title: Molecular epidemiology of malaria in Cameroon. XXX. sequence analysis of Plasmodium falciparum ATPase 6, dihydrofolate reductase, and dihydropteroate synthase resistance markers in clinical isolates from children treated with an artesunate-sulfadoxine-pyrimethamine combination.
abstract: Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes are reliable molecular markers for antifolate resistance. The P. falciparum ATPase 6 (pfatp6) gene has been proposed to be a potential marker for artemisinin resistance. In our previous clinical study, we showed that artesunate-sulfadoxine-pyrimethamine is highly effective against uncomplicated malaria in Yaoundé, Cameroon. In the present study, dhfr, dhps, and pfatp6 mutations in P. falciparum isolates obtained from children treated with artesunate-sulfadoxine-pyrimethamine were determined. All 61 isolates had wild-type Pfatp6 263, 623, and 769 alleles, and 11 (18%) had a single E431K substitution. Three additional mutations, E643Q, E432K, and E641Q, were detected. The results did not indicate any warning signal of serious concern (i.e., no parasites were seen with quintuple dhfr-dhps, DHFR Ile164Leu, or pfatp6 mutations), as confirmed by the high clinical efficacy of artesunate-sulfadoxine-pyrimethamine. Further studies are required to identify a molecular marker that reliably predicts artemisinin resistance.
authors: Organisation de Coordination pour la Lutte Contre les Endémies en Afrique Centrale, Institut de Recherche pour le Développement, Yaoundé, Cameroon.
authors: Virginie
authors: V
authors: Menemedengue
authors: Khalifa
authors: K
authors: Sahnouni
authors: Leonardo
authors: L
authors: Basco
authors: Rachida
authors: R
authors: Tahar
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D000077332:Artesunate; D002163:Cameroon / Q000453:epidemiology; D002648:Child; D004094:Dihydropteroate Synthase / Q000737:chemistry / Q000378:metabolism; D004338:Drug Combinations; D004351:Drug Resistance; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism; D017720:Molecular Epidemiology; D010963:Plasmodium falciparum / Q000737:chemistry / Q000201:enzymology / Q000302:isolation & purification*; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000008:administration & dosage / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; C501005:MT-ATP6 protein, human; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D025261:Mitochondrial Proton-Translocating ATPases; D011739:Pyrimethamine