Evidence for a reduced effect of chloroquine against Plasmodium falciparumin alpha(+)-thalassaemic children

Alpha-thalassaemia is common in malaria-endemic regions and is considered t o confer protection from clinical disease due to infection with Plasmodium falciparum. In vitro, sensitivity to chloroquine (CQ) of P. falciparum infe cting alpha-thalassaemic erythrocytes is reduced. We examined, in a cross-s ectional study of 405 Nigerian children, associations between alpha-globin genotypes, blood concentrations of CQ, and P. falciparum parasitaemia. Of t he children, 44% were alpha(+)-thalassaemic (36.8% heterozygous, 7.6% homoz ygous). CQ in blood and P. falciparum-infection were observed in 52 and 80% , respectively. CQ was more frequently found in homozygous alpha(+)-thalass aemic (71%) than in non-thalassaemic children (50%; odds ratio, 2.42; 95% c onfidence interval, 1.01-5.8). Among children with CQ in blood and despite similar drug concentrations, alpha+-thalassaemic individuals had fewer infe ctions below the threshold of microscopy which were detectable by PCR only, and they had a higher prevalence of elevated parasitaemia than non-thalass aemic children. No such differences were discernible among drug-free childr en. CQ displays a lowered efficacy in the suppression of P. falciparum para sitaemia in alpha(+)-thalassaemic children; hence protection against malari a due to alpha(+)-thalassaemia may be obscured in areas of intense CQ usage . Moreover, alpha(+)-thalassaemia may contribute to the expansion of CQ res istance.