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.
Mockenhaupt
F P
FP
Institute of Tropical Medicine and Medical Faculty Charité, Humboldt-University Berlin, Germany. frank.mockenhaupt@charite.de
May
J
J
Bergqvist
Y
Y
Meyer
C G
CG
Falusi
A G
AG
Bienzle
U
U
D000818:Animals; D000962:Antimalarials / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009549:Nigeria / Q000453:epidemiology; D016017:Odds Ratio; D018512:Parasitemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D017085:alpha-Thalassemia / Q000097:blood / Q000150:complications* / Q000235:genetics
D000962:Antimalarials; D002738:Chloroquine