAPEUTIC REGIMEN FOR SECONDARY PORPHYRIA Systemic/chronic chlamydial infections have been noted to have an associated secondary porphyria. Porphyrins, including water-soluble porphyrins (e.g., delta-aminolevulinic acid and porphyrobilinogen) and fat-soluble porphyrins (e.g., coproporphyrin III and protoporphyrin) may produce clinical episodes of porphyria. The presence of such porphyrins in an individual patient with chronic/systemic chlamydial infection can be confirmed pre- and during therapy by appropriate porphyrin tests such as obtaining 24-hour urine and 24-hour stool specimens for porphyrins. It is recommended that a therapeutic regimen addressing porphyria should be instituted along with the use of antimicrobial agents. This therapeutic regimen is aimed at controlling the chlamydial-associated secondary porphyria that may be present prior to antimicrobial therapy and/or may be triggered or increased during antimicrobial therapy of the chlamydial infection. This "porphyric reaction" to antimicrobial therapy should be recognized as such and differentiated from an expected cytokine-mediated immune response. Specific measures for the therapy of porphyria as derived from published medical literature on porphyria are employed and include:

    1. High Carbohydrate Diet Approximately 70% of the daily caloric intake should be in the form of complex carbohydrates such as those found in bread, potato, rice, and pasta. The remaining 30% of calories in protein and fat ideally should be in the form of white fish or chicken. 2. High Oral Fluid Intake Drink plenty of oral fluids in the form of water (e.g., bicarbonated water or "sports-drinks" [water with glucose and salts]). This helps flush water-soluble porphyrins. Moreover, dehydration concentrates porphyrins and makes patients more symptomatic. The color of the urine should always be almost clear rather than dark yellow. 3. Avoid Red Meats Red meats, including beef and dark turkey as well as tuna and salmon contain tryptophan and should be avoided as much as possible. 4. Avoid Milk Products Milk products contain lactose and lactoferrin, both of which should be avoided as much as possible. 5. Glucose, Sucrose and Fructose Glucose is an important source of cellular energy: cellular energy is reduced with chlamydial infections. Increasing the availability of glucose provides optimal conditions for the cells to produce energy. However, sucrose is not the best way to increase the glucose availability. Sucrose is a mixture of glucose and fructose. Fructose is the sugar contained in fruit. Because high levels of fructose act as a signal to the liver to store glycogen, an excess of fructose may temporarily reduce the availability of glucose at the cellular level. Fructose should be avoided as much as possible. Instead, "sports-drinks" containing glucose (as well as containing important cations/anions) can be used. Glucose tablets also can be used. 6. Avoid Alcohol. Alcohol is a well-known aggravator of porphyria and should be avoided as much as possible.

    Vitamins/Antioxidants/Supplements 7. B-Complex Vitamins Glucose is needed by host cells that are infected by chlamydiae. The availability of glucose to the host is assisted by taking B-complex vitamins. These include folic acid (400 mcg twice per day), vitamin B-1 (thiamin 10 mg twice per day), vitamin B-2 (riboflavin 10 mg twice per day), vitamin B-5 (pantothenate 100 mg twice per day), vitamin B-6 (pyridoxine 100 mg twice per day or pyridoxal-5 phosphate 25 mg twice per day), and vitamin B-12 (5000 mcg sublingual three to six per day). 8. Antioxidants Antioxidants and related agents should be taken twice per day. These should include vitamins C (1 gram twice per day) and E (400 units twice per day) as well as L-carnitine (500 mg twice per day), ubiquinone (coenzyme Q10; 30 mg twice per day), biotin (5 mg twice per day), and alpha-lipoic acid (400 mg twice per day). Bioflavinoids (also called proanthocyanidins of which pygnoginol and quercetin are two examples) are very effective antioxidants. Selenium (100 mcg twice per day) should be taken with the vitamin E. L-Glutamine (2 - 4 grams twice per day), querceten (400 - 500 mg twice per day), glucosamine (750 - 1000 mg two or three times per day) and chondroitin sulfate (250 - 500 mg twice per day) should also be included.

    Antiporphyrinic Drugs 9. Benzodiazapine Drugs The specific benzodiazapine drugs used depends, in part, on the symptoms. For example, if panic attacks are the problem, xanax (0.5 mg three or four times per day) can be used. If sleeping is a problem, restoril (30 mg at night) can be used. 10. Hydroxychloroquine Hydroxychloroquine (100 - 200 mg once or twice per day) is often used to treat porphyria. For patients with symptoms of porphyria, a single 100 mg dose of hydroxychloroquine may be tried. If this trial dose relieves the symptoms, hydroxychloroquine may be continued. The hydroxychloroquine dose must be adjusted for each patient. This is done by increased the dose slowly, starting with 100 mg every other day, then slowly increasing to a maximum dose of no more than 200 mg twice per day. Most patients do well on 100 mg once per day. Visual/eye exams should be done periodically as per manufacturerís recommendations (See PDR).

    Miscellaneous 11. Oral Activated Charcoal Activated charcoal absorbs fat-soluble porphyrins. Treatment with oral activated charcoal, which itself is nonabsorbable, binds these porphyrins in the gastrointestinal tract and hence prevents them from being reabsorbed in the small intestine. Start with 2 grams (eight 250 mg capsules) of activated charcoal taken three times per day on an empty stomach (i.e., 2 hours after and 2 hours before a meal). Gradually increase this to 4 grams taken three times per day. Much more activated charcoal can be safely taken; up to 20 grams six time a day for nine months has been taken without any adverse side effects. It is important that this charcoal be taken on a completely empty stomach without any food, vitamins, or medications taken within 2 hours before or 2 hours after charcoal ingestion as the charcoal may absorb the food, vitamins, or drugs as well as the porphyrins. Activated charcoal can be obtained from <puritanspride.com>.

    II. THERAPEUTIC REGIMEN FOR VITAMIN B12 DEFICIENCY Many patients with systemic/chronic chlamydial infection appear to have a subtle and unrecognized vitamin B12 deficiency at the cellular level. This functional B12 deficiency can be documented in an individual patient by obtaining both a vitamin B12 level (usually normal or low) and serum homocysteine and methylmalonate levels (one or both of these metabolites will be elevated). This vitamin B12 deficiency can corrected by high-dose vitamin B12 therapy as follows: 1. Vitamin B12 Therapy Prior to Chlamydial Therapy Adults normally have approximately 3,000 mcg of vitamin B12 in body stores, mostly in the liver. Initial vitamin B12 therapy before chlamydial therapy includes replacement therapy for any vitamin B12 deficit in these body stores. Therefore, over the first several days of antiporphyrin therapy, 6,000 mcg of parental (intramuscular or subcutaneous) vitamin B12 is given. For each of the next 3 weeks, 6,000 mcg of parental vitamin B12 is given once per week. 2. Vitamin B12 Therapy During Chlamydial Therapy Chlamydial antimicrobial therapy is associated with increased need for vitamin B12. Therefore, 6,000 mcg of parental vitamin B12 (3,000 mcg in each anterior thigh) is given once per week while the patient is receiving antimicrobial therapy for systemic/chronic chlamydial infection. This is in addition to the 5,000 mcg of sublingual vitamin B12 taken three times each day. 3. Vitamin B12 Therapy Post Chlamydial Therapy Following the completion of antimicrobial therapy of systemic/chronic chlamydial infection, the vitamin B12 and serum homocysteine/methylmalonate levels should be rechecked. If the methylmalonate level remains elevated, it suggests a continued vitamin B12 deficiency. Oral therapy with 5,000 mcg of sublingual cobalamin three times per day should be continued. After several months, 6,000 mcg of parental vitamin B12 may be given as a therapeutic trial. If the patientís energy is not increased by the parental dose, continued therapy with sublingual vitamin B12 is probably adequate. Periodic trials of parental vitamin B12 can be used to assess the sublingual therapy.

    For years, vitamin B12 languished as the vitamin that cures anemia. Hardly any research was done into what this vitamin could do for non-anemic people. It turns out that it may do a lot. New studies show that the right amount of B12 can protect against dementia, boost immune function, maintain nerves, regenerate cells and more. B12 is in the news because it lowers homocysteine and protects against atherosclerosis. It's also vital for maintaining methylation reactions that repair DNA and prevent cancer. One of the crucial areas for B12 is the brain. It's not surprising that people with B12 deficiency develop mental disorders. The vitamin is crucial for the synthesis or utilization of important neuro-factors including monoamines, melatonin and serotonin. In addition, B12 is absolutely critical for the function and maintenance of nerves themselves. B12 is needed for methylation reactions that maintain these cells, and enable them to function. B12 contributes to brain function by lowering homocysteine. Homocysteine is a toxic by-product of methionine metabolism that can damage neurons. Importantly, homocysteine interferes with the methylation reactions critical for brain function. Studies show that people with elevated homocysteine can't think.

    Jim K Wed, 2006-02-08 11:18

    How Cpn causes porphyria: pdfs of Stratton/Mitchell Articles

    How Cpn causes porphyria: pdfs of Stratton/Mitchell Articles

     Two downloadable pdf files are included here for those who want more detail on Cpn and secondary porphyria.



    1) This link will download an important and classic article by Dr.'s Stratton & Mitchell called

    The Pathogenesis of Systemic Chlamydial Infections:
    Theoretical Considerations of Host Cell Energy Depletion
    and Its Metabolic Consequences

     Download   Alternate Download

    It explains in detail the impact of Cpn cellular parasitism on ATP depletion and on heme synthesis and resulting porphyria. 


     
    2) This link will download an excerpt from Stratton & Mitchell's Patent #6,884,784 specifically on the cellular biology of Cpn and porphyria. A succinct and clear explanation for those of us who are biology geeks.

    Excerpt from Stratton & Mitchell's Patent #6,884,784 on Cpn & Secondary Porphyria

    Download Patent Excerpt

    Jim K Sun, 2006-03-19 14:14

    Secondary Porphyria in Cpn: Extracts from Stratton/Mitchell Patent

    Secondary Porphyria in Cpn: Extracts from Stratton/Mitchell Patent

    I thought this should be available to Cpnhelp users. This is extracted from the Mitchell/Stratton (Vanderbilt) patent:

    Secondary Porphyria In Cpn

    • Extracted and edited from: US Patent Issued on June 29, 2004

    • Chlamydia is a parasite of normal energy production in infected eukaryotic cells. The energy shortage also causes the host cell mitochondria to attempt to synthesize certain critical enzymes involved in energy production in order to increase energy production. The energy (ATP) shortage produced by Cpn infection results in incomplete heme production and resulting porphyrins.Because Chlamydia also prevents this synthesis from completing, these enzyme's precursors, called porphyrins, build up in cell and often escape into the intracellular [mileau] milieu. Porphyrins readily form free-radicals, that, in turn, damage cells. Thus, there is an obligate secondary porphyria that accompanies many chlamydial infections.

    Impact of porphyrins on the body:
    Inadequate energy- Host cells have insufficient energy available for their normal functioning.
    Neurotoxicity- Porphyrins are highly neurotoxic and produce oxidative damage to cells.
    Tissue damage from oxidation- If these reactive oxygen species (porphyrins) are released into the extracellular space, as seen in acute porphyria, autooxidation of surrounding tissue may result. … Reactive oxygen species have been noted to disrupt membrane lipids, cytochrome P-450 (impairing metabolism of drugs and toxins) and DNA structure (increasing cancer risk).
    Impairment of liver function- When hepatic cells are infected with Chlamydia species, the decreased energy in the host cell does not allow heme biosynthesis to go to completion and porphyrins in the liver/entero-hepatic circulation are increased. When hepatic cells are infected with Chlamydia species, the decreased energy in the host cell does not allow heme biosynthesis to go to completion and porphyrins in the liver/entero-hepatic circulation are increased. When the chlamydial infection involves hepatic cells, the use of any pharmacologic agents that are metabolized by cytochrome P-450 in the liver will increase the need for cytochrome P-450, which is a heme-based enzyme. Hence, the biosynthesis of heme in the liver becomes increased (resulting in worsening of the porphyria!).
    Chronic oxidative stress- the accumulation of porphyrinogens/porphyrins in human tissues and body fluids produces a condition of chronic system overload of oxidative stress with long term effects particularly noted for neural, hepatic and renal tissue.. If reactive oxygen species are released into the extracellular space, as seen in acute porphyria, autooxidation of surrounding tissue may result. Long term effects particularly noted for neural, hepatic and renal tissue.
    Glucose disruption—described under treatment below.
    Accumulation in tissues and cells of porphyrins- The clinical result of the intracellular and extracellular accumulation of porphyrins, if extensive, is a tissue/organ specific porphyria which produces many of the classical manifestations of hereditary porphyria.
    • (symptoms of porphyria here)
    Sub-clinical B-12 deficiency (i.e. not measurable by blood levels of B-12). The pathogenesis of chronic/systemic chlamydial infection is unique in that the intracellular infection by this parasite results in a number of … unrecognized concomitant … metabolic/autoimmune disorders including secondary porphyria with associated autoantibodies against the porphyrins. Cross reaction with Vitamin B12 can result in a subclinical autoimmune-mediated Vitamin B12 deficiency. These associated disorders often require diagnosis and preventive and/or specific adjunctive therapy.

    • As the chlamydial-infected host cells lyse, as happens in the normal life cycle of Chlamydia, the intracellular porphyrins are released and result in a secondary porphyria. It also has been noted that any host cell infected with Chlamydia species has an increased amount of intracellular porphyrins that are released when antimicrobial agents kill the microorganism.
    • …chlamydial-associated secondary/obligatory porphyria, symptoms of which can actually increase during antimicrobial therapy of the chlamydial infection. This porphyric reaction to antimicrobial therapy should be recognized as such and differentiated from the expected cytokine-mediated immune response precipitated by antigen dump during anti-chlamydial therapy.

    Diagnosis
    • The diagnosis of chlamydial-associated secondary porphyria may be difficult as the porphyria may be minimal and tissue-specific.
    • The measurement of 24 hour urine porphyrins is not sensitive enough in every case of chlamydial infection to detect the secondary porphyria caused by chlamydial infection.
    • There may not be an abnormal amount of porphyrinogen precursors and porphyrins in the blood, urine, or stool.

    D. Reducing Porphyrin Levels
    • Therapy for this secondary porphyria, which is adjunct to anti-chlamydial therapy, involves at least three strategies:
    a) Supplement the cellular energy supply to mitigate cell malfunction and the formation of porphyrins;
    b) reduce the levels of systemic porphyrins; and
    c) mitigate the harmful effects of the porphyrins.

    • Dietary and pharmaceutical methods can be used to reduce systemic porphyrin levels (both water-soluble and fat-soluble).
    • It is recommended that a patient suffering from porphyria avoid milk products. Milk products contain lactose and lactoferrin, and have been empirically shown to make symptoms of porphyria worse.
    • Patients should also avoid Red meats, including beef, dark turkey, tuna and salmon as they contain tryptophan which worsens porphyria (see below).
    Glucose disruption
    o Red meats, including beef, dark turkey, tuna and salmon, contain [tryprophan] tryptophan. Increased levels of tryptophan in the liver inhibit the activity of phosphoenol pyruvate carboxykinase with consequent disruption of gluconeogenesis. This accounts for the abnormal glucose tolerance seen in porphyria.
    o (Ed: in addition to which, Cpn induces its host cell to absorb more glucose from the blood stream so it can produce more ATP. In wide spread Cpn infection this can produce low blood sugar more rapidly than otherwise, such as when patients fast or skip meals).

    • Intake of glucose gives short term energy boost to depleted cells (increasing ATP and lessening porphyrin production), and in the case of infected liver cells (major producer of heme in the body) glucose shuts down further immediate heme production.
    • Plenty of oral fluids in the form of bicarbonated water or "sports drinks" (i.e., water with glucose and salts) should be incorporated into the regimen. This flushes water-soluble porphyrins from the patient's system. Drinking seltzer water is the easiest way to achieve this goal. The color of the urine should always be almost clear instead of yellow. It is noted that dehydration concentrates prophyrins and makes patients more symptomatic.

    Activated charcoal can be daily administered in an amount sufficient to absorb fat-soluble porphyrins from the enterohepatic circulation. Treatment with activated oral is charcoal, which is nonabsorbable and binds porphyrins in the gastrointestinal tract and hence interrupts their enterohepatic circulation, has been associated with a decrease of plasma and skin porphyrin levels. Charcoal should be taken between meals and without any other oral drugs or the charcoal will absorb the food or drugs rather than the porphyrins. For those who have difficulty taking the charcoal due to other medications being taken during the day, the charcoal can be taken all at one time before bed. Taking between 2 and 20 grams, preferably at least 6 grams (24×250 mg capsules) of activated charcoal per day (Perlroth et al., Metabolism, 17:571-581 (1968)) is recommended. Much more charcoal can be safely taken; up to 20 grams six times a day for nine months has been taken without any side effects.

    • For severe porphyria, chelating and other agents may be administered, singularly or in combination, to reduce levels of porphyrins in the blood. Examples of chelating agents include but are not limited to Kemet (succimer; from about 10 mg/kg to about 30 mg/kg); ethylene diamine tetracetic acid (EDTA); BAL (dimercaprol; e.g., 5 mg/kg maximum tolerated dosage every four hours), edetate calcium disodium (e.g., from about 1000 mg/m2 to about 5000 mg/m2 per day; can be used in combination with BAL); deferoxamine mesylate (e.g., from about 500 mg to about 6000 mg per day); trientine hydrochloride (e.g., from about 500 mg to about 3 g per day); panhematin (e.g., from about 1 mg/kg to about 6 mg/kg per day), penacillamine.

    Quinine derivatives, such as but limited to hydroxychloroquine, chloroquine and quinacrine, should be administered to the patient daily at a dosage of from about 100 mg to about 400 mg per day, preferably about 200 mg once or twice per day with a maximum daily dose of 1 g. Hydrochloroquine is most preferred. The mechanism of action of hydroxychloroquine is thought to involve the formation of a water-soluble drug-porphyria complex which is removed from the liver and excreted in the urine (Tschudy et al., Metabolism, 13:396-406 (1964); Primstone et al., The New England Journal of Medicine, 316:390-393 (1987)).

    E. Mitigating the Effects of Porphyrins

    • Antioxidants at high dosages (preferably taken twice per day) help to mitigate the effects of free radicals produced by porphyrins. Examples of suitable antioxidants include but are not limited to Vitamin C (e.g., 1 gram per dosage; 10 g daily maximum); Vitamin E (e.g., 400 units per dosage; 3000 daily maximum); L-Carnitine (e.g., 500 mg per dosage; 3 g daily maximum); coenzyme Q-10 (uniquinone (e.g., 30 mg per dosage; 200 mg daily maximum); biotin (e.g., 5 mg per dosage; 20 mg daily maximum); lipoic acid (e.g., 400 mg per dosage; 1 g daily maximum); selenium (e.g., 100 µg per dosage; 300 µg daily maximum); gultamine (e.g., from 2 to about 4 g per dosage); glucosamine (e.g., from about 750 to about 1000 mg per dosage); and chondroitin sulfate (e.g., from about 250 to about 500 mg per dosage).

    • The above-mentioned therapeutic diets can be combined with traditional or currently recognized drug therapies for porphyria. In one embodiment, benzodiazapine drugs, such as but not limited to valium, klonafin, flurazepam hydrochloride (e.g., Dalmanc™, Roche) and alprazolam (e.g., Xanax), can be administered. Preferably, sedatives, such as alprazolam (e.g., Xanax; 0.5 mg per dosage for 3 to 4 times daily), can be prescribed for panic attacks and flurazepam hydrochloride (e.g., Dalmane™, Roche or Restoril™ (e.g., 30 mg per dosage)) can be prescribed for sleeping. The rationale is based upon the presence of peripheral benzodiazepine receptors in high quantities in phagocytic cells known to produce high levels of radical oxygen species. A protective role against hydrogen peroxide has been demonstrated for peripheral benzodiazipine receptors. This suggests that these receptors may prevent mitochondria from radical damages and thereby regulate apoptosis in the hematopoietic system. Benzodiazepines have also been shown to interfere with the intracellular circulation of heme and porphyrinogens (Scholnick et al., Journal of Investigative Dermatology, 1973, 61:226-232). This is likely to decrease porphyrins and their adverse effects. The specific benzodiazipine will depend on the porphyrin-related symptoms.
    • The rationale for benzodiazepines) is based upon the presence of peripheral benzodiazepine receptors in high quantities in phagocytic cells known to produce high levels of radical oxygen species. A protective role against hydrogen peroxide has been demonstrated for peripheral benzodiazipine receptors. This suggests that these receptors may prevent mitochondria from radical damages and thereby regulate apoptosis in the hematopoietic system. Benzodiazepines have also been shown to interfere with the intracellular circulation of heme and porphyrinogens (Scholnick et al., Journal of Investigative Dermatology, 1973, 61:226-232). This is likely to decrease porphyrins and their adverse effects. The specific benzodiazipine will depend on the porphyrin-related symptoms.
    • Cimetidine can also be administered separately or in combination with benzodiazepine drugs. Cimetidine has been shown to effectively scavenge hydroxyl radicals although it is an ineffective scavenger for superoxide anion and hydrogen peroxide. Cimetidine appears to be able to bind and inactivate iron, which further emphasizes its antioxidant capacity. Cimetidine also is an effective scavenger for hypochlorous acid and monochloramine, which are cytotoxic oxidants arising from inflammatory cells, such as neutrophils. Cimetidine thus would be expected to be useful for the therapy of free-radical-mediated oxidative damage caused by chlamydial porphyria. Recent studies in Japan have found that cimetadine is effective for treating porphyria. The recommended amount of cimetadine is about 400 mg once or twice per day.

    Jim K Thu, 2008-05-01 22:59

    Porphyria......?

    I've read several posts on Porphyria, including the interview with Dr. Stratton (I think is who it was).  I'm still left wondering what I can do to combat porphyria as I definitely have it going on and it's something I want to deal with.

    As far as I know, the only thing that can be done is the following...

    • take activated charcoal in either powder or capsule form
    • wash it away with water
    • avoid eating protein / eat a diet consisting of 70% carbohydrate

    Have I left out something?  I'm left wondering if there is anything that can be done medically?  Would a medical measure to address it also lead to other undesireable side affects?

    take care

    John

    p.s.  signature not omitted intentionally

    Don't forget:

    • avoid sucrose and fructose, seek glucose.
    • Red meat, tuna, and dark turkey are verboten, too. Chicken, fish, nuts, and eggs -- and, as you say, not too much of them.
    • Alcohol is a real promoter of porphyria as well.

    I've never been quite sure whether the dairy prohibition is because of porphyria or because of rendering the doxy ineffective, so I didn't include that.

    Now, what else -- I'm sure that's not everything.

    Ron

    On Stratton protocol for CFS starting 01/06 (NE Ohio, USA).

    Ron

    On CAP for CFS starting 01/06 (NE Ohio, USA)

    Began rifampin trial 1/14/09

    Currently: on intermittent

    John- Other than those the only other one suggested is low-dose Plaquinal (125mg two or three times a week). Severe porphyria requires IV Hematin, which is a human blood product, very expeinsive and only obtainable for proven porphyric condition (mostly genetic in origin).

    Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndrome & Fibromyalgia- Currently: 150mg INH, Doxycycline/Zithromycin, Tinidazole pulses. Northern Ohio, USA

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    D W

    Cimetidine has been used in both hereditary and secondary porphyrias [Horie Y, et al., Cimetidine in the treatment of porphyria cutanea tarda. Intern Med. 1996 Sep;35(9):717-9.] It is very inexpensive.

    D W - [Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding metronidazole. No medication now. Morning BP typically 110/75]

    Thank you for posting this.

    http://www.journalarchive

    Kim's been having die-off reactions and and we're hoping to supplement the charcoal she takes at night.

    I looked Cimetidine up and found out that it's sold as Tagamet, which is an over the counter heartburn/ulcer medication. I further followed up to try and find out what the dosage might be. The way Tagamet is sold, dosage is:

    Tablets for Oral Administration : Each light green, film-coated tablet contains cimetidine as follows: 300 mg-round, debossed with the product name TAGAMET, SB and 300; 400 mg-oval Tiltab® tablets, debossed with the product name TAGAMET, SB and 400; 800 mg-oval Tiltab® tablets, debossed with the product name TAGAMET, SB and 800. I found this at: http://www.rxlist.com/cgi/generic/cimet.htm

    I'm hoping you might be able to recommend a dosage and or any other thoughts about taking this to help relieve die-off reactions. Thank you, Ken

    PS: I've also been looking into Oregano oil as noted in the CPn handbook. I checked this out at the Vitaminshoppe and found Oregano oil is mixed with olive oil, is this what folks are using? I'm not sure how much to use if we try this also. Is anyone using Oregano Oil? Are softgels ok?

    In pursuit of ABX

    Don't Allow What You Know To Get In The Way Of What Might Be

    Hi Ken, I am using the oregano oil in liquid form.  I put 1 -2 drops in my morning vitamin cocktail drink!

    I believe it helps keep yeast in check!

    CFIDS/ME 26yrs, FMS, IBS, EBV, CMV, Cpn, chronic insomnia, Lymes, HME, Natural HRT peri-M, NAC 2.5 gm, 6-07 Doxy 200 mg day pm, Azith 375 mg M/W/Fday, Pulse#9 750mg 5.5 day, 4-25-8

    CFIDS/ME, FMS, MCS, IBS, EBV, CMV, Cpn, H1, chronic insomnia, Chronic Lyme, HME, Babesia, Natural HRT-menopause, NAC 2.4 gm,Full CAP 6-2-07, all supplements+Iodorol, Inositol-depression, ultra Chitosan, L lysine Pulse#27 04-19-10 1gm Flagyl/day-5 days<

     Are you smooshing all your vits into a drink? I keep reading that you shouldn't do this as it can affect the potency, but others say it's OK with some coatings and not with others. Confused.

    Berkshire, UK. Diagnosed RRMS Feb 4th 2008.

    NAC 2400mg. All supplements. Doxy 200mg. Zith 250mg M/W/F.
    No GP/Neuro support. Self medicating with help from David Wheldon.
    Started CAP 20th April 2008.

    Berkshire, UK. Diagnosed RRMS Feb 4th 2008.

    NAC 2400mg. All supps. Doxy 200mg. Zith 250mg. Metro 400mg.
    No GP/Neuro support. Self medicating with help from David Wheldon.
    Started CAP 20th April

    Thanks for all the replies, I'm glad to get the additional information.

    I was also thinking that vitamin B12 counteracts porphyria due to being similar in molecular structure to a porphyrin but I can't remember if that's the case.  Does that sound correct? 

    all my best

    John

    RRMS/disability 4.5 on Wheldon Protocol since 04/12/2006

    best, John

    RRMS/EDSS was 4.5, 5, 6, 6.5, 6.9999, 6.5 on Wheldon/Stratton Protocol beginning 04/12/2006
    nac 4x600 mg/day
    doxycycline 2x100mg/day
    azithromycin 3x250mg/day MWF
    metronidazole 3x400mg/day then 3x500mg/day

    More on glucose & porphyria-

    Glucose has been the standard treatment for serious porphyric attachs, usually IV. This quote explains it further:

    Intravenous administration of glucose (a pure form of carbohydrate) is part of the standard treatment of acute attacks of porphyria. Glucose is given by vein because the stomach and intestine usually do not function properly during an attack, and material taken by mouth is not properly propelled through these organs. Glucose and other carbohydrates can repress the pathway for synthesis of herne in the liver. As a result, the overproduction of prophyrin precursors and porphyrins is repressed by carbohydrate administration. 

    http://theaipforum.tripod.com/

    The site above has some excellent dietary guidlines for porphyria.

    From the Cpn Handbook, Mitchell and Stratton note further:

    Increasing the availability of glucose provides optimal conditions for the cells to produce energy. However, sucrose is not the best way to increase the glucose availability. Sucrose is a mixture of glucose and fructose. Fructose is the sugar contained in fruit. Because high levels of fructose act as a signal to the liver to store glycogen, an excess of fructose may temporarily reduce the availability of glucose at the cellular level. Fructose should be avoided as much as possible.

     I think the molecular symetry of B12 is accurate but speculative about it's function. I think it's strong methylation effects and that it is used up rapidly for this purpose in porphyria is the original idea.

    Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndrome &amp; Fibromyalgia- Currently: 150mg INH, Doxycycline/Zithromycin, Tinidazole pulses. Northern Ohio, USA

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    On B12 from David Wheldon-

    I'll add this nice bit from David Wheldon's site on B12:

    High-dose sublingual Vitamin B12 (methylcobalamin) should be taken; initially 4000 - 5000 micrograms several times a day, reducing to once daily after three months. This is to flood the system with methylcobalamin as there is often a functional B12 deficit, as evidenced by raised serum methylmalonate or homocysteine. Vitamin B12 (together with B6 and folate) counteracts the hyperhomocysteinaemia which frequently accompanies chronic Chl pneumoniae infection and which is thought to cause connective tissue damage. Excess homocysteine is a potent neurotoxin with activity against cortical and hippocampal neurones. [1. Kruman II, Culmsee C, Chan SL, et al., Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 2000;20:6920-6:] [2. Den Heijer T, Vermeer SE, Clarke R, Oudkerk M, Koudstaal PJ, Hofman A, et al. Homocysteine and brain atrophy on MRI of non-demented elderly. Brain 2002;126:170-5:] [3. Leblhuber F, Walli J, Artner-Dworzak E, Vrecko K, Widner B, Reibnegger G, et al. Hyperhomocysteinemia in dementia. J Neural Tansm 2000;107:1469-74.] An excellent review of Vitamin B12 and multiple sclerosis can be recommended here: [Miller A, Korem M, Almog R, Galboiz Y. Vitamin B12, demyelination, remyelination and repair in multiple sclerosis. J Neurol Sci 2005 Jun 15;233(1-2):93-7.]
    http://www.davidwheldon.co.uk/ms-treatment.html 

     

    Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndrome &amp; Fibromyalgia- Currently: 150mg INH, Doxycycline/Zithromycin, Tinidazole pulses. Northern Ohio, USA

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Hi John Most of us try very hard to avoid or consume as required. I never had any luck avoiding milk and cheese. I do not eat much red meat (maybe a couple of ounces a couple of times a month) and my preferred fowl has always been dark but I have conformed to the rest for the most part. But I do eat lots of cheese, - 3 to 4 ozs a day at least - lots of raw vegetables, few eggs, very few fried foods and lots of fish. I always take all my supplements and abx. We have to have some freedom to indulge and it appears that for Paron and me, it may be dairy. As for porphyria, I took charcoal my last pulse (I have not needed it for a few months!) because I was so obviously having a really, really good one but it does get lots, lots better!

     

    Rica PPMS  EDSS 6.7 at beginning - now 2.  Began CAP Sept, 2004 with Rifampin 150 mg 2xd, Doxy 100 mg 2xd, added regular pulses Jan 2005. Jan 2006 switched to Doxy, Azith,  cont. flagyl  total 39 pulses NC USA

    3/9 Symptoms returning. Began 5 abx protocol 5/9 Rifampin 600, Amox 1000, Doxy 200, MWF Azith 250, flagyl 1000 daily. Began Sept 04 PPMS EDSS 6.7 Now good days EDSS 1 Mind, like parachute, work only when open. Charlie Chan  In for the duration.&am

    Hi Rica, thank you for writing me on this topic.  You may not be aware, but this is an old thread of discussion that I haven't touched since May of 2006, or so I believe.  Be that as it may, I am glad that you brought it up as there is a question I've had brewing on the topic of porphyria for a bit.

    I don't know if it was Jim K or Eric or someone else who created it, but there was a post some time ago that summarized the effects of porphyria.  I noted that the way in which I experience porphyria wasn't on the list which makes me wonder if what's going on with me is really porphyria at all.  It seems to coincidental not to be but that may be the case.

    In my case, I get the symptoms I thought/have believed were porphyria after eating.  Indeed, taking glucose before eating seems to alleviate much of it unless I really eat a lot.  My symptoms are that I become more lethargic, less coordinated, sometimes to the point where I have to be very careful with walking as I tend to drag my right foot which is exacerbated after eating.

    I had talked about these symptoms in another thread some time ago and had mentioned that if I begin drinking lots of water after having eaten, it tends to more quickly relieve these symptoms.  I believe it may have been Jim K who suggested that the water was sweeping away water soluble porphyrins, which sounds likely to me.

    Anyway, to summarize, I'm wondering whether or not these symptoms are actually porphyria or something else.  I think DW posted earlier on this thread about an imbalance in homocysteine or some such in people with MS.  I wonder if it's that instead, but have no real clue.  I guess the best thing I can do to have a better idea and understanding is probably do the poor man's porphyria test and see for myself. 

    all my best

    John

    RRMS/EDSS 4.5 on Wheldon Protocol (nac, doxycycline, azithromycin, metronidazole) since 04/12/2006

    best, John

    RRMS/EDSS was 4.5, 5, 6, 6.5, 6.9999, 6.5 on Wheldon/Stratton Protocol beginning 04/12/2006
    nac 4x600 mg/day
    doxycycline 2x100mg/day
    azithromycin 3x250mg/day MWF
    metronidazole 3x400mg/day then 3x500mg/day

    John, the symptoms you describe just sound to me like a person recovering from multiple sclerosis digesting his food.  Your body is concentrating on digesting the food rather than bothering about whether you drag your foot a bit.  Although I can now use a knife and fork very well, towards the end of the meal I can lose  lot of strength in my wrists and fingers and make really heavy going of cutting up the remaining food.  I can then drag my feet whereas previously I wasn't simply because I can't be bothered not to.  For a few minutes I just want to close my eyes.  Half an hour later, digestion nearly finished, I am back to my normal, alert self........Sarah   An Itinerary in Light and ShadowWheldon regime since August 2003, for very aggressive SPMS.  Intermittent therapy after one year. 2006 still take this, now two weeks every three months.  EDSS was about 7, now 2. United Kingdom.
    Completed Stratton/Wheldon regime for aggressive secondary progressive MS in June 2007, after four years, three of which intermittent.   Still improving bit by bit and no relapses since finishing treatment.

    Sarah       

    I'm at a loss to decide whether or not you're right about it being a digestive energy issue.  It doesn't seem to be as when I take glucose before eating, it does alleviate the problem either entirely or mitigates it to a great degree.

    Also, for those of you following this thread, my reponse to Rita yesterday stated I take glucose before eating.  As one might expect, taking it after eating has no effect, or at least, has no effect on me when I've done that in the past.  Definitely take it before eating, and at least about 10 minutes and not much less or more.  The longer the time, the less the effect, the shorter the time, the less time your body has to respond to it before responding to digestion/eating.

    all my best

    John

    RRMS/EDSS 4.5 on Wheldon Protocol (nac, doxycycline, azithromycin, metronidazole) since 04/12/2006

    best, John

    RRMS/EDSS was 4.5, 5, 6, 6.5, 6.9999, 6.5 on Wheldon/Stratton Protocol beginning 04/12/2006
    nac 4x600 mg/day
    doxycycline 2x100mg/day
    azithromycin 3x250mg/day MWF
    metronidazole 3x400mg/day then 3x500mg/day

    Neat to pop this discussion up again accidently. John, putting together Sarah's comment about energy going into digesting food and some comments made by Dr. Stratton: since Cpn is an ATP (energy molecule) parasite there's less available for other cellular and organ functions. Any other heavy use of ATP such as muscle activity or even digestion (active transport processes) will leave some cells at a deficit and incomplete heme... ie porphyria can result. Isn't there some old saw about the energy to digest celery is more than it provides, hence the perfect diet food?

    Another factor- Cpn up-regulates the host cell to absorb more glucose from the bloodstream, so it can make more ATP for the Chlamydia. So these big blood sugar crashes, which then result in more porphyria, all get rolled up together.

    Your symptoms are familiar to me from times past, but without the foot-drop:"...lethargic, less coordinated, sometimes to the point where I have to be very careful with walking." My kids used to call me a klutz because I was always banging into things, especially when low blood sugar and porphyric from die-off.

    CAP for Chlamydia pneumonia since 11/04. 25yrs CFS & FMS- Currently: 150mg INH, 300mg Rifampin, 200 Doxycycline, 500mg mwf Azithromycin, plus 500mg Tinidazole 2x/day pulses every two weeks. Whew! That's a lot!

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    John said he takes the glucose after eating...I thought the glucose was supposed to be taken before eating. Which is right?

    Joyce~caregiver-advocate in Dallas for Steve J (SPMS) / Cpn indicated by reactions; Mpn, EBV, CMV positive; elevated heavy metals; gluten+casein sensitive / Wheldon CAP since Aug. '06 - doxycycline+azithromycin+flagyl pulses; antivirals; chelation; LDN.

    Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity. 

    Joyce        

    See my last reply to Sarah.  I take glucose before eating, not after Image removed. 

    all my best

    John

    RRMS/EDSS 4.5 on Wheldon Protocol (nac, doxycycline, azithromycin, metronidazole) since 04/12/2006

    best, John

    RRMS/EDSS was 4.5, 5, 6, 6.5, 6.9999, 6.5 on Wheldon/Stratton Protocol beginning 04/12/2006
    nac 4x600 mg/day
    doxycycline 2x100mg/day
    azithromycin 3x250mg/day MWF
    metronidazole 3x400mg/day then 3x500mg/day

     It depends-- some people (Ella for example) need the glucose to help suppress porphyric nausea and get back appetite. John appears to be needing it after eating to avoid blood sugar drop and porphyria from the energy it takes to digest! At least that's the hypothesis. We see all kinds of twists and turns in this.

    CAP for Chlamydia pneumonia since 11/04. 25yrs CFS & FMS- Currently: 150mg INH, 300mg Rifampin, 200 Doxycycline, 500mg mwf Azithromycin, plus 500mg Tinidazole 2x/day pulses every two weeks. Whew! That's a lot!

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Jim's right, when Ella is in a porphyric state, and she is about to eat when hungry her mouth starts to water to such an extent that it pours out of her mouth, and she feels very sick.   When she is feeling this way now, she takes a glucose tablet and the symptoms stop more or less immediately.  If she ignores the symptoms she usually sicks up what she has eaten some 10 minutes after eating.

    This does not happen very often now but she still gets the following symptoms: stomach hunger and the feeling of nausea at the same time.   She has to make an effort to eat, as she does not feel like putting food in her mouth, but if she does she usually manages to keep it down.  

    Michele: Wheldon CAP1st May 2006 for ailments including IBS, sinusitis, alopecia, asthma, peripheral neuropathy. Spokesperson for Ella started Wheldon CAP 16th March 2006 for RRMS. Sussex UK

    Michèle (UK) GFA: Wheldon CAP 1st May 2006. Daily Doxy, Azi MWF, metro pulse.

    Red

    Hi all, just reading again about secondary porphyria and came across something interesting in Dr Stratton's article The Pathogenesis of Systemic Chlamydial Infections: Theoretical Considerations of Host Cell Energy Depletion and Its Metabolic Consequences that just didn't sink in before.

    Forgive me if you understood this before, but although I'd read the article before I guess I didn't catch this. In the last paragraph he mentions the implications of Cpn infection of liver cells and states:

    "Moreover, if chlamydiae were to infect hepatic cells, the use of any pharmacologic agents that are metabolized in the liver will increase the need for cytochrome P-450 which is a heme-based enzyme. Hence, the biosynthesis of heme in the liver is increased. If hepatic cells were infected with Chlamydia species, the decreased energy in the host cell would not allow heme biosynthesis to go to completion, and porphyrins in the liver/entero-hepatic circulation would increase."

    He also goes on to mention that when the antimicrobial agents kill the Cpn the accumulated intracellular porphyrins would be released. Luckily I managed to catch this concept the first time I read it prior to beginning treatment.

    The concept of increasing the need for P-450 by pharmacologic agents intrigues me in that I've noticed Vit D3 seems to increase porphyria symptoms for me. I recently read that apparently Vit D3 synthesis also requires P-450 enzymes in the liver and kidney:

    CYTOCHROME P450, SUBFAMILY IIR, POLYPEPTIDE 1; CYP2R1

    CYTOCHROME P450, SUBFAMILY XXVIIB, POLYPEPTIDE 1; CYP27B1

    I'm wondering if increased need for P450 might be a good part of the reason Vit D3 seems to increase porphyria symptoms (in addition to its pro-apoptosis effects)?

    BTW, I've also noticed caffeine seems to increase porphyria symptoms greatly for me now that I've added Vit D3 (particularly on flagyl pulses), and I just read that apparently P450 CYP1A2 is involved in caffeine metabolism:

    CYTOCHROME P450, SUBFAMILY I, POLYPEPTIDE 2; CYP1A2

    Does this make sense?

    On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

    Treatment for Rosacea

    • CAP:  01/06-07/07
    • High-Dose Vit D3, NAC:  07/07-11/08
    • Intermtnt CAP, HDose Vit D3:  11/08-01/09
    • HDose Vit D3, Mg, Zn: 01/09-

    Amazing, Red. Could this be one of the reasons that D is not metabolized in Cpn infected bodies because of this liver enzyme being in short supply? "I recently read that apparently Vit D3 synthesis also requires P-450 enzymes in the liver and kidney" BTW, caffeine is a big trigger for porphyria for me---but I seem to have musch less porphyria these days. What a complex puzzle. Thanks for th elinks, Raven

    Feeling 98% well-going for 100. Very low test for Cpn. CAP since 8-05 for Cpn/Mycoplasma P.,Lyme, Bartonella, Mold exposure,NAC,BHRT, MethyB12 FIR Sauna. 1-18-11 begin new treatment plan with naturopath

    Red

    Gosh, interesting question Raven, but I'm not sure what if anything might cause a short supply of the P-450 enzymes involved in Vit D metabolism. I'll see if I can find anything.

    Up to this point caffeine has been more of a help than a problem for me, but I'm now wondering if cutting it out might help with some of my remaining (and sort of still increasing) porphyria symptoms. I'm currently trying to cut it out slowly (one half mug at a time)...

    On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

    Treatment for Rosacea

    • CAP:  01/06-07/07
    • High-Dose Vit D3, NAC:  07/07-11/08
    • Intermtnt CAP, HDose Vit D3:  11/08-01/09
    • HDose Vit D3, Mg, Zn: 01/09-

    Red, the short story is that you are correct about both Vitamin D and caffeine being sources of making you sick, and your belated understanding of the role of Cpn in causing porphyria due to mitachondrial ATP theft.

    Both Vitamin D and caffeine require Phase I hepatic metabolism. In order to become bioactive, Vitamin D undergoes Phase I hepatic hydroxylation followed by another hydroxylation by the kidneys. Finally, when the body is done with Vitamin D, the liver hydroxylates it a third time to allow it to be excreted.

    Phase I hepatic metabolism first involves the synthesis of one or more of several different P450 isoenzymes. These isoenzymes have a half life of only a few seconds at most, and therefore can not be stored. In fact, they are synthesized upon demand, and the trigger for their synthesis is the presence of the substance that must be metabolized.

    Every one of these isoenzymes contains a heme entity, which itself must be manufactured upon demand. It is this induction of heapatic heme manufacture that ultimately results in porphyria for those of us who are prone to it.

    Porphria is a consequence of heme synthesis gone awry. Once triggered, heme synthesis takes eight sequential steps. If all goes well, completed heme falls out of the bottom of the synthetic pipeline and feeds back to signal the first step to halt, thereby halting all subsequent steps.

    If something goes wrong at one of the eight steps once the process starts, and finished heme does not result, the process does not stop, and intermediate precursors pile up at one or more of the steps. These precursors are called porphyrins, and are EXTREMELY potent radical oxygen species that are EXTREMELY neurotoxic, bringing on terrible systemic nervous system disruption and a consequently broad array of symptoms when released into the bloodstream.

    Cpn infection is one of the things that can damage the heme making machinery. Cpn sets up shop near the mitochondria and steals their ATP output, which is the body's principal source of energy. This ATP theft also clobbers the ability of mitachondria to perform their role in heme manufacture, since as it turns out, half of the steps to make heme occur INSIDE of the mitachondria.

    Cpn liver infection is thus particularly vicious because the liver is needed to metabolize many of the very substances that one needs to cure the infection, but because of damage by Cpn, those substances trigger porphyria. Nice survival mechanism, hey?

    Vitamin D, caffeine, alcohol, tobacco, about 80% of all pharmaceuticals, many food substances, and many endogenous substances require Phase I metabolism for activation and/or elimination. Those of us who are prone to porphyria must be extremely careful with the drugs we take and some of the foods we eat. Substances that are good for healty people, like blueberries and cruceriferious vegetables (for example), can be bad for us. And substances that might normally be unhealthy for healthy people, like grapefruit juice and cimetidine (for example), can be beneficial for us.

    Vitamin D made me extremely ill, and not just from its antibiotic effect, which is what lead me to do the research that made me realize that Vitamin D is just one more substance that can trigger porphyria.

    basil.

    If cats are outlawed, only outlaws will have cats.

    The quantities of Vitamin D involved are low enough that I doubt that the need to synthesize enzymes to modify Vitamin D has much to do with porphyria. Only micrograms of Vitamin D are present; in comparison, gluconeogenesis needs to operate on gram quantities, since it's generating the main fuel used by the body. (Avoiding gluconeogenesis is the reason for eating glucose to stop a porphyria attack.)
    Red

    Thanks so much Basil. I cannot tell you how helpful this information is. It really confirms my suspicions that Vit D3 seems to be causing porphyria symptoms for me too through this method (rather than just through apoptosis mechanisms). I found immediately upon starting Vit D3 that I became extremely alcohol intolerent. This explains why. I believe I now (after 6 months of 4000iu of Vit D3) that I've reached a point where I may be intolerent of caffeine as well. I'll continue to try to eliminate it slowly from my diet (to avoid withdrawal symptoms).

    Here's another question for you, glucose tabs seem to almost immediately provide relief of my symptoms (within @ 20 minutes or so). But within a couple of hours I notice greatly increased congestion symptoms that last for @ 8-12 hours or so. High carb meals seem to do the same. While I'm worried about candida/yeast problems, the quick onset of these symptoms (and then clearance) doesn't seem to make a lot of sense along these lines. I'm wondering if the increased glucose/carbs sets off some kind of inflammatory or oxidative type reaction with the porphyrins (to eventually help scavenge and clear them), but haven't been able to find much on this. Does this make any sense?

    Thanks again so much as always....

    On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

    Treatment for Rosacea

    • CAP:  01/06-07/07
    • High-Dose Vit D3, NAC:  07/07-11/08
    • Intermtnt CAP, HDose Vit D3:  11/08-01/09
    • HDose Vit D3, Mg, Zn: 01/09-

    Red, glucose and cimetidine provide me immediate relief as well when I realize I'm becoming porphyric. Actually, this immediate relief is not something I really expected, because I've always been under the impression that porphyrins are long-lived chemicals that are difficult to eliminate. And yet, such immediate relief would contradict that impression. Perhaps the body has the ability to deal with a certain amount of porphyrins rather handily, but if that amount is exceeded, the porphyrins accumulate.

    Regarding the congestion, one thing that could happen is that if you are prone to blood-sugar instability, a big dose of glucose or carbs could cause your insulin to rapidly spike and then drop, along with a rapid drop in blood glucose. This would be consistent with the time frame of your congestion onset. The above is a form of hypoglycemia disorder. Regarding symtoms that can result from the above process, I found this:

    "The symptoms of 'hypoglycemia' (the term we will continue to use here) are many. They consist of fatigue, irritability, nervousness, depression, insomnia, flushing, impaired memory and concentration. Anxieties are common as are frontal or bitemporal headaches, dizziness, faintness or actual syncope. There is often blurring of vision, nasal congestion, ringing in the ears, numbness and/or tingling of the hands, feet or face. Excessive gas, abdominal cramps, loose stools or diarrhea are common. Many complain of leg or foot cramps. These are the chronic symptoms of this condition and are present even during periods of normal blood sugar."

    I'm wondering if you perhaps have any of the above symptoms besides just the nasal congestion.

    basil.

    If cats are outlawed, only outlaws will have cats.
    Red

    Thanks Basil.   Many of these symptoms are VERY familiar to me, and I've always been more than a little sensitive to foods high in sugars so potentially this explanation makes a lot of sense in my case too.

    I think I'll continue to try to cut out caffeine and try bumping up my intake of complex carbs a bit to see if I can reach a happy medium state between porphyria and congestion/inflammation. 

    Thanks again and take care... 

     

    On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

    Treatment for Rosacea

    • CAP:  01/06-07/07
    • High-Dose Vit D3, NAC:  07/07-11/08
    • Intermtnt CAP, HDose Vit D3:  11/08-01/09
    • HDose Vit D3, Mg, Zn: 01/09-

    Thanks basil for the information on Hypoglycemia.  I have this disorder and keep the simple carbs down to a dull roar.  I see, like many other ailments, there are cross over symptoms - CFIDS/ME.

    When my intestinal flora gets out of what I know because I crave sugar.  It is a challenge being on abx & keeping the balance as in the past I have had a candida problem (I just did a cleanse in February).

    The change in the diet recommended during the protocol I feel will have me gaining alot of weight?  When I am able to do more exercise I increase the complex carbs accordingly.

    I hope I will be ok; I continue down the path

    Mad CAPper

    With Christ in Faith

    Ruth 

    CFIDS/ME, FMS, MCS, IBS, EBV, CMV, Cpn, H1, chronic insomnia, Chronic Lyme, HME, Babesia, Natural HRT-menopause, NAC 2.4 gm,Full CAP 6-2-07, all supplements+Iodorol, Inositol-depression, ultra Chitosan, L lysine Pulse#27 04-19-10 1gm Flagyl/day-5 days<

     Basil- Reading your post on the azith thread:

    Finally, I personally have suffered repeated porpyria attacks triggered by CAP, even though none of the substances I take require Phase I metabolism (and therefore would not be porphyria triggers). My attacks are not simply the result of porphyrin release from liver-cell apoptosis, but full blown, out-of-control, continuous-porphrin production attacks that can be stopped only by taking large amounts of gluecose and cimetidine (a P450 inhibitor).

    It got me thinking: could apoptosis and dump of intracellular porphyrins require Phase 1 processing by the liver, ie how are the fat soluble porphyrins processed by the liver? That would put a big demand on the liver which would trigger immediate porphyrin attack, and round and round.

    CAP for Chlamydia pneumonia since 11/04. 25yrs CFS & FMS- Currently: 150mg INH, 200 Doxycycline, 500mg MWF Azithromycin, 500mg Tini daily (Continuous protocol)

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Jim, I think you may have hit the nail on the head. Phase 1 processing is usually the first step in converting fat soluable compounds into water soluable compounds, with Phase 2 conjugation being the second and final step.

    The body has very very poor(almost non-existent) mechanisms for eliminating fat soluable compounds, hince the need for conversion to water soluability.

    I too just recently briefly wondered about the fat soluable porphyrins and whether they would undergo Phase I metabolism. But I didn't pursue the thought like I should have. But you did.

    That is, you've hypothesized that the body would attempt to utilize Phase I metabolism for the inital step in converting fat soluable porphyrins into water soluable compounds. However, this attempt at conversion would result in either triggering and/or sustaining a self-perpetuating porphyria attack.

    In the case where a porphyria attack had not yet started, but in which a person was prone to secondary porphyria attacks, if CAP-induced apoptosis of infected liver cells released too much intracellular porphyrins from diseased liver cells, then a secondary porphyria attack would be triggered, actually producing new porphyrins on top of the porphyrins released by the CAP. Furthermore, such an attack would be self-sustaining until abated by treatment with glucose/cimetidine/Panhematin, producing far more porphyrins than those originally dumped by cell apoptosis.

    This hypothesis very neatly explains why CAP induces self-sustaining secondary porphyria attacks. Based on my own experience, and others here, I've simply never believed that the amount of porphyrins dumped by cell apoposis was enough to make people as sick as they get. Furthermore, I have no doubt that CAP has triggered self-sustaining porphyria attacks in myself, and others here. One reason for this belief is that glucose and cimetidine should have no effect on porphyria symptoms produced by simple porphyrin dumping as a consequence of cell apoptosis, and yet myself and others have reported that these remedies bring relief from CAP-induced porphyria symptoms.

    I really think you may have discovered a very important piece of the puzzle.

    If this is all true, then this would also be one of the mechanisms that would sustain primary (genetic) porphyria attacks as well. Experimentally, this hypothesis shouldn't be too difficult to prove. Perhaps a murin model with induced porphyria cutanea tarda could be used. Once the mice are made PCT with the appropriate toxin, fat solulable porphyrins could be injected and it could be easily determined if a self-sustaining porphyria attack resulted. I wish I had the money to fund the research.

    I would be very, very interested in what Charles Stratton has to say about all of this.

    Great thinking! I'm jealous that I didn't figure this out myself!

    basil

    If cats are outlawed, only outlaws will have cats.

    yikes, all this talk about the liver & porphyrins.  scary.  I am glad I backed off the flagyl/metro as my liver, gallbladder, spleen area was very sore.  I guess that is porphyrin attack as after I cut the doseage in 1/2, about 4 days I had less pain in that area.

    The Nasty Cpn already triggered my Hemochromatosis - excess iron storage.  My inner Physician has been working overtime for years, I blame everything on the bacteria!! lol

    My best wishes

    With Christ in Faith

    Ruth 

    CFIDS/ME, FMS, MCS, IBS, EBV, CMV, Cpn, H1, chronic insomnia, Chronic Lyme, HME, Babesia, Natural HRT-menopause, NAC 2.4 gm,Full CAP 6-2-07, all supplements+Iodorol, Inositol-depression, ultra Chitosan, L lysine Pulse#27 04-19-10 1gm Flagyl/day-5 days<

    Some more thoughts on porphyria and Cpn

    Because it has been such a prominent part of my own illness, I've done quite a bit of research on porphyria. Almost everything in the literature refers to primary genetic porphyria, though there are a few references to secondary (non-genetic) porphyria caused by various liver-destroying processes.

    Primary porphyria is a genetic disease in which there is a deficiency of one of eight different enzymes, each of which is required to effect one of the eight sequential steps required to synthesis the iron-containing protein heme. The output at each step is the precursor for the next step of heme synthesis. A deficiency of one of the enzymes can cause accumulation of the precursor from the previous step and prevent the subsequent steps from producing heme.

    Normally, finished heme output feeds back to the first of the eight steps, and halts heme production when sufficient heme has been synthesized. 

    In primary genetic porphyria, heme production is compromised, and thus sufficient finished heme feedback doesn't occur to halt the continued attempt to make heme, and one of the precursors continues to accumulate.

    These precursors, called porphyrins, are highly neurotoxic, though normally they exist only transiently in the heme manufacturing pipeline. In primary genetic prophryia, not all porphyrins are converted to heme and accumulate to excess. When accumulated to sufficient levels, these porphyrins trigger the various manefestations of the various forms of porphyria.

    Primary genetic porphyria attacks are triggered when the body is called upon to make an amount of heme that exceeds the limit imposed by the insufficient enzyme level. Most porphyriacs can make sufficient heme for ordinary activities, but are unable to make larger amounts of heme required for exceptional circumstances.

    Thus, porphyria is an episodic illness that occurs when the body is occasionally called upon to make more heme than  can be  produced by the compromised  heme-making machinery.

    While all cells manufacture some amount of heme, the greatest amount of heme is manufactured during the production of red blood cells. Most of the rest of the body's heme is manufactured by the liver. However, red blood cell production is a relatively steady-state operation, and would thus not be expected to be involved in requirments to make exceptional amounts of heme, and would thus not be expected to be involved in porphyria attacks.

    The liver, on the other hand, is involved in large numbers of  processes that are anything but steady state. An examination of classical porphyria triggers such as alcohol consumption, tobacco consumption, intense exercise, illicit and licit drug consumption, and dietary changes show that these are all environmental factors that heavily impinge upon liver function.

    Fundamentally, then, primary genetic porphyria is a disease of the liver. 

    Switching gears a bit now, Stratton has indicated that Cpn infection causes a disruption of heme manufacture via mitchondrial dysfunction. The pipe-lined steps of heme manufacture are disrupted due to lack of ATP either inside or outside of the mitochondria due to ATP-theft by Cpn, rather than due to enzyme insufficieny. However, the end result is the same as in primary genetic porphyria, namely accumulation of pophyrins.

    Thus, Cpn infection could be expected to produce acute porphyria attacks that mimic  the accute attacks seen in primary genetic porphyria, and such Cpn-mediated attacks could be expected to be triggered by classical primary genetic porphyria triggers.

    However, Cpn infection also seems capable of interfering with even normo-intensive heme manufacture, and thus can produce background level of porphyrins, even when classical triggers don't exist.

    Furthermore, when Cpn-infected host cells lyse as a consequence of Cpn RB destruction via antibiotics, accumulated intracellular porphyrins are released into the blood stream.

    Thus, Cpn infection produces three distinct porphyria phenomena:

    1. Acute porphyria attacks similar in nature to primary genetic porphyria and which are triggered by classical primary genetic porphyria triggers that induce calls for exceptional amounts of heme. Such Cpn-mediated attacks would be expected to produce elevated porhyrin levels similar to elevations seen in primary genetic porphyria acute attacks.

    2. Interference with  normo-intensive heme production, resulting in slightly and chronically elevated porphyrin levels at all times.

    3. Pulsed releases of relatively larger amounts of porphyrins than seen in Item 2 above during host cell apoptosis as a consequence of RB destruction due to antibiotic treatment, with such amounts related to the degree of preceding RB destruction.

    Finally, based upon the earlier explanation of primary genetic porhyria being fundamentally a disease of the liver, and leaving aside the possibiity of erythroid Cpn infection, I'm going to assert that essentially ALL clinical porphyria phenomena seen in Cpn infection are a function of Cpn infection of the liver specifically. Thus the degree of Cpn liver infection is going to influence the degree of the three Cpn porphyria phenomena.

    This explanation would account for the different degrees of difficulty experienced by those undergoing CAP treatment for Cpn infection. In particular, this may explain why many of those with MS (and perhaps certain other Cpn-caused conditions) do not experience the three Cpn porphyria phenomena, whereas those with CFS/CFID/MCS/GWS usually do. That is, people who experience porphyria symptoms have a Cpn liver infection, and those that do not experience porphyria symptoms don't have a Cpn liver infection. 

    Most people with CFS/CFID/MCS/GWS/ME most likely have Cpn liver infections since most of these people report porphyria symptoms. Those people with MS and other conditions who do not report porphyria symptoms most likely do not have a concurrent Cpn liver infection.
     

    basil. 

     

     

    Basil,  You definitely brought the best kind of baggage with you when you walked through this door.  Thank you for this terrific information.  I have a challenge for you.  Suppose someone with unsuspected/undiagnosed MS donates gallons and gallons of blood over a 30+ year period, thereby compelling his bone marrow to frequently rev up RBC production over those years.  Such an individual is later diagnosed with MS and even later experiences NAC flu.  What were the porphyric possibilities in that situation, and what toll might have been paid over that extended period?  Thanks,

     Joyce~caregiver-advocate in Dallas for Steve J (SPMS) / Mpn, EBV, CMV, elevated heavy metals; strong indications of Cpn, gluten+casein sensitive / Wheldon CAP since Aug. '06 - 200mg doxycyline/day + 250mg azithromycin every other day; antivirals; chelation; LDN.

    Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity. 

    Joyce, I'm not sure what the long term porphyric implications of induced red blood manufacture might be. My guess is that it is unlikely there would be any, particularly if you did not experience any symptoms of porphyria after donating blood. I've not run across any published research specifically implicating  red blood cell heme manufacture in porphyric processes, though I haven't actually gone to a medical library yet and studied porphyria in depth.

    NAC flu is an issue that is essentially unrelated to porphyria. It is a cytokine-mediated allergic reaction to the proteins released when EBs are killed. EBs, if you remember, are the extra-cellular "spore" form of Cpn, and are metabolically inert until they enter a cell to infect it, at which point they convert to the active RB intracellular form, which is the form that can interfere with heme production. Interestingly enough, I did not have any reaction to NAC, but had a major "flu" reaction 3 days after starting amoxicillin.

    I seriously doubt that you did any harm to yourself donating blood, though you must understand that I am not a doctor and I am not an expert.

    basil. 

    If cats are outlawed, only outlaws will have cats.

    Thanks, Basil. A very nice explanation for the, shall we say, porphyrially challenged like myself.

    There was that recent research about abnormal liver function and MS that I thought was interesting especially to those of us who think MS is caused by an infection. I do not know if this disruption of liver function that the researchers found in MSers is similar to what secondary prophyria could create. Do you?

    Here's the link:  http://tinyurl.com/y89lmb

    Lexy

    --------------- "Chance favors the prepared mind." --Louis Pasteur Husband treating MS with CAP

    Lexy, I found the PubMed abstract of the research article alluded to in your link:

     

    Liver test abnormalities in multiple sclerosis: findings from placebo-treated patients.

    * Tremlett H, * Seemuller S, * Zhao Y, * Yoshida EM, * Oger JD, * Petkau J.

    Faculty of Medicine, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, BC, Canada. tremlett@interchange.ubc.ca

    The risk of an abnormal liver test in 813 patients with multiple sclerosis or clinically isolated syndrome enrolled in placebo arms of clinical trials was greater than expected for alanine aminotransferase (ALT) (relative risk [RR] 3.7; 95% CI: 2.3 to 6.0) and aspartate aminotransferase (AST) (RR 2.2; 95% CI: 1.3 to 3.6), although not alkaline phosphatase (AP) or total bilirubin, at first presentation. Abnormal test results were associated with higher body mass index (ALT only), male gender (ALT only), and a relapsing-remitting (vs secondary-progressive) course (ALT and AST only).

    PMID: 17030771 [PubMed - indexed for MEDLINE]

     

    There's really not enough information in the abstract to draw very many conclusions. The article sounds like it would be interesting to read, though.

     

    basil.

    If cats are outlawed, only outlaws will have cats.

    Basil- as you see, I've linked your post to the Handbook as it's the clearest description of porphyria we have. Good to see your desperate work doing some good somewhere, eh? I'm not sure dividing this up according to strict diagnosis is best, since there is likely some overlap, ie some MS patients who have much more disseminated Cpn and other organ involvement (Raven is a case in point). Now that it's in the Handbook, do you want to edit up your commentary?

    I've lately been experimenting with Cimetadine (Tagamet) which has been shown to help in some of the porphyrias. It seems to have a useful effect, but I'm still experimenting. It might be useful to subject it to the Poor Man's Test.

     

    Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndrome & Fibromyalgia- Currently: 150mg INH, Doxycycline/Zithromycin, 300mg Rifampin, Tinidazole pulses. Northern Ohio, USA

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Jim, I agree with what you say about strict division. My intent was really to point out that porphyria symptoms are most likely an indication of Cpn liiver infection. I've altered my post to try and clarify that point.

     basil.

    If cats are outlawed, only outlaws will have cats.
    D W

    This is a really useful thread; thanks, Basil, for posting it, and thanks, Jim, for pointing out that the abnormal porphyrins appear to be cell-bound, but are released when apoptosis occurs. This makes good sense to me; in my own case I feel most porphyriac (and have tea-coloured urine) during periods of soft-tissue alteration and subsequent improvement. Apoptosis of unhealthy cells which contain toxins and perhaps bacterial remnants would account for this paradox. One of the pathologies of porphyria is a widespread pro-oxidant effect; one would suggest that antioxidants and agents capable of reversing glutathione depletion would help forestall pathological outcomes. Here is an apposite case-report of a 50 year old man, an exterior worker, who presented with skin blistering; he was found to have porphyria cutanea tarda with underlying Hepatitis C. He was also a heavy drinker. (link) The author gives a good resume of the disease and comments: 'Experimental treatments include 1)high dose Vitamin E, which was orignially shown in the late 1970s to prevent iron induced liver damage in rats; 2)N-acetyl-cysteine, for which there are a few case reports of benefit in patients with HIV (This agent is thought to work by prevention of skin damage from radical species by increasing intracellular glutathione); 3)Pyridoxine, which has been used in other porphyrias with light sensitive eruptions.' It's interesting that all three are recommended supplements for treating chronic C pneumoniae infection. Again, looking at my own experience, I find that, even though I have porphyriac symptoms, my skin is really healthy; all summer I cycled to work in a T shirt and shorts (changing when I got there) and was mildly sunburned but nothing unpleasant. (I covered up when taking doxycycline.) Secondary porphyria is, I am sure, very much underdiagnosed, and is unconsidered: but I am sure it's very common.

    Now a question: does chlorella bind to porphyrins in the gut? I have a feeling that it should, but cannot find references.

     

    D W - [Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding pulsed metronidazole. Improved; normotensive.]

     

    D W - [Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding metronidazole. No medication now. Morning BP typically 110/75]

    Thanks basil,  My only point in mentioning the NAC flu was as a demonstration of Cpn infection.  I would like to say Steve tested positive for it, but I can't.  For some mysterious reason, he was tested for C. psittaci instead of Cpn.  I also wish I knew if his urine was dark and/or foamy back in those days, but I wasn't around for most of those years.

    NAC flu is very different for each individual.  Steve's was barely noticeable until he doubled the dosage at the same time he added selenium and vitamin E to his regime.  That precipitated joint aches and a worsening of his MS symptoms.  For me, it was a strong and long respiratory reaction.  You might have had a reaction and didn't realize it at the time.

    Joyce~caregiver-advocate in Dallas for Steve J (SPMS) / Mpn, EBV, CMV, elevated heavy metals; strong indications of Cpn, gluten+casein sensitive / Wheldon CAP since Aug. '06 - 200mg doxycyline/day + 250mg azithromycin every other day; antivirals; chelation; LDN.

    Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity. 

    Basil, I don't see how it follows that Cpn-induced porphyria is mostly from the liver.  Even with less heme being synthesized outside the liver than inside it, one still might have a buildup of porphyrins in some other tissue, due to Cpn infection, with the liver for whatever reason remaining uninfected.  Then, either when the Cpn is killed by antibiotics, or there is mass cell die-off for other reasons (perhaps as in an MS relapse), those porphyrins would be released, and might overload the system even though normally that population of cells doesn't contribute much to the porphyrin body burden.

    This could, in a fashion, be tested: if it is liver cells whose dieoff produces the porphyria, then one would expect to see elevations of liver enzymes being correlated with elevations of porphyrins.

     Most of the body's heme is made during the process of red blood cell manufacture (85%), and almost all of the rest of the body's heme is made by the liver. Since accumulation of porphyrins results only from the dysfunctional  manufacture of heme, it follows that almost all porphyrin production due to dysfunctional circumstances must be a consequence of red blood cell production or liver function. If we discount erthyroid cell Cpn infection, then it follows that almost all prophyrins seen in a Cpn infection must therefore come from the liver, i.e, a liver infected with Cpn.

     Liver enzymes are rarely elevated in primary genetic porphyria as primary genetic porphyria rarely causes frank liver destruction. In my original post, I outlined three different types of Cpn porphyria phenomena. Only in Type 3 Cpn porphyria, namely rapid release of porphyins due to liver cell apoptosis of infected Cpn cells resulting from CAP (or other reasons as you point out) would one expect to see liver enzymes elevated due to liver cell destruction. In fact, a liver enzyme test might be a good way to assess whether CAP was proceeding too agressively in the case of an infected liver.

     

    basil. 

     

     

    Primary genetic porphyria rarely causes frank liver damage, and therefore elevated liver enzymes are rarely seen in primary genetic porphyria.

    If cats are outlawed, only outlaws will have cats.

    Interesting question about Chlorella, David. i was looking at one of Dr. Powell's handouts on Inflammatory Pathway Inhibitors and here's what it says about chlorella:

    "decreases IL-6, INF-gamma, 5-LOX, MMP-9, PTP and TNF-alpha. Blocks NFkB .....increases Natural Killer cell activity...."

    On this list the top performers that blocked the most inflammatory mediators were Curcumin, Luteolin and Niacinamide.

    As for Chlorella being a detoxifying agent, there is a lot of alternative health info out there about that. One article I found:

    http://findarticles.com/p/articles/mi_m0ISW/is_265-266/ai_n15622561

    Raven

     

    Feeling 98% well-going for 100. Very low test for Cpn. CAP since 8-05 for Cpn/Mycoplasma P.,Lyme, Bartonella, Mold exposure,NAC,BHRT, MethyB12 FIR Sauna. 1-18-11 begin new treatment plan with naturopath

    I still don't see anything that prevents porphyrins from building up in tissue outside the liver, then being released in quantities great enough to cause problems.

    Indeed, I think I've seen Stratton claim that there can be local porphyrias as well as general ones.  For instance, in an MS patient, one might get porphyria in the brain (and thus anxiety) without there being enough porphyrins outside the brain to produce, say, abdominal pain.  I even believe I've experienced that: on some occasions I've had both mild abdominal pain and mild anxiety, but on others stronger anxiety without abdominal pain.  The latter was shortly after taking Flagyl; presumably the released porphyrins hadn't had time to enter the general circulation.  At any rate, that's what I attributed it to at the time.  Let me see if I can dig up the Stratton reference... okay, US patent 6,884,784, page 33:

    "The clinical result of the intracellular and extracellular accumulation of porphyrins, if extensive, is a tissue/organ specific porphyria which produces many of the classical manifestations of hereditary porphyria. As the chlamydial-infected host cells lyse, as happens in the normal life cycle of Chlamydia, the intracellular porphyrins are released and result in a secondary porphyria. Moreover, when the chlamydial infection involves hepatic cells, the use of any pharmacologic agents that are metabolized by cytochrome P-450 in the liver will increase the need for cytochrome P-450, which is a heme-based enzyme. Hence, the biosynthesis of heme in the liver becomes increased.  When hepatic cells are infected with Chlamydia species, the decreased energy in the host cell does not allow heme biosynthesis to go to completion and porphyrins in the liver/entero-hepatic circulation are increased. It also has been noted that any host cell infected with Chlamydia species has an increased amount of intracellular porphyrins that are released when antimicrobial agents kill the microorganism."

    The patent also states (p.34):

    "The diagnosis of chlamydial-associated secondary porphyria may be
    difficult as the porphyria may be minimal and tissue-specific."


    Liver function tests are already recommended for those following the protocol, for the reason you state.  (Or, more directly, because a number of the antibiotics used have been known to damage the liver on occasion, as has niacin in large doses; but that is likely to be because they kill Cpn infecting the liver.)

    In other recent posts, I've pointed out that in all forms of porphyria, porphyrins are  extremely potent systemic neurotoxins, and that they produce extremely broad as well as extensive localized effects once released into the blood stream, regardless of where they originate.

    Excepting erythroid cells, porphyrins are not manufactured in appreciable quantities in most cells outside of the liver because heme is not manufacutured in appreciable quantities in most tissues outside of the liver. Unless a cell makes heme in appreciable quantities, then it is not going to be making prophyrins in appreciable quantities.  Period.

    One does not get porphyria in the brain or the gut, in the sense that the brain or the gut are sites for significant porphyrin production. It is well documented and accepted medicine that porphyrins arise primarily from the liver. However, both the brain and the gut are substantially affected by the neurotoxic properties of porphyrins once they are released into the blood stream, as are numerous other parts of the body.

     Many, many diseases of specific organs have wide-ranging systemic effects in locations far from the dysfunctional organ, including thyoid dysfunction,  adrenal dysfunction,  pancreatic dysfunction, etc.

     I'm not making this stuff up. I've merely been attempting to distill extensive research regarding porphyria into concise explanations relevant to Cpn infection.

     

    basil. 

    If cats are outlawed, only outlaws will have cats.

    Interesting discussion, Norman and Basil. I had not recalled such detail on porphyria in the patent materials, so it's good to be reminded of it. I'll have to go dig it up and read the whole damned thing again, as now I'm wondering what else I missed in my brain fog.

    David- I wondered that about Chlorella also, as it would be nice to have something other than charcoal or Questran to bind porphyrins in the gut, especially since these also bind medications. As far as I know, there are no warnings with Chlorella that it should not be taken with other vitamins or medications because it would bind them. I know that Chlorella is said to bind heavy metals like mercury and lead, and is used for this purpose in various treatments. This would suggest that it's binding capacity isn't lipid based. We need a chemist to look at the molecules in Chlorella and tell us what it might do for porphyrins.

    Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndrome & Fibromyalgia- Currently: 150mg INH, Doxycycline/Zithromycin, 300mg Rifampin, Tinidazole pulses. Northern Ohio, USA

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    D W

    Raven, thanks for the link.

    D W - Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding pulsed metronidazole. Improved; normotensive

     

    D W - [Myalgia and hypertension (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding metronidazole. No medication now. Morning BP typically 110/75]

     

    Eureka!  Thanks to Cpn Handbook and  Basil's wonderfully clear explanations I am finally getting my head around  secondary porphyria and beginning to realise how it could be a very important part of my illness.

    You have given me much food for thought and a whole new area of treatment to explore. No doubt, by the time I've assimilated it all and formulated my questions this forum will have moved on to the 'next big thing' and  you'll be able to look back and see me trailing along behind you all desperately trying to fight my way out of the big grey foggy cloud round my brain.  I can't believe how many clues my doctors have missed.

    Thank you for sharing it all

    'Evolved individuals do not accumulate.

    The more they do for others, the more they gain;

    The more they give to others, the more they possess.'  (Tao Te Ching)

     

    Elinor from England, UK..... on Wheldon protocol for ME/lyme borreliosis , positive for borrelia and Cpn.  Started  Aug 05, stopped Jan06, started again Sept 06.

    Elinor ..... from England  on CAP, doxy/roxi/tini  for ME/CFS/lyme borreliosis, positive Cpn and borrelia. Started Aug05, stopped Jan06, started again Sept 06.

    So what sort of numbers are we talking about?  Is heme production outside the liver a tenth of that in the liver, a hundredth, or a thousandth (omitting red blood cell heme production from both numbers in the ratio)?  If either of the former, you still have a situation where an accumulation of porphyrins over weeks or months, outside the liver, can be competitive, if released suddenly, with an amount produced by the liver in response to immediate demands.  Even if not enough to cause systemic porphyria, they might be enough to cause a local porphyria, before they dissipate.

    (Now that I think of it, I also don't see why you're ruling out Cpn infection of the red blood cell production process, which might be another source of porphyrins other than the liver.)

    Why porphyins are really, really bad! 

    Norman- these are great questions to run past Dr. Stratton. I'll accumulate them for my next contact with him. Re-reading the pages in the Patent you refer to on porphyria and it's treatment, it's clear that they had a whole bunch of lab measures available at that time for measuring porphyric load that are simply unavailable currently (until the lab goes up again). So, they might have looked at some of these questions of total porphyric load versus local porphyric reactions. It looks to me from the Patent discussion that the liver is considered one of the bigger sources, but other sources are referred to, such as the red blood cells you mention.

    Overall, re-reading these materials hammers home the critical importance of porphyria treatment during Cpn treatment, regardless of where the source of the load is coming from:

    • Porphyrins produce a lot of serious and bad symptoms.
    • Porphyrins are neurotoxic and actually damage neurons (independent of the damage Cpn causes).
    • Porphyrins are hugely oxidizing (read-- the opposite of antioxidizing, what we are encouraged to take all those antioxidants for). Their oxidant effect is damaging to our tissues and organs. Porphyrins kill our body organs and cells.
    • Porphyrins help generate B-12 antigens in our body which binds up B-12, leaving us in a B-12 deprived condition even if we appear to have adequate blood levels of it.

    There's probably more, but these are the ones I can pull up right now. 

    Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndrome & Fibromyalgia- Currently: 150mg INH, Doxycycline/Zithromycin, 300mg Rifampin, Tinidazole pulses. Northern Ohio, USA

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Maybe this is off topic, maybe not. One of the oddest things about CFS is Cheney's observation (quoted in Osler's Web) that about 1/3 of his CFS patients had to have their gall bladders removed within 6 months of the onset of CFS.

    When I started with CFS, my gall bladder immediately (within a week or two) began to cause me pain. I hesitantly asked three nurses, the surgeon, and my family doctor if the fatigue was related (hesitantly, because it made no sense to me.) They all assured me the two couldn't be related. The g.b. was removed 2 months later. Finding: one tiny stone. Just one. However, the surgeon also said, "SOMETHING was going on with that gall bladder, the wall was so thick."

    I think it bolsters the notion of a C.Pn-liver connection in CFS. I also realize it's hardly a smoking gun proof.

    Ron 


    On CAP for CFS starting 01/06 (NE Ohio, USA)

    Currently: doxy & zith -- continous; metronidazole -- 4days on, 7 days off.

    Ron

    On CAP for CFS starting 01/06 (NE Ohio, USA)

    Began rifampin trial 1/14/09

    Currently: on intermittent

    Liver Tests & MS - I have read the Tremlett et al paper (Neurology 2006,67:1291-1293). The summary says that for drug free MS patients liver tests may not be within normal ranges and the detailed paper gives full data.  For me a clinical action is that with MS patients a baseline liver assessment (ALT/AST) is taken.  This is needed before starting drugs which could impact liver function. Otherwise abnormal results later could mean that drugs are stopped or impacts on the liver are questioned when in fact drugs are not the problem.  If there is no limit for the number of liver function tests available then if would be useful to test MSers: before starting any drugs; after taking NAC but before adding abxs; after 3 months of abxs.  Never going to happen in the NHS (UK) but could give interesting results ........Mark.

    Mark Walker - Oxford, England.
    RRMS since 91, Dx 97. CFS from Jan03.  DW Patient-Feb06, started emp CAP(DW) in Mar06, with Copaxone. Pharma Consultant (worked til Jan 03).

    Mark Walker - Oxford, England.

    RRMS Nov 91, Dx 97. CFS Jan03. Copaxone + continuous CAP (NAC, Dox, Rox) Feb06 to May 07. Met pulses from Jun06. Intermittent Abx from June 07 onwards.

    Leap too far - Basil you presented lots of useful and interesting data and then say:
    "I'm going to assert that essentially ALL clinical porphyria phenomena seen in Cpn infection are a function of Cpn infection of the liver specifically."  I would want to see liver biopsy data before making such a leap.  The problem is that some website readers will take your thoughts as proven rather than  interesting conjecture.  Personally I did not see any bronze colour when I did a 'poor persons porphyria test' in sunlight during the summer........................Mark.

    Mark Walker - Oxford, England.
    RRMS since 91, Dx 97. CFS from Jan03.  DW Patient-Feb06, started emp CAP(DW) in Mar06, with Copaxone. Pharma Consultant (worked til Jan 03).

    Mark Walker - Oxford, England.

    RRMS Nov 91, Dx 97. CFS Jan03. Copaxone + continuous CAP (NAC, Dox, Rox) Feb06 to May 07. Met pulses from Jun06. Intermittent Abx from June 07 onwards.

    Mark, when I write, I've tried to distinguish between what I believe are "facts" found in the published medical literature, and my own person suppositions, which is why I use such words as "assert" when I make those suppositions, assuming that most readers here are educated enough to know what "assert" means. For those who might miss the distinction, I'm glad you've emphasized that point.

    One reason that I make such assertions, is that I would like to pique the interest of the medical research community to either confirm that I am right or explain why I am wrong based on their superior knowledege of the subject, or if the issues I raise are open questions, to ultimately be stimulated to perform the research to prove or disprove those assertions if they believe the issues I raise are important ones. I would think that liver biopsies coupled with PCR detection techniques would indeed be very very useful. Even used on cadavers such a technique might shed some light on the epidemiology of intracellular liver infection.

    basil. 

    If cats are outlawed, only outlaws will have cats.

    Let me mediate this a bit-- I think this has to do with one's perspective. As a clinical pharmacist Mark's orientation is to state what is known about a drug or condition clearly, and not go too much beyond that in speculation. Basil is orienting from stating what is know about the condition and then speculating as to the meaning of findings and links between them.

    As we have such a variety of people finding these pages, it behooves us to clearly mark "this is known" from "Speculations:..."

    I don't think "assertions" is clear enough language to mark this, where "Speculations based on these findings might be..." with more clearly ecquivocal language. Then rousing discussion can ensue about possible speculative outcomes. 

    Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndrome & Fibromyalgia- Currently: 150mg INH, Doxycycline/Zithromycin, 300mg Rifampin, Tinidazole pulses. Northern Ohio, USA

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Basil's explanation is excellent, and it made me question my porphyria assumptions and ask the same questions as Norman.

    Jim, I was curious whether Dr. Stratton had weighed in yet on Norman's questions (repeated below)? Is this something that will have to wait until the Cpn Lab reopens perhaps?

    I'm curious about the necessity of major liver infection as a cause of major porphyria episodes. My liver values always look perfect on labs, although, unless I'm on the wrong track with porphyria and need to keep looking for another explanation, I seem to have real problems with symptoms of porphyria. Perhaps standard liver tests aren't enough to go on?

    Thanks!

    Marysia

     

    So what sort of numbers are

    Submitted by Norman Yarvin on Mon, 2006-11-20 08:59.

    So what sort of numbers are we talking about? Is heme production outside the liver a tenth of that in the liver, a hundredth, or a thousandth (omitting red blood cell heme production from both numbers in the ratio)? If either of the former, you still have a situation where an accumulation of porphyrins over weeks or months, outside the liver, can be competitive, if released suddenly, with an amount produced by the liver in response to immediate demands. Even if not enough to cause systemic porphyria, they might be enough to cause a local porphyria, before they dissipate.

    (Now that I think of it, I also don't see why you're ruling out Cpni infection of the red blood cell production process, which might be another source of porphyrins other than the liver.)

     

     

    CDC Lyme + 02/06; Cpn, HHV6, and EBV + 03/08. 2 yrs slow improvement on variations of CAP for Lyme. Currently slowly resuming treatment and changing to newly discovered (for me) Cpn protocol after a severe porphyria attack 09/07 on Diflucan.

    Heme, porphryns and Questran- oh my!

    I'll relay what Dr. Stratton said to me per above. He speculated, based on his understanding of the heme synthasis processes (see references below):

    "Fat soluble porphyrins reach the liver and are made water soluble and excreted in the bile. In addition, the cytochromes including cytochrome P450 are heme based. Therefore, there is a lot of heme synthesis going on in the liver. I suspect that the persons who have a reaction to questran probably have liver involvement by Cpn. Those that don’t have a reaction don’t have much liver involvement. The reaction may well be due to reduced cholesterol. The reaction may not be “die off”, but may be increased heat shock proteins because the Cpn is going into persistent phase due to “starvation” conditions. "

    Let me mention that he has been suspecting that a lot of "die-off" reaction can be attributed not to LPS endotoxin as much as to HSP60 which is generated by Cpn as a part of cellular life form transformation process.  HS60 is highly inflammatory in nature, moreso than LPS endotoxin. 

    More than you ever wanted to know about Heme production in relation to porphyrins:

    http://themedicalbiochemistrypage.org/heme-porphyrin.html

    Also from a reference (I don't have a link) on porphyria by  Hervé Puy and Jean-Charles Deybach (emphasis added by me):

    "Excretion of porphyrins and of
    porphyrin precursors Porphyrins and porphyrin precursors are excreted in urine
    and/or bile (Table 1). In relation to the total rate of haem
    synthesis, excretion of porphyrins is very small;
    in other words,
    few porphyrins (and porphyrin precursors, ALA, PBG) ‘escape’
    during haem formation and therefore are not transformed into
    bilirubin. Each day, bone marrow and liver synthesize about
    375 mg of haem. In humans, the mean level of ALA excreted
    in urine is ~ 3 mg/day; this means that less than 0.5% of ALA
    synthesized each day has not been used for haem synthesis [8]... However, urine contains only 30–35% of the total coproporphyrin; the remainder is found in bile...

    Before its final faecal excretion, a significant
    proportion of protoporphyrin is reabsorbed in the intestine and
    may circulate through the enterohepatic system
    [13]. However,
    it is not yet known how much intestinal microorganisms or food
    contribute to the total fecal porphyrin excretion"

    Note that different porphyrin cogeners are referred to in the text, so you don't confuse them, as it is taken out of it's context.  

     

    CAP for Cpn 11/04. Dx: 25yrs CFS & FMS. Protocol: 200mg Doxy, 250mg MWF Azith, Tini 1000mg/day pulses; Vit D1000 units, Iodoral 50mg, T4 & T3

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Before its final faecal excretion, a significant proportion of protoporphyrin is reabsorbed in the intestine and may circulate through the enterohepatic system

     Jim - Thanks for posting this! 

     I had actually come to the conclusion that this was the case for my husband after digging in and  reviewing bile formation and the GI tract.  This reference confirms it!

    Using Questran has reduced the confusion my husband experiences relative to a Natural Elimination Event by 80 to 90 %.  Dramatic !

    Removing porphyrins (and whatever else) from the bile is having a profoundly positive result on our quality of life. 

    Now researching the Sasparilla.

     

     

    Daisy - Husband on CAP 5/07.   Roxy, Diflucan round three 4-4, Rifampin, Bactrim DS, Mepron 4-6, Prednisone, Novantrone, Doxy, Azithromycin, Flagyl, Mino

    Daisy - Husband on CAP 5/07.  Husband died from Acute Myelogenous Leukemia Secondary to the Infusion of Novantrone.  Ie - the treatment with the conventional MS drugs killed him.

    Daisy on her own CAP 11/2012. 

    Daisy,  Please add burbur to your list too.

    Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity. 

    Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity. 

    Joyce, why do you mention burbur?  Is it the herb Burbur?  I know that some people use this for helping to deal with Lyme die-off.

    Mark 

     

    UK Carer of bedridden Severe ME/CFS Feb06. CPN dx. Apr07. Samento 15 drops per day July07.  2400mg NAC 200mg Doxy Jan 08.

    UK Carer of bedridden Severe CFS Feb06. Tick bites Summer04.  CPN dx.Apr07. Borrelia dx Sept08. Samento 15 drps daily July07.  200mg Doxy Jan08.  300mg Roxy Apr08 Stopped abx Nov/Dec08. Building up on Supps again.

    Still just learning about herbs - sarsparilla and burbur and a few others are believed to help with endotoxin and HSP issues (both with lyme and CPN).  

    Loads of antedotal reports on the internet but I am looking for something with at least a little scientific research - even in rats :)

    Daisy - Husband on CAP 5/07.   Roxy, Diflucan round three 4-4, Rifampin, Bactrim DS, Mepron 4-6, Prednisone, Novantrone, Doxy, Azithromycin, Flagyl, Mino

    Daisy - Husband on CAP 5/07.  Husband died from Acute Myelogenous Leukemia Secondary to the Infusion of Novantrone.  Ie - the treatment with the conventional MS drugs killed him.

    Daisy on her own CAP 11/2012. 

    Mark,  I tripped over sasparilla and burbur while searching for substances to mop up Lyme neurotoxins.  So far, my search results have been as Daisy describes---alot of discussion and no meat.

    Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity. 

    Joyce~caregiver-advocate in Dallas for Steve J (SPMS).  CAP since August 06, Cpn, Mpn, B. burgdorferi, systemic candidiasis, EBV, CMV & other herpes family viral infections, elevated heavy metals, gluten+casein sensitivity. 

    Neurovisceral Features of Acute Porphyria Attacks

    Neurovisceral Features of Acute Porphyria Attacks Jim K Sat, 2007-12-22 10:11

    Chanced upon this link available above, to excerpts to a text on the Diseases of the Liver and Bile Ducts.  I have used this text while pondering my own set of circumstances, it is quite technical in nature, not an easy read.  I was surprised to find so much of it open for examination on the internet.  Thanks Jim for providing this link.  
    • CAP(TiniOnly): 06/07-02/09 for CFS
    • MethylationProtocolSupplements: Started08/08
    • Intermtnt CAP: 02/09-02/10
    • Full MethylProtocol & LDN 02/09
    • Off CAP: 02/10, cont LDN & MethlyProtocol support

    Thanks Louise. This post had strayed, so I added it to the Handbook under Secondary Porphyria.

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Jim, You might peruse the files located under the images tab/at the top of the page and see what else might be found that could use an additional easy to find location.  

    I found a lot of graphic type files located here;  http://www.cpnhelp.org/image/tid/80 

    by first visiting this page;  http://www.cpnhelp.org/image and clicking on the Chlamydia Pneumoniae Pictures file this is added for for anyone elses who might like to browse around. 

    • CAP(TiniOnly): 06/07-02/09 for CFS
    • MethylationProtocolSupplements: Started08/08
    • Intermtnt CAP: 02/09-02/10
    • Full MethylProtocol & LDN 02/09
    • Off CAP: 02/10, cont LDN & MethlyProtocol support

    Well, it was clearly a mis-file. I have no idea how it ended up in image files!

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Bumped into this post again.  Been a while since it surfaced so here it is again.   Louise

    • CAP(TiniOnly): 06/07-02/09 for CFS
    • MethylationProtocolSupplements: Started08/08
    • Intermtnt CAP: 02/09-02/10
    • Full MethylProtocol & LDN 02/09
    • Off CAP: 02/10, cont LDN & MethlyProtocol support
    Book excerpt from: HERE

    Combination Antibiotic Treatment Protocol's (CAP's)

    Combination Antibiotic Treatment Protocol's (CAP's)
    This section covers the most current update of the Combination Antibiotic Protocol's (CAP's) for treating Chlamydia Pneumoniae. New material includes an updated protocol from Dr. Stratton, his most current observations on protecting the liver during treatment, as well as new charts to help users organize and understand suggested supplementation.
    Jim K Tue, 2006-02-07 21:01

    Initial and Following Blood Tests in CAP's Treatment

    Initial and Following Blood Tests in CAP's Treatment

    Initial and following blood work is not just a matter of Cpn related indicators, but also relevant to your particular history and case, as determined by your doctor. Suggestions drawn from experts treating Cpn in a variety of conditions include the following.

    Initial blood work can be obtained for the following tests:

    1. CBC & Differential
    2. Liver function tests
    3. Uric acid
    4. Serum iron studies (typically depleted by Cpn: low iron levels are more diagnostic, and are not necessariy indicators to supplement, which may actually increase Cpn infection-- see references below).
    5. Red blood cell ALA dehydratase
    6. Red blood cell PBG deaminase
    7. Vitamin B-12 level
    8. Homocysteine levels
    9. Serum methymalonate level.
    10. Vitamin D levels
    11. Thyroid panels (standard plus free T4, free T3, revers T3) [Endocrine disturbances common in Cpn and associated diseases]
    12. Creatinine
    13. AST
    14. ALT
    15. 24-hour urine and 24-hour stool specimens for porphyrins

    Dr Stratton has noted relative to porphyrins:

    Homocystine levels are elevated with B12 and folate deficiency, but can be reduced by folate alone. On the other hand, serum methyl malonate levels are elevated in B12 deficiency and are not changed by folate. Therefore, serum methyl malonate levels are the best indicator of B12 deficiency.

    Another indicator, according to Dr. Stratton, is high hemoglobin and high hematocrit.

    Dr. Powell notes:

    I also tst DHEA-S and free testosteron in perimenopausal females. Both increase nitric oxide levels, which kills Cpn.  No point heading into treatment with low androgens.


    Regular Followup Tests

    1. CBC & Differential
    2. Liver function tests (especially important when using medications such as INH or Rifamcin which can have liver toxicity, and because die-off of liver cells infected with Cpn can affect liver function)
    3. Vitamin D levels (if supplementing deficiency)
    4. Thyroid panels (standard plus free T4, free T3, reverse T3) (if supplementing deficiency)
    5. AST
    6. ALT
    7. Others as determined by doctor relevant to your particular condition.


    Some References-

    Iron and the Role of Chlamydia pneumoniae in Heart Disease, http://www.cdc.gov/ncidod/eid/vol5no5/letters.htm

    Weinberg ED. Patho-ecologic implications of microbial acquisition of host iron. Reviews in Medical Microbiology 1998;9:171-8.

    Freidank HM, Billing H. Influence of iron restriction on the growth of Chlamydia pneumoniae TWAR and Chlamydia trachomatis. Clinical Microbiology and Infection 1997;3 Suppl 2:193.

    Chapuy MC, Preziosi P, Maamer M, Arnaud S, Galan P, Hercberg S, Meunier PJ. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int. 1997;7(5):439-43.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&do…

    Lips P, Chapuy MC, Dawson-Hughes B, Pols HA, Holick MF. An international comparison of serum 25-hydroxyvitamin D measurements.Osteoporos Int. 1999;9(5):394-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&do…

    Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004 Mar; 79(3):362-71.

    Heaney RP. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1706S-9S.

    May E, Asadullah K, Zugel U. Immunoregulation through 1,25-dihydroxyvitamin D3 and its analogs. Curr Drug Targets Inflamm Allergy. 2004 Dec;3(4):377-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&do…


    Jim K Sun, 2006-02-12 09:43

    Emerging Stratton Protocol 4/2008: a new approach to an old set of problems

    Emerging Stratton Protocol 4/2008: a new approach to an old set of problems

    Emerging Stratton Protocol 4/2008: a new approach to an old set of problems

    Reported by Jim K

    A number of dilemmas appear in treating Cpn. As we all know here at Cpnhelp, treating with protein-synthase inhibitors alone induces chlamydial persistence---conversion to the cryptic/persistent form of "aberrant" non-replicating RB's. Infectious EB's still remain in extracellular fluids and tissues to reinfect once antibiotics are withdrawn. The CAP which addresses all three phases has been the answer to this multi-phase nature of Cpn, but it has problems of its own. The biggest problem is the tendency to induce strong reactions to treatment which have been attributed to bacterial release of LPS endotoxin and inflammatory HSP60 endotoxin, and to secondary porphyria. This makes for the additional problem, which is the requirement of a gradual, slow, and long term process of treatment when addressing Cpn infections. There are more potent anti-chlamydials around, but using them kills the Cpn too fast for the body to tolerate resulting in mass apoptosis of infected cells and subsequent organ failure or neutropenia.

    Existing CAP protocols have been focused on first halting replication, kill a lot of the RBs and force the rest into non-metabolizing and non-replicating cryptic/persistent form, with the notion that this will stop the progression of the disease. The cryptic Cpn can then be dealt with at one's leisure, gradually over time.

    But emerging research has been suggesting that Cryptic Cpn is not benign even if it is not replicating. Cryptic Cpn is essentially a stressed form of Cpn, and stress causes it to generate of Heat Shock Protein (HSP60). HSP60 is many times more inflammatory than LPS endotoxin. LPS endotoxin is the one that causes the fever and chills and is released mostly when RB's are killed and lyse, or when EB's are killed. The inflammation of plaques in cardiovascular disease has been associated specifically with Cpn HSP60 and with the persistent (cryptic) form of Cpn. Inflammation by HSP60 when forcing Cpn into cryptic form may in fact, in Dr. Stratton's current view, be the major cause of so-called die-off reactions. "So-called" because HSP60 is induced not by the bacteria dying off, as the release of LPS is, but rather by the Cpn surviving in a stressed, cryptic form.

    Additionally, ongoing disease and tissue damage may be occurring as much from the cryptic form, this is apparently so in heart and lung disease, as it is occurring from replication and sub-optimal cell functioning by infected cells. Autoimmune diseases, for example, also exhibit antibodies to HSP.

    Some additional observations have collected together to add to this shift in viewpoint. A medical colleague who has treated Cpn through IV treatments using all the agents for all.

    So this new approach is based on inducing existing persistent/cryptic Cpn to convert back to RB form and limit the conversion into persistent/cryptic form by the threat of antibiotic.

    Paul Griffith, a non-medical friend researching this whole area, found that supplementing pyruvate might do the trick. Pyruvate may also have other beneficial effects. Basically, this approach uses 6 grams of calcium pyruvate one hour before taking the antibiotics, and an additional 6 grams if needed later for reactions when the antibiotics exert their effect. In theory the first dose of pyruvate encourages the cryptic/persistent form of Cpn to convert back into RB (replicating) form by supplying it with a ready source for generating cellular energy.

    In RB form it is:

    a) Susceptible to the regular antibiotics and,

    b) Can be killed when it is not in "stress" so it is not stimulated into producing and releasing so much the highly inflammatory HSP60.

    In essence, you are feeding it until it is comfy and sprawling in its chair at the dining table, and then whacking it upside the head before it can spew its hot sauce at you. I know, a terrible metaphor, but it's the best I could do. You get the point?

    In theory this approach should limit turning Cpn into cryptic form by the treatment and make it more directly susceptible to the protein synthase inhibitors (like doxycycline and azithromycin).

    In theory, it should also winnow down the cryptic load one has acquired, along with its inflammatory affects, without needing to kill it directly with flagyl. Flagyl would be used to "clean up" persistent/cryptic forms not gotten to by this approach.

    Also in theory, the second dose of pyruvate for reactions to the antibiotics should supply the fundamental cellular energy needed to help lower the generation of porphyrins.

    Dr. Stratton outlines below the experimental protocol that they have found, in a small subset of cases, to offer less difficult and faster treatment of Cpn. Please remember that this is experimental, and has not been clinically used with a wide array of Cpn related diseases yet, so should not be engaged in without a knowledgeable clinician to monitor treatment.

    From Dr. Charles Stratton, 4/24/08

    My thoughts on the current Stratton Protocol is that this is a work in

    progress, but given what we know now, it would be the following:

    NAC 600 mg one a day to test "Chlamydial Load."

    If no reaction, go to 1,200 mg twice a day.

    If a severe reaction ("Flu-Like" reaction), use low dose prednisone (5 mg per day) for the first few weeks of therapy.

    The next step would be two weeks of a macrolide (clarithromycin preferred because of higher levels obtained, roxithromycin, or azithromycin) with 6 grams of pyruvate given 1 hour prior to the antibiotic dose. In addition, 400 mg of Ibuprofen should be taken twice a day along with 1,200 mg of NAC twice a day. For those with severe reaction, low dose prednisone 5 mg per day. For those who get a severe reaction with the pyruvate/macrolide, 3-4 days of low dose prednisone could be tried. Also, using additional pyruvate (3-6 grams) for reaction should be tried.

    For those that have a major side effect on the pyruvate/macrolide alone, I'd continue to treat with the macrolide alone until the side effects are manageable. For those that don't, I'd add doxycycline 100 mg twice a day with 6 grams of pyruvate 1 hour before. Continue the NAC and Ibuprofen.

    After two weeks of doxycycline if all went well, I'd add metronidazole 500mg twice a day with 6 grams of pyruvate before that. If a reaction is seen.

    To the metronidazole, I'd then pulse it until the reactions were manageable.

    If minimal reactions, I'd continue therapy for at least 1 year and then recheck titers. If titers were low, I'd add rifampin or rifabutin (preferably), using the rifamycin with pyruvate taken 1 hour before the rifamycin. If no reactions to this, I'd consider the therapy to be complete.

    I would continue to monitor titers every several years. If the titers increased, I'd retreat with 6 months of clarithromycin or roxithromycin plus rifabutin plus pyruvate and ibuprofen. I'd continue the NAC for life.

    For people on the existing CAP who are being switched:

    For those on the current Doxycycline, Azithromycin, Metronidazole, and NAC protocol, my thoughts are that they should first switch from Azithromycin 250 MWF to Clarithromycin 500 mg twice a day (or Roxithromycin) and then add pyruvate

    Dr. Stratton adds that Levaquin may be used instead of Clarithromycin for a short period (one month) as it has excellent activity for a short period of time. Clarithromycin = higher levels. Levoquin Both when combined with pyruvate theoretically will provide better killing.

    Severe neutropenia among healthy volunteers given rifabutin in clinical trials

    Glen Apseloff, MD, Clinical Pharmacology & Therapeutics, December 2003

    This is probably why those "big" studies of 6 months of azithromycin showed no lowering of risk of heart disease---it's not caused by the replicating form of Cpn and the idiots never asked a microbiologist about what might kill cryptic Cpn!

    Heat shock protein 60 from Chlamydia pneumoniae elicits an unusual set of inflammatory responses via Toll-like receptor 2 and 4 in vivo.

    Da Costa CU, Wantia N, Kirschning CJ, Busch DH, Rodriguez N, Wagner H, Miethke T.

    Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany. Eur J Immunol. 2004 Oct;34(10):2874

    Effects of Repeated Chlamydia pneumoniae Inoculations on Aortic Lipid Accumulation and Inflammatory Response in C57BL/6J Mice†

    Liisa Tormakangas, et al

    INFECTION AND IMMUNITY, Oct. 2005, p. 6458-6466 Vol. 73, No. 10

    Worsened MRI Findings During the Early Period of Treatment with Penicillin in a Patient with General Paresis.

    Zhang SQ, Wan B, Ma XL, Zheng HM.

    J Neuroimaging. 2007 Nov 6

    Role of Heat Shock Proteins in Protection from and Pathogenesis of Infectious Diseases

    Ulrich Zugel and Stefan H.E. Kaufmann

    Microbiology Reviews, Jan. 1999, p. 19-39 Vol. 12, No. 1

    Ethyl pyruvate: a novel anti-inflammatory agent

    M. P. Fink

    2007 Blackwell Publishing Ltd Journal of Internal Medicine 261; 349-362

    Jim K Thu, 2008-05-08 22:51

    Stratton Combination Antibiotic Protocol Update: February 2006

    Stratton Combination Antibiotic Protocol Update: February 2006

    Dr. Charles Stratton writes: 

    As far as the ideal Cpn Antimicrobial Regimen is concerned, my thoughts (as of 2/06) are as follows:

    First, as a general rule, the sicker a patient is, the slower they should go. This is why our protocol started out with only one antibiotic and one dose, and then gradually adding the next dose/antibiotic as the reactions to each dose/antibiotic become apparent. These reactions, as you know, can be delayed by days to weeks.

    I still think that all patients should start with supplements/vitamins before they start any antibiotics. Baseline lab studies, including liver function studies, should be done and these parameters followed every 3-4 months, more frequently when INH is added. Our initial protocol, as you know, recommended this.

    I would add NAC to the supplements. We used amoxicillin in our regimen as an anti-elementary body agent, but NAC seems to work equally well and may offer additional benefits in boosting the immune system and protecting the liver. As far as supplements/vitamins are concerned, I think David's supplement/vitamin suggestions are very complete and should be the bench mark.

    Once antibiotics are ready to be started, I would start with a macrolide. We like azithromycin because it is easy to give and has become somewhat cheaper since it went off patent. I would still give just one 250 mg azithromycin tablet and then wait two weeks to see if there is any reaction to it. Then I would give two tablets, one on Monday and one on Wednesday. Once again I would wait two weeks.

    I'd continue in this way, adding each dose until the patient was taking 250 mg of azithromycin MWF. If the patient has severe reactions (meaning they can't work - most people are trying to work and take care of a family while they are on this therapy), I'd slow down the process.

    After the azithromycin, I'd add doxycycline - again doing this very slowly. Once the patient was taking both azithromycin and doxycycline, I'd start the metronidazole pulses - again, doing these slowly and working up to a once a month pulse.

    Once the patient could do the monthly pulse of metronidazole, I'd add rifampin, 150 mg BID. Once this was tolerated, I would add INH 300 mg QD to the metronidazole pulse, doing so slowly (i.e. pulsing both the metronidazole and INH together, Ed.).

    Once a patient could do this regimen without any reactions, I would continue it for at least a year and probably three for MS. It might take a year or two (or longer) to get to the point where there is no reaction to the metronidazole/INH pulse, depending on the chlamydia load, followed by 1-3 years of therapy. This might be a 5 year program, but should allow the patient to continue to work with minimal disruption. They, as you know, should also be gradually improving during this time. The sicker the patient is, the longer the therapy is going to be. There is no shortcut.

    With MS patients, due to the possible CNS damage that might occur by going slowly, I would move more quickly unless there were major reactions. This means compressing what might have taken a year into several months. (Ed note: David Wheldon has written his concurrence with this, "I think Chuck's update is excellent: it's clear in matters of detail. Where MS is rapidly progressive, and I know from experience that it can progress frighteningly fast, I too would speed things up with the protein-synthesis inhibitors, paying the price of reaction for stopping progression.")

     

    As you can see with Cpnhelp.org, the reactions patient have are varied - some are severe enough that they stop the antibiotics. That, of course, defeats the purpose of the therapy. It is very tricky and each patient needs to learn their own limitations. Cpn.help is very useful in providing support. When we started this, we were thinking of a hotline to answer questions that are now easily and better answered via the internet.

    Finally, I don't think this is the only regimen that will work nor do I think it will work better or faster. It is just what I would do in 2006 if I were treating a patient.

    Take care,

    -Chuck Stratton MD

    Jim K Tue, 2006-02-07 21:08

    B-12 Deficiency in Cpn Infection: Dr. Stratton's 2005 recommendations

    B-12 Deficiency in Cpn Infection: Dr. Stratton's 2005 recommendations

    As I could not find this in the current Handbook, I thought I'd create it's own page so it is more easy to locate! This is from a treatment handout created by Dr. Stratton in 2005, but the information is still relevant:

    II. THERAPEUTIC REGIMEN FOR VITAMIN B12 DEFICIENCY
        Many patients with systemic/chronic chlamydial infection appear to have a subtle and unrecognized vitamin B12 deficiency at the cellular level. This functional B12 deficiency can be documented in an individual patient by obtaining both a vitamin B12 level (usually normal or low) and serum homocysteine and methylmalonate levels (one or both of these metabolites will be elevated). This vitamin B12 deficiency can corrected by high-dose vitamin B12 therapy as follows:
    1. Vitamin B12 Therapy Prior to Chlamydial Therapy
        Adults normally have approximately 3,000 mcg of vitamin B12 in body stores, mostly in the liver. Initial vitamin B12 therapy before chlamydial therapy includes replacement therapy for any vitamin B12 deficit in these body stores. Therefore, over the first several days of antiporphyrin therapy, 6,000 mcg of parental (intramuscular or subcutaneous) vitamin B12 is given. For each of the next 3 weeks, 6,000 mcg of parental vitamin B12 is given once per week.
    2. Vitamin B12 Therapy During Chlamydial Therapy
        Chlamydial antimicrobial therapy is associated with increased need for vitamin B12. Therefore, 6,000 mcg of parental vitamin B12 (3,000 mcg in each anterior thigh) is given once per week while the patient is receiving antimicrobial therapy for systemic/chronic chlamydial infection. This is in addition to the 5,000 mcg of sublingual vitamin B12 taken three times each day.
    3. Vitamin B12 Therapy Post Chlamydial Therapy
        Following the completion of antimicrobial therapy of systemic/chronic chlamydial infection, the vitamin B12 and serum homocysteine/methylmalonate levels should be rechecked. If the methylmalonate level remains elevated, it suggests a continued vitamin B12 deficiency. Oral therapy with 5,000 mcg of sublingual cobalamin three times per day should be continued. After several months, 6,000 mcg of parental vitamin B12 may be given as a therapeutic trial. If the patient’s energy is not increased by the parental dose, continued therapy with sublingual vitamin B12 is probably adequate. Periodic trials of parental vitamin B12 can be used to assess the sublingual therapy.
    See the following note and web site for additional information on B12. Sublingual B12 can be obtained from <puritanspride.com>.

    Below is an introduction from the article: "Vitamin B12: Surprising New Findings" by Terri Mitchell

    The whole article can be found at: http://www.lef.org/magazine/mag2000/dec2000_report_b12_1.html

    For years, vitamin B12 languished as the vitamin that cures anemia. Hardly any research was done into what this vitamin could do for non-anemic people. It turns out that it may do a lot. New studies show that the right amount of B12 can protect against dementia, boost immune function, maintain nerves, regenerate cells and more. B12 is in the news because it lowers homocysteine and protects against atherosclerosis. It's also vital for maintaining methylation reactions that repair DNA and prevent cancer. One of the crucial areas for B12 is the brain. It's not surprising that people with B12 deficiency develop mental disorders. The vitamin is crucial for the synthesis or utilization of important neuro-factors including monoamines, melatonin and serotonin. In addition, B12 is absolutely critical for the function and maintenance of nerves themselves. B12 is needed for methylation reactions that maintain these cells, and enable them to function. B12 contributes to brain function by lowering homocysteine. Homocysteine is a toxic by-product of methionine metabolism that can damage neurons. Importantly, homocysteine interferes with the methylation reactions critical for brain function. Studies show that people with elevated homocysteine can't think.
     

    Jim K Mon, 2007-12-24 21:44

    Dr. Stratton Answers Some Questions:

    Dr. Stratton Answers Some Questions:

    In some recent correspondance with Dr. Stratton at Vanderbilt University, he kindly answered some of the questions which had formed as I've understood more about the combination antibiotic protocol and about Cpn. From the patient's perspective I wanted to correlate some observations about treatment reactions with his deeper understanding about the biology of the Cpn. I'll list the questions I put to him, and then his generous response below.

    1.  In an earlier correspondance you had mentioned pulsing the INH band metronidazole together.
            * Why do that rather than take it continuously?
            * My understanding is that INH is one of the anti-replicatives, and the point is to use these continuously to drive the bug into the cryptic phase where it will be obliterated by the flagyl/tini. Does INH act differently than the other antireplicatives?
            * I also understood that we use a dual abx to prevent developing resistance. Why can we use INH alone without developing resistance?
     

    2. Although doxy/azith/mino and the other antireplicatives are not supposed to kill Cpn, only inhibit it's replication, clearly everyone with any kind of bacterial load reports a die-off reaction as they start these agents. People commonly note some agents as causing more die-off than others, azith for example seems to create more die-off than doxy. This could, of course, be an inexact measure of immunomodulatory action or it's lack, but azith is definitely immunomodulatory. My experience and others on the site say that it generates more die-off. What do you think this die-off is from? Do the antireplicatives also kill Cpn? 

    3. About flagyl and energy increase: Although often this agent creates a more challenging die-off reaction, it can also result in a burst of energy and reduction in brain fog. The liberation of energy and brain fog after (sometimes during) pulses suggests to me that the so called "non-metabolizing" or "dormant" image of the cryptic phase is incorrect. If cryptic Cpn wasn't stealing host energy or gumming up the machinery in some way, it should not have such an energizing effect to kill it. After all, flagyl isn't killing the RB's which we know are actively using host ATP.

    JimK 

     Dr. Stratton responds:

    Here are some of my thoughts on your questions. First of all, remember that Cpn is able to shift to different phases in its life cycle. In order to eradicate the organism, you have to deal with all three phases and, I believe, you have to deal with them simultaneously. For example, INH alone does not eradicate Cpn from a cell culture, INH plus metronidazole does not eradicate Cpn from a cell culture, but INH plus metronidazole plus penicillamine does eradicate Cpn from a cell culture. (NAC does the same as penicillamine.)

    So, Stratton Rule Number One is that the best effect is going to be when all the antibiotics are present. It doesn’t mean that you have no effect if all are not present, just that the best effect is when all are present.

    One combination that we tried years ago was INH, Bactrim, and Amoxicillin (i.e., penicillamine). People got better while on the drugs, but relapsed when they were stopped, even after years of therapy. Therefore, Cpn was not eradicated.

    My educated guess would be that INH is more potent, but physicians are not happy prescribing INH. By the way, the most potent combination (in the original studies described in the patent materials) was metronidazole, INH, and penicillamine (NAC does the same thing.). My thoughts would be to pulse INH along with the metronidazole, starting slowly (1 pill at a time) so as to reduce the side effects. As long as you are also taking NAC, the metronidazole/INH pulse should root out Cpn very effectively. Again, the average physician is probably unwilling to do this. Because INH is known to have hepatotoxicity and physicians feel uncomfortable using it and thus must obtain monthly liver function tests when using it. This suggests to me that a pulse would be better (less risk of liver toxicity unmonitored), and if the best effect is when the metronidazole is present, that is when the pulse should be done.

    Now, on the resistance issue: INH is a prodrug and is converted to the active drug, a free-radical,  by catalases/peroxidases – which may be supplied by the pathogen or perhaps by the cell, if the cell is a monocyte/macrophage. Metronidazole is also a prodrug and is converted by electrons to the active drug, a free-radical. Free-radicals damage DNA/RNA and can destroy the pathogen and in some cases the host cell. Although it does happen, resistance to free-radicals is much less likely to occur.

    Why the antireplicatives create die-off-
    Moreover, Cpn can prevent apoptosis (natural cell death), a cell mechanism to deal with intracellular pathogens. When Cpn is shut down by macrolides or tetracyclines and can’t make the proteins that prevent apoptosis, apoptosis can happen and the cell dies. The more cell death, the more side effects.

    Finally, Cpn-infected cells are protected from additional Cpn entering the cell and causing more infection in the same cell. When infected cells are cleared, they can then be re-infected if elementary bodies are nearby. This is why a reducing agent such as NAC is so important as they eliminate the elementary bodies. Re-infection is why we like rifampin, which prevents the re-infection as it targets the DNA-dependant RNA polymerase – elementary bodies need this enzyme to transform to a reticulate or cryptic body.

    Also, both the replicating phase and the cryptic phase may be stealing ATP – but the cryptic phase may also have anaerobic metabolism at work and thus be generating ATP as well. It’s all very complicated and much is theoretical. Hope this helps. Take care.

    -Chuck Stratton, M.D.
     

    Jim K Mon, 2006-01-30 22:13

    Dr. Stratton Cautions on Protecting the Liver

    Dr. Stratton Cautions on Protecting the Liver
    In recent correspondence, Dr. Stratton has been discussing reports in the medical literature that certain antibiotic agents can cause liver damage or failure. Noting that these agents are typically the most potent anti-chlamydials, he has drawn some important hypotheses from this that anyone on an antibiotic protocol should know about.

    His cautionary note is that use of some of the new, powerful agents against Cpn must be carefully monitored, and that a more gradual treatment for many is advisable. His observations also affirm the importance of supplements in their liver-protective role.

    Dr. Stratton notes:
    "A recent report of Ketek causing liver failure has crystallized some thoughts that I have had for some time. Cpn can infect the liver and the kidney, but in particular the liver is a target due to the Kupfer cells. Any drug that acts against Cpn (including statins) will therefore in some patients cause hepatic damage or even hepatic failure. The better the activity against Cpn of the agent (or combination of agents), the more likely the liver damage. Even penicillamine can cause liver damage, as does Augmentin.

    "Surprisingly, the only anti-chlamydial agent that did not cause hepatitis in some patients was NAC. In fact, NAC is recognized as being protective. See attached references. My conclusion is that NAC should be the first agent in an anti-chlamydial regimen and should be a constant part of the therapy for this protective effect, not to mention it’s effect against elementary bodies. This, of course, is another reason to go slowly, but liver damage has been seen with only a few days of Ketek, for example. Notice the NAC in the Clarithromycin-induced hepatic injury in the end seemed protective in that transplantation was not needed. I think this caveat needs to be in the therapy Website. Although we have not seen hepatitis in any of our patients at Vanderbilt, soon or later this could happen."

    Dr. David Wheldon concurs that this is a very important observation by Dr. Stratton, noting that it takes someone of Dr. Stratton’s depth of understanding about Cpn’s affect on body systems to recognize these reports as possibly Cpn related (ie not necessarily toxicity originating from the drug itself). Dr. Wheldon notes that, in addition to NAC, supplements such as Alpha-Lipoic Acid, acetyl-L-carnitine, selenium and zinc, are also important liver protectors. These all have been recommended supplements for people taking a combination antibiotic protocol for Cpn.

    Dr. Wheldon also noted that in his protocol, recommendations for using agents such as doxycycline, azithromycin and NAC were considered both because of their antichlamydial affect, but are less known for liver toxic. Dr. Wheldon also patterned his protocolo after Dr. Stratton’s early recommendations to start gradually and add to the combination only as patients tolerate die-off.

    References:
    Isoniazid- and rifampicin induced oxidative hepatic injury– protection by N-acetylcysteine
    Attri, S. et al
    Human & Experimental Toxicology (2000) 19, 517-522

    Long-term ethanol administration enhances age-dependent modulation of redox state in different brain regions in the rat: protection by acetyl carnitine.
    Calabrese V, Scapagnini G, Latteri S, Colombrita C, Ravagna A, Catalano C, Pennisi G, Calvani M, Butterfield DA.
    Int J Tissue React. 2002;24(3):97-104.

    Brief Communication: Severe Hepatotoxicity of Telithromycin: Three Case Reports and Literature Review
    Kimberly D. Clay, MD, MPH; John S. Hanson, MD; Scott D. Pope, PharmD; Richard W. Rissmiller, MD; Preston P. Purdum III, MD; and Peter M. Banks, MD
    21 March 2006 | Volume 144 Issue 6 |
    Carolinas Medical Center, Charlotte Gastroenterology and Hepatology, Carolinas HealthCare System, and Carolinas Pathology Group, Charlotte, North Carolina.

    Fulminant Liver Failure Associated with Clarithromycin
    Andreas Tietz, Markus H Heim, Urs Eriksson, Stephan Marsch, Luigi Terracciano, and Stephan Krähenbühl
    The Annals of Pharmacotherapy_2003 January, Volume 37,  57-60

    Role of nutritional fatty acid and L-carnitine in the final outcome of thioacetamide hepatotoxicity
    Sanjay Chanda and Harihara M. Mehendale
    Vol. 8 October 1994 The FASEB Journal 1061-1068

    Mitigation of oxidative stress in cyclophosphamide-challenged hepatic tissue by DL-alpha-lipoic acid.
    Selvakumar E, Prahalathan C, Mythili Y, Varalakshmi P.
    Mol Cell Biochem. 2005 Apr;272(1-2):179-85.

    Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress
    Tory M. Hagen, Jiankang Liu, Jens Lykkesfeldt, Carol M. Wehr, Russell T. Ingersoll, Vladimir Vinarsky, James C. Bartholomew, and Bruce N. Ames
    1870 –1875  PNAS  February 19, 2002  vol. 99  no. 4 www.pnas.org

    Abrogation of Nuclear Factor-Involved in Zinc Inhibition of Lipopolysaccharide-Induced Tumor Necrosis Factor- Production and Liver Injury
    Zhanxiang Zhou, Lipeng Wang, Zhenyuan Song, Jack T. Saari, Craig J. McClain, and Y. James Kang*
    American Journal of Pathology, Vol. 164, No. 5, May 2004

    Jim K Tue, 2006-02-07 21:35

    Case Reports from the Mitchell, Stratton et al patent

    Case Reports from the Mitchell, Stratton et al patent
    patent 6,838,552
                                 TABLE 11
    Serological and PCRi Responses to Combination Antibiotic Therapy
    Months of
    Combination
    Pa- Titer Antibiotic
    tient Diagnosisa IgMi IgGi Therapy PCR Status
    PH FM 800 800 6 months + Asymptomatic
    3200 1600 +
    800 200 wk+
    BL MSi 2000 500 9 months + Dramatic
    400 3200 9 months wk+ Improvement:
    MM CFSi/AND 3200 800 1 month.sup. + Improvement;
    400 1600 + Relapse
    (non-
    compliant)
    PM CFS 2000 25 6 months + Asymptomatic
    400 800 wk+
    AM IBD 800 0 6 months wk+ 90%
    3200 400 + Improvement
    FO MS 800 3200 10 months st+ Improvement
    800 800 + in speeds and
    400 600 wk+ bowl contin-
    400 800 + ence
    WM CF 25 25 Pre-illness wk+ Asymptomatic
    1000 25 serum <-- st+
    50 800 Antibioticsi +
    50 1600 start wk+
    50 400 -
    HM CF 2000 100 6 months + Asymptomatic
    3200 3200 +
    200 800 wk+
    CN CFS 3200 800 8 months + 75%
    800 800 wk+ Improvement
    AN MS/CFS 400 400 wk+ Strength .uparw.
    200 3200 st+ Fatigue .dwnarw.
    JS CFS 2000 2000 5 months st+ Asymptomatic
    (severe) 2000 2000 +
    200 800 -
    AG IBD 3200 400 9 months + Improvement
    800 400 + in joint Sx
    800 800 +
    800 400 -
    AT CF 3200 3200 9 months + Asymptomatic
    1600 1600 +
    1600 1600 +
    800 800 +
    400 400 +
    LH RAi 3200 1600 6 months wk+ Improvement
    600 400 wk+
    200 50 +
    HS MS 2000 400 5 months + Improvement
    3200 800 +
    50 200 -
    ST CFS/FM >1000 100 7 months wk+ Asymptomatic
    1000 100 wk+
    400 100 +
    800 3200 +
    100 100 +
    RV CF 1000 100 10 months + Asymptomatic
    400 1600 +
    400 400 -
    a CF = Chronic Fatigue < 6 months
    CFS = Chronic Fatigue Syndromei
    FM = Fibromyalgiai
    IBD = Inflammatory Bowel Diseasei
    MS = Multiple Sclerosisi
    AND = Autonomic nervous dysfunction (neural-mediated hypotension)
    RA = Rheumatoid Arthritis
    IgM >> IgG .fwdarw. immunei tolerance to the antigeni
    IgG >> IgM .fwdarw. successful immune control of the antigen

    CAP for Chlamydia pneumonia since 11/04. 25yrs CFS & FMSi- Currently: 300mg INHi, 200 Doxycyclinei, 500mg MWF Azithromycini, 1000mg Tinii daily (Taking a break from continuous protocol)


     Even more detailed case

     Even more detailed case descriptions in the latter part of Patent: 6,884,784

    Response to Antibiotic Therapy

    Table 13(a) illustrates typical responses to combination antibiotic therapy in a variety of patients with diagnostic evidence of an active infection by C. pneumoniae. Unlike typical immunei responses to infection with infectious agents, most of the included patients have not only detectable IgMi titers against the chlamydial genus but in many cases very high IgM titers. With specific therapy over time the IgM titers generally fall, with a rise in IgGi titer (as expected). Current methods of detecting antibodies against C. pneumoniae (Indirect immunofluoresence, MIF) are incapable of accurately identifying high IgM titers against C. pneumoniae. Moreover, current procedures are genus specific and not species specific as are peptide-based ELISAs.

    With clearing of the pathogen, the IgG titers fall. Concomitant with combination antibiotic therapy, there is generally an improvement of patient symptoms associated with the specific diagnosis indicative of evidence of an active chlamydial infection.

    Table 13(b) describes the course of therapy for a number of individuals treated with a combination of agents and their clinical outcomes.

    Table 13(c) describes the detailed case histories of the patients undergoing combination therapy, as reported in Table 13(b).

    Table 13(d) provides a listing of drugs and standard dosages for those used herein.

                                TABLE 13a
    Serological and PCRi Responses to Combination Antibiotic Therapy
    Pa- Diag- Titer Time on
    tient nosisa IgM IgG Therapy PCR Status
    PH FM 800 800 6 months + Asymptomatic
    3200 1600 +
    800 200 wk+
    BL MSi 2000 500 9 months + Dramatic
    400 3200 wk+ Improvement
    MM CFSi/ 3200 800 1 month + Improvement;
    AND 400 1600 + Relapse
    (non-compliant)
    PM CFS 2000 25 6 months + Asymptomatic
    400 800 wk+
    AM IBD 800 0 6 months wk+ 90% Improvement
    3200 400 +
    FO MS 800 3200 10 months st+ Improvement in
    800 800 + speech and bowel
    400 800 wk+ continence
    400 800 +
    WM CF 25 25 Pre-illness wk+ Asymptomatic
    1000 25 serum st+
    50 800 <--Anti- +
    50 1600 biotics wk+
    50 400 start -
    HM CF 2000 100 6 months + Asymptomatic
    3200 3200 +
    200 800 wk+
    CN CFS 3200 800 8 months + 75%
    800 800 wk+ Improvement
    AN MS/ 400 400 wk+ Improved Strength
    CFS 200 3200 st+ Fatigue decrease
    JS CFS 2000 2000 5 months st+ Asymptomatic
    (severe) 2000 2000 +
    200 800 -
    AG IBD 3200 400 9 months + Improvement
    800 400 + in joint Sx
    800 800 +
    800 400 -
    AT CF 3200 3200 9 months + Asymptomatic
    1600 1600 +
    1600 1600 +
    800 800 +
    400 400 +
    LH RAi 3200 1600 6 months wk+ Improvement
    800 400 wk+
    200 50 +
    HS MS 2000 400 5 months + Improvement
    3200 800 +
    50 200 -
    ST CFS/ >1000 100 7 months wk+ Asymptomatic
    FM 1000 100 wk+
    400 100 +
    800 3200 +
    100 100 +
    RV CF 1000 100 10 months + Asymptomatic
    400 1600 +
    400 400 -
    a CF = Chronic Fatigue < 6 months, CFS = Chronic Fatigue Syndromei,
    FM = Fibromyalgiai, IBD = Inflammatory Bowel Diseasei, MS = Multiple
    Sclerosis, AND = Automatic nervous dysfunction (neural-mediated
    hypotension), RA = Rheumatoid Arthritis
    IgM >> IgG: immune tolerance to the antigeni; IgG >> IgM:
    successful immune control of the antigen


    TABLE 13b
    Treatment Regimens
    Treatment Regimen
    Phase of Chlamydial Life Cycle
    EBi (Extra- or EB->RB Stationary Replicating
    RB->EB Duration
    Patient Sex Diag Intracellulari) Transition Phase RB RB
    Transition Enhancer (months) Comments
    BL M MS Rifampin Flagyli Floxin
    2
    Flagyl Bactrim,
    5
    Levaquin
    -- -- -- -- --
    3 Took a break, had relapse
    Flagyl Bactrim,
    2
    Levaquin
    Penicillimine Flagyl Bactrim,
    Penicillimine 7
    Levaquin
    Penicillimine Rifampin INHi INH
    Penicillimine Probenicid 3
    MC M MS Rifampin INH INH
    9
    Flagyl
    Levaquin
    6 Probably not compliant
    Minocyclinei
    -- -- -- -- --
    -- Discontinued
    JM M MS Flagyl Floxin
    7
    Bactrim
    Minocycline
    Amoxicillini Levaquin
    Amoxicillin 4
    Bactrim
    Amoxicillin Levaquin
    Amoxicillin Probenicid 3
    Bactrim
    LL F MS Flagyl Levaquin
    15
    Minocycline
    Penicillimine Levaquin
    Penicillimine Probenicid 1
    Minocycline
    AN F MS Tenitizole Floxin
    7 She was given a copy of the
    protocol, but ran her own
    therapy
    FO M MS
    Prednizone 0.25 Phased in over several days
    to mitigate effect of therapy
    Flagyl Biaxin
    2
    Biaxin
    1 Stopped flagyl due to
    persistance of side effects
    Kemet Biaxin Kemet
    0.5
    Kemet Flagyl Biaxin Kemet
    6 Began phasing Flagyl back
    in over a month
    Kemet Flagyl Biaxin Kemet
    1 Began 2 week switchover to
    Amoxicillin
    Amoxicillin Amoxicillin
    Amoxicillin Flagyl Biaxin
    Amoxicillin 2
    Amoxicillin Flagyl Biaxin
    Amoxicillin Probenicid 6 Began 6 week phase in of
    probenicid
    JC F MS Amoxicillin
    Amoxicillin 1 Phased in over 7 months.
    Amoxicillin
    Amoxicillin Probenicid 1
    Amoxicillin Bactrim
    Amoxicillin Probenicid 1
    Amoxicillin INH Bactrim
    Amoxicillin Probenicid 7
    FW M MS Penicillimine Flagyl Doxicycline
    Penicillimine 7
    Penicillimine INH INH
    Penicillimine Probenicid 5
    Bactrim
    -- -- -- -- --
    -- Stopped treatment
    LH F RA Penicillimine Flagyl Minocycline
    Penicillimine 11
    Penicillimine Flagyl Minocycline
    Penicillimine Probenicid 3
    -- -- -- -- --
    -- 3 PCR negative, symptom
    free, but titer @ 1:800.
    Decided to stop.
    Penicillimine Flagyl Minocycline
    Penicillimine Probenicid 2 After symptoms flared, PCR
    went positive, and titer to
    1:1600, restarted therapy
    XX F IC Amoxicillin INH INH
    Amixicillan Probenicid 4 Symptoms gone after 4
    Bactrim
    months of treatment
    NC F PG Amox INH INH
    Amoxicillin 7 Continued improvement
    Bactrim
    CH M PG Amoxicillin INH INH
    Amoxicillin 3
    Levaquin
    Amoxicillin INH INH
    Amoxicillin 2
    Bactrim
    -- -- -- -- --
    -- Discontinued after all ulcers
    cleared up except for those
    in poorly blood-supplied leg
    RI M PG
    Missing patient chart
    PL M PG Amoxicillin INH INH
    Amoxicillin 2 Non-compliant because
    Bactrim
    could not afford medicines
    -- -- -- -- --
    -- 1
    Amoxicillin INH INH
    Amoxicillin 0.5 Would often only take what
    Bactrim
    he had left.
    -- -- -- -- --
    -- 2 Off for 2 months, then flared
    Amoxicillin INH INH
    Amoxicillin 1 No subsequent follow-up
    Zithromaxi
    TW M PG Flagyl Minocycline
    4
    Amoxicillin INH INH
    Amoxicillin 2
    Levaquin
    -- -- -- -- --
    1
    Amoxicillin Levquin
    4 No improvement
    -- -- -- -- --
    Moved to topical antibioticsi
    AM M UC Flagyl Biaxin
    11
    Amoxicillin Flagyl Biaxin
    Amoxicillin 2
    INH INH
    Amoxicillin Flagyl Bactrim
    Amoxicillin Probenicid 5 Now doing very well
    INH INH
    AG F UC Flagyl Doxycyclinei
    6
    -- -- -- -- --
    -- Discontinued after
    symptoms resolved.
    DM F IBD Flagyl
    7
    Cupramine1 Flagyl Doxycycline
    Cupramine Probenicid 5
    -- -- -- -- --
    -- Discontinued after doing
    well clinically; wanted to
    start a family.
    RP F UC Flagyl Biaxin
    5
    -- -- -- -- --
    -- Discontinued after impvt
    AB F CD Flagyl Doxycycline
    7
    -- -- -- -- --
    -- Non-compliant
    EU F UC Flagyl Doxycycline
    9
    -- -- -- -- --
    -- 1 Stopped
    Amoxicillin Flagyl Doxycycline
    Amoxicillin Probenicid 2 Restarted after symptoms
    flared. Now doing well again
    RR CD Flagyl Doxycycline
    2 Colectomy 2 months prior
    Amoxicillin Flagyl Doxycycline
    Amoxicillin Probenicid 6 Now doing well; no
    evidence of active disease
    1 125 mg BID


    TABLE 13c
    Detailed Case Histories
    Patient Diag Test data1 Case History
    BL MS Row 2 First symptoms began with numbness of the left arm
    and leg which rapidly
    progressed to a partial Brown-Sequard syndrome
    (i.e.-cord myelitis) with an
    associated urinary retention. Despite therapy with
    corticosteroids, and Beta
    interferon he rapidly progressed over the next
    three months with an EDSS - 8.0
    (triplegic plus speech and swallowing impairments).
    A positive CSF PCR and
    culture for C. pneumoniae led to treatment with
    combination antibiotics. The
    patient improved on all spheres of neurologic
    function over the following six
    months. HIS EDSS score 9 months later was 3.0 with
    return to work and routine
    athletic activities (e.g.-jogging). His
    neurological status remains stable and he
    continues on an anti-chlamydial combination
    regimen.
    MC MS This patient had a ten year history of MS with
    evidence of progressive ataxia and
    weakness in the legs. Over 5 months his EDSS score
    worsened from 7.0 to 8.0.
    His CSF was positive by PCR for C. pneumoniae and
    he was placed on
    combination antibiotics. Over the next six months
    he gradually improved in his
    balance, coordination and lower extremity strength.
    His most recent EDSS score
    was 6.5.
    JM MS Initially seen with rapidly progressive paraparesis
    secondary to MS. He failed to
    response to corticosteroids on two successive
    occasions. Five months later, his
    EDSS score was 7.5. Following a positive C.
    pneumoniae PCR he was placed on
    combination antibiotics. He has gradually gained
    strength in his lower
    extremities and five months later was able to walk
    with a walker (EDSS = 6.5)
    while being maintained on combination antibiotics.
    LL MS Patient with a long history (14 years) of secondary
    progressive MS with recent
    progressive bulbar symptoms, axtaxia, and
    paraplegia (EDSS = 8.5). PCR for the
    MOMP gene of C. pneumoniae in the CSF was positive.
    She was placed on
    combination antibiotics with no further progression
    of symptoms for the last six
    months.
    AN MS Row 10 Long history of MS and wheel chair bound for
    approximately ten years. She has
    received continuous physical therapy to retain leg
    muscle tone. Following
    approximately 6 months of combination antibiotics,
    she was able to stand
    unaided and take several unaided steps. She reports
    a significant decrease in
    fatigue and cognitive dysfunction. She remains on
    combination antibiotics and
    other supportive medications.
    FO MS Row 6 Wheel chair bound with a long history of MS with a
    2-3 year progression of
    severe dysarthriae and incontinence. On combination
    antibiotics (14 months) he
    has had improvement of speech and incontinence.
    Speech, ability to open
    mouth for dentist, stamina all improved. Can stand
    better on his own mid-
    transfer. He remains wheel chair bound.
    JC MS Diagnosis of MS with development of a foot drop
    approximately one year prior
    to therapy requiring the use of a cane in walking.
    Approximately four months
    after initiation of combination antibiotic therapy,
    patient reports reversal of foot
    drop and no longer requires a cane. She continues
    on antibiotic therapy.
    FW MS Male executive in late 50s with a year history of
    MS. Used a cane for a rolling,
    unstable gait. Easily fatigued: After 12 months of
    combination antibiotics, was
    able to walk without cane or excessive fatigue,
    although his gait can still wander.
    Can easily make it across the parking lot, which
    had previously been a challenge.
    Stopped antibiotics even though was still PCR
    positive; plans to restart therapy if
    he has another flare-up.
    LH PA Row 14 Patient LH had an active case of RA which was
    moderately debilitating.
    Following two months of combination antibiotic
    therapy, her RA is in complete
    remission.
    XX IC She responded to combination antibiotics with
    complete remission of symptoms
    after one month. Cessation of antibiotics resulted
    in a return of IC symptoms.
    NC PG PCR + 61 year old man who had had lesions for several
    years. Large ulcerated lesions
    on feet that resolved on combination antibiotic
    therapy. Only residual
    hypertrophic scars remain.
    CH PG PCP + 75-year-old male diabetic with multiple, large,
    severe lesions on both legs,
    abdomen, and arms. Lesions first formed in 1993.
    Severity of process required
    chronic nursing home care at an estimated cost of
    $300-400 per day. All lesions
    above the knee have resolved on combination
    antibiotic therapy: lesions only
    remain on right lower leg, where inadequate blood
    supply offers poor prognosis.
    The patient no longer requires nursing home care.
    RI PG PCR + Original severe PG lesions on legs required
    bilateral amputation. Lesions now
    occurring on arms. Treatment with combination
    antibiotics has resulted in
    resolution of lesions although not complete to
    date. [No update - chart missing]
    PL PG PCR + 18 year old female with history of leg ulcers.
    Multiple PG lesions completely
    healed on combination antibiotic therapy. Patient
    then lost his job and could
    not afford to maintain drug regimen. Upon
    re-flaring of ulcers, re-started
    therapy and ulcers improved again.
    TW PG Severe PG, initiated after a chemical burn in 1991,
    but with PCR negative
    serologyii for C. pneumoniae. Patient did not
    initially respond to combination
    antibiotic therapy. A positive biopsy culture for
    C. pneumoniae resulted in the
    recent re-institution of combination antibiotics.
    However, after no
    improvement, patient went off therapy.
    AM IBD Row 5 This is a 35 year old male who first presented as a
    prostititisi ten years ago at the
    age of 25. This progressed to acute ulcerative
    colitis, involving the entire colon,
    which was associated with severe arthritis, iritis,
    and weight loss. Diagnosis was
    biopsy confirmed. Control required high doses of
    corticosteroids and azacol.
    Attempts to reduce steroids resulted in partial
    control of symptoms. Six months
    prior to initiation of combination antibiotic
    therapy, patient was experiencing
    frequency (20-25 times per day), frank bleeding,
    and mucus in the stool. Patient
    on combination antibiotics for one year. Following
    significant stress, patient had
    significant increase in symptoms. Alteration of
    antibiotic combination has
    resulted in normal bowel habits with no mucus and
    minimal blood. Associated
    neuropsychiatric manifestations of cognitive
    dysfunction and depression have
    resolved. Steroids have been discontinued.
    AG IBD Row 12 This is a 27 year old white female with two month
    history of fulminate,
    progressive ulcerative colitis which had not
    responded to the usual medical
    therapy. A total abdominal colectomy with ileostomy
    and rectal pouch was
    done. The microscopic appearance confirmed
    ulcerative colitis. Following the
    colectomy, the patient experienced neurologic
    symptoms, fatigue, myalgias,
    arthralgias, and a acneoform skin rash. Serology
    was performed for C.
    pneumoniae and was positive with an IgM of 1:3200,
    IgG 1:400, and PCR positive.
    Therapy with combination antibiotics was initiated.
    After six months of
    antimicrobial therapy, her serology was IgM 1:800,
    IgG 1:400, and PCR positive.
    The neurologic symptoms, fatigue, myalgias,
    arthralgias, and acneoform rash
    resolved completely. There was no further evidence
    of inflammatory bowel
    disease, and the ileostomy was successfully
    anastomised to the rectal stump. The
    patient has felt more energetic. Serology after 1
    year was PCR negative.
    DM IBD This 37 year old female had a six year history of
    inflammatory bowel disease
    (uncertain CD or UC) associated with painless
    rectal bleeding, arthritis, myalgias,
    skin ulceration, abdominal cramping/diarrhea, and
    rectal fistulas. She had
    increasing fatigue which caused her to frequently
    miss work as a minor
    executive. On combination antibiotic therapy, all
    symptoms resolved but
    recurred with cessation of antibiotics while on
    vacation. Reinstitution of
    combination antibiotics resulted in a second
    remission of symptoms.


    Prior to
    combination antibiotic therapy, she had not gone
    longer than 3 months without
    an anal manifestation of IBD. She has been symptom
    free of IBD for over a year.
    RP IBD Patient presented with proctocolectomy and
    ileostomy due to UC. Following a
    flu-like illness in 1993, she became fatigued and
    anemic with blood-tinged
    diarrhea. Examination of her ileostomy pouch
    revealed inflammationi and
    ulcerations. Upper GI series/small bowel series
    revealed no abnormalities and
    no cause of her anemia was diagnosed. On
    combination antibiotics her
    ileostomy activity was more regular and less
    spastic. She claimed to feel better
    with higher energy levels and ceased antibiotic
    therapy. Six months post-
    antibiotic therapy she remained asymptomatic other
    than a moderate anemia.
    AB IBD Patient with long history of CD involving small
    bowel, large bowel, and anus.
    She had been treated with a small bowel resection
    and fissurectomy. She
    continued to suffer from numerous rectal fistulas.
    On combination antibiotics
    she experience some symptomatic improvement but
    failed to completely resolve
    her IBD symptoms. She discontinued antibiotics due
    to a probable chronic
    Herxheimer reaction. Currently she is lost to
    follow-up.
    EU IBD Colitis with inflamed distal sigmoid colon and
    proctitis associated with frequent
    loose stools with significant mucus. Following six
    weeks of combination
    antibiotic therapy with a significant reduction in
    symptoms. Shortly after
    cessation of antibiotics her symptoms return.
    Reinstitution of antibiotics
    resulted in a second remission of the majority of
    her symptoms with resolution
    of her proctitis on visual exam.
    NM CFS Vanderbilt University initial patient that resulted
    in our first association of C.
    pneumoniae, initially complained of the insidious
    onset of debilitating fatigue.
    This was associated with a severe cognitive
    dysfunction that disrupted his ability
    to function as the supervisor of a clinical
    diagnostic laboratory. Despite six
    months of intensive diagnostic efforts by the
    Infectious Disease Clinic at
    Vanderbilt no definitive or presumptive diagnosis
    could be made. A subsequent
    high antibody titer against C. pneumoniae led to
    standard anti-chlamydial
    antibiotic therapy over a three month period with
    gradual disappearance of
    fatigue and cognition symptoms. On cessation of a
    fluroquinolone antibiotic,
    symptoms returned within two weeks. He was placed
    on combination
    antibiotics with complete reversal of symptoms
    after six months. He remains
    asymptomatic.
    JS CFS Row 11 Academic physician with a greater than 10 year
    history of CFS. Cognition
    problems resulted in his grounding himself as a
    private pilot. Initial treatment
    with combination antibiotics results in an apparent
    Herxheimer reaction with
    resolution over a two week period with gradual
    improvement in symptoms.
    After three months therapy, he piloted a light
    aircraft under instruments from
    Florida to North Carolina. He remains on
    combination antibiotics for over a
    year and is asymptomatic.
    PM CFS Row 4 Physician with long-standing CFS. Treated with
    combination antibiotics with
    gradual resolution of symptoms. During course of
    treatment developed cardiac
    myopathy. Currently asymptomatic from CFS. Cardiac
    myopathy resolved over
    six month period on combination antibiotics.
    MM CFS Row 2 CFS and AD. Resolution of postural tachycardia over
    1 month combination
    antibiotic therapy. Partial reversal of fatigue
    during this period. Patient non-
    compliant after one month and lost to follow-up.
    PH FM Row 1 Three year history of debilitating FM following the
    stress of being a stalking
    victim. Patient relatively asymptomatic after nine
    months combination
    antibiotic therapy.
    CN CFS Row 9 Five year history of severe CFS with debilitating
    cognitive dysfunction and
    depression. Gradual improvement on combination
    antibiotics for
    approximately nine months. Estimated 75% of normal
    function.
    PG CFS Ten year history CFS with cognitive dysfunction.
    Complete response to
    combination antibiotics over a course of one year.
    AT CF Row 13 Moderate fatigue and cognitive dysfunction
    following acute infectious illness.
    Depression was major problem. During one year
    course of combination
    antibiotics fatigue and cognitive dysfunction
    largely reversed. During mid-
    course of therapy patient developed acute anxiety
    attacks relieved by anti-
    porphyrin therapy.
    WM CF Row 7 CF following acute stress. Pre-illness serum
    negative for anti-Chlamydia
    pneumoniae antibodies which peaked six weeks
    following stress. Pre-illness PCR
    was weak positive that became strongly positive. On
    combination antibiotic
    therapy at 3 months became asymptomatic. Cessation
    of antibiotics resulted in
    symptomatic relapses. Currently asymptomatic with
    low serum antibodies and
    negative PCR.
    HM CF Row 8 Medical student with short history of CF and
    cognitive dysfunction affecting
    studies. Combination antibiotics over a multi-month
    course resulted in
    complete reversal of symptoms.
    ST CFS Row 17 Mother of Patient AT. Three year history of CFS
    with FM. Combination
    antibiotic therapy has resulted in partial reversal
    of symptoms allowing her to
    retain a job in jeopardy. Estimated 80-90% normal
    function currently.
    RV CF History of fatigue although non-incapacitating.
    Combination antibiotic therapy
    has resulted in 100% return to normal function.
    EB CFS Teen-ager with long history of CFS resulting in
    home-bound schooling. On
    combination antibiotic therapy returned to school
    and recently graduated.
    Recovery has not been complete probably secondary
    to non-compliance in
    therapy.
    Jim K Wed, 2007-08-22 22:06

    Dr. Michael Powell: A Rheumatologist Treating Cpn in CFIDS, FM, Lupus and other "auto immune" disorders

    Dr. Michael Powell: A Rheumatologist Treating Cpn in CFIDS, FM, Lupus and other "auto immune" disorders

    I spoke with a rheumatologist in California, Dr. Michael Powell, who is cautiously using a combination of antibiotics in conjunction with standard therapeutics for the treatment of nanobacterium (including Cpn) in patients suffering from FM, CFS and autoimmune disorders. His results with this treatment program have been encouraging. He faxed me some examples of patient feedback forms, excerpts from which you can see below. Recovery is not instantaneous, but tends to occur over a 6 to 12 month period. The graphs of subjective improvement are drawn from visual analogue scores compiled during each visit. When summarized in this manner these data give a time-lapsed impression of the response to treatment.

    One of the interesting things he mentioned was in relation to negative patient serology for Cpn when other clinical signs lead him to suspect some involvement. Serologic assays for IgG, IgM and IgA are sent to confirm infection prior to treatment. He would like to see a positive serology in patients before engaging them in a combination antibiotic protocol, but recognizes that patients may not have antibody reactions. This may be due to the ability of intracellular organisms like Cpn to evade a humoral response (antibody production), immunoglobulin depletion, or other factors. In these cases, when there is a high index of suspicion for the infection without a humoral response, he tests the spouse of the partner for Cpn. He sees the "non-symptomatic" partner as a good indicator of Cpn in the patient, given the infectious nature of Cpn. Thus far, most spouses are positive when an ill family member is non-reactive.

    In our discussion Dr. Powell pointed out the many similarities between TB and Cpn.  Both organisms  can evade our immune system.  Both organisms can be carried from the lungs, the original site of infection, and infect other tissues. Both require prolonged treatment with multiple drugs to eradicate the infection.  Both are sensitive to stress levels. Optimal therapy is being evaluated at various research centers and new medications for Cpn are on the horizon (see activbiotics.com).

    INH and supplements for endotoxins-
    Dr. Powell finds most patients improve on a standard combination antibiotic protocol for Cpn. Rheumatologist have apparently been using doxycycline for many years with success for inflammatory arthritis but there is evidence that using doyxcycline in combination with rifampin is even more effective. Some patients plateau after about 8 months of treatment he has found variations in the treatment protocol have made a difference. One protocol he uses involves the use of NAC 600 mg twice daily, INH 300 mg once daily before breakfast, and metronidazole 500 mg twice daily pulsed with 5 days on and two weeks off.  It is essential to start each agent separately and gradually increase the dose over weeks or months as tolerated.  The use of Vitamin C 500 - 1000 mg four times daily (the half life of vitamin C is 30 minutes and little remains after 3 hours) to offset the release of toxins during therapy.  B6 is important to control INH related peripheral neuropathy.  Monthly laboratory evaluation of AST, ALT, Cr, and CBC are recommended for all who engage in this protocol.  It is not uncommon for liver enzymes to show a mild elevation during the initial stages of treatment.  Antibiotic therapy should be temporarily discontinued during periods of toxicity, should it arise. He emphasized the importance of insuring that yeast and fungal infections do not overgrow during protracted antibiotic use. He recommends the use of acidophillus, nystatin, diflucan, oregano oil, and/or grapefruit seed extract as needed to prevent secondary opportunistic infection during treatment.

    Covering for the possibility of yeast and fungal overgrowth during antibiotic therapy is essential.  If diarrhea develops, stool must be evaluated for antibiotic associated diarrhea (C. difficile).  This is not a simple protocol and it is best if it is guided by an experienced clinician who is familiar with the medications and methods of minimizing toxicity related to killing the nanobacterium.

    A link to Dr. Powells clinic may be found on our links page. Dr. Powell does do telephone consultations by arrangement and may be a resource for those who have had difficulty finding a Cpn knowledgeable doctor in their area. He requires an initial visit with a physical examination before initiating therapy (lab work can be performed prior to the initial visit to facilitate diagnosis and treatment), and monthly laboratory testing with monthly phone consults are then the norm. Treatment of related hormone imbalances in the thyroid system and nutritional support, temporary antidepressant support as needed, and sleeping medications are useful adjuncts to the antibiotic protocol. It is necessary for patients to have a primary care physician to monitor health matters that are unrelated to FM, CFS and autoimmune disease.

     

     65 year old patient

    52 year old patient 

    39 year old patient 

    Jim K Sun, 2005-11-06 16:33

    Comments on CAP variations from Dr. Michael Powell

    Comments on CAP variations from Dr. Michael Powell

    I asked Dr. Powell to comment directly on concerns that have been mentioned over time as to whether he uses the CAP with his new patients. I received his response a number of weeks ago but have had no time to put it together in a cogent context. But continued posts on these questions has mobilized me to get his comments to our readers here. But context is, as we say, everything.

    A problem with reading posts on a website such as www.cpnhelp.org is that one does not really have the whole context of that particular person's illness, medical history, the complexity of what is happening in their body as a result of more and more systems being affected by more than one thing going on. While it is perfectly fitting that our site here has it's mission focus of treating Cpn via combined antibiotic (and other relevant antichlamydial agents such as Vitamin D, tocotrienols, etc.), a physician is treating, hopefully, a patient rather than a bacterium.

    I'm a clinician myself, although a psychologist rather than a physician. One of the things that becomes clear is that the particular clinical population one sees, the kind of clinical practice you have, shapes your understanding of what's needed in order to help people. If you are curious and growing as a professional, you are always learning from the particular complexity of what you see in your patients: what helps them, what doesn't; how general approaches fit and don't fit; and how you need to go beyond the standard approach to respond to what's real, where the standard prescriptive algorithms "You must always do these things and these things only..." fails utterly to help those you must care for.

    A doctor who sees mostly patients with neurological problems related to chronic infection as from Cpn will get attuned to how those conditions respond and to the complex interactions of treatment with the rest of the person's health process. A physician who sees rheumatological patients learns what works well and what doesn't in that population, and the nuances of attuning treatment to the whole spectrum of patients, even to see the difference of patients who have the same disease label.

    A physician who sees a lot of complicated cases has two options as a professional. One is to learn to think more broadly and reject the formulaic, in order to account for and encompass, that complexity. The other is to narrow their viewpoint to the accepted practice and say, "Well I do this, I don't know about those other things." The latter is perfectly acceptable to my thinking, as we all need to know our professional limits. But I thank God for those who are willing to grasp the former position, such as Dr. Stratton, Dr. Wheldon, and Dr. Powell amongst others, and dig deeper into things.

    You see, I'm one of those complicated-type cases, and it has taken a nuanced and complex approach to get treated properly. I'd been sick so long and with so many different systems affected, and likely not just by Cpn, that it has taken a complex clinician to weed through the layers of debris, gradually clearing the tangled mess my health had become. Cpn and the CAP has been at the center of my treatment, hence my devotion to maintaining this website, but it has not been the only thing in my treatment, nor the only concern of my physician.

    Dr. Powell reflects below on the questions and concerns that have evolved for him through many years of treating Cpn and other infectious inflammatory conditions in his rheumatology practice. He was among the first physicians to use Dr. Stratton's protocol actively in his practice, and has a lot of cases under his belt using the CAP. And he found out about Dr. Stratton's work through his own researches and insistent curiosity. No websites were then available to inform him. That should tell you something about his intellect and curiosity. I think his questions are good ones for any of our readers to ask and consider. They might just help us broaden our thinking the way we hope that our physicians will be willing to broaden theirs.

    **********************************

    Dear Jim,

    Thank you for bringing these concerns to my attention. I am not opposed to treating infected people with antimicrobials. But I do think we all need to ask a few important questions before we start CAP. What is it we expect from CAP? What is CAP this month? Can we clear Cpn? Is Cpn like herpes viruses that can not be cleared, only pushed back? If one has an overgrowth of Cpn does that say something about their immune system? How many other infections does the average Cpn person have? Do you treat the viruses first or second? Could the viruses flare while you are stirring up die off reactions with antibiotics? Does the oxidative stress of these die off reactions have negative consequences to the immune system, neurological system and key infection opposing nutrient levels? For how long do we want to take antibiotics?

    These are reasonable questions to ask.

    It is important to understand that:

    1.) No one knows which CAP combination is optimal.
    2.) No one knows how long to treat. 3 months? 12 months? 3 years? Longer?
    3.) No one knows if the infection can be cleared...clearing every elementary body, every cryptic, every reticulocyte form? Is that a realistic expectation?
    4.) No one knows how many other infections are present and whether it might be better to begin with those, such as by using antivirals, before starting CAP.
    5.) No one knows what impact genetics are playing in these infections and few people know how to compensate for genetic predisposing factors (e.g supporting methylation defects helps to oppose infection).

    People need to be realistic when they are considering CAP treatment and make sure they are not approaching these infections with the expectation that taking multiple antibiotics for a few months is going to restore their vitality. Please be sure to mention that you and I have seen CAP fail.

    I have seen antiviral therapy work tremendously well with some who have failed CAP. That means something. I have seen people recovering faster with sauna, Iodoral and infection-opposing nutrients (weeks rather than months) and that is why I may start with these. When people are done having die off with these measures, they tolerate antivirals and antibiotics better and can get back to working and living full lives faster.

    If someone comes to me with a 2/10 ratings of their energy and depleted levels of essential nutrients and hormones, the worst thing I can do is send their energy to 0/10 by increasing the demands on their system through premature initiation of antibiotic therapy. I have patients who say that the T3, Vitamin D and infrared sauna have had the largest impact on their health. Some patients respond best to antiviral medication while others respond best to NAC, Zithro, Flagyl. Some patients seem to respond better to NAC, Rifampin, Doxy, Nifedipine. Some patients do very well with IM or IV gammaglobulin if they are hypogammaglobulinemic. Last week I saw a gentleman who failed CAP and antiviral therapy, but he has returned to work feeling better in years after adding niacin therapy. A recent study from Harvard confirms the antibacterial and antiviral properties of niacin, but liver enzymes need to be watched if the dose is increased about the RDA. The doctor can not know in 2008 which modality will work best because we do not know who we are dealing with in terms of these mixed infections and varied genetic mutations.

    Starting treatment by restoring depleted nutrient levels before starting antibiotics is not a bad idea. Running into battle with your nutritional levels around your ankles is short sighted and likely to cost you more in than preparing properly and building a strong defense before going for the antibiotics and antivirals. I would be surprised if most of the people who dropped out after I recommended sauna actually tried sauna twice daily for 20 minutes as recommended. I have had so many patients swear by this benign method and I have seen recovery occur much faster for those who do daily sauna. Seriously, people tend to respond in weeks rather than months if they are doing daily sauna therapy.

    In summary, there is no proof that even 3 years of CAP will clear Cpn in humans. I have seen CAP work wonders for those whose illness is linked to Cpn or other polymorphic bacterial infections, which is why I continue to recommend this important therapy. It is wise to minimize antibiotic exposure as much as possible and most patients want to transition from antibiotics to infection opposing supplements as soon as possible. There is no test that can prove to the patient or the physician that Cpn or any other chronic infection is eradicated, so we are forced to use clinical symptoms as a guide. Herpes viruses persist forever, but when herpes is in remission people do not feel the infection. It may be that this is also true for Cpn.

    We believe the best way to address these infections and restore health is to begin by strengthening the immune system rather than stress the patient's system in the initial stages of treatment. We have tried it both ways and we have better results by starting treatment with measures that support methylation, restore depleted nutrients, increase body temperature and WBC function. Then when the die off from these measures has subsided, antivirals and antibiotics are discussed and can be started more safely. I can't say this enough times, there is no proof that you can ever clear these infections or even know how many different organisms are involved. Check the websites for Lyme, Mycoplasma and other occult infections...relapse is very common. That is why we think it is essential to build one's defenses and improve immune function as the primary focus of therapy. It is wishful thinking to presume that 6-12 months of CAP will restore health in most fatigued patients. If only it were that simple.

    Best regards,

    Michael Powell, D.O.

    Jim K Sun, 2008-03-09 22:42

    Expert Comments

    Expert Comments

    Note: In a few cases these expert comments may have been superceded by updates to the particular protocols mentioned. Please use the CAP's descriptions in the Cpn Handbook as the most up to date versions of the protocol's using these Expert comments as useful sidebar information where they differ from current practice. 

    Comments by physicians treating various diseases with a Cpn protocol and by scientists and researchers studying Cpn.

    Comments by David Wheldon

    Comments by David Wheldon on antibiotics in his protocal and the Vanderbilt protocal

    Comments by David Wheldon MD on treating MS with Cpn protocal"

    David Wheldon on Relapse and Pseudo-Relapse treating MS for Cpn

    David Wheldon comments on Cpn endotoxins & reactions

    David Wheldon comments on steroid use with Cpn infection 


    Comments by Dr A

    Expert close to Vanderbilt work describes thorough treatment of Cpn: an interview.

    Dr. A comments on EB load and severity of illness.

    Dr A comments on Flagyl use. 

    Picture of EB's riding on Red Blood Cells 


      Dr. Michael Powell

     

    A Rheumatologist Treating Cpn in Chronic Fatigue, Fibromyalgia and other auto immune disorders-

     Dr. Powell Comments on Niacin in Cpn Infection and other supplements


     

    Dr. Charles Stratton

    Indicator of B12 deficiency 

    <!--break-->

     

    Jim K Wed, 2005-08-24 08:06

    First Report: Results of CAP's Treatment Survey #1

    First Report: Results of CAP's Treatment Survey #1

    Finally we have the results of our first survey of CAP's treatment!

    The detail hounds might find a few numbers that don't add up. If so, let me know and I'll double check the data. It's as accurate as I could get it given mostly hand tabulation. I'm relying on you to keep me honest, as I'm only one day post Tini and not seeing everything clearly this morning!

    Please remember that these are small numbers reporting in, and a rather rough set of questions. It's a survey, not a statistical study. The charts are impressive, but should be taken with caution as visual aids can look better than the data set they come from!

    Find it at:

    First Report: Results of CAP's Treatment Survey #1 

    Jim K Tue, 2006-04-04 10:09

    Stratton/Mitchell & Siram Case Reports

    Stratton/Mitchell & Siram Case Reports

    Does it work?

    It has been noted that most users of the combination antibiotic protocols commenting here have not been on the treatment long enough to give a big enough pool of reports to feel assured of the efficacy of this approach. I had asked Drs. Stratton, Wheldon, and Powell to perhaps tally up at least some basic numbers from their case experience to help us out with this problem, but this would involve problems of confidentiality and use of private data, etc.  

    Then, I suddenly realized that we already have a good list of anecdotal reports of response to treatment reported data available to us... right in the Stratton/Mitchell patent materials! (Sheepish, embarrassed grin). So I took it as a project to summarize this data by disease treated. Occasionally I have used the exact wording from the patent materials as they were brief and descriptive. We have the full text referenced in our treatment and links if you want to see more detail.

    All reported had with positive serology for Cpn using the highly sensitive tests developed by Stratton/Mitchell. I left out a few whose diagnosis was not clear to me, you can see them in the patent materials #6,884,784
    All on some form of the combination antibiotic therapy protocol.

    MS

    1. EDSS score 8.0- Treatment nine month- EDSS 3.0
    2. EDSS score 8.0 Treatment six months- EDSS 6.5
    3. EDSS score 7.5.  Treatment five months- EDSS 6.5.
    4. EDSS score 8.5  Treatment six months- no further progression of symptoms
    5. 10 years wheel chair  bound  Treatment six months- stands unaided, several steps, dec fatigue and cognitive dysfunction.
    6. Long hx MS with 2-3 year progression   Treatment fourteen months- improved incontinence, stamina, speech. Continues to be wheel chair bound.
    7. One year MS, foot drop, walks with cane.   Treatment four months- no longer requires cane.
    8. One year MS. Cane, rolling gait, fatigue.   Treatment twelve months- no cane, no fatigue on walking

     

    RA

    Treatment two months. Complete remission of RA symptoms.

    IC

    Treatment two months. Complete remission of symptoms. Stopped tx, return of IC symptoms.

    IBD

    1. Treatment six months. No further evidence of IBD. Bowel habits normal, no steroids, cognitive dysfunction and depression resolved.
    2. Treatment six months. No further evidence of IBD. Neurologic, fatigue, myalias, athralgias, rash resolved.
    3. Six year history of inflammatory bowel disease (uncertain CD or UC) associated with painless rectal bleeding, arthritis, myalgias, skin ulceration, abdominal cramping/diarrhea, and rectal fistulas. She had increasing fatigue. Symptom free (after going off abx on vacation and relapsing) after one year of treatment. On combination antibiotics her ileostomy activity was more regular and less spastic. She claimed to feel better with higher energy levels and ceased antibiotic therapy. Six months post- antibiotic therapy she remained asymptomatic other than a moderate anemia.
    4. On combination antibiotics she experience some symptomatic improvement but failed to completely resolve her IBD symptoms. She discontinued antibiotics due to a probable chronic Herxheimer reaction. Currently she is lost to follow-up.
    5. Colitis with inflamed distal sigmoid colon and proctitis associated with frequent loose stools with significant mucus. Following six weeks of combination antibiotic therapy with a significant reduction in symptoms. Shortly after cessation of antibiotics her symptoms return. Reinstitution of antibiotics resulted in a second remission of the majority of her symptoms with resolution of her proctitis on visual exam.

     

    CFS

    1. Insidious onset of debilitating fatigue. This was associated with a severe cognitive dysfunction that disrupted his ability to function. Combination antibiotics with complete reversal of symptoms after six months. He remains asymptomatic.
    2. 10 year history of CFS with severe cognition problems. Herxheimer reaction with resolution over two week period on treatment. He remains on combination antibiotics for over ayear and is asymptomatic.
    3. Physician with long-standing CFS. Treated with combination antibiotics with gradual resolution of symptoms. During course of treatment developed cardiac myopathy. Currently asymptomatic from CFS. Cardiac myopathy resolved over six month period on combination antibiotics.
    4. Five year history of severe CFS with debilitating cognitive dysfunction and depression. Gradual improvement on combination antibiotics for approximately nine months. Estimated 75% of normal function.
    5. Ten year history CFS with cognitive dysfunction. Complete response to combination antibiotics over a course of one year.
    6. Moderate fatigue and cognitive dysfunction following acute infectious illness. Depression was major problem. During one year course of combination antibiotics fatigue and cognitive dysfunction largely reversed. During mid-course of therapy patient developed acute anxiety attacks relieved by anti-porphyrin therapy.
    7. Fatigue following acute stress. On combination antibiotic therapy at 3 months became asymptomatic. Cessation of antibiotics resulted in symptomatic relapses. Currently asymptomatic with low serum antibodies and negative PCR.
    8. Short history of CF and cognitive dysfunction affecting studies. Combination antibiotics over a multi-month course resulted in complete reversal of symptoms.
    9. Three year history of CFS with FM. Combination antibiotic therapy has resulted in partial reversal of symptoms allowing her to retain a job in jeopardy. Estimated 80-90% normal function currently.
    10. History of fatigue although non-incapacitating. Combination antibiotic therapy has resulted in 100% return to normal function.
    11. Teen-ager with long history of CFS resulting in home-bound schooling. On combination antibiotic therapy returned to school and recently graduated. Recovery has not been complete probably secondary to non-compliance in therapy.



    FM

    Three year history of debilitating FM following the stress of being a stalking
    victim. Patient relatively asymptomatic after nine months combination
    antibiotic therapy.

    Siram's cases

    You will find followup reports from Dr. Siram's cases by a man who actually tracked down personally those he could find. These are all MS cases, and all report improvement, some quite spectacular, such as the wheelchair bound tri-pelegic former cop who was able to resume his former job! But please note: some people used flagyl, and other antibiotics only. The inconsistencies of degree of improvement seems mostly due to this factor in my read. Remember that this was in 1994 when the understanding of the importance of the whole protocol, especially the critical importance of flagyl, was still evolving. Click here for link.

    Jim K Sat, 2006-01-21 20:33

    Summary Chart of Different CAP Protocols

    Summary Chart of Different CAP Protocols

    We have been preparing this for an eventual overhaul of the Handbook, but there have been a number of requests, especially by new folks, to help clear up confusion.

    Combination Antibiotic Protocols-
    These charts are presented to give the brain-fogged an overview of protocols to understand the general approach, and why you may read of people on www.cpnhelp.org as using differing combinations of meds. These charts are meant for clarification only and should not be used as a starting point for doing a CAP protocol. Everyone’s case is different, and requires individual considerations. Also, understanding the many facets of Cpn and treatment reactions is crucial before engaging in treatment. Don’t start any of these without reading further in the Cpn Handbook.

     

    Summary chart of different CAP protocols

    Note:

    Jim, I'm sorry not to have read this sooner, but you appear to be making a mistake about David's regime.  You don't mention NACi until way down the list and the first alternative is given appears to be azithromycini by itself, which is incorrect as can be seen here:

    http://www.davidwheldon.co.uk/ms-treatment1.html

    A schedule of treatment.

    This is one schedule which strikes all stages of the organism's life-cycle. Other equally good schedules are possible. It is preferable that a committed care-giver (for instance, spouse, partner or parent) should ensure that medication is given, and swallowed, consistently.)

    N-acetyl cysteine (NAC) 600mg - 1,200mg twice a day, should be taken continuously. This is a commonly-taken dietary supplement, available at health-food stores. It is an acetylated sulphur-containing amino-acid, and may be expected to cause chlamydial EBs to open prematurely, exposing them to starvation; more on this and other benefits on page 4. This should be started at the lower dose of 600mg twice a day; the dose should be doubled when well-tolerated. NAC offers liver protection; this may be useful, as rapid bacterial die-off may compromise hepatic function.

    When NAC is well tolerated, Doxycyclinei 100mg once daily is added. It is taken with plenty of water.

    When the two above are well tolerated, Azithromycin 250mg orally, three times a week should be added. (Roxithromycini, 150mg twice daily, is an alternative.)

    When all three agents are well tolerated, the dose of Doxycycline is increased to 200mg daily.

    The reason for this slow, step-wise introduction of antichlamydials is to minimize any reactions caused by bacterial die-off. These can be unpleasant. NOTE: in rapidly progressive MSi it may be prudent to offset the benefits of stopping progression against the risk of reactions, giving full doses of azithromycin and doxicycline from the beginning.

    This combination is taken continuously.

    Also, The implication might be taken by some people that metronidazolei and tinidazolei are taken during a five day break fro the bacteristatics an this also applies to the Stratton Protocol.  This would seem to answer my query as to why so many newbies were asking me this question..........Sarah  

     

    Jim K Sun, 2007-07-22 11:12

    Wheldon Protocol

    Wheldon Protocol

    David Wheldon MB CHB, FRCPath (Fellow of the Royal College of Pathology) Cpn Protocol

    Dr. Wheldon's site has an excellent summary of Cpn and it's implication in disease, especially MS, and a much more complete description of the Cpn and of his treatment protocal than is given here. David updates his site regularly, and it has the best up-to-date information on supplements for Cpn treatment as well. Make sure you consult it for the latest information.

    Dr. Wheldon is a consulting medical microbiologist in England whose wife, Sarah, was diagnosed with Multiple Sclerosis. When her worsening condition and lack of useful treatment from conventional medical resources occured, Dr. Wheldon explored the emerging evidense for bacterial causation. Although Sarah did not show any serological results for Cpn, he used the Vanderbilt (Stratton and colleagues) work and his own microbiology knowledge to formulate his own protocol.

    His protocol calls for the use of two bacteriostatic agents continuously, both of which can cross the blood-brain barrier and thus are particularly geared to MS, and short pulses of Flagyl (metronidazole) an anearobic bacteriacide.

    Sarah, as well as others he has treated, has shown both symptomatic reversal and clear reduction of brain lesions shown by radiological study.

    We recommend you read his site in detail and download his treatment pdf before initiating any treatment.

    The following is extracted from his website (as of 02/07/06) and may not be complete or up to date. His website is updated frequently with new material and should be read thoroughly by anyone using a CAP for Cpn.

    Wheldon Regime

    Why doxycycline and roxithromycin (or azithromycin)?

    Both are oral, both are active against Chlamydia pneumoniae, both are relatively inexpensive. They are relatively risk-free. They act synergically against test strains of the organism; giving both together would be the equivalent of giving a four-fold increase of each drug were it to be given alone. The drugs work on different steps in the bacterial protein synthesis pathway. Combination therapy reduces the chance of the emergence of resistance. Both drugs pass into the brain. Both reach good levels inside cells. This is very important. Both are well tolerated. Azithromycin is an alternative to roxithromycin. They deplete the organisms slowly: this is very important, as the release of bacterial endotoxins should not be sudden.

    Rifampicin may also be considered. It, too, is synergic with doxycycline, penetrates the brain and is active intracellularly. It is not suitable for intermittent use. It is highly active, and, in patients with a large bacterial load, it may give rise to intense reactions.


    Why are later short courses of metronidazole to be taken together with these antimicrobials?


    Chlamydiae are complex organisms. Long ago their ancestors must once have been free-living bacteria which possessed their own energy-generating pathways. The transformation from EB to RB is an active change, and an active change implies the retention of at least some of these pathways. The ones with the most utility for this purpose would be anaerobic, and thus susceptible to metronidazole.

    Doxycycline and roxithromycin block the replicating phase by inhibiting protein synthesis and may be expected to force the organism to maintain itself by using its own primitive anaerobic respiratory mechanisms. In this suspended state it would be susceptible to anti-anaerobic agents such as metronidazole.

    This is borne out by clinical evidence. The administration of metronidazole after doxycycline in a patient with likely high-load Chl pneumoniae infection causes a bacteriolytic reaction more severe than that following the original administration of doxycycline.

    However, there is a difference: in this leg of treatment there is no risk of the emergence of resistance, for the organism is unable to replicate. Metronidazole need thus be given in courses only as long as can be tolerated.

    Five-day courses of metronidazole at three-week intervals, during continuous treatment with doxycycline and roxithromycin, would seem reasonable; at first, metronidazole may be limited to one or two doses on one or two days to judge the severity of reaction.

    The eventual aim would be to give all three agents intermittently. This, the final leg of treatment, would entail a 14 day course of doxycycline and roxithromycin, with metronidazole given from day five for five days. (The reason for continuing doxycycline and roxithromycin for a few days after the metronidazole has been stopped is because these drugs both possess anti-inflammatory activity which may prevent a reaction to the organisms killed by metronidazole.) This course would be given once a month. After several months the intervals between the antibiotics would be cautiously extended.


    Why this complex antibiotic regime?

    The literature is filled with instances of treatment-failure in serologically-proven chronic Chl pneumoniae infections of non-CNS systems, whether macrolides, tetracyclines or rifampicin have been used. When the drug is stopped, even after months of treatment, serology rises, and the patient relapses.

    The intensive cyclical regime of combined antimicrobials outlined here corrals the pathogen, initially halting replication, then eliminating stalled intracellular forms. Extracellular forms may be depleted by giving N-acetyl cysteine (see below.)

    No single antimicrobial agent can be expected to achieve this effectiveness against every phase of the organism's life.


    What are the expected reactions to the antibiotics?

    There seems to be two components to the reactions experienced on taking the antibiotics.

    The first is caused by elimination of bacterial fragments — endotoxins — and is characterised by shivering, influenzal symptoms and general malaise.

    The second is caused by the release of metabolic toxins; waves of giddiness and feelings of unreality are quite common. They are alarming if not known about and understood. The strength and duration of these reactions depends largely on the bacterial load. In MS, particularly early relapsing-remitting MS, the bacterial load is likely to be small, and the reaction brief. In other conditions, particularly those with multi-system involvement, the bacterial load may be large and the reaction to antibiotics unpleasant and prolonged.

    It may seem unlikely that doxycycline, roxithromycin and rifampicin can kill chlamydiae; they are, after all, considered to be bacteriostatic agents — normally they inhibit rather than kill bacteria. However, intracellular Chlamydia pneumoniae must continuously elaborate proteins to ensure its own survival within the host-cell.

    The reaction to the metronidazole component of treatment is particularly severe as at this stage numerous bacteria are being killed. For this reason it may be best to give an initial course of one single day, followed by review. Prochlorperazine, 10mg orally, may be useful.

    The patient can be reassured that a reaction to the antimicrobials are evidence of bacterial destruction and that they will end. And, too, the morale induced by physical improvement has to be set against them.


    Isn’t giving antibiotics for a long time is a bad thing?

    That depends on the illness. Long-term doxycycline is used fairly routinely for certain kinds of gum disease and for acne. Doxycycline is also used long-term in malaria prophylaxis.

    Long-term use of these antibiotics engenders no real risk of an increase of resistance in other bacteria within the wider community.

    What might a schedule of treatment comprise?

    What might a schedule of treatment comprise?

    Antimicrobials
    Doxycycline
    200mg once daily with plenty of water.
    Roxithromycin 150mg twice daily or Azithromycin 250mg three times a week.
    These are maintained without a break for at least six months.

    N-acetyl cysteine 600mg - 1,200mg twice a day, should be taken continuously. This is a commonly-taken dietary supplement, available at health-food stores. It is an acetylated sulphur-containing amino-acid, and may be expected to cause chlamydial EBs to open prematurely, exposing them to starvation; more on this and other benefits here.

    Two or three months into the treatment regimen, or when the patient is experiencing few problems with reactions, three-weekly cycles of intermittent oral Metronidazole are added. During the first cycle metronidazole is given only for the first day. If problems with reactions are found, the period of administration is kept short. When metronidazole is well tolerated the period of administration in each cycle is increased to five days.

    The dosage of metronidazole is 400mg three times a day. If it is suspected that a patient may have a heavy chlamydial load a smaller daily dose may be given.

    The eventual aim is to give all three agents intermittently so that the patient has a respite from antibiotics. This, the final leg of treatment, may entail a 14 day course of doxycycline and roxithromycin, with a five day course of metronidazole in the middle. This course is given once a month. After several months the intervals between the antibiotics may be cautiously extended.

    Rifampicin is not suitable for intermittent use, and azithromycin may be given instead.


    Adjuncts

    The brain has extraordinary powers of repair, but must be provided with the building-blocks by which to do it. This infection is intracellular; the organism interferes with mitochondria, the cells' powerhouses. Many of the symptoms of the disease - particularly the fatigue - may be due to mitochondrial exhaustion. Toxins known as free radicals are released as various synthetic pathways are disrupted. If this oxidative stress continues unchecked for too long irreversible mitochondrial damage may occur. A combined dietary supplementation of antioxidants is strongly recommended. (See Syburra C, Passi S. Oxidative stress in patients with multiple sclerosis. Ukr Biokhim Zh. 1999 May-Jun;71(3):112-5.)

    Vitamin C 1G daily
    E 800iu daily
    Omega 3 fish oil daily
    Evening primrose oil 1G daily
    Acetyl L-Carnitine 500mg daily
    Alpha Lipoic acid 150mg daily
    Ubiquinone (Coenzyme Q10) 200mg daily
    Selenium 200 micrograms daily.
    N-acetyl cysteine 600mg twice daily
    melatonin 1.5mg at night may be considered.

    This may seem like polypharmacy, but there are good reasons to consider these agents. This is because the mitochondrial membrane is the bottle-neck for numerous key cellular reactions, and it is exactly here that chlamydiae hover as they control the host cell and steal its vital molecules via tiny projections. These agents are available at health food stores and are obtainable on-line.

    More details on how antioxidants can act synergistically to enhance their effects, and to regenerate each other can be found on this page.

    Apart from mitochondrial support, Vitamin D is needed. There is evidence that a relative Vitamin D deficiency is common in MS, and may allow the disease process to begin. High dose supplementation - 4000iu is recommended. (less may be needed in infections other than MS) A page on this is given here.

    In addition, B complex, Magnesium, 300mg and Calcium 500mg supplements in the evening (remote from the time of taking doxycycline) daily.

    Vitamin B12 injections once weekly for 3 months, then monthly for the duration of continuous treatment; B12, (together with B6 and folate) counteracts the hyperhomocysteinaemia which accompanies chronic Chl pneumoniae infection and which is thought to cause connective tissue damage. (There is now evidence that oral B12 is satisfactorily absorbed, except in patients with pernicious anaemia. High dose supplementation is recommended.)

    Regular Lactobacillus acidophilus, daily, either as a supplement or in capsules. This is to maintain bowel flora in the face of antibiotic treatment. Tablets of Lactobacillus sporogenes spores may be considered. These have the advantage of getting into the small bowel in large numbers.

    It would be wise to avoid foods containing artificial trans-fats. These are hard fats made from unsaturated oils which, after heating under pressure, are hydrogenated in the presence of a catalyst. They are widely used because they have a long shelf life and are inexpensive. With certain exceptions hydrogenated fats are not found in nature, and are metabolized with difficulty in the body. They alter cell and mitochondrial membrane functions. Two studies in animal models have found that artificial trans-fats affect mitochondrial efficiency as measured by a reduction of ATP synthesis. [Blomstrand R, Svensson L. The effects of partially hydrogenated marine oils on the mitochondrial function and membrane phospholipid fatty acids in rat heart. Lipids. 1983 Mar;18(3):151-70; De Schrijver R, Privett OS. Energetic efficiency and mitochondrial function in rats fed trans fatty acids. J Nutr. 1984 Jul;114(7):1183-91.] Dietary intake of trans-fats increases systemic inflammatory markers in humans. [Mozaffarian D, Pischon T, Hankinson SE, et al. Dietary intake of trans-fatty acids and systemic inflammation in women. Am J Clin Nutr. 2004;79:606–12.; Baer DJ, Judd JT, Clevidence BA, Tracy RP. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets: a randomized crossover study. Am J Clin Nutr. 2004;79:969–73.] If the words 'hydrogenated oil' or 'partially hydrogenated oil' appear in a list of ingredients then trans-fats are likely to be present. (It may be noted that dairy products and animal fats also contain a small proportion of trans-fats, but these naturally occurring trans-fats are digestible and were beneficial in animal studies; evidence is less clear-cut in humans. [reviewed by Wang Y, Jones PJ. Dietary conjugated linoleic acid and body composition. Am J Clin Nutr. 2004 Jun; 79(6 Suppl): 1153S - 1158S.])

    Turmeric, the yellow spice used in Indian cooking, may be very useful. The active ingredient, curcumin, moderates the pro-inflammatory effects of bacterial endotoxin, probably by restraining the activation of nuclear factor-kappa B. 'Nuclear factor kappa B has been implicated in autoimmune and inflammatory diseases, infection, cell survival, and cell transformation with subsequent promotion of cancer.'
    [Reviewed by Holmes-McNary M. Nuclear factor kappa B signaling in catabolic disorders. Curr Opin Clin Nutr Metab Care. 2002 May;5(3):255-63.]

     

    Why this complex antibiotic regime?

    The literature is filled with instances of treatment-failure in serologically-proven chronic Chlamydia pneumoniae infections of non-CNS systems, whether macrolides, tetracyclines or rifampicin have been used. When the drug is stopped, even after months of treatment, serology rises, and the patient relapses. The intensive cyclical regime of combined antimicrobials outlined here corrals the pathogen, initially halting replication, then eliminating stalled intracellular forms. Over a number of cycles it is expected that the load of extracellular forms will be reduced to negligible levels. There is evidence that in persistent infections the extracellular forms are scarce. No single antimicrobial agent can be expected to achieve this.

    What are the expected reactions to the antibiotics?

    There seems to be two components to the reactions experienced on taking the antibiotics.

    The first is caused by elimination of bacterial fragments — endotoxins — and is characterised by shivering, influenzal symptoms and general malaise. The second is caused by the release of metabolic toxins; waves of giddiness and feelings of unreality are quite common. They are alarming if not known about and understood. The strength and duration of these reactions depends largely on the bacterial load. In MS, particularly early relapsing-remitting MS, the bacterial load is likely to be small, and the reaction brief. In other conditions, particularly those with multi-system involvement, the bacterial load may be large and the reaction to antibiotics unpleasant and prolonged.

    The early bacteriolytic (Herxheimer) reaction can be alarming. And, as Sarah found, as-yet unorganised repair can cause function to worsen in the short term. This could easily lead to an early impression that antibiotics were unhelpful or even harmful and could have led to their discontinuance.

    Jim K Tue, 2005-08-23 22:08

    Clinical Outcomes: a small data-set

    D W

    Clinical outcomes. Here is a summary of the clinical outcome of treatment on the ten patients seen in my laboratory, with established progressive MS (or progressive neurological illness with MS-like features.) The diagnosis of MS was made at consultant neurologist level.

    10 patients were seen and received treatment and were followed up.

    In 7 of these progression of the disease was halted.
    In all 7 there was some resolution of symptoms.
    In all 7 resolution continues.
    6 of these 7 patients had cognitive deficits; these were reversed in all 6.

    In 3 of the 10 patients progression continued despite 6M treatment.
    In 1 of these patients there was little doubt over compliance with medication.
    In 2 of these patients compliance with medication was doubtful.

    Acute relapse was seen in no patient.

    It is a very small number. It includes only those patients seen and followed up on at least three occasions by myself, so does not include self-reporting or anecdotal cases. (It should be borne in mind that the natural history of progressive disease is towards deterioration: although there may be plateaux of stability, the likelihood of a spontaneous global remission is very slim.) David

    Thank you, David.  The part I like best is "In all 7 the resolution continues".   The part I am sorry about is so little faith, so little compliance.  Personally, I have other things I would rather do, but the trade-off is  -  let me see, should I make a list beginning with thinking, dressing, swallowing, walking..........17 months, every day  and my list continues to grow.

    Rica 

    Ignorance is voluntary bad luck.  Lauritz S.   A true Viking

    If you come to a fork in the road, take it. Yogi Berra

    3/9 Symptoms returning. Began 5 abx protocol 5/9 Rifampin 600, Amox 1000, Doxy 200, MWF Azith 250, flagyl 1000 daily. Began Sept 04 PPMS EDSS 6.7 Now good days EDSS 1 Mind, like parachute, work only when open. Charlie Chan  In for the duration.&am

     David- Thanks for posting this. Really important to have actual data sets available. So many of us "in process" here that it's hard to stand back and know how powerful this work is. These results are unheard of for MS. Guess this isn't just a pet theory, huh? This goes in the Handbook!

    On Wheldon/Stratton protocol for Cpn in CFS/FMS since December 2004.

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Here is a very interesting and very positive 9-month-long trial for spondyloarthropathy in which chlamydial involvement was suspected. Doxy alone did very little. The patients in the "real" treatment arm, doxy plus rifampin, saw ~2x reductions in multiple measures - pain (visual analog scale), morning stiffness (hours), tender joint count, swollen joint count.

    J Rheumatol 31.10.1973-80, 2004.

    I think there are also some negative trials out there for a similar patient population. One would want to examine whether the regimes used in such trials might simply have been far too weak.

    More great news - thank-you so much for the report!

     

     

     

    On Wheldon protocol for MS since April, 2006.  LDN 1994

    5oo mgs Ceftin 2 x/day, 500 mgs Zithromax, 500 mgs 2 x tini pulses,100 mg diflucan, 4.5 ldn; Wheldon protocol for MS April, 2006 to May 2008. 2008 MRI shows NO NEW DISEASE ACTIVITY, 2012 MRI no new disease activity.

    David Wheldon Comments on How Flagyl/Tinidazole works on Cpn

    David Wheldon Comments on How Flagyl/Tinidazole works on Cpn
    There are reasons for thinking that the MBC (Minimum Bacteriocidal Concentration) of metronidazole against cpn 'frozen' by protein-synthesis inhibitors may be quite low. Metronidazole enters the bacterial cell by passive diffusion. Of itself it has little antibacterial activity, but in susceptible bacteria its highly reactive metabolites break the bacterial DNA at the AT base-pair; these are single-strand breaks, and are repairable. In ordinary anaerobic bacteria the outcome (death or survival) is decided by the equation of breakage versus repair.

    Under normal circumstances, the organism, at the first sign of DNA damage, will switch on its 'last chance saloon' repair mechanism. However, this repair mechanism requires the synthesis of at least 15 proteins. The 'frozen' organism is unable to make them. Thus DNA damage is likely to be ongoing and remain unrepaired. New metronidazole is also entering the bacterial cell by passive diffusion all the time, there being a concentration-gradient across the bacterial cell-wall as the intracellulari metronidazole is converted to active metabolite. Further, one might postulate that the endosome is likely to maintain a high concentration of active metabolite: the organism's refuge becomes its death-chamber. If this is the case, one could make an argument for a sustained rather than a high-dose medication. Speaking from my own experience I experienced little during my first five-day pulse of metronidazole (400mg three times a day): the fireworks came on day 4 of the second pulse, and continued long after stopping the drug. And what fireworks they were. I wish I had filmed the muscle fasciculationsi. Metronidazole does not now affect me, apart from its rather nauseating taste.

    The metronidazole is active against chlamydia only when protein-synthesis inhibitors have forced the chlamydia to switch to a sluggish anaerobic pathway. The same protein-synthesis inhibitors then prevent repair of DNA damage caused by metronidazole-metabolite. Synergy on two fronts: I have to say it again - it's one of the neatest concepts in antimicrobial therapeutics. My admiration goes to the Vanderbilt workers who first considered this.
    Jim K Fri, 2006-03-03 22:09

    Cpn Handbook Table of Contents

    Cpn Handbook Table of Contents Jim K Sat, 2006-02-18 22:25

    Recommended Supplements and Adjuncts to CAP's

    Recommended Supplements and Adjuncts to CAP's

    Supplements and other treatments are considered essential, not optional, when using CAP's. They are important to counter secondary porphyria symptoms, counter the endotoxins from Cpn die off as well as the cytokine inflammation, protect the vital organs of the body from Cpn toxins, and help provide the elements need for the body to rebuild and regenerate cells lysed (killed) when the Cpn infecting them is killed.

    David Wheldon's website contains vital and important discussion of many of these supplements and should be basic reading for all using any of the CAP's.

    Charts covering the supplements are available in this section to help organize the handfuls of pills that go along with thee project. 

    Jim K Wed, 2006-02-08 07:49

    B12 - benefits and methods of administration

    B12 - benefits and methods of administration

    B12 information

    Through the research carried out by members we have collected the following information on the benefits, forms and methods of administration of Vitamin B12.

    Sarah

    I looked up B12 patches

    http://www.b12patch.com/product.html

    It is cyancobalamin, not methylcobalamin, which is what I take sublingually. Cyancobalamin converts to methylcobalamin in the body, so it seems sensible to short cut the process. If you suck the stuff it is absorbed in the mouth or oesophagus, so doesn't come into contact with stomach acids. I used to have B12 shots, but the burst of energy didn't last, so I started taking tablets every day which seemed more sensible.

    A patch gives you 1000 mcg of cyancobalamin a week. At the moment I am taking 4 x 5000 mcg of methylcobalamin a day and I am certainly feeling the benefit. Plus I quite like the taste.......

    I use either Source Naturals or Jarrow formula 5000 mcg of methylcobalamin B12. The first is smaller, the second I like the taste of. The difference is, I have taken to use 4 a day, just as an experiment: http://www.cpnhelp.org/neural_ectoderm_and_my_ha

    Not everyone might want to see how long they can grow their hair, but it works for neural ectoderm as well. You just need to suck the lozenges, or munch them up and swallow the small particles. If they are absorbed anywhere before they hit the stomach, the effect will be the same, according to DW. I used to laboriously suck them and take an extra one if I accidentally swallowed one, now I save money by not bothering..

    2.5 micrograms is the recommended daily dose for normal people. Everyone, apart from vegans, is almost bound to get this with a normal diet. Everyone here, not just people with MSi need much more than this, but unfortunately most neurologists seem to be rather vitamin challenged so it was never even suggested to me.

    My GP offered me weekly shots of 1000 mcg of cyancobalamin which did seem to give me a boost for a few days. Being a water soluble vitamin, I reckoned that I needed it every day, so started supplementing in between times. Eventually, because I hated going to the surgery so often, I stopped and relied solely on supplementation.

    I don't personally think that a patch supplying 1000 mcg a week of cyancobalamin is enough for someone with MS, but like me and my weekly shots at my GP's, you could always supplement as well, but that's kind of defeating the object plus costing too much.....

    Mark

    B12 Products - There a number of cheap ways to get sufficient B12 and it is a matter of personal choice and how much you want to spend.

    Some basic info:

    2 microgrammes a day of B12 is required daily (one thousand microgrammes is one milligramme). B12 is important for nerve support.

    1% of a sublingual tablet enters the blood stream under the tongue (this is achievable for most patients, some will do better).

    B12 is water soluble and any un-needed B12 is excreted.

    Products available include:
    Lozenges (fancy name for a suckable tablet) of 1mg to 5mg give plenty of B12 and are cheap. Choice is often around product flavour as this is important for ease of use.

    Patches - easy to use but a lot more expensive than the oral products.

    Microdots - 500 microgrammes - are very cheap and as they are very small, so should be easy to keep under the tongue, until fully dissolved.

    Liquid (5mg in 5ml) for people who don't like tablets under the tongue.

    Injections give an immediate boost in B12 levels but are no more effective than the oral products for on-going supplementation.

    So make your choice and pay your money.

    Lexy

    As an aside, we have found a sublingual that is 5 MG. For those metrically challenged (that's me) that is 5000 micrograms.

    This has worked quite well as evidenced by Jim's B-12 blood levels which are quite high (1500)-a good thing that pleased his doctor very much.

    At first - early in treatment, Jim actually took one tablet three times per day and achieved one B-12 blood reading of 1900, now he only takes the 5 MG once under the tongue per day.

    The brand is Source Naturals Methylcobalamin and we have bought it at both Iherb and Vitacost for a very nominal fee. I don't know if it is better to spread out dosage throughout the day, but for convenience this 5 mg sure has helped.

    Michèle Tue, 2007-03-20 05:11

    Can someone help me with my schedule for treatment?

    Can someone help me with my schedule for treatment? karen b Tue, 2006-09-05 11:42

    We have starded the treatment last week. We found a really nice doctor in are nebeirhood that has accept to prescribe the treatment (antibiotics). the only thing is that I'm the one that has to make the schedule of when to take what. It is a bit overwelming for me. I dont whant to make any mistakes. the protocole is in english and some time's, I am worried that I dont understand the right thing (I am french) we live in Québec, canada. So to make sure, I would appreciate some help. This is the schedule I made, hope it's find. If not, please tell me, and help me with the next step. I included the other medication's that was already prescribed and should be continued as are doctor suggested. Thank you in advance for your help!!!! It is very appreciaded! What would we have done without this amasing site??????

    Breakfest (9h00-10H00)


    (4 total)

    Vit C (1g)

    Q10 (100mg)
    Gabapentin

    11h30
    Doxycycline (100 mg) (strarded sept. 4) for 21 days

    12h30


    (3 + powder)
    Vit E (8000ui)
    Selenium (200mg)
    Omega 3
    n-acetyl cysteine 600mg (powder)

    16h30 (3)
    Lipoec (150mg)

    17h30 (supper)
    (3)
    Q10 (100mg)
    Evening primerose oil 1G

    19h30
    (2)
    Doxycycline (100 mg)
    Gabapentin

    Before bed


    (3½)
    Melatonin (1.5mg)
    Clonazépam (2 mg)
    Amitriptyline (50 mg)
    gabapentin

    Has received Vit. B12 the 2006/08/30. Next one in a month.

    Going to start azithromycine next week (monday-wednesday-friday) for 3 weeks.

    what is the next step? (I dont whant to understand something wrong because I am a frenchy hi! hi! hi!

    Karen b for my dad "Pete" and who know's, maybe me in a while (that is another story)

     

    I am by no means an expert, and I had the exact same question as you in the beginning.

    Most people divide the supplements into two doses a day so your Dad wouldn't have to take pills so many times per day.  One thing that I see missing is acidophilus to replenish the good gut bacteria the antibiotics will destroy. Acidophilus should be taken at least two hours after any abx. Finally, many find it easier, especially when adding the azithromycin, to take the two doxys at once.

    Here's a sample schedule:

    Breakfast: 7:a.m.-Doxy with breakfast

                   9:a.m.-Vitamins/Acidophilus

    Lunch:      12:p.m.-more Acidophilus

    Dinner:     5: p.m.-azithromycin (every other day)

                    7:p.m-Vitamins/Acidophilus

    Bedtime:   Melatonin              

    I would, if you haven't, print out the Supplement Chart available on the home page of this website.

    Hope this helps

    Lexy

    --------------- "Chance favors the prepared mind." --Louis Pasteur Husband treating MS with CAP

    Karen, I will list my schedule as simply as possible - with am coffee - about 6:30 - 7:   acidophilus, magnesium, acetyl-L-Carnetine, "super" b-complex, vit C, glucosamine/chondroitin,  vit D, alpha-lipoic-acid, sub-lingual B-12, a multivitamin-mineral, calcium, B 6, folic acid, 2 - 600 mg NAC, Co enzyme Q 10, fish oil..  Two hours later I take  200 mg Doxycycline and Azithromycin  (if MWF)   After abx I wait at least an hour before eating.  In the afternoon or around dinner:   acidophilus, vit C, glucosamine/chondroitin, vit D, alpha-lipoic-acid, sub-lingual B-12, calcium, B 6,  2 - 600 mg - NAC, Co enzyme Q 10, fish oil, selenium, vit E.  If it is flagyl time I take the 1st with am pills, 2nd with afternoon pills, 3rd at bedtime.   Bon voyage (or suitable salutation!)

    In 2 weeks I will have been on this protocol for 2 years   3 weeks of these abx is only long enough to send these "bugs" into hiding. 

    Rica        EDSS 6.7 at beginning - now 2
    Ignorance is voluntary bad luck.  Lauritz S.   A true Viking
    If you come to a fork in the road, take it. Yogi Berra

    3/9 Symptoms returning. Began 5 abx protocol 5/9 Rifampin 600, Amox 1000, Doxy 200, MWF Azith 250, flagyl 1000 daily. Began Sept 04 PPMS EDSS 6.7 Now good days EDSS 1 Mind, like parachute, work only when open. Charlie Chan  In for the duration.&am

    Karen, I'll email you something tomorrow, but you do realise that your father needs to take the antibiotics for at least a year, full-time, don't you?  Maybe your GP does need to contact David.  If she can't speak English very well, I can help out........Sarah

     

    Started the Wheldon regime in August 2003, due to very aggressive SPMS.  Moved to intermittent therapy after one year.  In May 2006 still take this, two weeks every two months.  EDSS was about 7, now less than 2.

    An Itinerary in Light and Shadow  Berger.

    Completed Stratton/Wheldon regime for aggressive secondary progressive MS in June 2007, after four years, three of which intermittent.   Still improving bit by bit and no relapses since finishing treatment.

    Hi Karen,

    Here is what Ella started on, it is a bit different now, she takes CAL/MAG as one preparation for example.   This is the most efficient way we found of handling things, mainly because now that Ella is looking after herself it has to stay simple...

     

     

    April 2006

    Vitamins and supplements chart

     

    Taken at meal time

    Amount taken daily

    Suggested break down

    Notes

    Vitamin C

    2000mg

    2 X 1000mg

     

    E 800iu

    800iu

    2 X 400mg

     

    Omega 3 fish oil

    1000mg

    1 X 1000mg

     

    Evening primrose oil

    1000mg

    1X1000mg

     

    Acetyl L-Carnitine

    500mg

     

    Break down tab. dependant

    Alpha Lipoic acid

    150mg

    1 X 150mg

     

      Coenzyme Q10

    200mg

     

    Break down tab. dependant

    Selenium

    200mcg

    1 X 200mcg

     

    N-acetyl cysteine

    1200mg

    2 X 600mg

     

    Vitamin D

    4000iu

    2 X 2 1000iu

     

    B complex,

    1 tablet

    1 X 1 tablet

     

    Vit B6

     

    50mg

    1 X 50mg

     

    Antibiotics (doxy – Azi (MWF))

     

     

     

    Bedside AM/PM Supplements

     

     

     

     

    Magnesium,

    300mg

    PM x 300mg

     

    Calcium

    500mg

    PM x 500mg

     

    Acidophilus

     

    AM + PM

     

    N-acetyl cysteine

    PM x 600mg

    PM x 600mg

     

    Turmeric

    PM x 500mg

    PM x 500mg

     

    Chlorella

    200mg

    1 x AM 1 x PM

     

     

    Sublingual B12 at least 4 times a day

    Antibiotics at meal times 

    Hope this helps 

     

    Michele:  on Wheldon protocol since 1st May 2006 for a variety of long standing ailments, also spokesperson for Ella started Wheldon protocol 17th March 2006 for RRMS

    Sussex, UK

    Michèle (UK) GFA: Wheldon CAP 1st May 2006. Daily Doxy, Azi MWF, metro pulse.

    I'm going to add this as a page in the handbook since it covers the question quite well. Keep adding any other versions to it. It's a great resource! 

    Combined Antibiotic Protocol for Chlamydia pneumonia in Chronic Fatigue Syndrome &amp; Fibromyalgia- Currently: 150mg INH, Doxycycline/Zithromycin, Tinidazole pulses. Northern Ohio, USA

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

    Hi Karen, here is my list of supplements, many things combined so you don't have to take too many different items. It is good both for beginners and people wanting a maintenance schedule. In between times many people are going to experiment somewhat. They all come from the same place to make ordering easier and from a very reliable company with good quality, good dosages and very good prices.

    You can take most of them at any time you wany, but take care not to have the cal/mag too close to the doxycycline - leave about two hours between these. Also take the acidophilus as far apart from abx as you can manage. Take both doxycyclines together early in the day, with azithromycin on M/W/F, then the day is yours. When flagyl/tinidazole is started, it will be a little more difficult, but that is only for a few days at a time.......Sarah

     

    NAC, the wonder antioxidant but also to avoid reinfection of CPn.  Work up to four of these: http://tinyurl.com/m8n6x

     

    B12 - essential for helping to repair CNS damage: http://tinyurl.com/p4hhs

    B and C combined, includes adequate amounts of thiamin and niacin: http://tinyurl.com/nqp7a

     

    CoQ10 - for cell energy, which obviously ends up as personal energy: http://tinyurl.com/qdfmf  I take two of these, but not neccesarily at the same time.

     

    Acetyl l-carnitine with ALA - ditto above but from a slightly different angle: http://tinyurl.com/ohfzh

     

    Vitamin D - essential, especially if you don't go out much in the sun: http://tinyurl.com/s9fqd  Up to 4 a day

     

    Fish oil, complete, making evening primrose oil superfluous: http://tinyurl.com/rs7l8

     

    calcium and magnesium combined - http://tinyurl.com/pdwnu

     

    Multivitamin - Source Natural's Visual Eyes because it contains enough of other things I don't mention like selenium, vit e and beta-carotene and it is very good for eyes: http://tinyurl.com/q65vn

    Acidophilus with fructo oligo-saccharides, which means you don't need to store it in the fridge and risk forgetting to take it: http://tinyurl.com/pouqz  

     

    Started the Wheldon regime in August 2003, due to very aggressive SPMS.  Moved to intermittent therapy after one year.  In May 2006 still take this, two weeks every two months.  EDSS was about 7, now less than 2.

    An Itinerary in Light and Shadow  Berger.

    Completed Stratton/Wheldon regime for aggressive secondary progressive MS in June 2007, after four years, three of which intermittent.   Still improving bit by bit and no relapses since finishing treatment.

    Hi, i have'nt started the protocol yet as i have only just found out about it and i still have to find a receptive doctor (which i hope to do today). The protocol from where i am sitting (have to legs for most of the times are wheels not the brum, brum kind the manual ones) seems very daunting but i am excited about the prospect. I am also very glad i found this web site as i am sure i will need a lot of help and support.

    Thanks jennie

    SPMS diagnosed 1992, edss 8.5, currently taking all recommende abx's and supplements, currently at pulse 26.Other problems are asthma, mucous membrane phemigoid, terrible dry skin and rosecea.

    Hi Jen.

    I hope you are lucky with your search for a doctor... I know that you have MS, but others won't until you add a signature statement at the end of your post.   You can do that by going to your profile and editing it.   At the bottom of the page you will find a window in which you can write something about yourself that might make it easier for us to understand your questions.   As Rica says, we are good listeners here and most of us are either undergoing the treatment of helping someone that is.   I am both... 

    Michele: on Wheldon protocol since 1st May 2006 for a variety of long standing ailments including IBS, sinusitis, alopecia, asthma, peripheral neuropathy, also spokesperson for Ella started Wheldon CAP 16th March 2006 for RRMS

    Michèle (UK) GFA: Wheldon CAP 1st May 2006. Daily Doxy, Azi MWF, metro pulse.

    Jen, have you been in touch with David?  You should be able to find his email address here: http://www.davidwheldon.co.uk/ms-treatment.html except it seems to have fallen off the bottom, so I'll PM you with it.  He would be more than willing to give advise to your doctor about this.  You might also like to print out this PDF file to give him/her.  I can also send you some useful papers which you can give to your doctor if you send me your email address..........Sarah

    An Itinerary in Light and Shadow.Wheldon regime since August 2003, for very aggressive SPMS.  Intermittent therapy after one year. 2006 still take this, now two weeks every three months.  EDSS was about 7, now 2. United Kingdom.
    Completed Stratton/Wheldon regime for aggressive secondary progressive MS in June 2007, after four years, three of which intermittent.   Still improving bit by bit and no relapses since finishing treatment.

    What a great thread! I study my hubby's list of supplements, and ABX, and wonder if he's taking things at the right time... I try to spread his vitamins out over the day, so he doesn't have so many to take at once. But, most people take all of theirs at once? I guess the body absorbs them okay when all are taken at the same time? Thanks all. Best wishes.

    Hubby DX 10-05 by LLMD; positive for Borreliosis; took 200-400 mg Doxy for 2 mons; followed by zith daily for 6 wks; small does of flagyl daily for 3 mons; tested by ID for Cpn 6-06;  Tested positive and took Ketek for 6 weeks; Began Cap 8-06

    Hubby DX 10-05 by LLMD; positive for Borreliosis; took 200-400 mg Doxy for 2 mons; followed by zith daily for 6 wks; small does of flagyl daily for 3 mons; tested by ID for Cpn 6-06;  Tested positive and took Ketek for 6 weeks; Began Cap protocol

    Hi, forgive my ignorance but what is ABX. Jen

    SPMS diagnosed 1992, edss 8.5, currently taking all recommende abx's and supplements, currently at pulse 26.Other problems are asthma, mucous membrane phemigoid, terrible dry skin and rosecea.

    Jen, Put your pointer over the little " i " next to the word and you will get a little definition of the word or abbreviation. abx is antibiotics, agents used to kill microorganisms. You're not ignorant. We all had to learn as we went along...

    The difference between what we do and what we are capable of doing would suffice to solve most of the world’s problems.  Mohandas Gandhi

    The difference between what we do and what we are capable of doing would suffice to solve most of the world’s problems. Mohandas Gandhi

    I just noticed this 'tentative schedule' says doxy for 21 days. We're all clear on the fact that doxy is taken daily, with no days 'off' doxy, not ever, right???

    The difference between what we do and what we are capable of doing would suffice to solve most of the world’s problems.  Mohandas Gandhi

    The difference between what we do and what we are capable of doing would suffice to solve most of the world’s problems. Mohandas Gandhi

    Thanks for catching that! These things floated up to 'recent posts' because I rearranged some book chapters. Good we review these from time to time. 

    CAP for Chlamydia pneumonia since 11/04. 25yrs CFS & FMS- Currently: 150mg INH, 300mg Rifampin, 200 Doxycycline, 500mg mwf Azithromycin, plus 500mg Tinidazole 2x/day pulses every two weeks. Whew! That's a lot!

     

    CAP for Cpn 11/04. Dx: 25+yrs CFS & FMS. Currently: 250 aithromycin mwf, doxycycline 100mg BID, restarted Tini pulses; Vit D2000 units, T4 & T3, 6mg Iodoral