John Cummins, M.P. Delta-South Richmond

News Release

FOR IMMEDIATE RELEASE
November 14, 1994

Possible Adverse Effects of Mefloquine

The following are excerpts from the paper, Medical Operations in Somalia, Surgical Section, he delivered at the Canadian Forces medical conference, Op Med 93, on October 26, 1993:

Abstract:

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Mefloquine malarial prophylaxis caused one psychiatric repatriation and may have had a role in a suicide attempt. Members of surgical section, amongst others, suffered neuro-psychiatric side-effects. Mefloquine may affect nerve cell function by blocking Na channels. It is perhaps causing previously unrecognized, widespread, sub-clinical impairment of cognition. Pending definitive research, alternatives to mefloquine prophylaxis could be considered for those in jobs needing judgement, including military command roles.

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Mefloquine:

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Mefloquine is well known to have neurologic side effects. The manufacturer's literature states that reactions are rare, but include convulsions, psychosis, nightmares, dizziness, headache, confusion, anxiety and depression. There are over 100 case reports of such serious reactions requiring hospitalization. From the medical literature, it seems that such reactions occur in 1 per 2,000 people when prophylactic doses are given, or I per 200 when stronger, treatment doses are given.

Less severe reactions (not requiring hospitalization) are more common, but the incidence is not known. We had one psychiatric hospitalization in Belet Uen, which did not respond to the usual treatment of battle stress. The diagnosis made by the psychiatrists at NDMC, after he was evacuated, was an organic brain syndrome, probably due to mefloquine. The suicide attempt in theatre may also be mefloquine related.

There are three of us presenting on Somalia today. Two of us had minor neuropsychiatric problems which occurred regularly in the 24 to 48 hours after our weekly mefloquine doses. If there are two of us, these reactions aren't so "rare". Burke in The Lancet, June 1993, writes, "As a demographer with a quarter of a century's experience, I know that if I encounter finite numbers of a supposedly rare occurrence, the true rate is higher." He goes on to recommend alternatives to mefloquine.

In 1992, mefloquine was the best choice as an anti-malarial. However, we realized some of the risks, and did not prescribe this medication for pilots. The U.S. military has also rejected mefloquine use for their aircrew, because of the neuropsychiatric side effects.

The mechanism of mefloquine effects on the brain (like its effects on malaria) is unknown. However, it is structurally similar to quinine and quinidine. Mefloquine can cause additive effects with these drugs. Quinine and quinidine are known to be blockers of the fast sodium channel. This sodium channel is found on the cell membrane of nerve cells, and is activated early when nerve cells fire. Specifically, it is believed that agents similar to mefloquine block the sodium channel, by locking closed the "inactivation gate" in the channel. Some sodium channel blockers, such as Dilantin (diphenylhyandantoin), have been clearly shown to have adverse effects on cognition. According to my literature review, these neuropsychiatric tests have not been done on any subject taking mefloquine.

Further, it should be better known that the mefloquine malaria pills taken by the Canadian Forces, are 10% stronger than those given to the American Forces, despite both being labelled as 250 mg. (250mg of mefloquine base in the Basel manufactured pills, vs. 250mg of mefloquine salt in the U.S. produced pills).

I believe that mefloquine causes sub-clinical adverse effects on cognition. The usual soldier taking the drug is not aware of any problems. Nevertheless, his thinking could be impaired. Like many people tipsy after 2 or 3 alcohol-based drinks, he would not recognize that his judgement was diminished. He would not recognize this because the adverse effect is on cognition, including impaired insight. Like the impaired drinker who feels fine, our soldier would feel fine, despite his impairment.

I would suggest a further restriction on mefloquine use. An alternative drug (doxycycline, as for pilots) is available. For example, in a tour group, the tour director could take doxycycline or another prophylactic drug. His tour group could continue to use the cheaper, and more effective mefloquine for malarial prophylaxis. They would rely on the director's guidance for navigation and administrative control of the guided tour. Presumably, one could consider an equivalent in the military command structure, if one worries that mefloquine impairs judgement. Those in command and control positions could use alternative drugs.

Definitive proof regarding the effects of mefloquine on thinking would require a randomized, double-blind, placebo-controlled study. The measurements would be taken by neuropsychiatric testing (the same techniques used to prove the adverse neurologic effects of low-dose alcohol).

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For more information, please contact:

John Cummins, M.P.
(604) 940-8040 or 970-0937 (cell)