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In Vitro Activity of Halofantrine and its Relationship to other Standard Antimalarial Drugs against African Isolates and Clones of Plasmodium Falciparum

The in vitro activity of halofantrine was studied in chloroquine-susceptible and chloroquine-resistant African clones of Plasmodium falciparum over a period of six months. The susceptibility level remained stable in both clones. The chloroquine-susceptible clone (50% inhibitory concentration [IC₅₀] 6.88 nM) was less susceptible to halofantrine than the chloroquine-resistant clone (IC₅₀ 2.98 nM). Using an isotopic semimicro drug susceptibility test, the in vitro activity of halofantrine was compared with the activities of chloroquine, quinine, and mefloquine to study the cross-resistance patterns against 76 African isolates of P. falciparum isolated from cases of malaria imported into France. Chloroquine-resistant isolates (n = 47) were significantly less susceptible to quinine (IC₅₀ 234 nM), but were more susceptible to both mefloquine (IC₅₀ 3.20 nM) and halofantrine (IC₅₀ 1.14 nM) compared with the chloroquine-susceptible isolates (n = 29; IC₅₀ 147 nM for quinine, 7.16 nM for mefloquine, and 2.62 nM for halofantrine). A significant positive correlation was found between the activities of chloroquine and quinine and between those of mefloquine and halofantrine, indicating cross-resistance between these drugs, while a negative correlation was observed between chloroquine and mefloquine or halofantrine. The responses to quinine and mefloquine or halofantrine showed no correlation with each other. These results reinforce the importance of a cautious use of antimalarial drugs in Africa.

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