Update on Gulf War Illnesses: Relationship to Fibromyalgia Syndrome, Chronic Fatigue Syndrome and the Possible Role of Vaccines
February 15, 2002
By Prof. Garth L. Nicolson
The Institute for Molecular Medicine (Website www.immed.org) 15162 Triton Lane, Huntington Beach, CA 92649-1401
Fibromyalgia Syndrome (FMS), Chronic Fatigue Syndrome/Myalgic Encepthalomyelitis (CFS/ME) and Gulf War Illnesses (GWI) are characterized by similar chronic signs and symptoms. This is why we proposed that GWI is a CFS/ME illness . Other chronic illnesses, such as Rheumatoid Arthritis (RA), Inflammatory Bowel Disease, among others, also show many of these same signs and symptoms, suggesting that there may be some overlap in the underlying causes of these conditions or at least in the factors that may result in sickness (morbidity) or illness progression .
Microorganisms Cause Morbidity in Many FMS, CFS/ME and GWI Patients
Although the causes of the above chronic illnesses are for the most part unknown, the complex signs and symptoms that evolve in many, perhaps even a majority of patients, may be due, in part, to systemic chronic infections (bacteria, viruses, fungi). Such infections can follow acute or chronic chemical or other insults (viral, environmental, trauma, etc.) that have the potential to suppress the immune system . Thus these illnesses probably evolve over time as a multistep process that may require multiple toxic exposures, including infections that can be causative for the illness in some patients, cofactors for the illness (not causative but important to morbidity) in others or opportunistic in immune-compromised patients. Chronic infections that are usually held in check by our immune systems can take hold if they can avoid immune surveillance and penetrate and hide in various tissues and organs, including cells of the Central and Peripheral Nervous Systems. When such infections occur, they can cause many of the complex signs and symptoms seen in CFS/ME, FMS, RA and GWI, including immune dysfunction . Changes in environmental responses as well as increased titers to various endogenous viruses that are commonly found to be expressed in these patients as well as bacterial (Mycoplasma, Chlamydia, Borrelia, Brucella, etc.) infections have been commonly seen in FMS, CFS/ME, RA and GWI patients [2, 3].
One type of airborne infection that has received renewed interest of late as an important cause, cofactor or opportunistic infection in these disorders is represented by various primitive classes of bacteria . These microorganisms, principally Mycoplasmas and other bacteria (Chlamydia, Coxiella, Brucella, Borrelia, etc.), although not as well known as other agents in causing disease, are now considered important emerging pathogens in various chronic diseases, especially CFS/ME, FMS, among others, where a majority of patients have evidence of these infections in their blood. In our recent study on CFS/ME and FMS patients, most patients had multiple infections, especially if they had been sick for many years or had severe signs and symptoms . These infections invade the vascular system and cause coagulation problems. They can cause or increase the risk of coronary diseases.
Chronic infections may also be important cofactors in some illnesses, including HIV-AIDS and other immunodeficiency disorders, skin diseases and some autoimmune diseases . It is proposed that autoimmune signs and symptoms are caused when intracellular pathogens, such as mycoplasmas and other bacteria, escape from cellular compartments. Microorganisms like mycoplasmas can incorporate into their own structures pieces of host cell membranes that contain important host membrane antigens that can trigger autoimmune responses, and they can also mimic host cell antigen structures. Thus patients with such infections may respond immunologically to microorganism antigens as well as their own membrane antigens, producing unusual autoimmune signs and symptoms.
Diagnostic Results in GWI Patients Confirmed
We previously found that about 45% of GWI patients had mycoplasmal infections, principally from Mycoplasma fermentans . This result has now been replicated by a large Department of Defense (DoD) and Department of Veterans’ Affairs (DVA) study at more than 30 DoD and DVA medical centers around the country. As reported by one of the principal investigators of this study (Cooperative Clinical Study Program #475) at a recent meeting of the NIH Chronic Fatigue Syndrome Coordinating Board, the DoD/DVA study is finding almost exactly what we previously published. That is, ~40% of over one thousand GWI patients have mycoplasmal infections, and >80% of these infections are caused by M. fermentans. Patients in this large clinical trial are undergoing 12 months treatment with doxycycline or placebo to determine the effectiveness of this antibiotic in the treatment of GWI. The results of the blinded trial will not be known until later this year, but we expect that similar to the diagnostic results the treatment outcomes will parallel our published treatment results.
Possible Source of Microorganisms found in GWI Patients
Most microorganisms like mycoplasmas are not considered as important human pathogens when they are found at superficial sites, such as the oral cavity or gut, but some species, such as M. fermentans, M. penetrans, M. pneumoniae, M. genitalium, M. pirum and M. hominis, among others, have the capacity to penetrate into the blood circulation and colonize various tissues, and these cell-penetrating microorganisms have been closely associated with various human diseases . Do such infectious agents actually cause CFS/ME, FMS, GWI or RA? Probably not on their own, but microorganisms like Mycoplasma, Chlamydia, Brucella, Coxiella and other bacteria and some viruses, in particular HHV-6 and CMV, appear to be important in causing chronic illness progression and patient morbidity, exacerbating the major signs and symptoms seen in patients with chronic illnesses. Our recent results have shown that the combination of multiple bacterial and viral infections can be particularly difficult for patients to overcome.
How do patients contract the bacterial and viral infections found in FMS, CFS/ME, RA and GWI? The answer to this is not known, but many patients may already have these infections in dormant or latent forms, and their triggering of illness may be associated with a decline in the ability of the immune system to hold them in check. In other patients, infections may occur by a variety of routes, including airborne transmission, fluid exchange (such as blood transfusions), or in contaminated vaccines. Only rarely are vaccines contaminated, and most vaccinations would not be expected to cause illness, but in some commercial vaccines contamination has been documented. For example, some of the more common contaminants of commercial vaccines are mycoplasmas .
In the case of GWI, the multiple vaccines that the Armed Forces received upon deployment to the Persian Gulf have recently been associated with GWI. Unwin and colleagues  studied British Gulf War veterans with GWI and found an association with the multiple vaccines that they received during deployment. In the U.S. there has been a rash of GWI signs and symptoms in Armed Forces personnel who recently received the anthrax vaccine. In some cases this has resulted in chronic illnesses in as many as 7-10% of personnel receiving the vaccine . The chronic signs and symptoms associated with anthrax vaccination are very similar to those found in GWI patients, suggesting that at least some of the chronic illnesses suffered by veterans of the 1991 Gulf War may have been caused by vaccines in combination with other exposures . The anthrax vaccine, in particular, should not be used in Armed Forces personnel because of valid questions concerning its safety and efficacy.
Antibiotic and Antiviral Treatments for Chronic Illnesses
When microorganism infections are identified in blood fractions of subsets of patients with FMS, CFS/ME, GWI or RA, these patients can be treated as medical not psychological or psychiatric patients, just like any other patients with blood bacterial infections. This does not mean that psychological or psychiatric problems are not important in some chronic illness patients. But if such infections are important in these disorders, then appropriate treatments with antibiotics, antivirals or other medications that suppress chronic infections should result in improvement and even recovery. This is exactly what has been found .
Long-term treatment with antibiotics is required for FMS, CFS/ME, GWI and other patients with chronic bacterial infections. Few patients recover after only a few cycles of therapy [3, 5, 9], possibly because of the intracellular locations of the infections and the slow-growing nature of most of these microorganisms. We now recommend that patients who have been diagnosed with blood infections receive continuous antibiotics for at least 6 months before using 6-week cycles of treatment. Although patients starting such therapy usually have Herxheimer reactions and feel initially worse due to die-off or release of toxic materials from damaged microorganisms, they eventually stabilize and then slowly begin to recover. Unfortunately, the treatment requires long-term therapy and recovery is usually very slow. Patients that have been sick for many years are unlikely to recover within a year of therapy. We are also examining oxygen therapy using hyperbaric medicine, and we have established a new clinical unit for this purpose (see www.hyperbaricmedicine.com).
The clinical responses with antibiotics that are seen are not due to placebo effects, because administration of some antibiotics, such as penicillins, resulted in patients becoming more not less symptomatic. In addition, they are not due to immunosuppressive effects of some of the antibiotics, because other antibiotics that do not cause immune suppression are also effective but only if they suppress the chronic infections. Some patients recover to a certain point and then fail to continue to respond to the recommended antibiotics, suggesting that other problems, such as viral infections, environmental exposures and other toxic events also play an important role in these illnesses, and may even play a predominant role in some patients.
Since many patients also have viral (HHV-6, CMV, etc.) infections, these must be treated as well as. For severe infections, there are some antivirals that can help, but most patients do well on immune enhancement and nutritional supplements (see www.immed.org for further information).
Complex Role of Toxic Exposures in Chronic Illnesses
Do chronic infections explain illnesses like FMS, CFS/ME or GWI? It is unlikely that there are only one or even a few explanations for complex chronic illnesses. Rather, these illnesses are probably due to a combination of multiple toxic exposures, chemical and biological, in combination with genetic susceptibility (immune systems and/or detoxification systems) that determines whether a person becomes chronically ill. These considerations probably also play an important role in determining who will recover to various extents on different types of therapy. In addition, recovery can be complicated by patients’ over-dependence on drugs, such as certain antidepressants or other drugs that can suppress portions of the immune system.
The treatments of chronic illnesses that are due to toxic exposures from chemical or radiological agents are quite different from the treatment of chronic infections . The treatment of chemically exposed patients usually involves removal of offending chemicals from the patient's environment, depletion of chemicals from the patient's system and treatment of the signs and symptoms caused by chemical exposure(s). Chemically exposed patients are often extremely sensitive to a variety of commonly encountered chemicals, including perfumes and air fresheners, petrochemical fumes, chlorine, cleaning solutions and solvents, among others. They are also very sensitive to certain foods, and special diets are often necessary, and in some cases direct skin contact with certain substances can cause strong cutaneous reactions. Therefore, an important part of treatment for chemical exposures requires limiting exposures to a variety of common chemicals and gradual removal of the toxic chemical .
For Further Information
The Institute for Molecular Medicine and its certified reference diagnostic lab, International Molecular Diagnostics (www.imd-lab.com) can test patients for evidence of bacterial and viral infections of the types that are associated with chronic diseases like FMS, CFS/ME, GWI and RA and autoimmune diseases. The website for further information is: www.immed.org.
Prof. Garth L. Nicolson
The Institute for Molecular Medicine (website: www.immed.org)
15162 Triton Lane, Huntington Beach, CA 92649-1401
Tel: 714-903-2900 Fax: 714-379-2082
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Nicolson GL, Nasralla M, Hier J, et al. Mycoplasmal infections in chronic illnesses: Fibromyalgia and Chronic Fatigue Syndromes, Gulf War Illness, HIV-AIDS and Rheumatoid Arthritis. Med. Sentinel 1999; 4:172-176.
Nicolson GL, Nasralla M, Franco AR, De Meirlier K, et al. Mycoplasmal infections in chronic diseases. J. Chronic Fatigue Syndr. 2000; 6(3/4):23-39.
Nasralla M, Haier J, Nicolson GL. Multiple mycoplasmal infections detected in blood of Chronic Fatigue and Fibromyalgia Syndrome patients. Eur. J. Clin. Microbiol. Infect. Dis. 1999; 18:859-865.
Nicolson GL, Nicolson NL. Diagnosis and treatment of mycoplasmal infections in PersianGulf War Illness-CFIDS patients. Intern. J. Occup. Med. Immunol. Tox. 1996; 5:69-78.
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Unwin C, Blatchley N, CokerW, et al. Health of UK servicemen who served in the Persian Gulf War. Lancet 1999; 353:169-178.
Nicolson GL, Nass M, Nicolson NL. The anthrax vaccine controversy. Questions about its efficacy, safety and strategy. Med. Sentinel 2000; 5:97-101.
Nicolson GL, Nasralla M, Franco AR, et al. Diagnosis and Integrative Treatment of Intracellular Bacterial Infections in Chronic Fatigue and Fibromyalgia Syndromes, Gulf War Illness, Rheumatoid Arthritis and other Chronic Illnesses. Clin. Pract. Alt. Med. 2000; 1(2):92-102.
Rea WJ, Pan Y, Johnson AR, Ross GH, et al. Reduction of chemical sensitivity by means of heat depuration, physical therapy and nutritional supplementation in a controlled environment. J. Nutrit. Environ. Med. 1996; 6: 141-148.
For FMS, CFS/ME or RA or other autoimmune disease patients, The Institute for Molecular Medicine suggests the following lab tests (codes are IMD or CPT codes). Please note that patients should be off all antibiotics and immune enhancement products for 4 weeks prior to testing to insure that the test will not be a false-negative due to the antibiotic suppression of a blood infection.
1. Test Panel 1007 (CPT: 87798x3, 87581)—Mycoplasma species panel of 4 pathogenic mycoplasmas (M. fermentans, M. penumoniae, M. hominis, M. penetrans) by PCR. Specimen Requirements: one (1) 5 cc Lavender top Plastic Tube (EDTA). The blood is collected, immediately mixed and placed on ice, then shipped on wet ice or immediately flash frozen and shipped with dry ice by courier (foreign shipments) to IMD to arrive within 24-36 hours.
2. Test 1006 (CPT: 87486)—Chlamydia pneumoniae by PCR. Specimen Requirements: one (1) 5 cc Lavender top Plastic Tube (EDTA). Specimen Requirements: one (1) 5 cc Lavender top Plastic Tube (EDTA). The blood is collected, immediately mixed and placed on ice, then shipped on wet ice or immediately flash frozen and shipped with dry ice by courier to IMD to arrive within 24-36 hours.
3. Test 07056 (CPT: 87486)—Brucella species by PCR. Justification: Specimen Requirements: one (1) 5 cc Lavender top Plastic Tube (EDTA). Specimen Requirements: one (1) 5 cc Lavender top Plastic Tube (EDTA). The blood is collected, immediately mixed and placed on ice, then shipped on wet ice or immediately flash frozen and shipped with dry ice by courier to IMD to arrive within 24-36 hours.
4. Test 07047 (CPT: 87476)—Borrelia burgdorferi (Lyme Disease) by PCR. Specimen Requirements: one (1) 5 cc Lavender top Plastic Tube (EDTA). Specimen Requirements: one (1) 5 cc Lavender top Plastic Tube (EDTA). The blood is collected, immediately mixed and placed on ice, then shipped on wet ice or immediately flash frozen and shipped with dry ice by courier to IMD to arrive within 24-36 hours.
5. Test 07039 (CPT: 87532)—Human herpes virus 6 (HHV-6) test by PCR. Specimen Requirements: Collect blood in one (1) 5 cc Lavender Top Plasma Tubes (EDTA), mixed and separate blood plasma by centrifugation. The plasma is then shipped on wet ice or immediately flash frozen and shipped with dry ice by courier to IMD to arrive within 24-36 hours.
6. Test 07034 (CPT: 87496)—Cytomegalovirus (CMV) test by PCR. Specimen Requirements: Collect blood in one (1) 5 cc Lavender Top Plasma Tubes (EDTA), mixed and separate blood plasma by centrifugation. The plasma is then shipped on wet ice or immediately flash frozen and shipped with dry ice by courier to IMD to arrive within 24-36 hours.
7. Test 04651 (CPT: 85610)—Prothrombin Time (PT) by photo-optical method. Specimen Requirements: one (1) 5cc Blue top (citrated) Plastic tube. Spin for 15 min, pipet plasma into plastic vial and freeze. Send as frozen sample with dry ice by courier to IMD to arrive within 24-36 hours.
8. Test 03140 (CPT: 85730)—Activated Partial Thromboplastin Time (PTT) by photo-optical method. Requirements: one (1) 5cc Blue top (citrated) Plastic tube. Spin for 15 min, pipet plasma into plastic vial and freeze. Send as frozen sample with dry ice by courier to IMD to arrive within 24-36 hours.
9. Test 07073 (CPT: 85384)—Fibrinogen by nephelometry method. Requirements: one (1) 5cc Blue top (citrated) Plastic tube. Spin for 15 min, pipet plasma into plastic vial and freeze. Send as frozen sample with dry ice by courier to IMD to arrive within 24-36 hours.
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