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The Institute For Molecular Medicine


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).

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