title: Emergence of a dhfr mutation conferring high-level drug resistance in Plasmodium falciparum populations from southwest Uganda.
abstract: The S108N, C59R, and N51I mutations in the Plasmodium falciparum gene that encodes dihydrofolate reductase, dhfr, confer resistance to pyrimethamine and are common in Africa. However, the I164L mutation, which confers high-level resistance, is rarely seen. We found a 14% prevalence of the I164L mutation among a sample of 51 patients with malaria in Kabale District in southwest Uganda in 2005 and a 4% prevalence among 72 patients with malaria in the neighboring district of Rukungiri during the same year. Surveillance at 6 sites across Uganda during 2002-2004 reported a single case of infection involving an I164L mutant, also in the southwest, suggesting that this is a regional hot spot. The spatial clustering and increasing prevalence of the I164L mutation is indicative of local transmission of the mutant. Targeted surveillance is needed to confirm the extent of the spread of the I164L mutation and to monitor the impact of I164L on the efficacy of antifolates for intermittent preventive treatment of pregnant women and/or infants with falciparum malaria.
authors.affiliation: Disease Control and Vector Biology Unit, Department of Infectious Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lynch
authors.forename: Richard
authors.initials: R
authors.lastname: Pearce
authors.forename: Hirva
authors.initials: H
authors.lastname: Pota
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cox
authors.forename: Tarekegn A
authors.initials: TA
authors.lastname: Abeku
authors.forename: John
authors.initials: J
authors.lastname: Rwakimari
authors.forename: Inbarani
authors.initials: I
authors.lastname: Naidoo
authors.forename: James
authors.initials: J
authors.lastname: Tibenderana
authors.forename: Cally
authors.initials: C
authors.lastname: Roper
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D006239:Haplotypes; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000469:parasitology / Q000635:transmission; D008297:Male; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D014454:Uganda
chemical_list: D013762:Tetrahydrofolate Dehydrogenase