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Background   Plasmodium falciparum , the deadliest causative agent of malaria, has high prevalence in Nigeria. Drug resistance causing failure of previously effective drugs has compromised anti-malarial treatment. On this basis, there is need for a proactive surveillance for resistance markers to the currently recommended artemisinin-based combination therapy (ACT), for early detection of resistance before it become widespread.    Methods  This study assessed anti-malarial resistance genes polymorphism in patients with uncomplicated  P. falciparum  malaria in Lagos, Nigeria. Sanger and Next Generation Sequencing (NGS) methods were used to screen for mutations in thirty-seven malaria positive blood samples targeting the  P. falciparum  chloroquine-resistance transporter ( Pfcrt ),  P. falciparum  multidrug-resistance 1 ( Pfmdr1 ), and  P. falciparum kelch 13  ( Pfk13 ) genes, which have been previously associated with anti-malarial resistance.    Results  Expectedly, the NGS method was more proficient, detecting six  Pfmdr1,  seven  Pfcrt  and three  Pfk13  mutations in the studied clinical isolates from Nigeria, a malaria endemic area. These mutations included rare  Pfmdr1  mutations, N504K, N649D, F938Y and S967N, which were previously unreported. In addition, there was moderate prevalence of the K76T mutation (34.6%) associated with chloroquine and amodiaquine resistance, and high prevalence of the N86 wild type allele (92.3%) associated with lumefantrine resistance.    Conclusion  Widespread circulation of mutations associated with resistance to current anti-malarial drugs could potentially limit effective malaria therapy in endemic populations.

Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria