The results have been published of three prospective population-based studies evaluating the tolerance of malaria prophylaxis with mefloquine. The references are: Lobel HO, Miani M, Eng T, Bernard KW, Hightower AW, Campbell CC. Long-term malaria prophylaxis with weekly mefloquine. Lancet 1993;341:848-851. Steffen R, Fuchs E, Schildknecht J, Naef U, Funk M, Schlagenhauf P, Phillips-Howard P, Nevill C, Sturchler D. Mefloquine compared with other malaria chemoprophylactic regimens in tourists visiting East Africa. Lancet 1993;341:1299-1303. Boudreau E, Schuster B, Sanchez J, Novakowski W, Johnson R, Redmond D, Hanson R, Dausel L. Tolerability of prophylactic Lariam regimens. Trop Med Parasit 1993;44:257-265.

In the two major comparative prophylactic trials (Lobel, 1993, Steffen, 1993), mefloquine was not associated with more dizziness or depression than chloroquine or chloroquine plus proguanil. In fact, in the European study, rates of minor adverse events were 18.8% for mefloquine (N=50,053), 17.1% for chloroquine 300mg base/week (N=3,354), 30.1% for chloroquine plus proguanil (N=20,150). Nausea was the most frequent side effect reported, and the rate was highest in the chloroquine plus proguanil group. Dizziness was reported slightly more often by the mefloquine group, however the chloroquine group reported greater insomnia. There were no differences found with respect to depression. Mefloquine was also found to be well tolerated by Peace Corps Volunteers during long-term prophylaxis in Africa. There were no serious adverse effects in this group and minor adverse events (e.g. dizziness, insomnia, strange dreams) occurred with the same frequency in those taking mefloquine as in those using chloroquine. Such events were reported at higher frequencies in a random sample of 1,242 Peace Corps volunteers around the world, most of whom did not use any malaria prophylaxis. Boudreau compared weekly chloroquine with weekly mefloquine and a three-day loading dose mefloquine regimen. No significant difference in tolerance was found between these regimens.Transient central nervous system toxicity such as seizures or psychotic events have been reported at an overall frequency of 1/13,000 among European short-term travelers. The rate is higher (up to 1/1700 - 1/1200) when mefloquine is used at therapeutic doses (15mg/kg - 25mg/kg).

Anecdotal reports of side effects associated with malaria prophylaxis are of concern but verification of a causal relationship with a drug requires formal investigations, such as cohort or case-control studies. It is likely that many of the adverse reactions in the studies and in anecdotal reports are attributable to travel-related stress or other risk factors and are not due to the malaria prophylaxis. Hans O. Lobel, M.D./CDC