Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes
Sutherland, CJ; Alloueche, A; Curtis, J; Drakeley, CJ; Ord, R; Duraisingh, M; Greenwood, BM; Pinder, M; Warhurst, D; Targett, GA; (2002) Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes. The American journal of tropical medicine and hygiene, 67 (6). pp. 578-85. ISSN 0002-9637
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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