Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes.

Colin J SutherlandDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. colin.sutherland@lshtm.ac.uk

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Ali AllouecheDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. colin.sutherland@lshtm.ac.uk

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Jill CurtisDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. colin.sutherland@lshtm.ac.uk

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Chris J DrakeleyDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. colin.sutherland@lshtm.ac.uk

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Rosalynn OrdDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. colin.sutherland@lshtm.ac.uk

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Manoj DuraisinghDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. colin.sutherland@lshtm.ac.uk

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Brian M GreenwoodDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. colin.sutherland@lshtm.ac.uk

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Margaret PinderDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. colin.sutherland@lshtm.ac.uk

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David WarhurstDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. colin.sutherland@lshtm.ac.uk

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Geoffrey A T TargettDepartment of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. colin.sutherland@lshtm.ac.uk

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Polymorphisms in two genes of Plasmodium falciparum (P. falciparum multidrug resistance 1 [pfmdr1] and P. falciparum chloroquine [CQ] resistance transporter [pfcrt]) are associated with CQ treatment failure. We found significant linkage disequilibrium between these loci among isolates from symptomatic Gambian children (P = 0.026) and strong selection for the resistance-associated alleles pfmdr1-86Tyr and pfcrt-76Thr in children with persistent or re-emerging P. falciparum trophozoites during post-treatment follow-up (P = 1.9 x 10(-7)). Therefore, this genotype is characteristic of resistant infections among our study population. Since the long-term public health impact of parasites carrying such resistant genotypes depends upon their transmissibility, we examined the prevalence of pfmdr1-86Tyr and pfcrt-76Thr among Gambian children harboring sexual stage parasites during post-treatment follow-up. Gametocytes that emerged after successful treatment with CQ were significantly more likely to be of this genotype than were those emerging after other treatments (P = 4.83 x 10(-4)), and were infective to Anopheles mosquitoes. Therapeutic success may thus be accompanied by public health failure as cured children pass resistance genes on to mosquitoes at an enhanced rate.

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