title: Short report: molecular markers associated with Plasmodium falciparum resistance to sulfadoxine-pyrimethamine in the Democratic Republic of Congo.
abstract: Sulfadoxine-pyrimethamine (SP) is the first line antimalarial treatment in the Democratic Republic of Congo. Using polymerase chain reaction, we assessed the prevalence of mutations in the dihydrofolate reductase (dhfr) (codons 108, 51, 59) and dihydropteroate synthase (dhps) (codons 437, 540) genes of Plasmodium falciparum, which have been associated with resistance to pyrimethamine and sulfadoxine, respectively. Four hundred seventy-four patients were sampled in Kilwa (N = 138), Kisangani (N = 112), Boende (N = 106), and Basankusu (N = 118). The proportion of triple mutations dhfr varied between sites but was always > 50%. The proportion of dhps double mutations was < 20%, with some sites as low as 0.9%. A quintuple mutation was present in 12.8% (16/125) samples in Kilwa; 11.9% (13/109) in Kisangani, 2.9% (3/102) in Boende, and 0.9% (1/112) in Basankusu. These results suggest high resistance to pyrimethamine alone or combined with sulfadoxine. Adding artesunate to SP does not seem a valid alternative to the current monotherapy.
authors.affiliation: Epicentre, Paris, France; Médecins Sans Frontières, Brussels, Belgium; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Cohuet
authors.forename: Maryline
authors.initials: M
authors.lastname: Bonnet
authors.forename: Michel
authors.initials: M
authors.lastname: Van Herp
authors.forename: Chantal
authors.initials: C
authors.lastname: Van Overmeir
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Guthmann
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D003062:Codon / Q000235:genetics; D015023:Democratic Republic of the Congo; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D009154:Mutation / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D015995:Prevalence; D011739:Pyrimethamine / Q000494:pharmacology*; D013413:Sulfadoxine / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D000962:Antimalarials; D003062:Codon; D004338:Drug Combinations; D005819:Genetic Markers; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine