Many African countries currently use a
sulfadoxine-pyrimethamine combination (SP) or
amodiaquine (AQ) to treat uncomplicated
Plasmodium falciparum malaria. Both drugs represent the last inexpensive alternatives to
chloroquine. However, resistant P. falciparum populations are largely reported in Africa, and it is compulsory to know the present situation of resistance. The in vivo World Health Organization standard 28-day test was used to assess the efficacy of AQ and SP to treat uncomplicated
falciparum malaria in Gabonese children under 10 years of age. To document treatment failures, molecular genotyping to distinguish therapeutic failures from
reinfections and drug dosages were undertaken. A total of 118 and 114 children were given AQ or SP, respectively, and were monitored. SP was more effective than AQ, with 14.0 and 34.7% of therapeutic failures, respectively. Three days after initiation of treatment, the mean level of
monodesethylamodiaquine (MdAQ) in plasma was 149 ng/ml in children treated with
amodiaquine. In those treated with SP, mean levels of
sulfadoxine and
pyrimethamine in plasma were 100 microg/ml and 212 ng/ml, respectively. Levels of the three drugs were higher in patients successfully treated with AQ (MdAQ plasma levels) or SP (
sulfadoxine and
pyrimethamine plasma levels). Blood concentration higher than breakpoints of 135 ng/ml for MdAQ, 100 micro g/ml for
sulfadoxine, and 175 ng/ml for
pyrimethamine were associated with treatment success (odds ratio: 4.5, 9.8, and 11.8, respectively; all P values were <0.009). Genotyping of merozoite
surface proteins 1 and 2 demonstrated a mean of 4.0 genotypes per person before treatment. At reappearance of
parasitemia, both recrudescent parasites (represented by common bands in both samples) and newly inoculated parasites (represented by bands that were absent before treatment) were present in the blood of most (51.1%) children. Only 3 (6.4%) therapeutic failures were the result not of treatment inefficacy but of new
infection. In areas where levels of drug resistance and complexity of
infections are high, drug dosage and parasite genotyping may be of limited interest in improving the precision of drug efficacy measurement. Their use should be weighted according to logistical constraints.