Time for military to get real about risks of anti-malaria drug

OTTAWA—The Canadian Armed Forces are excellent at many things, but tropical medicine is definitely not one of them. For months now, over the rising howls of veterans and scientists, the CF has obstinately refused to reconsider its plans to use a controversial malaria medicine, mefloquine, which is associated with psychoses and various other neuropsychiatric harms in a small number of users. The American, Australian, British, French, and German militaries moved off mefloquine, but, stubbornly, the Canadian Armed Forces are not doing so. All that the Canadian Armed Forces’ surgeon general will say is that the matter is being reviewed, which is usually a euphemism for doing nothing. As writers with a past in the military chain of command, in Veterans Affairs, and in malaria epidemiology, we think this position ignores the realities of our allies and the warnings of science. Canada’s soldiers deserve better. Much better. The rap sheet on mefloquine is certainly worrying. Patient medication information published by the manufacturer of mefloquine warns that "it can cause serious mental problems in some people. These serious side effects may occur suddenly and may last for months to years after stopping mefloquine… thoughts of suicide or harming yourself." Since the 1990s, Health Canada has required a warning on each pack of mefloquine that it can lead to suicidal thoughts. A 2015 scientific review on mefloquine in military use, titled, "Rational Risk-Benefit Decision-Making in the the Setting of Military Mefloquine Policy," published but the U.S. National Library of Medicine adds that “in addition to concerns of self-directed violence, mefloquine is strongly associated in post marketing studies with risk of violence towards others, including homicide, magnifying concerns of these consequences with the drug's use among military personnel who are likely to be heavily armed during use of the drug. Owing to the known association of the drug with agitation and aggression, which may affect between one and 10 in 1,000 users, and the to the drug's known association with symptoms of more acute intoxication including dissociative and paranoid psychosis, there has been reasonable speculation by military and government officials that mefloquine intoxication may have contributed to cases of homicidal violence overseas and among returned service members." It seems a poor idea to give heavily armed soldiers a drug capable of driving them into murderous or suicidal psychosis. The Canadian Forces would not disagree with that or deny that this is what studies have shown. Instead, its surgeon general, Brig.-Gen. H.C. MacKay, bellows that the studies are “not strong science.” How odd that he thinks he knows clinical science better than the experts at Health Canada, but that is his belief. Now, a just-published epidemiological study in the American Journal of Tropical Medicine and Hygiene appears to prove that the Canadian Forces are wrong. Beginning in 2009, the U.S. military phased out mefloquine and substituted it with other antimalarial drugs. That policy switch gave rise to a giant, though unplanned, natural experiment, because researchers could probe and compare the side-effects in more than 360,000 soldiers prescribed one drug or another. Canada’s military could never do a massively powerful study like this; our military is a fraction that size. What the American researchers found is not reassuring. Compared to other antimalarial drugs, mefloquine raised the risk of clinical anxiety in deployed soldiers, raised the risk of post-traumatic stress disorder (PTSD) in non-deployed soldiers, and caused hearing loss to a statistically significant extent. Compared to other antimalarial drugs, mefloquine raised the risk by 12 per cent of clinical anxiety in deployed soldiers, raised the risk by 83 per cent of post-traumatic stress disorder (PTSD) in non-deployed soldiers, and in both groups raised the risk of hearing loss 81 per cent, in a statistically significant manner that powerfully suggests these findings aren’t just flukes. There is also a worrying hint, albeit not one with statistical significance (so skepticism is warranted) that for persons already having a psychiatric diagnosis, mefloquine may be associated with another bout of psychiatric trouble. Some will argue that these elevated risks are small, and that most soldiers would not experience the more severe side-effects. But that misses the point, because in a high-stakes setting like the military, it is wrong to believe that a risk must be large and ubiquitous before being taken seriously. The Armed Forces have stress and danger enough without the added complication of being psychologically disturbed by a drug that puts people, or perhaps mission success, at risk. Fortunately, there are alternatives. The Public Health Agency of Canada says two other antimalarial drugs, doxycycline and atovaquone-proguanil, are similarly effective in most settings. Both have only mild side-effects—certainly not psychosis—and are the usual drugs of choice for civilian travellers. It begs the question of why the Canadian Armed Forces surgeon general favors a drug that civilian doctors tend to avoid. He has never explained. So what would happen if the Canadian Armed Forces, badly prepared, undertook a mission amid highly endemic P. falciparum type malaria—perhaps the UN peacekeeping effort in Mali now being considered? First, some soldiers will get malaria, no matter which drug they use. No medicine reaches 100 per cent effectiveness in actual use because not everyone follows doctors’ or commanders’ orders (atovaquone-proguanil tops out around 96 per cent). The Canadian Armed Forces someday will encounter malaria in their operations. They can enter into that either with level-headed preparation, as our closest allies have done, or with the radical denialism of the surgeon general, who accuses those allies and the biomedical professions of “not strong science.” It is hardly a serious choice, and so we call on the chief of the defence staff to dismiss the advice of the surgeon general, and do as our allies have done about mefloquine. Amir Attaran is a lawyer, immunologist, and former member of WHO’s Malaria Advisory Committee. Michel Drapeau is a former combat logistician and now a lawyer and author specializing in military law. Pat Stogran is a former task force commander in Afghanistan and was Canada’s first veterans ombudsman. The Hill Times