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American Academy of Environmental Medicine Newsletter (Winter 1997), p.1
New Treatments for Chronic Infections Found in CFS,
Fibromyalgia Syndrome and Gulf War Illnesses
Garth L. Nicolson, Ph.D.
The Institute for Molecular Medicine
16371 Gothard St. H, Huntington Beach, CA 92647
and Professor of Internal Medicine,
The University of Texas Medical School at Houston
Chronic Fatigue Syndrome (CFS), Fibromyalgia Syndrome (FMS) and Gulf War Illnesses (GWI) are
characterized by their complex, multi-organ chronic signs and symptoms, including neurological,
muscular-skeletal, rheumatic, mucocutaneous, gastrointestinal, sinopulmonary, and constitutional,
among others. Also included in this complex clinical picture are increased sensitivities to various
environmental agents and enhanced allergic responses. Often such patients have cognitive problems
and are seen by psychologists or psychiatrists who usually decide in the absence of contrary laboratory
findings that the condition is a somatoform disorder. However, there is another, quite different
possibility--these patients may suffer from chronic infections that can penetrate the CNS and PNS as
well as other tissues and organs and cause the complex signs and symptoms seen in CSF, FMS and
GWI, including immune dysfunction that may underlie some of the environmental responses as well as
increased titers to various endogenous viruses that are commonly found to be expressed in these
patients.
Few infectious agents can produce the complex chronic signs and symptoms found in CFS, FMS and
GWI patients, but one type of airborne infection that has received renewed interest of late as an
important element in these disorders is represented by the class mollicutes.
These organisms,
principally mycoplasmas and other rather primitive bacteria, although not well known agents, are now
considered important emerging pathogens in causing chronic diseases and may be important cofactors
in some illnesses, including AIDS [1]. Interestingly, as these illnesses progresses, there are a number
of accompanying problems, including in some patients MS-like, ALS-like, Lupus-like and arthritis-like
signs and symptoms, and the presence of usually rare autoimmune responses is consistent with
mycoplasmal infections that penetrate into nerve cells, synovial cells, etc. As mycoplasmas escape
from cellular compartments, they can leave with pieces of cell membranes containing important
antigens that can trigger immune responses.
Although most mycoplasmas are not considered important human pathogens, some species, such as M.
fermentans, M. penetrans, M. pneumoniae, M. genitalium, and M. hominis, among others, have been
American Academy of Environmental Medicine Newsletter, p.2
closely associated with various human diseases [1].
In a majority of CFS and FMS patients examined we and others, principally Dr. Daryl See of the
University of California College of Medicine, Irvine, are finding strong evidence for mycoplasmal
blood infections that can explain their chronic conditions. In our studies on GWI, a CFS/FMS-like
condition [2], we have found mycoplasmal infections in approximately one-half of patients, principally
one species, M. fermentans [3, 4].
Moreover, in approximately one-half of the civilians with CFS,
FMS or arthritis we are finding a variety of pathogenic mycoplasmas, such as those listed above, in the
leukocyte fractions of blood samples. The tests that we use to identify mycoplasmal infections,
polymerase chain reaction and nucleoprotein gene tracking [5], are very sensitive and highly specific.
These tests are a dramatic improvement over the relatively insensitive serum antibody tests that are
routinely used to assay for systemic mycoplasmal infections.
The identification of mycoplasmal infections in the leukocyte blood fractions of a rather large subset of
CFS, FMS and arthritis patients suggests that mycoplasmas, and probably other chronic infections as
well, may be an important source of morbidity in these patients. If such infections are important in
these disorders, then appropriate treatment with antibiotics should result in improvement and even
recovery. This is exactly what has been found [6]. The recommended treatments for mycoplasmal
blood infections require long-term antibiotic therapy, usually multiple 6-week cycles of doxycycline
(200-300 mg/d), ciprofloxacin or Cipro (1,500 mg/d), azithromycin or Zithromax (500 mg/d) and
clarithromycin or Biaxin (500 mg/d). Multiple cycles are required, because few patients recover after
only a few cycles [4], possibly because of the intracellular locations of mycoplasmas like M.
fermentans and M. penetrans, and the slow-growing nature of these microorganisms. Treatment
recommendations for mycoplasmal infections are similar to those used to treat Lyme Disease, caused
by other slow-growing intracellular bacteria that are difficult to identify and treat. Interestingly, CFS,
FMS, and GWI patients that recover after several cycles of antibiotics are generally less
environmentally sensitive, suggesting that their immune systems may be returning to pre-illness states.
If such patients had only chemical exposures as the reason for their illness, they should not respond to
the recommended antibiotics and recover.
Before systemic mycoplasmal infections can be considered important in causing disease, certain
criteria must be fulfilled [7]: (1) The incidence rate among diseased patients must be higher than in
those without disease. This has been found for M. fermentans. Although this mycoplasma has been
found in asymptomatic adults, the incidence is low, usually a few percent compared to almost one-half
of Gulf War Illness patients [3, 4]. (2) More of the mycoplasma must be recoverable from diseased
patients than from those without disease. This has been found [3, 4]. (3) An antibody response should
be found
American Academy of Environmental Medicine Newsletter, p.3
at higher frequency in diseased patients than in those without disease. This has been found but usually
not until the disease has progressed. According to Lo et al. [8-10] M. fermentans hides inside cells and
does not elicit a strong immune response until near death. (4) A clinical response should be
accompanied by elimination of the mycoplasma. This is exactly what has been seen [3, 4]. (5) Clinical
responses should be differential depending on the type of antibiotic. This is what has been found.
Only antibiotics that are effective against the pathogenic mycoplasmas result in recovery, and some
antibiotics, such as penicillins, can worsen the condition [3, 4]. (6) The mycoplasma must cause a
similar disease in susceptible animals. The best description comes from Lo et al. [8], where injection of
M. fermentans into monkeys resulted in development of a fulminant disease that leads to death. These
animals display many chronic signs and symptoms [8]. (7) The mycoplasma must cause a similar
disease when administered to volunteers. This has not been done, because of ethical considerations.
(8) A specific anti-mycoplasma antibody reagent or immunization protects against disease. This has
not yet been done to my knowledge. Therefore, six out of eight of the above criteria have been
fulfilled, at least for M. fermentans, strongly suggesting that certain mycoplasmas can cause human
disease.
Are chronic, systemic mycoplasmal infections the answer to CFS, FMS, GWI and other disorders?
Of course not! This is likely to be an appropriate explanation for a rather large subset of CFS, FMS,
GWI and some arthritis patients, but certainly not every patient will have the same chronic infections.
Some patients may have chemical exposures or other environmental problems as the underlying
reason for their chronic signs and symptoms. In these patients antibiotics should have no effect
whatsoever.
The identification of specific infectious agents in the blood of chronically ill patients may allow many
patients with CFS, FMS, GWI or arthritis to obtain more specific diagnoses and effective treatments
for their illnesses. Blood samples can be sent to the Institute for Molecular Medicine for mycoplasma
and other testing. (Website for further information: www.immed.org).
Garth L. Nicolson, Ph.D.
The Institute for Molecular Medicine (Tel: 714-903-2900)
16271 Gothard St. H, Huntington Beach, CA 92647
and Professor of Internal Medicine,
The University of Texas Medical School at Houston
References Cited
1. Baseman, J.B. and Tully, J.G. Mycoplasmas: Sophisticated, reemerging, and burdened by their
notoriety. Emerg. Infect. Diseases 1997; 3: 21-32.
2. Nicolson, G.L. and Nicolson, N.L. Chronic fatigue illness and Operation Desert Storm. J. Occup.
Environ. Med. 1996; 38: 14-16.
3. Nicolson, G.L. and Nicolson, N.L. Diagnosis and treatment of mycoplasmal infections in Persian
Gulf War Illness-CFIDS patients. Int. J. Occup. Med. Immunol. Tox. 1996; 5: 69-78.
4. Nicolson, G.L., Nicolson, N.L. and Nasralla, M. Mycoplasmal infections and Chronic Fatigue
Illness (Gulf War Illness) associated with deployment to Operation Desert Storm. Intern. J. Med.
1998; 1:80-92.
5. Nicolson, N.L. and Nicolson, G.L. The isolation, purification and analysis of specific genecontaining nucleoproteins and nucleoprotein complexes. Meth. Mol. Genet. 1994; 5: 281-298.
6. Nicolson, G.L. and Nicolson, N.L. Doxycycline treatment and Desert Storm. JAMA 1995; 273:
618-619.
7. Taylor-Robinson, D. Infections due to species of mycoplasma and ureplasma: an update. Clin.
Infect. Dis. 1996; 23: 671-682.
8. Lo, S.-C., Wear, D.J., Shih, W.-K., Wang, R.Y.-H., Newton, P.B., Rodriguez, J.F. Fatal systemic
infections of nonhuman primates by Mycoplasma fermentans (incognitus strain). Clin. Infect.
Diseases 1993; 17(Suppl 1): S283-288.
9. Lo, S.-C., Buchholz, C.L., Wear, D.J., Hohm, R.C., Marty, A.M. Histopathology and doxycycline
treatment in a previously healthy non-AIDS patient systemically infected by Mycoplasma
fermentans (incognitus strain). Mod. Pathol. 1991; 6: 750-754 .
10. Lo, S.-C., Dawson, M.S., Newton, P.B., Sonoda, A.A., Shih, W.-K., Engler, W.F., Wang, R.Y.-H.,
Wear, D.J. Association of the virus-like infectious agent originally reported in patients with AIDS
with acute fatal disease in previously healthy non-AIDS patients. Amer. J. Trop. Med. Hyg. 1989;
41: 364-376 .