Plasmodium falciparumin Madagascar:in vivoandin vitrosensitivity to seven drugs

Abstract

The sensitivity level of Plasmodium falciparum isolates to chloroquine and the activity of six other antimalarials were studied in the different climatic zones of Madagascar in 1983. In vivo tests were done with 10 and 25 mg kg⁻¹ of chloroquine and amodiaquine. Early recrudescence or RII resistance was observed after treatment with 10 mg kg⁻¹ of these drugs in 34% of the cases for chloroquine and 6·5% for amodiaquine, and after the 25 mg kg⁻¹ dose in 7% and 0% of the cases respectively. In vitro sensitivity of 84 P. falciparum isolates to seven drugs were studied with a semi-microtest. For chloroquine, 9% of the isolates had an IC₅₀ above 250 nM, indicating resistance. In vitro activity of piperaquine was high for all isolates except two. In vitro activity of amodiaquine, dichlorquinazine, quinine, mefloquine and halofantrine was good against all isolates (maximum IC₅₀ was 76, 92, 560, ⩽ 20 and ⩽ 12 nM, respectively). Correlation between the WHO standard field test and the in vitro semi-microtest was good. Resistance of P. falciparum to chloroquine was observed in the six survey areas, but the other tested drugs showed good activity. Since no cross-resistance to 4-aminoquinolines seems to exist in Madagascar, amodiaquine (the only one available at present) should be studied as an alternative to chloroquine in the prevention and treatment of falciparum malaria in this area.