Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes.
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.
Sutherland
Colin J
CJ
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. colin.sutherland@lshtm.ac.uk
Alloueche
Ali
A
Curtis
Jill
J
Drakeley
Chris J
CJ
Ord
Rosalynn
R
Duraisingh
Manoj
M
Greenwood
Brian M
BM
Pinder
Margaret
M
Warhurst
David
D
Targett
Geoffrey A T
GA
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use*; D016054:DNA, Protozoan / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics*; D005714:Gambia; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D016054:DNA, Protozoan; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine