The inhibitory effect of a drug combination on the development of mefloquine resistance inPlasmodium berghei

Mefloquine hydrochloride [WR 142,490; alpha-(2-piperidyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanol hydrochloride] was tested for suppressive effect on sporozoite-induced malaria in nonimmune volunteers living in an area where malaria is not naturally transmitted. Single doses of 250 mg were given at weekly intervals, 500 mg at intervals of 2 weeks and 1,000 mg at intervals of 4 weeks, to men bitten by 10 to 15 mosquitoes heavily infected with a chloroquine- and pyrimethamine-resistant strain of Plasmodium falciparum. None of the individuals so treated developed infections during the period of drug delivery or during the follow-up period of 60 days. Doses of 250 or 500 mg produced no adverse reactions; mild epigastric discomfort occurred in all three men given 1,000 mg. Sporozoite-induced P. vivax infections were suppressed by single doses of 250 mg of mefloquine given at weekly intervals, but malaria developed after completion of the course. At treatment intervals longer than 1 week, vivax malaria was not suppressed.