In vitro drug sensitivity and clinical aspects of Plasmodium falciparum malaria in African children

In vitro Plasmodium falciparum drug sensitivity was investigated in 115 brazzavillians children, between 1 year and 10 years of age. On the basis of clinical aspects, four groups were constituted: Group 1: 39 asymptomatic school children, Group 2: 16 children with uncomplicated malaria, Group 3: 40 with severe but not pernicious malaria and Group 4: 20 with pernicious malaria. The drugs tested were chloroquine (CQ), quinine (QN) and mefloquine (MQ). The sensitivity level was assessed by a 48-hour in vitro maturation test involving the uptake of tritiated hypoxanthine, the initial blood level of parasite being > or = 0.1% in all cases. For QN and MQ, the median IC50 values showed no significant difference related to clinical status, age or parasitaemia levels. For CQ, the proportion of resistant strains and the 50 inhibitory concentration (IC50) values were greater in the cases of children hospitalised for malaria but there were no differences related to clinical severity of these hospitalised children nor, within each group, to the age or parasitaemia levels. The percentage of subjects with an IC50 value greater than the 90 percentile of the IC50 of the asymptomatic group, which we propose as the severity index related to chemoresistance, was 15% for uncomplicated malaria, 38% for severe but non-pernicious forms and 35% for pernicious malaria. The IC50 for QN was significantly higher in CQ-resistant strains and there was a positive correlation for CQ vs QN and for QN vs MQ.