Mefloquine therapy for Plasmodium falciparum malaria in children under 5 years of age in Malawi: in vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome

The in vivo and in vitro response of Plasmodium falciparum to a singleel oral dose of mefloquine (25 mg/kg body weight (M25) or 15 mg/kg (M15) was studied in children under 5 years of age in Malawi. Of the children who received mefloquine, 35 per cent vomited at least once, and 10 per cent did not tolerate the drug because of vomiting. The therapy failure rates for the M25 group on day 7, 14 and 28 were 15 per cent, 18 per cent, and 42 per cent, respectively, and these did not differ significantly from those for the M15 group (4 per cent, 18 per cent, and 59 per cent). In contrast, 34 in vitro microtests (17 per group) showed schizont inhibition at /= 32 pmol mefloquine per test well. On day 7, the concentration of mefloquine in samples of blood was significantly lower in both the M25 and M15 groups for children who were parasitaemic on day 7 than in samples from those who were aparasitaemic. A positive blood smear on day 7 was strongly associated with a low mefloquine concentration of 500 ng/ml blood on day 2 or day 7 (P0.0003). Vomiting was associated with a low mefloquine concentration on day 2 but not day 7. These results suggest that mefloquine is effective against P. falciparum in Malawi but that for your children the therapy appears to be complicated by frequent vomiting(AU)