TOLERANCE OF MEFLOQUINE CHEMOPROPHYLAXIS IN DUTCH MILITARY PERSONNEL

From June until October 1993, a battalion of Dutch marines was station ed in Cambodia for a United Nations deployment. In 73 volunteers who u sed mefloquine as malaria chemoprophylaxis, possible mefloquine-relate d adverse events were monitored with special emphasis on QT prolongati on. All participants started mefloquine chemoprophylaxis with a loadin g dose (250 mg a day for three days) one week before departure, follow ed by a weekly dose (250 mg) for approximately 25 weeks. One month bef ore (t - 1) and one (t + 1) and three (t + 3) months after mefloquine prophylaxis was started, an at rest electrocardiogram was made. Freque ncy, PR-, and QT-intervals were measured; blood samples for liver tran saminases, total white blood cell count, and mefloquine concentration were obtained after one and three months. Adverse events such as dizzi ness, headache, coordination problems, and nausea were spontaneously r eported in one (1.4%) and three (4.1%) persons at t + 1 and t + 3, res pectively, while specific questioning revealed adverse events in nine (12.3%) and five (6.9%) persons, respectively, at the same time point. Three months after starting chemoprophylaxis, the heart rate at rest and total white blood cell count were lower (P < 0.05), while the QTc- interval was longer and levels of liver transaminases increased (P < 0 .05), although both were still within the normal range. There was no e xtreme prolongation of the QTc-interval or increased levels of liver t ransaminases that resulted in a need to stop the chemoprophylaxis. No accumulation of mefloquine in the serum occurred, and no relationship was observed between the incidence of adverse events and serum mefloqu ine concentrations. The incidence of self reported mefloquine-related adverse events was low. In conclusion, mefloquine chemoprophylaxis was safe and well-tolerated in this group.