The committee recommends research on genetic factors (e.g., genetic polymorphisms of butyrylcholinesterase [BuChE] and paraoxonase [PON1]) that may alter susceptibility to the effects of PB.

Differences in genetic susceptibility are proving important in many disease conditions and will likely emerge as a major determinant of neurotoxicity in humans. The observation that a small percentage of troops taking PB has more severe acute side-effects than the majority, which experienced little or no discomfort, suggests a spectrum of vulnerabilities in sensitive individuals, where genetic differences may contribute to their ability to absorb and metabolize PB. Polymorphisms in BuChE have long been recognized, but whether they play a role in determining the outcome of PB exposure is unknown. The potential relevance of genetic polymorphisms of paraoxonase to PB toxicity is also unclear since PB is not a substrate for these enzymes. However, the role of genetic variations influencing the toxicology of PB is an attractive target for research.

The committee recommends epidemiologic studies on the possible long-term health effects of PB.

As previously noted in this report, there has been little attention given to studying long-term health effects of PB. However, preliminary clinical findings suggesting effects of PB on cognitive function, cardiovascular disease, and visual function warrant future study.

Epidemiologic studies that observe long-term adverse effects in patients with myasthenia gravis might be a first step. Although patients with myasthenia gravis may provide an opportunity to study the long-term health effects of PB, the higher doses of PB prescribed to these patients and the characteristics of their disease may make it difficult to draw comparisons from myasthenics to a group of healthy individuals.

VACCINES

As noted throughout this report, medical record keeping for Gulf War veterans was extremely poor. It is difficult, if not impossible, to understand the effect of vaccinations without adequate records documenting individual vaccination histories. The committee urges the Department of Defense (DoD) to implement proper practices for medical record keeping and systematic collection of baseline and follow-up health data related to vaccination.

The committee is aware of efforts by the DoD to collect data on health outcomes of the recipients of the anthrax vaccination and to conduct a long-term study of this cohort. The DoD has an opportunity to properly monitor recipients of this vaccine and to provide invaluable information about potential long-term health effects. This research should be a priority for the DoD.



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