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Faculty Profile online.
Curriculus Vitae, 39 page, pdf, born 1945.
Associate Professor of Pathology and Medicine, and Director of the Clinical Microbiology Laboratory. Long publishing history in microbiology. Co-Founder, Merlin Technologies. Dr. Stratton is the Deputy Chairman of the Infection Control Committee and also serves on the Pharmaceuticals Committee. He is also an Attending Physician on the Infectious Disease Service.
Dr. Stratton's primary research is in pharmcodynamics, particularly the mechanisms of resistance. He has authored or co-authored over 200 papers on this subject and is recognized as an international authority in this area. Dr. Stratton has served on a number of editoral boards and is the Editor-in-Chief of the Antimicrobic and Infectious Diseases Newsletter. Dr. Stratton is a full Colonel in the U.S. Army Reserves. He received the Bronze Star for service in the Persian Gulf War.
Dr. Stratton is a member of numerous professional organizations, and is a fellow in the American College of Physicians, College of American Pathologists , American Society of Clinical Pathologists, American Academy of Microbiology, and Infectious Diseases Society of America. For 14 years, he served as editor of "Topics in Clinical Microbiology", a bimonthly section of Infection Control and Hospital Epidemiology .
Dr. Stratton also serves as editor for Infectious Diseases Newsletter and the Antimicrobics and Infectious Diseases Newsletter . Dr. Stratton is the author of many articles, research publications, review publications, chapters, and abstracts. He has lectured extensively at teaching activities, meetings and conferences.
Vanderbilt researchers Charles W. Stratton, MD and William Mitchell, MD, PhD, and Boston biotech entrepreneur, Gary Magnant, co-founded Merlin in 1996.
Merlin Technologies, Inc. (Boston), an early stage pharmaceutical company ... Merlin also received exclusive worldwide licensure of Vanderbilt intellectual property covering the diagnosis and treatment of certain bacterial stealth infections. Stealth infections, especially persistent infections by Chlamydia pneumoniae, have been linked to heart disease, multiple sclerosis and many other deadly ailments. ..
ImmuneSupport Article
Chlamydia Pneumoniae in CFS and FM - An Opinion.
http://www.immunesupport.com/library/
showarticle.cfm?id=7938&T=CFIDS_FM&B1=EM042507C
25-04-2007
by Patient Advocate James Kepner
ImmuneSupport.com
What is Chlamydia pneumoniae?
Extensive information about this organism and associated research is offered at the Cpnhelp.org site and in this article. Briefly, Chlamydia pneumoniae is a bacterial organism first described in 1988 that is most commonly contracted by breathing droplets floating in the air after a person who carries it has coughed - as with the organism that causes tuberculosis. Cpn can then infect the "mucous-moving" cells lining the airways. It can paralyze those cells because it survives by stealing their energy, and may cause a serious respiratory infection.
Then, if the body's immune response is unable to kill the invading Cpn bacteria, they can be disseminated via "mononuclear cells" in the bloodstream to infect other cells in the body, such as those that line the blood vessels, nerve tissues, brain, muscles, and even immune cells. There again Cpn bacteria metabolize and damage these cells by "stealing" energy.
Further, the Cpn bacteria are drawn to newly formed mononuclear blood cells, which tend to be generated where there is inflammation in the body - and where the Cpn can cause a secondary infection. And finally, Cpn passes through three forms in its life cycle, so that research indicates a combination of antibiotics may be necessary to kill it off in all forms.
"If you have inflammation, a spider bite, a viral joint infection, viral meningitis, or encephalitis," Dr. Stratton has said, "it doesn't matter what it is, if a Chlamydia-infected cell happens to end up in that inflamed area, you may have just started yourself a Chlamydia farm." In which case Chlamydia may not be the cause of the disease, but may play an important role in its progression.1A
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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 was actually not first directed at Multiple Sclerosis, as is more commonly believed, but looked at Cpn in Chronic Fatigue Syndrome. The first grant monies received by Dr. Stratton for Cpn research, using the highly sensitive tests they have developed, were from the Massachusetts Chronic Fatigue Foundation in the mid to late 1990s.
Dr. Stratton was asked to test blood samples submitted by the well-known Chronic Fatigue Syndrome physicians Paul Cheney, MD, Daniel Peterson, MD, and David S. Bell, MD to explore the possible involvement of Cpn in their CFS 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, Doctors Cheney, Peterson, and Bell sent blood samples from their own CFS patients to Dr. Stratton's Vanderbilt Chlamydia pneumoniae Research Lab for testing. According to Dr. Stratton, they tested hundreds if not thousands of such blood samples. These were tested using both ELISA-based serologic methods and PCR [polymerase chain reaction] testing using the tests developed by Stratton, et al. at the Vanderbilt Cpn lab. Dr. Stratton's lab found that the majority (almost 100%) of CFS patients were PCR positive for Cpn in blood samples.
That the selected patient group of CFS patients had almost 100% positive PCR tests for Cpn (actual proteins, which means actual presence of the bacterial particles - not only an antigen response, which could be a remnant from prior infection) is an extraordinary finding. Further, the majority also had either elevated IgM or IgG antibodies to Cpn major outer membrane protein, cross-confirming the PCR-based findings.
Of course, this in and of itself does not mean Cpn is the cause of CFS.
The presence of Cpn could be due to some third factor that is part of CFS (such as immuno-suppression, etc). But such a high correlation with one specific organism outweighs every other 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 criterion 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 - that is, suggest 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 pneumonia 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 [incidence] found in recent research with healthy, young blood donors. 9 That these earlier Vanderbilt studies found the percentage of Cpn occurring in healthy donors replicating the current accepted findings (which range from 18% to 25%) lends credence to the accuracy and sensitivity of the tests used to study this original CFS sample. In other words, post hoc data suggest 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 anti-chlamydial and see if reduction of PCR signal for Cpn correlated with reduction in CFS symptoms. This was done by Doctors Cheney, Peterson, and 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 the CpnHelp.org 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 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 Cpn 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 the CpnHelp.org website) would completely eradicate Cpn 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), 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 Doctors Cheney, Peterson, and Bell, as well as by Dr. Stratton with his own CFS 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 or CAP for CFS was very high.
Many patients were unable to see it through to the endpoint of the whole 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.
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Die-off Reactions.
When combinations [of antibiotics] were used, the die-off reactions from this potent mix could be as bad as or worse than the CFS itself. Little was yet known about how to support patients through these reactions or what exactly their nature was. [See the explanation of “worsening” later in this article.]
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Length of Treatment.
Moreover, the length of treatment of Cpn with these combination antibiotic protocols for CFS 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 CFS 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 For those patients (a small number) whom Dr. Stratton treated personally and who continued after the end of the study through the full course of the protocol there was, says Dr. Stratton, "100 percent improvement of symptoms."
Why did the eradication of Cpn cause such a 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 because it attacked all of the phases of the Cpn life cycle. A single antibiotic only kills Cpn in one of its life phases. The symptoms of CFS are related to Cpn's toxic and inflammatory impact on the body. The more you kill at once, the greater these reactions.
Second, 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 Cpn 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.
... The longer one has had the disease,
* The more organ systems affected, and
* The less resilient the patient from age, additional illnesses, etc.,
...the longer and more challenging is the treatment required.
As a group, patients with CFS/FMS appear to have higher Chlamydia pneumoniae loads in more different organs and tissues, compared with, say, Multiple Sclerosis patients - making treatment with the CAP more challenging and 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 CFS patients. There ensued a deluge of protest from medical colleagues who objected to research with CFS being conducted at Vanderbilt. According to Dr. Stratton, the objections were "quite heated."
Why would microbiological research, as hard-science an aspect of medicine as one could imagine, stir such heated outrage?
At that time, the late 1990's, the diagnosis of CFS 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 on 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 that 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 toward an area of research on Cpn with less diagnostic controversy, and where Vanderbilt did have its own disease-based clinic. Dr. Stratton and his colleagues, spearheaded by Dr. Subramaniam Sriram, MD, 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 use of 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 combination antibiotic protocol 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 that 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:
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No improvement - leading to the assumption that no bacterial presence is involved.
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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.
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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.
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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.
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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 is 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 that engenders further misery and suffering. Reports of strong reactions to antibiotics, and particularly to metronidazole, have led 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 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.
CFS/FMS 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 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. [ATP, or Adenosine triphosphate, transports chemical energy within the body’s cells.]
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 [the deep red iron containing component of hemoglobin], 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 its structure, such as LPSi and HSPi-60. These endotoxins cause widespread inflammation (cytokine cascades) and a host of other metabolic disturbances. These are released chronically in small amounts in Chlamydia 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, which 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.
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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
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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 references29).
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
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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.
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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 its own replication process.
Heart muscle is one of the most ATP demanding cells.
Cp 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 recovery time. This is the "over-exert one day, payback for three days" report common to many CFS patients.
Gastrointestinal Problems
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CFS and FMS patients often have concomitant gastrointestinal problems, ranging from Irritable Bowel Syndrome, poor nutrient absorption, and other problems.
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Cpn infects endothelial tissues, as its 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.
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Porphyria is notorious for causing chronic gut distress: nausea, intestinal cramping, etc. Chlamydia pneumoniae infection of gut endothelial tissue.
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Gut co-infections from fungi, bacteria, or yeast resulting from general immunosuppression, or specific Cpn infected gut-immune system will further add to gastrointestinal problems.
Sleep Disorder
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Porphyrins block GABA receptors, a main cause of anxiety and agitation in porphyria, and likely to interfere with sleep.
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Melatonin serves a number of functions that are related to protecting cells from oxidation as well as binding inflammatory endotoxins 24 and activating immune functions. 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 its influence on inducing sleep.
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Hypothalamic infection and disturbance by Chlamydia pneumoniae could be a contributing factor.
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Cytokine disturbance of sleep regulation.
Anxiety & Depression
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Porphyrins- noted previously for causing anxiety, depression, even psychosis.
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Depletion of melatonin noted above causes depletion of serotonin in the brain. Inadequate serotonin results in depression, as well as increased pain sensitivity.
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Cytokine depression
- cytokines are clearly linked to causing depressive symptoms.27
Endocrine Disturbance (Thyroid, Periods, Etc.)
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Infection of endocrine gland cells: thyroid, pancreas islet cells, pituitary, pineal, etc.
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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 episodes of these hypoglycemic symptoms over the course of treatment.
Headaches
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Porphyrins.
One of the neurotoxic effects of porphyrins is headaches.
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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.
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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 its being one of the most life-impacting symptoms for the sufferer. Cpn infection explains this very well.
- Secondary porphyria induced by it and the impact of porphyrins on brain functioning.
- Cerebral inflammation from circulating cytokines.
- Brain infection.
- Endotoxins.
FIBROMYALGIA SYMPTOMS
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. See http://www.cpnhelp.org/how_chlamydia_pneumoniae_
- Porphyrins blocking GABA receptors will also lower pain tolerance.
- Generalized cytokine load causes broad based "feels lousy all over."
SUMMARY CONCLUSION
The case for Cpn in CFS does not prove that Cpn is always the causal element.
As a syndrome, CFS 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, see original article
http://www.immunesupport.com/library/
showarticle.cfm?id=7938&T=CFIDS_FM&B1=EM042507C"
Chlamydia pneumoniae not caught like you thought.
http://www.mc.vanderbilt.edu/reporter/index.html?ID=779
April 23, 1999
Copyright © 2007, Vanderbilt University Medical Center
Say Chlamydia pneumoniae and before you get to pneumoniae most people think of a sexually transmitted disease.
"As soon as people hear the name Chlamydia their ears shut down," said Dr. Charles W. Stratton, associate professor of Pathology. "They either don't hear or don't understand the second part - pneumoniae. They think of Chlamydia trachomatis, a common cause of sexually transmitted diseases. Chlamydia pneumonia is the one that's not fun to catch."
The Chlamydia pneumoniae (C. pneumoniae) organism, first described in 1988, is not the sexually-transmitted type. It is an airborne organism that you get from breathing after a person carrying the organism has coughed.
"They float around as droplet nuclei, similar to TB.
People cough and up come these infectious bodies. They float around a room.
You breathe. In they come and now you've got your own."
It's how they work inside the body that Stratton, Dr. William M. Mitchell, professor of Pathology, and colleagues have been looking at for the past five years.
The study of the organism has intensified as Stratton's colleagues at Vanderbilt and other medical centers around the country, including Johns Hopkins and The Mayo Clinic, look at the role of Chlamydia in diseases such as Multiple Sclerosis, Rheumatoid Arthritis, Pyoderma gangrenosum, Coronary Artery Disease and Interstitial Cystitis.
Stratton said that Chlamydia is sneaky.
When viruses invade a cell, if they are active, they integrate in the human DNA and basically take over the cell.
"They tell the cell, 'Ok, today, we're going to do nothing but make viruses and the cell often dies in this process," Stratton said.
Chlamydia works in a different way.
First, when you breathe in Chlamydia, it can infect the ciliated cells, the cells lining the airways. Ciliated cells are like an escalator that moves mucus along. Chlamydia can paralyze the ciliated cells because it steals their energy. So the host has a nasty respiratory infection.
When you have an active infection of any kind, the body has an immune response to it. Part of the immune response is that monocytes and macrophages try to engulf the pathogen and kill it.
But they can't always kill Chlamydia.
Instead, they disseminate the organism to peripheral blood mononuclear cells and the organism can silently infect other cells in the body.
"With these cryptic infections, you don't have symptoms.
And because Chlamydia isn't really a virus, when it's causing a cryptic infection, it's metabolizing. It's eating, drinking, singing and dancing. It's alive."
Since Chlamydia can't make its own energy, it has to steal energy from the human cell.
This means the chlamydia-infected cell doesn't work well.
"If Chlamydia is actively metabolizing in a cell, it's up to no good.
It's stealing energy. I can't picture anything good coming from chlamydia being in a human cell."
Chlamydia also likes to infect endothelial cells, the cells that line blood vessels.
When there's inflammation in the body, there often is angiogenesis, meaning new blood cells are formed. And Chlamydia is drawn to those cells.
So if Chlamydia is in the peripheral blood mononuclear cells and there's an inflammation in the host's body, you're "unlucky," Stratton said. Any secondary inflammatory process could become secondarily infected by Chlamydia no matter what the source of the inflammation, Stratton said.
"Now you've got a chronic problem," Stratton said.
"Now you've got a major chronic infection in the tissue, whether it's the brain (MS) or in the joints
(Rheumatoid Arthritis).
"If you have inflammation, a spider bite, a viral joint infection, viral meningitis or encephalitis, it doesn't matter what it is, if a Chlamydia-infected cells happens to end up in that inflamed area, you may have just started yourself a Chlamydia farm."
Stratton said this doesn't necessarily mean that Chlamydia causes the disease, but it may play heavily into how the disease progresses. There may be many causes of MS, Rheumatoid Arthritis or other diseases in which Chlamydia is believed to play a role.
"One thought is that Chlamydia is not the cause of anything other than pneumonia but once it causes a lung infection and gets into your peripheral blood mononuclear cells, it's available to cause secondary infections in other tissues if the infected white cells happen to go to those tissues.
"It may be that MS is an infection of the brain that is caused by viruses, and most people who get that viral infection of the brain have a headache for a week, then get better. If you happen to have Chlamydia, however, you may go on and have a chronic illness that we have defined as ??
Still a killer: pneumonia targets the ill, the elderly.
http://www.encyclopedia.com/doc/1G1-5073383.html
From: FDA Consumer | Date: 6/1/1987 | Author: Lecos, Chris W.
Pneumonia can be caused by bacteria, viruses, mycoplasma(microscopic organisms that are smaller than bacteria but larger than viruses), fungi, and even toxic chemicals that are inhaled and impede the ability of the respiratory system to obtain oxygen. The word "pneumonia' actually is a general term for describing a variety of diseases that cause inflammation or infections of the lungs. In the healthy individual, the lower respiratory system (the lungs) is usually free of microorganisms, while the upper respiratory system (the nose, throat and mouth) readily harbors bacteria and other organisms during the normal process of eating and breathing. What protects most people from microbial invasion of the lungs is the body's complex system of natural defenses. ...
Mycoplasmal pneumonia tends to occur more frequently among people under 35.
Its onset is usually slower than the bacterial pneumonias. It may take two weeks or longer before serious symptoms appear. Chills are less common, fever may not get above 101 degrees Fahrenheit, and not much sputum is produced. Outbreaks have occurred among school and military populations. This type of pneumonia accounts for about one-third of all cases in the general population and as many as three-fourths of the pneumonias among youngsters 5 to 19 years of age. Few die from it, and only a small percentage of patients require hospitalization. Generally, tetracylines and erythromycin are the antibiotics used to treat the disease. ...
Meeting the Challenge of a New Generation of...
www.macmcm.com/pcp/pcp2000_10.htm
Published on: 7/24/2001
"Community-acquired respiratory tract infections continue to be among the most common and important infections seen by practicing physicians," said Charles W. Stratton, MD, director, Clinical Microbiology Laboratory, The Vanderbilt Clinic, Nashville, TN. These infections involve the sinuses, the airways, and/or the lungs, and can be caused by a wide variety of microorganisms, including viruses. Community-acquired respiratory tract infections caused by bacterial pathogens are usually defined as acute exacerbations of chronic bronchitis, community-acquired pneumonia (CAP) or acute bacterial sinusitis (ABS).
Acute exacerbations of chronic bronchitis are important because the incidence of chronic bronchitis is rising. Chronic bronchitis comprises 90% of all cases of chronic obstructive pulmonary disease (COPD). Risk factors for COPD include smoking, a family history of obstructive lung disease, exposure to tobacco smoke and pollutants, and recurrent respiratory tract infections, particularly during infancy.
"Acute bacterial sinusitis is a major problem, with approximately 31 million cases of acute and chronic sinusitis reported annually in the United States," said Dr. Stratton. The annual direct and indirect costs of ABS in the United States are more than $3.4 billion. The diagnosis of acute bacterial sinusitis can be difficult, and involves localized maxillary facial pain, poor response to decongestants, history of purulent nasal secretions or discharge, and abnormal transillumination.
Antimicrobial therapy of ABS is important, because the complications of these sinus infections include chronic sinusitis, orbital complications, and intracranial complications such as meningitis, epidural abscess, subdural empyema, venous sinus thrombosis and cerebral abscess. ABS is the fifth most common diagnosis for which antimicrobial agents are prescribed. The dominant bacterial pathogen in ABS is S pneumoniae.
"There are important problems associated with choosing therapeutic options for bacterial respiratory tract infections," said Dr. Stratton. When purulent nasal discharge or expectorated sputum specimens are available, a Gram stain is often quite useful in guiding the initial choice of antimicrobial agents; however, a precise microbiological diagnosis is often difficult because of the specialized and invasive procedures needed to obtain a specimen, and treatment is often empirical.
Even when specimens can be collected, the differentiation of infection from colonization or contamination is a problem, and mixed infections occur frequently. A number of newly identified respiratory tract pathogens, such as C pneumoniae and Simkania, are difficult to detect, and are still being assessed in terms of their pathogenic potential. Finally, resistance of the most common bacterial pathogens has emerged and is increasing.
"Given the broad spectrum of respiratory tract pathogens and the problem of resistance, it is clear that there are currently few, if any, ideal antimicrobial agents for respiratory tract infections," said Dr. Stratton. The ideal agent should have excellent activity against the broad spectrum of respiratory tract pathogens, and low potential for the development of resistance. It should have a high clinical success rate with empirical therapy. It should have a favorable safety profile, convenient dosing with both oral and intravenous formulations, and a short required treatment course.
Older classes of antimicrobial agents, such as the beta-lactams, macrolides, azalides, and fluoroquinolones, all have members that have been useful in treating respiratory tract infections. Unfortunately, the emergence of newer pathogens and resistant organisms has lowered the clinical efficacy of these drugs.
Antibiotic slows atherosclerosis
in people with Chlamydia pneumonia antibodies.
Author: Dirk Sander, M.D.
Co-authors include Kerstin Winbeck, M.D.; Jurgen Klingelhofer, M.D.; Thorleif Etgen, M.D. and Bastian Conrad, M.D.
October 16, 2002
Oct 16 (American Heart Association) -
Long-term antibiotic treatment may slow the progress of early atherosclerosis in stroke patients who have antibodies to a pneumonia-causing bacteria in their bloodstream. Scientists reported these findings in yesterday's rapid access issue of Circulation: Journal of the American Heart Association.
"Our data imply for the first time to our knowledge that antibiotic treatment in patients over age 55 with Chlamydia pneumoniae (Cp) antibodies and prevalent cerebrovascular disease is associated with a reduced progression of early stages of carotid atherosclerosis,"
says study author Dirk Sander, M.D., a researcher with the neurology department at Technical University of Munich.
Chlamydia pneumoniae - the bacteria that causes pneumonia - has been associated with atherosclerosis. Studies have also associated the Cp antibody with heart attack and stroke. Other research has corroborated the association of Cp with atherosclerosis based on the organism's presence in atherosclerotic lesions and its absence in healthy artery tissue.
Other researchers have also described the benefits of antibiotics on vessel disease.
Sander's team evaluated the effect of the antibiotic roxithromycin on progressive thickening of the carotid (neck) artery in 272 stroke patients (average age 64) for two years. Of the 125 that tested positive for the Cp antibody, 62 received a twice-daily, 150-milligrams dose of roxithromycin, while 63 got twice-daily placebo for 30 days. Of the 147 Cp-negative patients, 74 were assigned to the drug and 73 to placebo.
Researchers measured intima to media thickness (IMT) of the common carotid artery with ultrasound. Increased IMT indicates atherosclerosis. Each patient had undergone both IMT and blood tests for Cp antibodies at least three years before the start of the study's antibiotic regimen. Patients infected with Cp in the past have antibodies that react when their blood is exposed to the microorganism in the laboratory.
C-reactive protein (CRP) levels were also established for each patient.
CRP is a marker of general systemic inflammation, including irritation of vascular walls.
In the baseline period, IMT progressed in Cp patients at a rate of 0.12 millimeters a year (mm/year) compared to 0.07 mm/year in patients without the antibody, regardless of other cardiovascular risk factors.
After two years of antibiotic treatment, progression was significantly reduced Cp positive patients compared to Cp-positive patients who did not receive roxithromycin. The progression was 0.07 mm/year in patients taking antibiotics versus 0.11 mm/year in untreated patients.
Treatment significantly decreased CRP levels in treated Cp-positive patients but not in the placebo Cp-positive group, an effect that remained unchanged even after adjusting for smoking, age, diabetes, blood pressure or cholesterol levels. ...
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