The use of the drug mefloquine – also known by its trade name, Lariam – has been controversial for years. Developed by the U.S. Army in the 1970s, it was the standard medication to fight malaria provided to U.S. troops headed to Afghanistan, Iraq, and Somalia.
But soldiers complained that taking Lariam in pill form once a week made them feel strange. There were reports of mental ailments – including anxiety, hallucinations, depression and suicidal thoughts – associated with its use.
Yet the Army marched on to the beat of its own drug. “Military personnel will die of malaria if MQ not available,” the science director of the Walter Reed Army Institute of Research – the outfit that developed the drug – warned in 2004.
But reports of problems with the Army-invented drug proved significant enough that its civilian manufacturer, the Swiss company F. Hoffman-La Roche, stopped producing it in the U.S. in 2009. That same year, the U.S. military returned to daily doses of doxycycline, the U.S. military’s pre-Lariam anti-malarial choice, as its primary drug for fighting the mosquito-borne tropical disease, estimated to kill more than 1 million people a year.
So what has happened now that soldiers no longer routinely take Lariam? Are they dying of malaria more often, as the science director of the Walter Reed Army Insitute of Research predicted eight years ago would happen if they didn’t use it?
A recent article in the American Journal of Tropical Medicine and Hygiene reported that 61% of soldiers complied with doxycycline’s daily dosing, while only 38% given Lariam took it once a week as directed.
That caught the eye of Remington Nevin, a former Army public-health doctor now pursuing graduate work at the Johns Hopkins University in Baltimore.
“By conventional wisdom these results appear counterintuitive, and they stand in contrast to earlier findings among civilian travelers and military personnel that suggest observed compliance should be higher with weekly dosing,” he noted in a letter published in the latest issue of the journal.
Even more strikingly, Nevin says that malaria cases dropped dramatically since troops switched to doxycycline.
“Among U.S. military personnel in Afghanistan, over these past three years, and co-incident with the shift away from mefloquine as a preferred chemoprophylaxis, the rate of malaria has actually fallen over 70%,” Nevin said. “Today in Afghanistan, malaria affects only about 1 U.S. service member per 1,000 per year; this rate is extremely low by historical standards, particularly as compared with rates during prior operations in areas of comparable endemicity, including Somalia, where they were nearly ten times higher.”
It seems that no matter how well a medicine may be in controlled trials, it won’t work if people don’t take it as prescribed in the real world.
“Today’s soldiers may be less likely to adhere to mefloquine chemoprophylaxis because of growing awareness of its strong association with psychiatric symptoms and its potential to induce neurotoxicity,” Nevin concluded. “Senior U.S. military medical officials now acknowledge that the neuropsychiatric side effects caused by mefloquine may confound the diagnosis and management of post-traumatic stress disorder and traumatic brain injury, making its routine use less desirable.”
Nevin, who recently testified before a Senate panel on the chronic effects of mefloquine, said the Food and Drug Administration has convened a panel of neurotoxicologists and other experts to review the safety of the drug, based on recent reports of brainstem damage. These reports, Nevin suggests, represent “the tip of the iceberg” and that “thousands of veterans may suffering from the neurologic and psychiatric effects of mefloquine toxicity”