By Paula M. Carnes, Patient Advocate
The San Diego, CA conference center is about a half a mile long, so just walking from one session to another for a chronic fatigue/fibromyalgia (cfs/fms) patient can be daunting. I have been on long-term antibiotics for a mycoplasma infection that seems to be a major factor in my cfs. As a result it was not too difficult for me to walk the distance. I was looking for clues that several infections might be involved in cfs/fms.
One of my first positive clues came when I viewed the research poster from Igenex.1 I told Dr. Jyotsna S. Shah, Ph.D, CMLD, MBA I was reporting for ImmuneSupport regarding cfs/fms. Her instant reply was, “Chronic fatigue syndrome IS Lyme disease. You have come to the right place.” She asked me to inform everyone that Igenex has been finding more cases of babesia in Switzerland, Missouri, and the west coast of the U.S. Igenex testing has been validated by other labs in the U.S. Patients wishing to be tested for tick borne pathogens can contact Igenex at 800-832-3200. Their website is http://www.igenex.com.
Following this encouraging chat with Dr. Shah, I looked forward to the “meet the experts” session on Lyme disease. Drs. Sunil Sood, MD and Gary P. Wormser presented “Recent Advances in Lyme disease.”(2) The news was disappointing.
Their main points were:
1. Most tick bites do not result in long-term illness.
2. The recombinant OspA vaccine for Lyme was safe and effective but was recently discontinued in spite of FDA approval.
3. New diagnostic tests for Lyme pathogens should be evaluated in terms of existing tests that Sood considers “reliable.”
4. Sood was very cautious about using antibiotics for longer than two months and had difficulty recommending antibiotics for children because doxycycline, his antibiotic of choice for adults, is inappropriate for children. He was concerned about the “high incidence of side effects” with antibiotics.
5. He stated in his presentation that “the internet is also a source of misinformation for our patients.” Indeed, his comment on long-term antibiotics for chronic Lyme disease was turning patients into “victims.” He stated that there was no such disease as “chronic” Lyme disease, but he did not state what such an apparent illness would be called, perhaps an autoimmune disorder.
In conclusion, he posted a list of symptoms such as headache, fatigue, loss of balance with percentages beside each symptom. He commented to the audience of doctors, many from Europe and asking what to do for patients who had been bitten by ticks and were sick, “Note the percentages of symptoms…and these were in the healthy controls!” A ripple of laughter went up from the audience. I felt sick to my stomach as I realized those of us with chronic something were being laughed at by the very people we looked to for help. I managed to stay in my seat and hand a pamphlet on Igenex Labs to the doctor from Lebanon seated in front of me.
6. Sood presented a study he claimed was the only study testing long-term antibiotics on “chronic” Lyme patients. He did not clarify where this study had been done. The controls were seronegative patients who had been bitten by ticks and had an illness that looked like “chronic” Lyme disease. The test group included patients with the same symptoms but tested seropositive. One third of both groups got better on antibiotics, one third of both groups got worse, and one third stayed the same.
His conclusion was that antibiotics were obviously of no effect. It occurred to me that I would have concluded just the opposite. All the patients (seropositive or negative) had some form of Lyme disease, and one third of all of them responded to the antibiotics given, for some reason. Never mind what seemed to be common sense, there will be no more testing of long-term antibiotics from that group.
BARTONELLA or CAT SCRATCH FEVER
It seems that many cfs/fms patients are pet owners. Therefore I was interested to see what research was finding in a disease transmitted to humans by a cat scratch. There were two abstracts presented, one from the Pasteur Institute in France,(3) and one from Cleveland Clinic Foundation, Cleveland, OH.(4) The goal of both studies was to determine if a PCR of infected tissue would indicate bartonella. In both studies the PCR testing appeared to be an accurate diagnosis. The interesting detail of the Pasteur study was that there was a control group who only had two symptoms, enlarged lymph nodes and they owned a cat. Many doctors might not have diagnosed bartonella, yet the PCR testing indicated these cases did, indeed, have cat scratch fever.
J. Rupp of the University of Luebeck, Luebeck, Germany won one of the awards for best poster presentation.(5) He demonstrated that c.pneumoniae can infect vascular cells (artery lining) within 4 days in vitro. Another study by M.G. Netea of the Netherlands indicated that c. pneumoniae induced IL-18 inflammation in arteries.(6)
But the research on c. pneumoniae most relevant to cfs/fms came from the University of South Florida.7 They had studied blood from healthy blood donors and found that a “very high percentage of healthy blood donors carry C. pneumoniae with growth potential in their peripheral blood mononuclear cells (PBMCs).” The infected PBMCs were cultured and then treated with Azithromycin, clarithromycin, minocycline and tosfloxacin. “…even though 10 fold blood concentrations (~40 ?g/ml) of antibiotics were utilized to treat PBMCs, only partial inhibition of C. pneumoniae growth in PBMCs was observed. These results indicate that eradication and/or inhibition of resident C. pneumoniae in PBMCs may be difficult by treatment with antibiotics tested.”
G. Falck’s study from Sweden and Canada8 suggested similar findings in regard to persistent c. pneumoniae. “Chlamydia pneumoniae (Cpn) can cause acute as well as chronic respiratory tract infections (RTI). Chronic rhinitis, chronic pharyngitis, asthma and COPD have been associated with Cpn infections. Individuals with persistent Cpn infection may be the reservoir for infection.
Increased levels of specific Cpn IgA antibodies (ab) suggest chronic infection…The aim of the investigation was to characterize the course of Cpn infection in patients followed for 8 – 10 years…Treatment with antibiotics gave symptomatic relief but did not affect the specific ab titers. Family members of 4 index cases had specific Cpn ab levels indicating spread within the family. Conclusions: Persistent Cpn infection with increased specific IgA ab levels is associated with persistent symptoms from the respiratory tract. Intra-familiar spread of the infection is likely. High specific Cpn ab titers remain for several years. Cpn could not be eradicated by antibiotic treatment. New treatment strategies have to be evaluated or devised.”
I asked Dr. Yamamoto what he felt was the significance of this study. His comments were as follows:
1. Stress such as surgery, accidents, lack of sleep, emotional stress that depressed the immune system could lead to reactivation of c. pneumoniae.
2. Disease results could include atherosclerosis and possibly “autoimmune” diseases such as MS or cfs/fms.
3. PCR identification had to be done within the first 24 hours. After the first passage Cpn was not detectable.
4. Treatment would need to be with antibiotics that are capable of moving into the lymphocytes. He suggested ciprofloxacin and midecamycin.
Rifalazil™ for c. pneumoniae was a new antibiotic recommended in research by J. B. MAHONY of McMaster University, St. Joseph's Healthcare, Hamilton, ON, Canada.(9)
Pfizer completed a large-scale study on antibiotic potential to reduce cardiovascular events and announced results in March of 2002. We talked with them in regard to doing a study on antibiotic therapy and cfs/fms. They indicated that they would be interested.
R. D. Hardy from the University of Texas Southwestern Medical Center, Dallas, TX 10described his study in which mice were infected with live mycoplasma pneumoniae and UV killed mycoplasma. They were then treated with clarithromycin. The mice with the live mycoplasma recovered. The mice with the dead mycoplasma did not recover from the inflammation. Apparently dead mycoplasma is still capable of triggering an autoimmune reaction. We have been told that minocycline is anti-inflammatory. That is why it is effective for autoimmune diseases such as rheumatoid arthritis. This study would suggest that antibiotics, effective when the pathogen is still alive, are not effective as anti-inflammatories.
C.M. Bebear from Bordeaux, France recommended treating mycoplasma hominis with a combination of quinalones and doxycycline for a minimum of two to three weeks. She also suggested testing the susceptibility of the pathogen to the antibiotic.(11) Her studies showed that m. hominis was resistant to macrolides.(12)
Gum infections are caused by porphyromonas gingivalis. There is an invasive form of this pathogen that causes inflammation in atherosclerotic plaque. It is significant in diabetes, atherosclerotic plaques, and low term births due to stimulation of prostaglandins (animal models). This invasive strain may lead to increased risk of stroke and heart disease. Although this study was done in mice, mice are good animal models for this disease.(13)
NITRIC OXIDE IN PNEUMOCOCCAL PNEUMONIA TREATMENT
Nitric oxide seems to facilitate bacterial eradication in pneumococcal pneumonia. Nitric oxide may have further uses in treating infection.(14)
HORMONAL TREATMENTS FOR AIDS
There seems to be indications that cfs/fms patients have disrupted hypothalamus and pituitary function. This same problem seems to occur in AIDS patients. The following studies seem to be similar to cfs/fms patients.
1. Free T4 thyroid levels are hypothyroid. This low level seems to be related to low CD4 levels and may be caused by infection.(15)
2. Hypothyalmic-pituitary failure is caused by CNS infections such as HIV. It can be treated with growth hormone. There are studies linking growth hormone deficiency to cfs/fms.(16)
3. Hypogonadism is found in AIDS patients and is determined by measuring free testosterone. Injections of testosterone caused spiking levels. At the high levels there was a good sense of well being followed by a crash. Prostatetic hypertrophy and viscous blood could be negative side effects. Testosterone gels were found to produce stable levels in which the patient felt better in general without these side effects.(17)
4. Growth hormone promotes nitrogen retention and increases body fat mass in limbs, reduces fat in the abdomen and prevents wasting.(18)
[Author's Note: The previously reported dose of 4 mg may be a misprint. Anyone deciding to pursue growth hormone therapy needs to consult an endocrinologist who specializes in this treatment for adults who are growth hormone deficient, as overdosing can have serious side effects.]
NON-SPECIFIC IMMUNE BOOSTERS
Dr. Anthony Fauci spoke Sunday morning on bioterrorism. Fauci’s primary focus on the development of vaccines against biological weapons. He mentioned non-specific immune system boosters, such as interferon gamma, might be useful to aid the public in case of a biological attack. Although these types of drugs were not specifically presented at ICAAC they would certainly be useful for infectious disease treatment. Ampligen from Hemispherx Biopharma would fit in this category.
Lyme pathogens, Chlamydia pneumoniae, mycoplasmas, gum infections, and more may all be involved in the disease syndrome we call chronic fatigue and fibromyalgia syndromes. Antibiotics, antivirals, and endocrine treatments may prove to be useful in treating cfs/fms. There may be immune modulating treatments available in the future which were not presented at ICAAC. One thing is certain, we need more research into the diagnosis and treatment of these chronic infections.
1. PCR Assay for Direct Detection of Babesia-Wa1 in Whole Blood Category: P. Parasitology J. S. SHAH1, M. MAO 2, S. WARD 1, P. MARIANO 1, R. STRICKER 3, N. S. HARRIS 1;
1IGeneX, Palo Alto, CA, 2IGeneX Inc, Palo Alto, CA, 3450 Sutter Street, San Francisco, CA. Presentation Number: P-782
2. Value of the Detection of Bartonella henselae by PCR in the Diagnosis of Cat Scratch Disease (CSD) Category: D. Diagnostic Lab, Tests: Methods for Antibacterial Susceptibility Testing Y. HANSMANN1, B. JAULHAC 2, P. MARIET 2, R. HELLER 2, D. CHRISTMANN 1, Y. PIEMONT 2;
1Hôpitaux Universitaires de Strasbourg, Strasbourg, France, 2Institut de Bacteriologie, Strasbourg, France. Presentation Number: D-1999
3. Real-Time PCR in the Diagnosis of Bartonella Infections Category: D. Diagnostic Lab, Tests: Methods for Antibacterial Susceptibility Testing O. TACHOPOULOU1, G. PROCOP 2, J. GOLDFARB 3, C. SABELLA 3, L. DOYLE 2, A. TAEGE 1, C. ISADA 1,4;
1Infectious Disease, Cleveland, OH, 2Clinical Microbiology, Cleveland, OH, 3Pediatric Infectious Disease, Cleveland, OH, 4Cleveland Clinic Foundation, Cleveland, OH. Presentation Number: D-2000
4. Recent Advances in Lyme Disease Category: None selected SUNIL K. SOOD, MD1, GARY P. WORMSER 2;
1North Shore Univ. Hosp, Manhasset, NY, 2New York Med. Coll., Valhalla, NY.
5. Chlamydia pneumoniae Infected Blood Monocytes Induce Angioproliferative Signal Transduction in a Transendothelial Migration Model Category: B. Therapy in Animal Models, Pathogenesis and Host Defenses J. RUPP, M. KOCH, G. VAN ZANDBERGEN, J. GIEFFERS, M. MAASS;
Institute of Medical Microbiology and Hygiene, University of Luebeck, Luebeck, Germany. Presentation Number: B-283
6. Chlamydia pneumoniae Stimulates Production of IL-18 through Toll-Like Receptors (TLR) -2 and -4 Independent Mechanisms Category: B. Therapy in Animal Models, Pathogenesis and Host Defenses M. G. NETEA, B. KULLBERG, A. F. H. STALENHOEF, J. W. M. VAN DER MEER;
Nijmegen University Medical Center, Nijmegen, Netherlands. Presentation Number: B-285
7. Reactivation of Chlamydia pneumoniae in Peripheral Blood Mononuclear Cells Obtained from Healthy Donors and Inhibition by Antibiotics Category: B. Therapy in Animal Models, Pathogenesis and Host Defenses H. IKEJIMA1, H. FRIEDMAN 1, G. F. LEPARC 2, Y. YAMAMOTO 1;
1University of South Florida, College of Medicine, Tampa, FL, 2Florida Blood Services, St. Petersburg, FL. Presentation Number: B-282
8. Long Term Follow-Up of patients with Chlamydia pneumoniae Respiratory Tract Infection Category: L3. Other Studies of Adult Community-Acquired Infections G. FALCK1,2, J. IRVINE 2, J. GNARPE 3, H. GNARPE 4;
1Inst. of Family Med., Univ., Uppsala, Sweden, 2Apoteksgårdens Health Care Ctr, Kopparberg, Sweden, 3Inst. of Med. Microbiol. and Immunol., Univ. of Alberta, Edmonton, AB, Canada, 4Inst. of Med. Sci., Univ., Uppsala, Sweden. Presentation Number: L-996
9. Antimicrobial Activity of Rifalazil™ for Chlamydia pneumoniae Category: E. In Vitro Antibacterial Susceptibility Studies and Drug Combination Interactions J. B. MAHONY1, X. SONG 2;
1McMaster University, St. Joseph's Healthcare, Hamilton, ON, Canada, 2St. Joseph's Healthcare, Hamilton, ON, Canada. Presentation Number: E-1652
10. Microbiologic and Immunologic Activity of Clarithromycin in a Murine Model of Mycoplasma pneumoniae Pneumonia Category: B. Therapy in Animal Models, Pathogenesis and Host Defenses R. D. HARDY, A. M. RIOS, S. CHAVEZ-BUENO, H. S. JAFRI, J. HATFIELD, B. B. ROGERS, G. H. MCCRACKEN, O. RAMILO;
University of Texas Southwestern Medical Center, Dallas, TX. Presentation Number: B-701 Poster
11. Selection and Frequency of Mycoplasma hominis Mutants Having Acquired Resistance to Gatifloxacin, Moxifloxacin, and Levofloxacin Category: C1. Antibiotics: Mechanisms of Action, Biochemistry and Genetics of Resistance C. M. BÉBÉAR, A. CHARRON, H. RENAUDIN, C. BÉBÉAR;
Université Victor Segalen Bordeaux 2, Bordeaux, France. Presentation Number: C1-20 Poster Board
12. Characterization of Mycoplasma hominis Natural and Acquired Resistance to Macrolides: Transport, Binding to Ribosomes and Mutations in 23S rRNA Category: C1. Antibiotics: Mechanisms of Action, Biochemistry and Genetics of Resistance S. PEREYRE, P. GONZALEZ, B. DE BARBEYRAC, H. RENAUDIN, A. CHARRON, S. RAHERISON, C. BÉBÉAR, C. M. BÉBÉAR;
Université Victor Segalen Bordeaux 2, Bordeaux, France. Presentation Number: C1-1614
13. Oral Infection with Invasive Porphyromonas gingivalis Stimulates Accelerated Atherosclerotic Plaque Accumulation in ApoE-/- Mice Category: B. Therapy in Animal Models, Pathogenesis and Host Defenses F. C. GIBSON, III 1, C. HONG 2, J. WANG 3, C. A. GENCO1,3;
1Department of Medicine, Boston University School of Medicine, Boston, MA, 2Department of Endodontics, Boston University Goldman School of Dental Medicine, Boston, MA, 3Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine, Boston, MA. Presentation Number: B-799
14. Improved Therapy of Pneumococcal Pneumonia by the Combination of a Nitric Oxide Donor (Sodium Nitroprusside) and Ceftriaxone Category: B. Therapy in Animal Models, Pathogenesis and Host Defenses Y. NADEAU, N. OUELLET, Y. BERGERON, M. G. BERGERON;
Infectious Diseases Res. Ctr., Laval Univ., Quebec, PQ, Canada. Presentation Number: B-704
15. Relationship between CD4 Cell Counts and Free Thyroxine (FT4) in Clinically Stable HIV-infected Patients Category: H. HIV/AIDS and Other Retroviruses, Including Resistance J. COLLAZOS, S. IBARRA, J. MAYO;
Hospital de Galdácano, Vizcaya, Spain. Presentation Number: H-1910 Poster Board Number: 1910 Keyword: thyroid hormones, CD4 lymphocytes, antiretroviral drugs
16. Growth Hormone Deficiency in Children with Perinatally Acquired Human Immunodeficiency Virus Infection Category: H. HIV/AIDS and Other Retroviruses, Including Resistance E. EZEANOLUE, S. L. HARDY, G. NUNLEE-BLAND, W. R. J. FREDERICK;
Howard University Hospital, Washington, D.C., DC. Presentation Number: H-1913
17. A Prospective Study of the Safety and Efficacy of a Topical Transdermal Testosterone Gel versus Intramuscular Injections of Testosterone for the Treatment of Testosterone Deficiency in Male HIV-Infected Patients Category: H. HIV/AIDS and Other Retroviruses, Including Resistance G. R. COHAN, P. R. WOLFE, P. G. ANDERSON;
Pacific Oaks Medical Group, Los Angeles, CA. Presentation Number: H-1912 Poster Board Number: 1912 Keyword: hypogonadism, HIV, testosterone therapy.
18. Growth Hormone Improves Appearance and Lean Mass in Lipoatrophic Patients and These Benefits are Maintained with Alternate Day Dosing Category: H. HIV/AIDS and Other Retroviruses, Including Resistance G. MOYLE, C. BALDWIN, B. LANGROUDI, B. GAZZARD; Chelsea and Westminster Hospital, London, United Kingdom. Presentation Number: H-1935 Poster Board Number: 1935 Keyword: Lipodystrophy, Growth Hormone, Lean body mass