Diagnosis of Chronic Fatigue Syndrome (CFS) Infections

Chronic illnesses, such as Chronic Fatigue Syndrome or Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) are characterized by a number of chronic (longer than 6 months duration) signs and symptoms that do not resolve with rest.

Among these are disabling fatigue, intermittent fevers, joint and muscle pain and loss of joint mobility, impairments in short-term memory, headaches, skin rashes, diarrhea, coughing, nausea and gastrointestinal problems, diminished vision and other signs and symptoms.

Other chronic illnesses, such as Fibromyalgia Syndrome (FMS), Gulf War Illness (GWI), 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.

We have proposed that the complex signs and symptoms found in many CFIDS, FMS, GWI and RA patients maybe due, in part, to systemic chronic infections following chemical or other insults that have the potential to suppress the immune system [1, 2]. Thus these illnesses probably evolve as a multi-step process that may require multiple toxic exposures, including chronic infections as causative, cofactors or opportunistic in compromised patients.

Chronic infections that are usually held in check by a host’s immune system can take hold if they can avoid immune surveillance and penetrate various tissues and organs, including cells of the Central and Peripheral Nervous Systems [3]. When such infections occur, they can cause many of the complex signs and symptoms seen in CFIDS, FMS, RA and GWI, including immune dysfunction [2].

Changes in environmental responses as well as increased titers to various endogenous viruses that are commonly found to be expressed in these patients have been seen in CFIDS, FMS and GWI. If infectious agents are involved, few can produce the complex chronic signs and symptoms found in these patients. 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 [3].

These microorganisms, principally mycoplasmas and other rather primitive bacteria, although not well known agents in causing disease, are now considered important emerging pathogens in chronic diseases and may also be important cofactors in some illnesses, including AIDS and other immunodeficiency disorders, skin diseases and some autoimmune diseases [3].

As chronic illnesses such as GWI (and in some cases CFIDS, FMS and RA) progress, there are a number of accompanying clinical problems, particularly increases in autoimmune problems. These include in some patients acquiring some of the signs and symptoms of Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig’s Disease), Lupus, Graves’ Disease, RA and other complex autoimmune diseases. Such usually rare autoimmune responses are consistent with certain chronic infections, such as mycoplasmal infections that penetrate into nerve cells, synovial cells and other cell types.

It is proposed that these autoimmune signs and symptoms are caused when intracellular pathogens, such as mycoplasmas and other bacteria, escape from cellular compartments. Some 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. Thus patients with such infections may be responding to microorganism antigens as well as their own membrane antigens, producing unusual autoimmune signs and symptoms.

Microorganisms Cause Morbidity in Many CFIDS, FMS, GWI and RA Patients

Most microorganisms like mycoplasmas are not considered as important human pathogens when they are found at superficial sites, such as the oral cavity, 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 blood and colonize various tissues and have been closely associated with various human diseases [3].

Do these agents cause CFIDS, FMS, GWI or RA? Not necessarily on their own, but microorganisms like Mycoplasma, Chlamydia, Brucella, Coxiella and other bacteria and some viruses appear to be important in illness progression, causing patient morbidity, or exacerbating the major signs and symptoms seen in patients with chronic illnesses. If such microorganisms are associated with chronic illnesses, is there any evidence for microorganism infections in CFIDS, FMS, GWI or RA patients?

The answer is YES. In about 60% of CFIDS, 70% of FMS, 50% of GWI and 55% of RA patients examined we and others, principally Dr. Daryl See of the University of California College of Medicine, Irvine, and Eli Mortechai of Medical Diagnostics of New Jersey, are finding strong evidence for mycoplasmal blood infections that can explain much if not most of the chronic signs and symptoms found in these patients.

In our studies on GWI, a CFIDS-like illness [4], we have found mycoplasmal infections in the blood of about one-half of over 200 patients, and these patients were found to have principally one infectious species of mycoplasma, M. fermentans [4-6]. However, in about 60% of the >200 civilians with CFIDS and FMS patients that we have examined we are finding a variety of pathogenic mycoplasma species, such as M. fermentans, M. penetrans, M. pneumoniae, M. genitalium, M. pirum and M. hominis, in the white blood cell fractions of blood samples [6].

The tests that we use to identify mycoplasmal infections, polymerase chain reaction and nucleoprotein gene tracking, are very sensitive and highly specific for mycoplasmas. These tests are a dramatic improvement over the relatively insensitive serum antibody tests that are currently used to assay for systemic mycoplasmal infections.

Antibiotics/Vitamins/Nutritional Supplements

When microorganism infections are identified in the white blood cell fractions of subsets of patients with CFIDS, FMS, GWI or RA, these patients can be treated as medical not psychological or psychiatric patients. If such infections are important in these disorders, then appropriate treatments with antibiotics should result in improvement and even recovery. This is exactly what has been found [7, 8].

The recommended treatments for mycoplasmal blood infections require long-term antibiotic therapy, usually multiple 6-week cycles of doxycycline (200-300 mg/day), ciprofloxacin or Cipro (1,500 mg/day), azithromycin or Zithromax (500 mg/day) or clarithromycin or Biaxin (750-1,000 mg/day). Multiple cycles are required, because few patients recover after only a few cycles [4-6], possibly because of the intracellular locations of mycoplasmas and the slow-growing nature of these microorganisms.

The clinical responses 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, and they are not due to immunosuppressive effects of some of the antibiotics because others that do not cause immune suppression are also effective but only if they suppress mycoplasmal infections.

Some of these 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, chemical exposures and other toxic events also play an important role in these illnesses, and may play a predominant role in some patients. It is thus unlikely that there exists only one explanation for these chronic illnesses. Rather, it is probably 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.

Treatment recommendations for CFIDS, FMS, GWI and RA patients with 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, these patients that slowly 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 illnesses that were caused by psychological or psychiatric problems or by environmental or chemical exposures, they should not respond to the recommended antibiotics and recover their health. In addition, if such treatments were just reducing the autoimmune responses, then patients should not recover after the treatments are discontinued.

The treatments of chronic illnesses due to toxic exposures from chemical or radiological agents are quite different from the treatment of chronic infections [1]. 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 chemicals [9, 10].

A comprehensive approach to the therapy of chronic illnesses must be undertaken [8]. In addition to antibiotics or removal of toxic agents, these patients often have nutritional and vitamin deficiencies that must be corrected. For example, these patients are often depleted in vitamins B, C and E and certain minerals.

Unfortunately, patients with these chronic illnesses often have poor absorption. Therefore, high doses of some vitamins must be used, and others, such as vitamin B complex, cannot be easily absorbed by the gut, so sublingual natural B-complex vitamins in small capsules or liquids should be used instead of oral capsules that are swallowed. General vitamins plus extra C, E, CoQ-10, beta-carotene, folic acid, bioflavonoids and biotin are best. L- cysteine, L-tyrosine, L-carnitine and malic acid are reported by some to be useful. Certain minerals are also often depleted in these patients, such as zinc, magnesium, chromium and selenium.

There are also other considerations [8]. Antibiotic use that depletes normal gut bacteria can result in over-growth of less desirable bacteria. To supplement bacteria in the gastrointestinal system yogurt and especially Lactobacillus acidophillus tablets are recommended.

One product is a mixture of Lactobacillus acidophillus, Lactobacillus bifidus and FOS (fructoologosaccharides) to promote growth of these “friendly” bacteria in the gut. In addition, number of natural remedies that boost the immune system, such as whole lemon/olive extract drink or an extract of olive leaves with antioxidants are available and are potentially useful, especially during or after antibiotic therapy has been completed.

Although these products appear to help some patients, their clinical effectiveness in these patients has not been evaluated. They appear to be useful during therapy to boost the immune system or after antibiotic therapy in a maintenance program to prevent relapse of illness [8].

For Further Information

The Institute for Molecular Medicine can test patients for evidence of mycoplasmal and other infections of the types that worsen human diseases like CFIDS, FMS, GWI and RA. Blood samples can be sent to the Institute for Molecular Medicine for mycoplasma and other testing.


Prof. Garth L. Nicolson

The Institute for Molecular Medicine

15162 Triton Lane

Huntington Beach, CA 92649-1401

Tel: 714-903-2900

Fax: 714-379-2082



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Nicolson, G.L., Nasralla, M, Hier, J. and Nicolson, N.L. Diagnosis and treatment of chronic mycoplasmal infections in Fibromyalgia Syndrome and Chronic Fatigue Syndrome: relationship to Gulf War Illness. Biomed. Therapy 1998; 16: 266-271.

Nicolson, G.L. and Nicolson, N.L. Doxycycline treatment and Desert Storm. JAMA 1995; 273: 618-619.

Nicolson, G.L. Considerations when undergoing treatment for chronic infections found in Chronic Fatigue Syndrome, Fibromyalgia Syndrome and Gulf War Illnesses. (Part 1). Antibiotics Recommended when indicated for treatment of Gulf War Illness/CFIDS/FMS (Part 2). Intern. J. Med. 1998; 1: 115-117, 123-128.

Ziem GE. Multiple chemical sensitivity: treatment and followup with avoidance and control of chemical exposures. Toxicol. Ind. Health 1992; 8: 73-86.

Rea WJ, Pan Y, Johnson AR, Ross GH, Suyama H, Fenyves EJ. 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.

Source: This article reprinted with permission from the author, Garth L. Nicolson.

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