Analysis of sulphadoxine/pyrimethamine resistance-conferring mutations of Plasmodium falciparum from Mozambique reveals the absence of the dihydrofolate reductase 164L mutant

• Autor(a) principal: Fernandes, Natércia
• Data de Publicação: 2007
• Outros Autores: Figueiredo, Paula, Rosário, Virgilio Estólio do, Cravo, Pedro
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/117237
• topic: Adolescent; Animals; Antimalarials; Artemisinins; Child; Child, Preschool; Codon; Dihydropteroate Synthase; Drug Combinations; Drug Resistance, Multiple; Female; Humans; Infant; Malaria, Falciparum; Male; Mozambique; Mutation; Plasmodium falciparum; Pyrimethamine; Sesquiterpenes; Sulfadoxine; Tetrahydrofolate Dehydrogenase; Journal Article; Research Support, Non-U.S. Gov't; Genetics; Parasitology; SDG 3 - Good Health and Well-being

BACKGROUND: Plasmodium falciparum is the predominant human malaria species in Mozambique and a lead cause of mortality among children and pregnant women nationwide. Sulphadoxine/pyrimethamine (S/P) is used as first line antimalarial treatment as a partner drug in combination with artesunate. METHODS: A total of 92 P. falciparum-infected blood samples, from children with uncomplicated malaria attending the Centro de Saude de Bagamoyo in the Province of Maputo-Mozambique, were screened for S/P resistance-conferring mutations in the pfdhfr and pfdhps genes using a nested mutation-specific polymerase chain reaction and restriction digestion (PCR-RFLP). The panel of genetic polymorphisms analysed included the pfdhfr 164L mutation, previously reported to be absent or rare in Africa. RESULTS: The frequency of the S/P resistance-associated pfdhfr triple mutants (51I/59R/108N) and of pfdhfr/pfdhps quintuple mutants (51I/59R/108N + 437G/540E) was 93% and 47%, respectively. However, no pfdhfr 164L mutants were detected. CONCLUSION: The observation that a considerably high percentage of P. falciparum parasites contained S/P resistance-associated mutations raises concerns about the validity of this drug as first-choice treatment in Mozambique. On the other hand, no pfdhfr 164L mutant was disclosed, corroborating the view that that this allele is still rare in Africa.