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Evidence for a reduced effect of chloroquine against Plasmodium falciparum in alpha+‐thalassaemic children

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