Roles of specific Plasmodium falciparum mutations in resistance to amodiaquine and sulfadoxine-pyrimethamine in Burkina Faso.
ABSTRACT We evaluated associations between key polymorphisms in target genes and responses to treatment with sulfadoxine-pyrimethamine (SP) or amodiaquine (AQ) for uncomplicated Plasmodium falciparum malaria in Bobo-Dioulasso, Burkina Faso. Presence of the dihydrofolate reductase (dhfr) 108N or 59R mutations (but not dhfr 51I or dihydropteroate synthetase [dhps] 437G) and P. falciparum chloroquine resistance transporter (pfcrt) 76T or P. falciparum multidrug resistance 1 (pfmdr1) 86Y or 1246Y mutations (but not pfmdr1 184F) predicted recrudescence after treatment with SP and AQ, respectively. Treatment led to significant increases in the prevalence of the same mutations (except 1246Y) in new infections that presented after therapy. The dhfr 164L and dhps 540E mutations were not seen in any isolates. These results clarify the key roles of a small number of mutations in P. falciparum resistance to SP and AQ in west Africa.
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ABSTRACT: After years of disuse of chloroquine (CQ) as first-line anti-malarial drug in Ghana, reports from molecular studies conducted in parts of the country indicate varying prevalence of T76 mutation in the pfcrt gene. This situation has several health implications, one being that mutations that confer resistance to CQ have been reported to show substantial cross-resistance to other anti-malarial drugs. It is important to identify some of the factors contributing to the continuous presence of CQ resistance markers in the country. This study determined the prevalence of T76 mutation in pfcrt gene of Plasmodium falciparum isolates collected from selected areas of the Central region of Ghana and correlated with the level of CQ use in these areas.Malaria Journal 06/2014; 13(1):246. DOI:10.1186/1475-2875-13-246 · 3.49 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.
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ABSTRACT: The imported malaria has been a great challenge to the public health in China due to the decreased local transmitted cases and frequently exchange worldwide. Among them, P. falciparum was mainly responsible for the increasing impact. Currently artesunate plus amodiaquine, one of the Artemisinin Combination Therapy recommended by World Health Organization, was mainly used to against the uncomplicated P. falciparum in China. However, the drug-resistance marker polymorphism in the returning migrant workers has not been demonstrated. Herein we have evaluated the prevalence of pfmdr1 and pfcrt polymorphism, as well as the K13-propeller gene, a molecular marker of artemisinin resistance in the clustered migrant workers back from Ghana to Shanglin County of Guangxi province in 2013. A total of 118 blood samples were randomly selected and used for the assay. The mutation of pfmdr1 gene was found in 11 isolates that covered codons 86, 184, 1034 and 1246. Mutations at codons N86Y (9.7%) was more frequent than others, and Y86Y184S1034D1246 was the most prevalent (63.6%) of all four haplotypes. The mutation of pfcrt gene was observed in 17 isolates that covered codons 74, 75, and 76, and M74N75T76 was common (70.6%) in three haplotypes. Eight different genotypes of K13-propeller were firstly observed in ten samples in China, of which including 2 synonymous mutations (V487V and A627A) and 6 nonsynonymous mutations. C580Y was the most prevalence (2.7%) found in all samples. The present data might be helpful for enrichment of molecular surveillance of antimalarials resistance, and will be useful for developing and updating the antimalarials guidance in China.Antimicrobial Agents and Chemotherapy 10/2014; 59(1). DOI:10.1128/AAC.04144-14 · 4.45 Impact Factor