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

Malaria Journal

Research

Hervé Bogreau¹  Aurelie Pascual¹  Sébastien Briolant¹  Houssem Bouchiba¹  Leonardo K. Basco¹  Bruno Pradines²  Ali Ould Mohamed Salem Boukhary³  Mohamed Salem Ould Ahmedou Salem³  Khadijetou Mint Lekweiry³ 

[1] Unité Parasitologie et entomologie, Département des maladies infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France;Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Aix-Marseille Université, UM 63, CNRS 7278, IRD 198, Inserm 1095, AP-HM, Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005, Marseille, France;Unité Parasitologie et entomologie, Département des maladies infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France;Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Aix-Marseille Université, UM 63, CNRS 7278, IRD 198, Inserm 1095, AP-HM, Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005, Marseille, France;Centre national de référence pour le paludisme, Marseille, France;Unité de Recherche «Génomes et Milieux», Faculté des Sciences et Techniques, Université de Nouakchott Al-Aasriya, BP 5026, Nouveau campus universitaire, Nouakchott, Mauritania;

关键词: Plasmodium falciparum;    Drug resistance;    Chloroquine;    Amodiaquine;    Antifolate drugs;    Lumefantrine;    Artemisinin-based combination therapy;    Mauritania;    Cross-border malaria;   

DOI  :  10.1186/s12936-017-1791-2

 received in 2017-01-27, accepted in 2017-03-26,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2017