The relationship between the response of Plasmodium falciparum malaria to mefloquine in African children and its sensitivity in vitro

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Abstract
The clinical efficacy of two doses of mefloquine (15 and 25 mg/kg body weight) was evaluated in 85 children suffering from acute symptomatic falciparum malaria. The cure rate on day 28 was 100% in both groups. There was no significant difference (P>0·05) in the mean parasite and fever clearance times in both groups (48·5±14·6 and 32·0±12·7 h respectively for the 25 mg/kg group and 49·0±15·1 and 30·0±13·3 h respectively for the 15 mg/kg group). There was also no significant difference (P>0·05) in these values between children with hyperparasitaemia (53·6±11·0 and 36·0±17·0 h respectively) and those without hyperparasitaemia (49·1±13·6 and 31·8±14·6 h respectively). Recurrence of parasitaemia was observed after day 30 in 2 patients in the 15 mg/kg group and in 1 patient in the 25 mg/kg group. In vitro, 3 of 21 isolates showed reduced susceptibility to mefloquine, with minimum inhibitory concentrations (MIC) >67 nm/litre. The MIC and 50%, 90% and 99% inhibitory concentrations were 200·8, 6·27, 31·7 and 119·6 nm/litre respectively. Four of 22 isolates were resistant to chloroquine (MIC > 108 nm/litre). Isolates that showed low sensitivity to mefloquine in vitro were sensitive to chloroquine in vitro, and the 4 that were resistant to chloroquine were sensitive to mefloquine. Irrespective of MIC and dose of mefloquine, parasitaemia cleared in all subjects in 96 h or less. It is concluded that both standard and reduced doses of mefloquine are effective in the treatment of P. falciparum malaria in south-western Nigeria, even with isolates with reduced or low sensitivity to the drug in vitro.