title: Selection of antifolate-resistant Plasmodium falciparum by sulfadoxine-pyrimethamine treatment and infectivity to Anopheles mosquitoes.
abstract: Resistance-conferring mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in Plasmodium falciparum are selected by treatment with sulfadoxine pyrimethamine (SP). We assessed the association between these mutations and transmission capacity of parasites to Anopheles mosquitoes on the Pacific coast of Colombia. Patients with uncomplicated P. falciparum malaria received SP treatment and were followed-up to compare the prevalence of DHFR and DHPS mutations before and after SP treatment. Membrane feeding assays were used to measure infectivity to mosquitoes of post-treatment gametocytes with and without these mutations. Per-protocol treatment efficacy was 95.0% (132 of 139). Gametocytes carrying resistance-conferring mutations were selected after SP treatment and were infective to mosquitoes. Seven days after treatment, infections with two DHFR mutations had a 10-fold higher probability of infecting mosquitoes than infections with no DHFR mutations (odds ratio = 10.23, P < 0.05). Low-level drug resistance mutations have the potential to enhance transmission of P. falciparum and spread resistant parasites.
authors.affiliation: Escuela de Salud Pública, Universidad del Valle, Cali, Colombia. famendez@univalle.edu.co
authors.forename: Fabián
authors.initials: F
authors.lastname: Méndez
authors.forename: Sócrates
authors.initials: S
authors.lastname: Herrera
authors.forename: Bermans
authors.initials: B
authors.lastname: Murrain
authors.forename: Andrés
authors.initials: A
authors.lastname: Gutiérrez
authors.forename: Luz A
authors.initials: LA
authors.lastname: Moreno
authors.forename: María
authors.initials: M
authors.lastname: Manzano
authors.forename: Alvaro
authors.initials: A
authors.lastname: Muñoz
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D000962:Antimalarials / Q000494:pharmacology*; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D016017:Odds Ratio; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D017354:Point Mutation; D011739:Pyrimethamine / Q000494:pharmacology*; D012641:Selection, Genetic; D013413:Sulfadoxine / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics