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 single 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% vomited at least once, and 10% did not tolerate the drug because of vomiting. The therapy failure rates for the M25 group on day 7, 14, and 28 were 15%, 18%, and 42%, respectively, and these did not differ significantly from those for the M15 group (4%, 18%, and 59%). In contrast, 34 in vitro microtests (17 per group) showed schizont inhibition at less than or equal to 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 mefloquine concentration of less than 500 ng/ml blood on day 2 or day 7 (P less than 0.0003). 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 young children the therapy appears to be complicated by frequent vomiting

Clinical trials with halofantrine hydrochloride in Malawi

Two clinical trials of the phenanthrene treatment of Plasmodium falciparum were conducted in Malawi; in areas where the parasite was known to be chloroquine resistant. Of 49 children followed up for 14 days; 47 became aparasitaemic -ie; the cure rate was 96 percent. In both trials the drug was very well tolerated. Halofantrine hydrochloride seems to be effective against P. falciparum chloroquine sensitive and resistant strains in Africa

In vivo efficacy of chloroquine treatment for Plasmodium falciparum in Malawian children under five years of age

In 1984 the government of Malawi instituted a program to reduce malaria mortality and morbidity in children less than 5 years of age as a part of the Combatting Childhood Communicable Diseases (CCCD) program. To define the appropriate malaria therapy regimen; investigators used a quality assurance design in a simplified 7-day in vivo drug response study with follow-up observations on day 2 (D2) ; D3; and D7 after the initial day of the study (D0). The efficacy of oral chloroquine was assessed in 224 children who were enrolled at 6 sites; 2 in each of the 3 administrative regions of Malawi. Parasitological failure; defined as failure of parasitemia to decrease by 75 percent of the value by D3 or presence of any detectable parasitemia on D7; ranged from 41 percent -65 percent following administration of chloroquine 25 mg (base)/kg. However; only 8 percent of children who were parasitemic on D7 were febrile or judged to be ill. Considering these therapeutic results and the higher cost and limited availability of alternative therapies; chloroquine 25 mg/kg therapy was adopted as the primary therapy for malaria