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Key Gulf War study lab looks for cellular invaders (12-15-99)

Dr. Joel Baseman’s microbiology laboratory is an important place these days, especially for U.S. veterans and families who want to know, finally, what causes Gulf War Illnesses. The mysterious symptoms—fatigue, muscle pain, memory deficits, headache, rash, nausea, joint pain and insomnia—have persisted throughout the 1990s in thousands of veterans and flare up intermittently in others.

The lab at The University of Texas Health Science Center at San Antonio, where Dr. Baseman is professor and chairman of the Department of Microbiology, is the central reference laboratory for a nationwide U.S. Department of Veterans Affairs (VA) study of Gulf War Illnesses. Blood samples from prospective enrollees are shipped daily to San Antonio from nearly 30 centers, and patients are enrolled based on the lab’s findings. The ultimate quest is to define a causative agent or agents for Gulf War Illnesses.

"We are performing highly specific tests for the presence of mycoplasmas in the bloods of Gulf War-ill patients, who by definition were deployed in the Persian Gulf in the early 1990s," Dr. Baseman said. Mycoplasmas, the smallest of bacteria, are cellular invaders that live off host cells’ nutrients in a parasitic relationship, he said. Dr. Baseman’s previous work has advanced the idea that mycoplasmas not only are primary pathogens (agents initiating certain diseases), but also are co-factors in various disease processes, including HIV infection.

The most widely known mycoplasma is M. pneumoniae, the infectious agent implicated in walking pneumonia though it is not frequently diagnosed. The VA study focuses on other mycoplasma species as well, including M. fermentans. "Mycoplasmas are highly advanced bacteria—advanced in the sense that they have such streamlined genomes (or complements of genes)," Dr. Baseman said. "They appear to have evolved to lose much of their DNA in favor of relying on host cells, which makes them very difficult to detect and to eradicate."

Dr. Baseman, a Ph.D.-trained microbiologist, admits he sits on the fence of a scientific-medical controversy. Some colleagues strongly endorse the view that mycoplasmas are the demons of Gulf War Illnesses and chronic fatigue; others say there is no proof for the position and that data surrounding mycoplasma involvement are not convincing. Mycoplasma infection is not found in every Gulf War patient. One previous study found that only about half of the blood samples of Gulf War veterans revealed positive DNA signals for mycoplasmas.

"We have a highly sensitive technique to detect the presence of mycoplasmas in the blood," Dr. Baseman said. "We have taken a fundamental technique, polymerase chain reaction or PCR, and modified it to maximize its specificity and sensitivity for mycoplasmas. That’s what we are using in our role as central laboratory to determine whether individuals with Gulf War Illnesses should be entered into this very large multicenter VA study."

The lab analyzed more than 600 samples in the first six months of the trial. The study consists of a one-year enrollment phase, one year of treatment and one year of data analysis. Participants must have served in the Gulf War between August 1990 and August 1991 and must be suffering from at least two of three otherwise unexplained symptoms: fatigue, muscle and/or joint pain, and memory and thinking problems.

Bacterial cousins such as E. coli and Salmonella are 10 times larger than the sleek mycoplasmas. "Mycoplasma infection is not easy to diagnose," Dr. Baseman said. "It takes specialized laboratories and tests, and there aren’t a lot of places that do it. We’re one of them and that’s how we got involved in this major study."

The VA study is randomized and placebo-controlled—half the veterans receive active medicine to treat Gulf War Illnesses and the other half receive a placebo. Neither veterans nor their doctors know who is receiving the active medicine. The active therapy is doxycycline, an antibiotic in use for more than 30 years. Previous smaller studies indicated it might be effective in treating Gulf War-ill veterans.

"The primary objective is to determine whether a year course of treatment with doxycycline in patients with Gulf War Illnesses, who are positive for mycoplasma species as determined by Dr. Baseman's laboratory, improves functional status in comparison to similar patients treated with placebo," said Joseph F. Collins, D.Sc., director of the Cooperative Studies Program Coordinating Center at the VA Maryland Health Care System in Perry Point, Md. The center provides nationwide coordination for the study.

The participating 26 VA centers and two U.S. Department of Defense centers are in every region of the country. Patient enrollment is ethnically representative. The South Texas Veterans Health Care System’s Audie Murphy Division, located in San Antonio, is part of a different VA Gulf War study focusing on exercise and behavioral therapy. The Houston VA is the Texas enrolling center for the antibiotic study.

A paper published in the June 1999 issue of the Journal of Occupational and Environmental Medicine noted that more than 10 percent of veterans who served in the Gulf War receive some kind of disability from the VA.

"It is important to explain the possible role of mycoplasmas in Gulf War Illnesses and chronic fatigue syndrome," said Dr. Baseman, who has studied mycoplasmas for 30 years and is regarded as one of the leading international experts on these microorganisms. "They attack cells and then hang around, sometimes inside of cells. They are hard to kill. Mycoplasmas exhibit a real parasitism with the host cells, resulting in the establishment of chronic infections.

"When we think of organisms or bacteria that could be associated with chronic fatigue syndrome and Gulf War Illnesses—two multiple-symptom disorders that are chronic—it makes sense to think of mycoplasmas. The proof is still lacking, however. That’s why we’re trying to do the science in this laboratory."

Contact: Will Sansom