Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon

• Autor(a) principal: Peterson, David S
• Data de Publicação: 1991
• Outros Autores: Di Santi, Silvia M, Póvoa, Marinete Marins, Calvosa, Vanja Suely Pachiano, Rosário, Virgílio E. do, Wellem, Thomas E
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
• Texto Completo: https://patua.iec.gov.br/handle/iec/2583
• topic: Malária; Plasmodium falciparum; Antimaláricos; Pirimetamina / uso terapêutico

Pyrimethamine resistance in cultivated laboratory isolates of Plasmodium fakiparum is linked to the dihydrofolate reductase mutation Asn-108, a mutation that acts by interrupting drug binding within the active site of the enzyme. To determine the prey alence ofthis mutation in endemic regions harboring pyrimethamine-resistant malaria, we used a mutation-specific polymerase chain reaction assay to survey P. fakiparum strains from a wide section ofthe Brazilian Amazon. Mutations were identified directly from blood samples without intervening steps of in vitro cultivation. Of 42 samples collected from four states in Brazil, 38 (90%) contained the Asn-108 codon AAC that confers pyrime thamine resistance, four samples contained only the wild-type Ser-l08 codon AOC, and none contained the Thr-l08 codon ACC found in cycloguanil-resistant pyrimethamine sensitive strains. These findings indicate that a very high incidence of the Asn-l08 DHFR mutation is responsible for pyrimethamine resistance in the Amazon, and they are con sistent with recent failure rates reported for Fansidar (pyrimethamine-sulfadoxine). We suggest that limited use of proguanil be evaluated as an alternative to pyrimethamine.