Editorial comment: A meta-analysis is a method which tries to group results from a number of different studies, statistically balancing for differences in the ways studies gather data as well as the numbers of subjects involved (and thus sensitivity levels) in different studies. There is a lot of controversy about the validity of the ways in which meta-analysis lumps apples and oranges together. Nonetheless, it is seen as a useful method to see the trends emerging when there is not yet a large-scale highly sensitive study of a problem area.This meta-analysis shows that MS is more strongly associated with Cpn DNA, and Cpn intrathecally synthesized immunoglobulins and immunoglobulins in the cerebrospinal fluid . While the association is not strong enough to be "causal" it is quite remarkable that a strong association is emergent from such disparite studies.
This pre-publication abstract is a remarkable piece of laboratory work. It strengthens the case for Cpn infection especially in MS and Alzheimer's, and other brain diseases. The two findings I've underlined which seem to have espeical importance is (1) the sensitivity of neuronal cells to infection, as big producers of EB's, and their particular sensitivity to necrosis (tissue death); and (2) the finding in microglial cells that they resist active replicating infection but appear to be potential reservoirs for persistant Cpn.
Neurobiol Aging. 2006 Apr 16; [Epub ahead of print] Chlamydia pneumoniae infection of brain cells: An in vitro study.Boelen E, Steinbusch HW, van der Ven AJ, Grauls G, Bruggeman CA, Stassen FR.Department of Medical Microbiology, CARIM (Cardiovascular Research Institute Maastricht), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands; Department of Cellular Neuroscience, EURON (European Graduate School of Neurosciences), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.Inspired by the suggested associations between neurological diseases and infections, we determined the susceptibility of brain cells to Chlamydia pneumoniae (Cpn). Murine astrocyte (C8D1A), neuronal (NB41A3) and microglial (BV-2) cell lines were inoculated with Cpn. Infection was established by immunofluorescence and real-time PCR at various time points. Productive infection was assessed by transferring medium of infected cells to a detection layer. Finally, apoptosis and necrosis post-infection was determined. Our data demonstrate that the neuronal cell line is highly sensitive to Cpn, produces viable progeny and is prone to die after infection by necrosis. Cpn tropism was similar in an astrocyte cell line, apart from the higher production of extracellular Cpn and less pronounced necrosis. In contrast, the microglial cell line is highly resistant to Cpn as the immunohistochemical signs almost completely disappeared after 24h. Nevertheless, significant Cpn DNA amounts could be detected, suggesting Cpn persistence. Low viable progeny and hardly any necrotic microglial cells were observed. Further research is warranted to determine whether these cell types show the same sensitivity to Cpn in an in vivo setting.PMID: 16621171 [PubMed - as supplied by publisher]
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.
David Wheldon offered this citation as another good reason to use alpha-lipoic acid as a supplement on the protocols here. This study notes it's anti-inflammatory effect through T-cell inhibition. Although this study is orienting from the autoimmune model of MS, David notes " I read this as positive, if you are taking antibiotics. While killing the organisms you want as little inflammation as possible."Alpha lipoic acid inhibits human T-cell migration: implications for multiple sclerosis.Marracci GH, McKeon GP, Marquardt WE, Winter RW, Riscoe MK, Bourdette DN.
Summary of our Cpn Treatment Poll:The poll was out for two weeks, and represents a snapshot of protocol users at this point in time. We had slightly different numbers participating in each section of the poll, perhaps some questions did not have exclusive answers for those voters. Obviously, 25-28 people is not enough to draw scientifically valid results from, but I intend to speculate on some suggestive patterns in the data. Gender: Female: 61% (17 votes) Male: 39% (11 votes) Total votes: 28 This ratio is commonly reported in CFS/FM, MS and other "autoimmune" diseases, so is not surprising. We would expect that if more people with Cardiac diseases were searching out Cpn treatment, with a higher male to female ratio, this might change. Age: 20-29 years = 7% (2 votes) 30-39 years = 14% (4 votes) 40-49 = 32% (9 votes) 50-59 years = 39% (11 votes) 60-69 years = 7% (2 votes) Total votes: 28 Our largest group is between ages 40 to 59. I suspect that this age does not reflect the period when people are morel likely to be infected, but rather a range where long term persistent infections are have accumulated enough damage to force us to seek out "desperate measures" such as the multi-antibiotic protocol recorded here. Primary diagnosis: Over half the total in the poll have a diagnosis of MS. The second largest group are those with a diagnosis of CFS/FMS. This likely influences the treatment response reported later which suggest that improvements are noticed most after 5 or more pulses. CFS/FM = 28% (8 votes) MS = 55% (16 votes) Asthma = 3% (1 vote) Cardiac disease = 3% (1 vote) OTHER = 10% (3 votes) Total votes: 29 Serology Positive blood test for Cpn 48% (12 votes) Negative blood test for Cpn 16% (4 votes) Not been tested for Cpn 36% (9 votes) Total votes: 25 Well over half either have negative or no serology for Cpn, suggesting that they are engaging in a completely empirical (based on symptoms or theoretical connection between disease and Cpn) protocol. Antibiotics I take AT LEAST TWO of: doxycycline/azithromycin/roxithromycin/rifamcin/minocycline/INH-: 73% (19 votes) Single antibiotic only: 20% (5 votes) I take only INH: 8% (2 votes) Total votes: 26 This poll speaks for itself. 73% are already on the dual antibiotics, a small number appear to be early in treatment, confirmed by findings below that 40% have not yet done a pulse of bacteriacidal, and have only added one agent. As INH is used as a single agent with the flagyl pulses in some versions of the Cpn protocol and, together with NAC for the EB phase I have reported it separately. Bacteriacidal Agent Used- I take metronidazole (Flagyl) for bacteriacidal pulses 81% (13 votes) I take tinidazole (Tinactin) for bacteriacidal pulses 19% (3 votes) Total votes: 16 Pulses of bacteriacidal I've done NO pulses yet of metronidazole/tinidazole 40% (10 votes) I've done some partial pulses of metronidazole/tinidazole 4% (1 vote) I have had LESS than 5 full pulses (at least 5 days each) of metronidazole/tinidazole 24% (6 votes) I have had MORE than 5 full pulses (at least 5 days each) of metronidazole/tinidazole 32% (8 votes) Total votes: 25 Over half in this small pole have done at least a full pulse of bacteriacidal agent, with only 8 people reporting 5 full pulses or more. This shows that we are still, as a group, in earlier phases of treatment. As the results below suggest, more significant improvement starts to accrue beyond 5 pulses of the bacteriacidal. Response to treatment- 1. On 1 0r 2 antibiotics ONLY My primary condition is the SAME or WORSE 13% (3 votes) 2. On 1 0r 2 antibiotics ONLY My primary condition is SOMEWHAT improved 13% (3 votes) 3. On 1 0r 2 antibiotics ONLY My primary condition is SIGNIFICANTLY improved 13% (3 votes) 4. Less than 5 full pulses: My primary condition is the SAME or WORSE 13% (3 votes) 5. Less than 5 full pulses: My primary condition SOMEWHAT improved 9% (2 votes) 6. Less than 5 full pulses: My primary condition SIGNIFICANTLY improved 4% (1 vote) 7. MORE than 5 full pulses: My primary condition is the SAME or WORSE 0% (0 votes) 8. MORE than 5 full pulses: My primary condition SOMEWHAT improved 13% (3 votes) 9. MORE than 5 full pulses: My primary condition SIGNIFICANTLY improved 22% (5 votes) Total votes: 23 These results are more obvious when grouped. If we collect together everyone in early phase of treatment (#1-6) and we see that 26% are the SAME or WORSE 28% are SOMEWHAT IMPROVED 17% are SIGNIFICANTLY IMPROVED Actually, to have 35% already reporting any improvement in their condition this early in the protocol is striking to me. I expected less noticeable improvement at this stage, especially given the numbers being treated for otherwise "intractable" diagnoses such as MS and CFS/FM. But it is when users of the protocol get to 5 pulses (#7-9) or more, in this small sample, that the number in SIGNIFICANTLY IMPROVED seems to begin to creep upwards. Perhaps when we get a better sample of longer term users we will be able to sort out the "magic number" of pulses where more significant improvements take place. From reports in blogs and forums on this site, somewhere around 7-9 pulses seems to be a period where people are feeling much better and more significant changes in their primary diagnosis are occurring.
Nitric oxide has long been suspected as the possible damaging factor in multiple sclerosis. The logic goes like this: The body for some unknown reason starts attacking the brain as if it were a foreign protein (like a bacteria). The microglia (the cells in the brain which are responsible for immune responses that might be needed inside the blood brain barrier-the regular white blood cells are kept out by the BBB)produce large amounts of nitric oxide (NO) which damage the nearby nerves and support cells. If only we could get rid of the NO then we could control MS. An example of this kind of research can be found HERE. Also another one HERE. It is clear that the researchers consider the production of NO an abherrent and undesirable response and a contributor to autoimmunity. You might note that they also are very clearly believing the autoimmune model. Many physicians and researchers forget that this is just a model, not a proven fact.
J Neurol Sci. 2004 Feb 15;217(2):181-8. Related Articles, Links
Intrathecal production of Chlamydia pneumoniae-specific high-affinity antibodies is significantly associated to a subset of multiple sclerosis patients with progressive forms.
Fainardi E, Castellazzi M, Casetta I, Cultrera R, Vaghi L, Granieri E, Contini C.
Multiple Sclerosis Center, Department of Neurology, University of Ferrara, Arcispedale S. Anna, Corso della Giovecca 203, I-44100, Ferrara, Italy. firstname.lastname@example.org
The purpose of this study was to provide further insight into the effective relevance of the association between Chlamydia pneumoniae and MS. We evaluated by ELISA technique cerebrospinal fluid (CSF) and serum levels of anti-C. pneumoniae IgG in 46 relapsing-remitting (RR), 14 secondary progressive (SP) and 11 primary progressive (PP) MS patients grouped according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity. Fifty-one patients with other inflammatory neurological disorders (OIND) and 52 with non-inflammatory neurological disorders (NIND) were used as controls. A C. pneumoniae-specific intrathecal IgG synthesis as detected by the relative specific index was present in a small proportion of MS (17%), OIND (22%) and NIND (2%) patients and was significantly more frequent in MS and in OIND than in NIND (p<0.001) and in SP and PP MS than in RR MS patients (p<0.02). Among the patients with C. pneumoniae-specific intratecally produced antibodies, CSF high-affinity anti-C. pneumoniae IgG were found in the majority of SP or PP MS, occasionally in OIND, but not in RR MS and NIND patients. 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.
Epidemiology. 2003 Mar;14(2):133-4.
Infection with Chlamydia pneumoniae and risk of multiple sclerosis.
Munger KL, Peeling RW, Hernan MA, Chasan-Taber L, Olek MJ, Hankinson SE, Hunter D, Ascherio A.
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
BACKGROUND: Chlamydia pneumoniae (Cpn) has been proposed as a possible etiologic agent for multiple sclerosis (MS), but results of previous studies are conflicting. METHODS: Using a nested case-control design, we examined the association between Cpn infection and MS in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II) cohorts. Among 32,826 women in the NHS and 29,722 women in the NHS II with blood samples, 141 incident cases of definite or probable MS were documented. Each case was matched to two healthy controls on year of birth and NHS cohort. Serum samples were tested for the presence of Cpn-specific immunoglobin G antibodies using microimmunofluorescence. RESULTS: Cpn immunoglobin G seropositivity was positively associated with risk of MS (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.1-2.7). This association did not change after adjusting for age at blood collection, ancestry, latitude of residence at birth, and smoking (OR = 1.9; CI = 1.1-3.1). Seropositivity for Cpn was only moderately associated with risk of relapsing-remitting MS (OR = 1.7; CI = 0.9-3.2), but it was strongly associated with risk of progressive MS (OR = 7.3; CI = 1.4-37.2). Geometric mean titers of Cpn-specific immunoglobin G antibody were similar in women with relapsing-remitting MS as compared with matched controls (44 vs 39), but they were elevated in women with progressive MS (99 vs 40). CONCLUSIONS: These results support a positive association between Cpn infection and progressive MS.
This important article...
My first encounter with MS happened in December, 1987 following an enormous “flu”. The right side of my head went numb, as was my mouth and tongue. There was a questionable tingling on the left side of my body, barely discernible, that even I had doubts. That event coincided with my new job and I ignored it telling myself that it was a Bell’s palsy. The trouble was it looked much more like the fifth cranial nerve palsy and even that seemed to be more extensive than expected. I decided to ignore the whole thing. It resolved in several weeks leaving me with hyperparesthesias of my scalp for the next year or so, and permanent, almost unnoticeable minimal right upper lip atrophy. In April 1993, I had a sudden problem with the right eye. Vision became blurry, pinkish, there was aching in the back of the orbit. I could not ignore it this time and paid a visit to my friend the ophthalmologist. She could not see what was wrong and delegated me to a retinologist, who after the myriad of the tests was also at loss. In meantime, my mother, my husband and I, all three physicians, decided that I should take high doses of steroids which I did. We went for vacation to Arizona. I had wonderful adventures there getting swollen like a balloon from the water retention, then going into acute, prerenal failure, to be followed by a very funny diuretic phase. When I came back I had a brain MRI, which showed two lesions, related to both events. The differential diagnosis was: infarcts, migraine, and MS. My eye problem was already going away, I chose to believe it was a migraine, even though I had never had headaches, and I kept working and paying more attention to enjoying my life. Somehow, I felt it might not be long till another disaster strikes.