Mefloquine is a quinoline-methanol compound structurally related to quinine.1 It is active against all the human malaria parasites, particularly multidrug resistant Plasmodium falciparum. Introduced a decade ago to treat falciparum malaria in Thailand, where multidrug resistance is a particular problem, it was formulated initially in a fixed combination with pyrimethamine-sulfadoxine to delay the onset of resistance. Unfortunately, that did not work, probably because of pharmacokinetic differences between the compounds and because P falciparum was already highly resistant to sulfadoxine and pyrimethamine when the combination was introduced.

By 1990, after five years of well controlled use, significant resistance to mefloquine was evident on the eastern and western borders of Thailand.2 This has increased steadily in these regions, and, although cure rates have improved since the treatment dose of mefloquine was raised from 15 mg base/kg to 25 mg/kg,3high grade resistance (that is, failure to clear parasitaemia) now occurs in about 15% of patients, and low grade resistance (recrudescence of the infection) in almost 50%. Fortunately, the situation is considerably better everywhere else in the tropics, although some strains of P falciparum from west and possibly east Africa are intrinsically resistant to mefloquine.

For treating uncomplicated …