December 5, 1997
CAPT Joyce Riley
Dear Joyce;
Thank you for your note. It is now agreed that many Gulf War veterans do have medical
problems but the signs and symptoms of Gulf War Illnesses (GWI) are still not well
established as criteria for specific diseases, and they do not readily fit into common
diagnosis categories used by military and veterans' hospitals. This has resulted in
veterans being placed in the category of 'unknown diagnosis', or they have been diagnosed
with psychological problems, such as Post Trauznatic Stress Disorder (PTSD). The military
personnel that we have surveyed were particularly disdainful of this latter explanation
for GWI and the attempts by military psychiatrists to brand them with mental instead of
medical disorders. Frequent problems reported are gastroenteritis, colitis, dermatitis,
and other symptoms not associated with traditional military or VA diagnostic categories or
specific ICD-9-coded diagnoses [1]. Many of the cases included nonspecific symptoms of
chronic fatigue, skin rashes, muscle and joint pain, headaches, memory loss shortness of
breath, gastrointestinal and respiratory symptoms, and other symptoms that do not readily
fit into a common case diagnosis. In the absence. of a clear and complete diagnosis and
effective treatment of symptoms for many veterans, the concept of a distinct syndrome
peculiar to the Persian Gulf Theater of Operations (GWI or Desert Storm Illness) has Been
advanced, although it has not been proven, and we considered it unlikely that veterans
have a completely new disorder or syndrome... The signs and symptoms of GWI fit with the
signs/symptom profile for Chronic Fatigue Syndrome (CFS) an/or Fibromyalgia Syndrome
(FMS). We have published that the signs and symptoms of CFS/FMS are essentially the same
as found in GWI [2]. The Surgeon General of the Army, Lt. Gen. Ronald Blanck, has stated
that agrees with our findings that GWI is a CFS-like disorder [3].
Finding out what you have does not necessarily result in a successful treatment. We have
been conducting research on mycoplasmal respiratory infections that cause a flu-like
illness that results in systemic CFS and/or FMS. Earlier we conducted a pilot study of
Desert Storm veterans and their families. This very preliminary study showed that 55/73
GWI patients, including symptomatic family members, responded to an anitibiotic
(doxycycline) that is effective against a variety of mycoplasmas, and most of the soldiers
and their symptomatic family members eventually recovered from their illness (4]. Since
this study we have continued to gather evidence that mycoplasmal infections, and probably
other chronic infectious agents, are causing the chronic signs and symptoms that are
similar to CFS/FMS in approximately one half of GWI cases, and these illnesses can be
successfully treated with antibiotics (5,6). As GWI progresses, there are a number of
accompanying problems, including MS4ike, ALS-like and Arthritis like signs/symptoms, and
this is also consistent with mycoplasmal infections that penetrate into nerve cells,
synovial cells, etc. If GWI patients had only chemical or chemical agent exposures as the
reason for their illness, then they would not respond to the antibiotics that we have
recommended (2O0-300 mg/d doxycycline, 6 wk per course; several courses are usually
required), Cipro (1,500. mg/d) or Zithromax (500 mg/d). We have developed new diagnostic
procedures (Gene Tracking and: forensic PCR) for analysis of the types of mycoplasmas
found in GWI, principally M.fermentans (incognitus strain). Interestingly, we are finding
mycoplasmal infections in about 50% of CFS/FMS patients, but the species of mycoplasma are
often different and more varied in civilians with CFS/FMS. We have also had success in
suggesting the same antibiotic regimen to patients that tested positive for mycoplasmal
infections in two CFS/FMS groups in Northern California; most of these patients are now
recovering from their illness. Currently we are using Gene Tracking to identify unusual
DNA sequences unique to mycoplasmas in blood leukocytes [7]. We have adapted forensic PCR
procedures for the accurate determination of invasive mycoplasmal infections. What is
interesting about these mycoplasmas is that they contain retroviral DNA sequences (such as
the HIV-1 env gene but not other HIV genes), suggesting that they may have been modified
to make them more pathogenic and more difficult to detect.
In conclusion, we are finding about 45% of GWI patients and ~50-60% of CFS/FMS patients
have such infections in their blood [6,7], and this has also been found by a certified
commercial diagnostic laboratory, Immunosciences Laboratories (-50%), Dr. See of the
Department of Medicine, Univ. of California, Irvine (70%) and Dr. Lesko of Del Mar, CA
(~60%). We are now developing additional tests for other infections. The Department of
Defense has begun to recognize that the patients that we have assisted in diagnosing
mycoplasmal infections are recovering on the antibiotic protocols that we recommended, and
they have agreed to fund a contract to train scientists and physicians from the Walter
Reed Army Medical Center and the Armed Forces Institute of Pathology in Washington D.C. in
the types of diagnostic tests that we use at the lnstitute for Molecular Medicine. In
addition, Walter Reed AMC has been studying our treatment protocol and has begun to use it
on selected patients, and there are military physicians who have used our advice to the
benefit of their patients, such as COL Norman Teer, M.D., a Desert Storm veteran and
commanding officer of a field hospital during the conflict. COL Teer (313-425-0780), who
recently retired, has successfully used our protocols on several of his patients.
Previously we were involved in helping Special Forces and Navy Seals recover from GWI, and
on the basis of this assistance my wife and I were made Honorary Full Colonels of the U.S.
Army Special Forces. This would have never happened if we were not providing effective and
meaningful assistance to these Special Forces patients.
I have listed below the criteria for judging whether the mycoplasmal infections that we
have found is pathogenic. Taylor-Robinson and collaborators (Clinical Infectious Diseases,
1996) listed the criteria that must be fulfilled: (1) The incidence rate among diseased
patients must be higher than in those without disease. [Yes, this has been found and
published for M.fermentans. Although this mycoplasma has been found in asymptomatic
adults, thc incidence is low, usually below 4% compared to almost one-half in Gulf War
illness patients, refs. 6,7]. (2) More of the mycoplasma can be recovered from diseased
patients than from those without disease. [Yes and published in refs. 6,7]. (3) An
antibody response is found in more diseased Pt than in those without disease. [Yes, but
not always. According to Lo et aL, this is true, but M. fermentans hides inside cells and
does not illicit a strong immune response until near death, ref. 9, 10]. (4) A clinical
response is accompanied by elimination of the mycoplasma. [Yes, and published in refs
1,2). (5) Clinical response is differential depending on the type of antibiotic. [Yes, and
published in refs. 4,6,7. Only antibiotics that are effective against the pathogenic
mycoplasmas work]. (6) The mycoplasma causes similar disease in susceptible animals. [Yes,
and published by the Armed Forces Institute of Pathology in ref. 8]. (7) The mycoplasma
causes a similar disease when administered to volunteers. [this has not been done because
it is not ethical to do this in the civilian sector.] (8) A specific anti-mycoplasma
antibody reagent or immunization protects against disease [Not yet done to my knowledge].
Six out of 8 of the criteria have been fulfilled, strongly suggesting that M. fermentans
can cause disease. The best description comes from Lo's papers on injection of M.
fermentans into monkeys, whereupon they develop a fulminate disease that leads to death
(81). And along the way, they display many of the same signs and symptoms that you have
probably had during your disease course (8).
Is this the whole answer to Gulf War Illness? Of course not! No one has ever said that it
was. This is likely an appropriate answer in a rather large subset of GWI as well as CFS
and FMS patients, but not every patient will have such chronic infections. Some patients
probably have chemical exposures or other problems as the underlying reason for their
chronic signs and symptoms. In these patients antibiotics should have no effect
whatsoever. The Institute for Molecular Medicine is a nonprofit corporation that is
recognized by the Federal Government as a charitable organization under Section 501(c)(3)
of the tax laws. As such we can accept tax-deductible contributions or patients may
consider membership in our 'Friends of the Institute's support program. Members of this
group can receive blood tests for mycoplasmal infections and advice on their illnesses. We
take pride in the accuracy of our procedures, and we are rare in the diagnostic area
because of our assistance to patients after their tests have been completed. At the
Institute for Molecular Medicine we remain committed to finding explanations for chronic
illnesses that can result in meaningful treatments.
Sincerely,
Garth L. Nicolson, Ph.D.
Chief Scientific Officer and Research Professor
Thc Institute For Molecular Medicine and
Professor of Internal Medicine
The University of Texas Medical School at Houston
The references quoted above are as follows:
1. NIH Technology Assessment Workshop Panel. The Persian Gulf Experience and Health. JAMA
272:
391-396 (1994)
2. Nicolson, G.L. and Nicolson, N.L. Chronic fatigue illness and Operation Desert Storm.
J. Occup. Environ. Med. 38:14-16, 1996).
3. Schmidt, P., Blanck, R.M. Gulf War Syndrome and CFS. CEIDS Chron. 8:25-27(1995).
4. Nicolson, G.L and Nicolson, N.L. Doxycycline treatment and Desert 5torm JAMA 273..
618-619 (1995).
5. 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. 5: 69-78(1996).
6. Nicolson, G.L., Nicolson, N.L. and Nasralla, M. Mycoplasmal infections and Chronic
Fatigue IIIness (Gulf War Illness) associated with deployment to Operation Desert Storm.
Intern. J. Med. in press (1997).
7. Nicolson, N.L. and Nicolson, G.L. The isolation, purification and analysis of specific
gene containing nucleoproteins and nucleoprotein complexes. Meth. Mol. Genet.
5:281-298(1994).
8. Lo, S.-C., Wear, DJ., 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 17(Suppl 1): S283-S288 (1993).
9. Lo, 5.-C., Buchholz, C.L., Wear, D.J., Hohin, 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 6: 75O-754 (1991).
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.
41: 364-376 (1989).