Abstract
BackgroundA malaria hotspot in the southeastern region of Mauritania, near the Malian border, may hamper malaria control strategies. The objectives were to estimate the prevalence of genetic polymorphisms associated with drug resistance in Plasmodium falciparum isolates and establish baseline data.MethodsThe study was conducted in two malaria-endemic areas in Hodh Elgharbi, situated in the Malian–Mauritanian border area. Blood samples were collected from symptomatic patients. Single nucleotide polymorphisms in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps were genotyped using PCR-restriction fragment length polymorphism, DNA sequencing and primer extension. The Pfmdr1 gene copy number was determined by real-time PCR.ResultsOf 280 P. falciparum-infected patients, 193 (68.9%) carried the Pfcrt 76T mutant allele. The Pfmdr1 86Y and 184F mutations were found in 61 (23.1%) of 264 isolates and 167 (67.6%) of 247 samples that were successfully genotyped, respectively. Pfmdr1 mutant alleles 1034C, 1042D and 1246Y were rarely observed. Of 102 P. falciparum isolates analysed, ten (9.8%) had more than one copy of Pfmdr1 gene. The prevalence of isolates harbouring at least triple mutant Pfdhfr 51I, 59R, 108 N/T was 42% (112/268), of which 42 (37.5%) had an additional Pfdhps 437G mutation. The Pfdhps 540E mutation was observed in four isolates (1.5%), including three associated with Pfdhfr triple mutant. Only two quintuple mutants (Pfdhfr-51I-59R-108N Pfdhps-437G-540E) were observed.ConclusionsThe observed mutations in Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt may jeopardize the future of seasonal malaria chemoprevention based on amodiaquine-sulfadoxine-pyrimethamine, intermittent preventive treatment for pregnant women using sulfadoxine-pyrimethamine, and treatment with artesunate-amodiaquine. Complementary studies should be carried out to document the distribution, origin and circulation of P. falciparum populations in this region and more widely in the country to assess the risk of the spread of resistance.
Highlights
A malaria hotspot in the southeastern region of Mauritania, near the Malian border, may hamper malaria control strategies
P. falciparum chloroquine resistance transporter (Pfcrt) and P. falciparum multidrug resistance gene 1 (Pfmdr1) encode membrane transporters that have been associated with resistance to chloroquine and amodiaquine (Pfcrt) or chloroquine, amodiaquine, and amino-alcohols
The objective of the present study was to compare the prevalence of Pfcrt, Pfmdr1, Plasmodium falciparum dihydrofolate reductase gene (Pfdhfr), and Plasmodium falciparum dihydropteroate synthase gene (Pfdhps) mutations and the copy number of Pfmdr1 gene in P. falciparum isolates collected in two areas with different malaria endemicity in Hodh Elgharbi region after the introduction of artemisinin-based combination therapy (ACT) in 2006, in order to establish a baseline database for monitoring drug-resistant P. falciparum in the malaria hotspot in the Malian–Mauritanian border area
Summary
A malaria hotspot in the southeastern region of Mauritania, near the Malian border, may hamper malaria control strategies. Before 2006, chloroquine and sulfadoxine-pyrimethamine were the first- and second-line drugs in Mauritania, respectively. The current anti-malarial treatment policy in Mauritania is based on artesunate-amodiaquine and artemether-lumefantrine as the first- and second-line treatment of uncomplicated malaria, respectively, regardless of Plasmodium spp. Dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) are known targets of pyrimethamine and sulfadoxine, respectively [4]. These drugs inhibit the enzymes of the folate pathway to kill the parasites. Some studies have suggested that point mutations in Pfmdr are associated with resistance to quinoline-like drugs and artemisinin derivatives, but their role is not yet well established [6, 7]. Recent studies have demonstrated that mutations in Kelch propeller 13 is directly associated with artemisinin resistance [12]
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