Frequencies distribution of dihydrofolate reductase and dihydropteroate synthetase mutant alleles associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum population from Hadhramout Governorate, YemenReportar como inadecuado




Frequencies distribution of dihydrofolate reductase and dihydropteroate synthetase mutant alleles associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum population from Hadhramout Governorate, Yemen - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Malaria Journal

, 14:516

First Online: 22 December 2015Received: 21 October 2015Accepted: 04 December 2015

Abstract

BackgroundMalaria in Yemen is mainly caused by Plasmodium falciparum and 25 % of the population is at high risk. Sulfadoxine–pyrimethamine SP had been used as monotherapy against P. falciparum. Emergence of chloroquine resistance led to the shift in anti-malarial treatment policy in Yemen to artemisinin-based combination therapy, that is artesunate AS plus SP as first-line therapy for uncomplicated malaria and artemether–lumefantrine as second-line treatment. This study aimed to screen mutations in the dihydrofolate reductase dhfr and dihydropteroate synthetase dhps genes associated with SP resistance among P. falciparum population in Hadhramout governorate, Yemen.

MethodsGenomic DNA was extracted from dried blood spots of 137 P. falciparum isolates collected from a community-based study. DNA was amplified using nested polymerase chain reaction PCR and subsequently sequenced for Pfdhfr and Pfdhps genes. Sequences were analysed for mutations in Pfdhfr gene codons 51, 59, 108, and 164 and in Pfdhps gene codons 436, 437, and 540.

ResultsA total of 128 and 114 P. falciparum isolates were successfully sequenced for Pfdhfr and Pfdhps genes, respectively. Each Pfdhfr mutant allele I 51 and N 108 in P. falciparum population had a frequency of 84 %. PfdhfrR 59 mutant allele was detected in one isolate. Mutation at codon 437 G 437 in the Pfdhps gene was detected in 44.7 % of falciparum malaria isolates. Frequencies of Pfdhfr double mutant genotype I 51 C59N 108 I164 and Pfdhfr-Pfdhps triple mutant genotype I 51 C59N 108I164-S436G 437K540 were 82.8 and 39.3 %, respectively. One isolate harboured Pfdhfr triple mutant genotype I 51 , R 59 , N 108 , I164 and Pfdhfr-Pfdhps quadruple mutant genotype I 51R 59N 108I164-S436G 437K540.

ConclusionHigh frequencies of Pfdhfr and Pfdhps mutant alleles and genotypes in P. falciparum population in Hadhramout, Yemen, highlight the risk of developing resistance for SP, the partner drug of AS, which subsequently will expose the parasite to AS monotherapy increasing then the potential of the emergence of AS resistance. Study findings necessitate the continuous monitoring of the efficacy of the national anti-malarial drugs policy in Yemen. In addition, monitoring SP efficacy using molecular markers that has shown to be a practical and informative method for monitoring the partner drug of AS.

KeywordsPlasmodium falciparum Pfdhfr Pfdhps Sulphadoxine–pyrimethamine resistance Molecular marker Hadhramout-Yemen  Download fulltext PDF



Autor: Omar A. A. Bamaga - Mohammed A. K. Mahdy - Yvonne A. L. Lim

Fuente: https://link.springer.com/



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