Welcome Doctors! Below are links to information available on this site which is especially pertinent to the inquiring and potentially prescribing physician. We recognize that your time is valuable and you need a quick way to get familiar with this material. This page is set up with this in mind and with annotations so you can get an idea of what you will read when you click the link and thereby choose the material most pertinent to your needs and current background.
THIS COLLECTION REPRESENTS A VERY SMALL PART OF OUR RESEARCH ARCHIVES ON CHLAMYDIA PNEUMONIAE. All of the links chosen here are on this page because they address the most obvious issues for the prescribing physician and are the best example of that information however, they are not necessarily the most current papers on the subject. For more on any particular subject you can read the pertinent section in the research pages. For example, the paper on persistance here may trigger another question in your mind. You can go to the reserach archives by clicking "Research", above, click that link and a number of papers will be available for you to study. The best place to start on this page is at the top with the protocols and work your way down reading what you like. I suggest you read both the protocols links at the top. You will then with just those two links have a good idea of the theory and model. Feedback is welcome!
Newly published Multiple Sclerosis: an infectious syndrome involving chlamydia pneumoniae We are proud to offer the abstract to this paper which was published in the November '06 Trends in Microbiology.
PROTOCOLS FOR TREATMENT
David Wheldon's Protocol for MS This paper is an outline for the Wheldon plan. Written in terms that your patients could likely understand as well, it includes background about the CPn lifecycle. Dr Wheldon is an MB FRCPath which is the equivalent of a physician specialist MD in the United States. He is a Consultant Microbiologist, 'consultant' in the UK meaning having passed the highest degree of testing in that field, similar to a board certified specialist in the US. So his specialty is germs. One of his internships was also in neurology addng to his unique background. He is especially qualified to work with this material and his clear rationale for the protocol outlined on this linked page is a must read. Includes many links to good research.
Here is a small tally of clinical outcomes in Dr Wheldon's practice Vanderbilt Protocol; Stratton et al. This is a paper which outlines the Vanderbilt Protocol. Lay terms. Researchers at Vanderbilt University have authored several peer reviewed published papers on CPn in MS. Their work was the earliest and in many ways the best of any to date. We have a number of the citations in total here on this site used with permission. Many of these are available in the links below.
V.U Protocol update Vitally important that you read this link as it updates the VU protocol with the newest and best approach and comments by Dr Stratton as of Feb '06.
Supplements with rationale from Dr Wheldon's site These protocols are challenging for the brain and body to cope with and this requires physiological support. These particular supplements are well presented and supported with good research on this page. If you read Dr Whldon's site in totality above this is a repeat of his supplement page.
GET THE BACKGROUND
Antibiotic combinations inhibit resistanceThis abstract indicates that bacteriostatics in combination inhibit resistance, an important affirmation of the Vanderbilt Protocol assertion.
Chlamydia pneumoniae infection in circulating monocytes is refractory to antibiotic treatment This study demonstrates the difficulty with treating for shorter periods of time when dealing with CPn. This is important to understand as you do not try this approach for a month or two. These protocols demand very long term treatment, and as you begin to study this may seem odd and perhaps even ill advised. As you read and learn more about CPn and how it behaves and resists treatment, and in particular how persistant states use monocytes for the host cell (Cpn is an obligate intracellular germ), it becomes clear why clearance is not linear or simply accomplished in a few months. Dr Stratton has commented that in MS we are probably looking at treatment time frames of 3-5 years.
Lifecycle of CPn. Technical taxonomy. This is one to study well.
Chlamydial Persistence: Beyond the Biphasic Paradigm This heavily cited and well referenced paper covers the lifecycle of CPn in depth. Persistence well described.
Slide Presentation by Charles Stratton MD on CPn Amazing pictures of these pleomorphic bacteria in action. This is necessary background. This will convince you of the quality of the research in this area.
Interview With Expert close to Vanderbilt on the protocol (scroll up for whole interview) This interview gives a clear overview of the V.U. protocol and explains the rationale for the specific antibiotics used. Includes overview of CPn lifecycle and pleomorphic forms. Note the two clickable comments by David Wheldon on the interview below for further elucidation
Expert Comments These comments make the protocols clear and give the extra information, for example why THESE antibiotics.
Chlamydia Pneumoniae and resistance A highly technical paper on resistance as it pertains to CPn. A link out. One page.
Second page here Page two is a slide presentation on CPn resistance.
Third page Rifamcin and CPn resistance: page delving into resistance.
GO DEEPER INTO RESEARCH SUPPORT FOR APPROACH
Nitric Oxide, CPn and MS NO is well known as the problematic feature of MS causing extensive tissue destruction. It is also created by gamma interferon to kill CPn in vitro. So which came first NO created abherrently by the faulty immune systme of the MS patient or is it physiological response to the presence of CPn possibly? Several works on NO in CPn infection included in this link.
Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages : Insights into the Phagosomal Environment This research makes clear the intracellular adaptations that essentially are equivalent to sophisticated resistence. If you don't have respect yet for the adaptive abilities of bacterial evolution, this will enlighten you!
Detection of chlamydia antibodies and antigens in patients with MS Think the evidence that CPn is present in MS brains is weak? Read this paper published Oct 1 '05. In this cohort the presence of CPn was established using several methods. Please note that many other researchers offering evidence that CPn is not present in MS brains use one test to see if it is there- which research has more authority?
Chlamydia Pneumoniae in Progressive MS These authors discovered that in the nurses study matched controls with progressive MS demostrated CPn posivity in higher titers than in RRMS. This is a key work because it is a large study with 141 subjects who are age matched with controls in a long term studied population.
Intrathecal production of Chlamydia pneumoniae-specific high-affinity antibodies is significantly associated to a subset of multiple sclerosis patients with progressive forms. And another focused on intrathecal evidence of CPn. Again, this good sized study with large cohorts showing that CPn is present much more often in progressive forms of MS.
A pilot study of the effect of antibiotics in RRMS This is the ACTUAL CITATION. Small cohort. Significant reduction in atrophy.
UNDERSTAND WHY THESE ANTIBIOTICS
Here is a paper outlining the development of resistence in CPn to rifampin in vitro after 12 passes. Combination therapy prevents this. Essentially you have two bacteriostatic agents and the bacteria cannot, with this blockade of proteins in two phases, become resistant. As a prescribing physician it is important to understand that the patient is protected over the long course of the protocol by using two agents so that resistance does not develop.
First choice antibiotics at subinhibitory concentrations induce persistence in CPn A must read. Lower doses are not an option with CPn disease.
Effects of Azithromycin and Rifampin on Chlamydia Trachomoatis infection in vitro This complete citation makes it clear that resistence and elimination of persistence is avoided by combining these antibiotics. It is clear that active RNA is still present with Azith alone, and resistence is a problem with rifampin alone. Once again, as a prescribing physician it is vital to understand why you want to give two antibiotics.
RELATED MATERIALS SUPPORTIVE OF THEORY
Positive PCR studies for MS and CPn With comment by David Wheldon about the wider implications. If you are saying to yourself 'What about the no CPn in CSF of MS studies' this is for you.
The Centers for Disease Control on CPn This link is to the CDC page for CPn. It has a wonderful synopsis of the current research about this cryptic and pleomorphic bug. It focuses primarily on the atherosclerosis research, but take note CPn is listed as an emerging disease. Some physicians are talking about CPn being implicated definitively in atherosclerosis any day and that CPn is "cardiology's helicobacter pylori". Might it be neurology's as well?
ASA inhibits CPn induced NFkB activation, cyclooxygenase 2 expression and prostaglandin E2 synthesis and inhibits chlamydial growth Fascinating. Recent work also indicates ASA works better than provigil to attenuate fatigue in MS. Connection?
Enhancement of ATP levels and glucose metabolism during an infection with CPn 1998 Journal Biological Chem.
Association of CPn with Chronic Human Diseases Article in Antimicrobials and infectious diseases newsletter
CPn induces Alzheimer-like amyloid plaque in brains of BALB/c mice Potentially treatable AD?
CPn infection of the CNS worsens EAE Possible mechanism for role of CPn in autoimmunity.
A Chlamydia pneumoniae-Specific Peptide Induces Experimental Autoimmune Encephalomyelitis in Rats This article pinpoints the possible CPn trigger for autoimmunity. The addition of this article to the above makes the CPn possibility in MS very appealing in the face of the large body of autoimmune research already present in the MS literature.
PATHOGENESIS OF CPn
Chlamydia Pneumonia pathogenesis Editorial
The pathogeneisis of Chlamydial species Article in Antimicrobials and Infectious Diseases newsletter. Pathogenesis.
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 newsletter
TREATMENT CONSIDERATIONS HERXHEIMER AND ENDOTOXIN
Bacterial Endotoxin in Human disease 35 page paper explaining in depth LPS reaction and treatment. Patients will react on this treatment to the LPS as CPn is a gram negative bacteria. Recognizing the clinical manifestations is important to maintaining therapy safely and avoids misunderstanding reactions as a worsening of the underlying pathology. Also see comments here on the psuedoexacerbation of MS during treatment
Acute Porphyrias a Case Report and Review An issue for people underging treatments outlined here. Testing ahead of treatment is advised as secondary porphyria is a known side effect.
Secondry porphyria page Explains the potential development of secondary porphyria.
Transport and storage conditions for cultural recovery of CPn It is possible to test, though reliability is unknown and negatives are possibly meaningless as persistent infection is theretically unculturable, though still inflammatory. SO what, then, does a negative test mean?