The role of microorganism infections in chronic illnesses:
Support for antibiotic regimens
By Garth Nicolson

Although the causes of chronic illnesses are for the most part unknown, the complex signs and symptoms that evolve in many patients with CFIDS, fibromyalgia (FM), Gulf War Syndrome (GWS) and rheumatoid arthritis (RA) may be due in part to systemic chronic infections from bacteria, viruses and 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.

These illnesses probably evolve over time as a multi-step 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) in others or opportun- istic 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 patients with CFIDS, FM, RA and GWS.

Microorganism infection 
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. Although they are not as well known as other agents in causing disease, these microorganisms,  principally Mycoplasmas and other bacteria (Chlamydia, Coxiella, Brucella, Borrelia, etc.), are now considered important emerging pathogens in various chronic diseases. They may also be important cofactors in some illnesses, including HIV/AIDS and other diseases.

Most microorganisms like mycoplasmas are not considered important human pathogens when they are found at superficial sites, such as the mouth or intestines, but some species, such as M. fermentans, M. penetrans, M. pneumoniae, M. genitalium, M. pirum and M. hominis, have the capacity to penetrate the blood circulation and colonize various tissues. These microorganisms probably do not actually cause CFIDS, FM, GWS or RA on their own, but they appear to be important in causing chronic illness progression or exacerbating the major signs and symptoms in patients with those illnesses.

There is evidence for microorganism infections in CFIDS, FM, GWS and RA patients. My lab and others (including Eli Mortechai of Medical Diagnostics of New Jersey) are finding mycoplasmal blood infections in about 60% of CFIDS, about 70% of FM and about 50% of GWS and RA patients examined. In our studies on GWS, a CFIDS-like illness, we found mycoplasmal infections in the blood of about 50% of more than 200 patients, and these patients were found to have principally one infectious species of mycoplasma, M. fermentans. We have found a variety of pathogenic Mycoplasma species, such as M. fermentans, M. penetrans, M. pneumoniae, M. genitalium and M. hominis in the white blood cells of about 60% of more than 200 civilians with CFIDS and FM. These infections are found in less than 10% of healthy controls. Interestingly, the majority of CFIDS and FM patients had multiple mycoplasmal infections (more than one species), but multiple infections were not found in any of the healthy control subjects.

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

Treatment with antibiotics
When microorganism infections are identified in blood fractions of subsets of patients with CFIDS, FM, GWS or RA, it provides further evidence why these patients should be treated as medical, not psychological or psychiatric, patients. This does not mean that psychological or psychiatric problems are not important in some chronic illness patients. But if such infections play an important role in these disorders, then appropriate treatments with antibiotics or other medications that suppress chronic infections should result in improvement and even recovery. This is exactly what has been found.

The recommended treatments for mycoplasmal blood infections require long-term antibiotic therapy, usually multiple six-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, possibly because of the intracellular locations of the infections and the slow-growing nature of these microorganisms. We now recommend that patients who have been diagnosed with blood infections receive continuous antibiotics for at least six months before using the six-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 who have been sick for many years are unlikely to completely recover within a year of therapy.

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. In addition, they are not due to the immuno-suppressive effects of some of the antibiotics, because 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.

Follow-up provides clues
Although a majority of patients diagnosed with chronic blood infections appear to benefit from antibiotic therapy, many patients respond and have some alleviation of most signs and symptoms but do not fully recover. A three-year follow-up of antibiotic therapy by the Shasta CFIDS Association of Northern California is instructive. According to Sharon Briggs, RN, a majority (about 80%) of patients from the Shasta CFIDS Group that were confirmed with mycoplasmal infections and went on the antibiotic therapy we suggested recovered from 50% to 100% of their pre-illness health within the three years. Similar to other therapies for chronic illnesses, not every patient benefitted from antibiotic therapy, and the time required for recovery was quite variable among the patients studied.

Do chronic infections explain illnesses like CFIDS? It is unlikely that there is only one or even a few explanations for complex chronic illnesses like CFIDS. 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 and to what extent. 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.

Interestingly, those patients who 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 those patients had illnesses that were solely 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 maintain recovery after the treatments are discontinued.

Toxic exposure vs. mycoplasmas
The treatment of chronic illnesses that are due to toxic exposures from chemical or radiological agents is quite different from the treatment of chronic infections, although toxic exposures may weaken the immune system and allow mycoplasmas to take hold. 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 skin 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.

Vitamins and nutrition
To be successful, a comprehensive approach to chronic illness must be undertaken with each patient. In addition to treatments like antibiotics or removal of toxic agents, these patients often have nutritional and other deficiencies that must be corrected. For example, these patients are often depleted in vitamins B, C and E, among others, and certain minerals. Unfortunately, patients with  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 intestines, 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, bioflavoids and biotin are best. Also, L-cysteine, L-tyrosine, L-carnitine, malic acid and especially flaxseed oil are reported by some to be useful. Certain minerals are also often depleted in these patients, such as zinc, magnesium, chromium and selenium, and these should be supplemented as well. One problem with taking these supplements is that they cannot be taken at the same time as antibiotics because they may inhibit antibiotic uptake.

There are also other consider-ations. Antibiotics deplete normal bacteria in the gastrointestinal system, resulting in overgrowth of less desirable bacteria. Lactobacillus acidophillus tablets can supplement the normal bacteria present. One product is a mixture of Lactobacillus acidophillus, Lactobacillus bifidus and other bacteria with FOS (fructo-ologosaccharides) to promote growth of these "friendly" bacteria.

A number of natural remedies that boost the immune system can be useful in the therapy of chronic illnesses. Among these are whole lemon/olive extract drink or an extract of olive leaves with antioxidants, plant extracts or purified plant products and milk proteins such as whey. These products are especially useful during or especially after antibiotic therapy has been completed. Although these products appear to help some patients, their clinical effectiveness in treatment of various chronic illnesses has not been carefully evaluated. They may have value during therapy to boost the immune system or especially after antibiotic therapy in a maintenance program to prevent relapse of illness.

For more information
The Institute for Molecular Medicine provides information and can test patients for evidence of mycoplasmal and other infections of the types that are associated with CFIDS, FM, GWS and RA. Blood samples can be sent to the Institute for Molecular Medicine for mycoplasma and other testing. The website for further information is www.immed.org.
 
Garth L. Nicolson, PhD, is the Chief Scientific Officer and Research Professor at the Institute for Molecular Medicine in Huntington Beach, California. He was formerly Professor of Internal Medicine and Professor of Pathology and Laboratory Medicine at the University of Texas Medical School at Houston.

Gulf Ware Syndrome, CFIDS link gains more recognition
The Department of Defense (DoD) is beginning to acknowledge that many of the symptoms of gulf war syndrome (GWS) are similar  to the profile of CFIDS or fibromyalgia. Although the CDC recognized the link two years ago, as reported in the Summer 1997 Chronicle, the Surgeon General of the Army only recently agreed GWS is a CFIDS-like disorder.

The DoD also has recognized that some individuals with GWS can be helped by antibiotics. A pilot study conducted by Dr. Garth Nicolson showed 55 of 73 GWS patients, including Gulf War veterans and symptomatic family members, responded to doxycycline, an antibiotic that is effective against a variety of mycoplasmas.

The DoD subsequently agreed to train scientists and physicians from the Walter Reed Army Medical Center and Armed Forces Institute of Pathology in Washington, D.C., in the types of diagnostic tests Dr. Nicolson uses. In addition, the Veterans Affairs Administration (VA) will fund a clinical trial beginning at 30 VA centers this summer to look for mycoplasmas in veterans’ blood before and after a year of treatment with doxycycline.

So why has recognition of the possible benefits of antibiotic treatment for GWS been so long in coming? Possibly because mycoplasmas are still relatively mysterious organisms. According to an article in the April 1999 Popular Science, mycoplasmas are difficult to detect in patients’ blood, requiring very sensitive tests and careful handling of samples. In addition, they are not easy to cultivate in the laboratory, which further complicates research studies.

Despite those barriers, Nicolson hopes that the VA clinical trial will shed light on the role of mycoplasmas in chronic illnesses.