Carriage of chloroquine-resistant parasites and delay of effective treatment increase the risk of severe malaria in Gambian children

Two hundred thirty-four Gambian children with severe falciparum malaria who were admitted to the pediatric ward of a rural district hospital each were matched for age with a same-sex control subject presenting as an outpatient with uncomplicated falciparum malaria. Severe malarial anemia (SMA) was the most common presentation ( 152 cases), followed by cerebral malaria ( 38 cases) and hyperparasitemia ( 26 cases). Children presenting with SMA were significantly younger and more likely to carry gametocytes than were children with other severe presentations. Alleles of the genes pfcrt and pfmdr1 associated with chloroquine-resistant parasites occurred together among cases presenting with SMA alone more often than among their matched controls (odds ratio, 2.08 [95% confidence interval, 1.04 - 4.38]; P = .039). Costs of travel to the hospital of more than US $0.20, use of mosquito repellents, and carriage of resistant parasites were identified as independent risk factors for severe malaria in the case-control analysis. We conclude that, in this setting, poor access to the hospital and a high prevalence of chloroquine-resistant parasites lead to a delay of adequate treatment for young children with malaria, who may then develop SMA.