Characterization of Plasmodium falciparum genes associated with drug resistance in Hodh Elgharbi, a malaria hotspot near Malian–Mauritanian border

• Published in: Malaria Journal
• Main Authors: Mohamed Salem Ould Ahmedou Salem, Khadijetou Mint Lekweiry, Houssem Bouchiba, Aurelie Pascual, Bruno Pradines, Ali Ould Mohamed Salem Boukhary, Sébastien Briolant, Leonardo K. Basco, Hervé Bogreau
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2017
• Subjects: Plasmodium falciparum; Drug resistance; Chloroquine; Amodiaquine; Antifolate drugs; Lumefantrine; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-017-1791-2; https://doaj.org/article/3d5b54642454430690d06052cf369cfb

Abstract Background A 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. Methods The 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. Results Of 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. Conclusions The 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.