Full Length Research Paper
The development of resistance to antimalarial drugs is a major challenge for global malaria control. Full Plasmodium falciparum resistance to dihydroartemisinin–piperaquine treatment has been reported recently in Cambodia. These events were directly associated with increased copy number variations (CNVs) in the plasmepsin system, including the PfPlasmepsin 2 gene. Pfplasmepsin 2 copy number was the most significant molecular signature associated with dihydroartemisinin–piperaquine treatment failure. Even though the piperaquine resistance has not been observed in regions in which artemisinin resistance has not been documented, it is possible to find an amplification of the Pfplasmepsin 2 gene in these regions. In this present study, we investigate to do a surveillance of Pfplasmepsin 2 copy number variations in Senegal by qPCR. Pfplasmepsin 2 copy number was assessed in 120 P. falciparum positive patients, 60 from Dakar and 60 from Kedougou by qPCR and an amplification of the Pfplasmepsin 2 genes was measured by using five standards of mixed synthetic gene fragments. Using a copy number threshold of 1.7 and 1.73% carried a multiple copies of Pfplasmepsin 2, whilst one copy of the gene was found in 98.26% of the isolates. Our results show that the CNVs associated with resistance to piperaquine are probably already frequent in Senegal. Paradoxically, Pfplasmepsin 2 multi-copy is generally found in parts of Africa where dihydroartemisinin–piperaquine failures are rare and resistance to piperaquine has not yet been described. However, it is no evidence to confirm piperaquine resistance in Senegal.
Key words: PfPlasmepsin 2 copy number, Senegal, Piperaquine, resistance, drug resistance.
CNV, Copy Number Variation; ACT, Artemisinin combination therapy; WHO, World Health Organization; NMCP, National Malaria Control Programme; AL, Arthmeter-Lumefantrine; DHA-PPQ, Dihydroartemisinin–Piperaquine; IPT, intermittent preventive treatment; SP, Sulfadoxine–Pyrimethamine; SMC, seasonal malaria chemoprevention; PfPM2, Plasmodium falciparum plasmepsin 2; DNA, deoxyribonucleic acid.
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