Randomized, Controlled Trial of Combination Treatment With Pyridostigmine, DEET, and Teremethrin
Final rept. 1 Oct 2000-30 Jun 2005
HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLE MD
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The U.S. military uses the insect repellents DEET and permethrin. If enemy nerve agent use is threatened, pyridostigmine bromide PB is also used, to reversibly inhibit 20-40 of neuromuscular junction acetyleholinesterase AChE, preventing irreversible binding by nerve agents. Animal and human studies had demonstrated safe independent use of PB, DEET, and permethrin. However, some blamed the combination for a variety of ill-defined symptoms reported by some Gulf War veterans. One study reported synergistic neurotoxicity in chickens subjected to very large doses of pyridostigmine, DEET and permethrin. Another study indicated that PB crosses the blood-brain barrier in stressed but not non-stressed mice. Previous human studies simply asked about CNS symptoms, and were subject to selection andor recall biases. An Institute of Medicine panel concluded studies are needed to resolve uncertainties about whether PB, DEET, and permethrin have additive effects. Sample size calculations indicated that 64 participants would allow sufficient power to determine whether significant differences in neurocognitive or physical outcomes could be identified with treatments compared to placebo controls. The target number of 64 healthy young volunteers was achieved, along with another 17 who completed between one and three of the four study sessions, but did not complete the full study due to scheduling obstacles. After obtaining baseline measurements, subjects were studied for four days at least one week apart. In random order, subjects receive all three treatments, or placebo versions of each treatment, under both stress and non-stress conditions. Neurocognitive and physical outcomes were measured.