Abstract
BackgroundThe occurrence of artemisinin resistance (ART)-associated polymorphism of Plasmodium falciparum K13-propeller (pfk13) gene before and after the introduction of artemisinin-based combination therapy (ACT) in two regions of Nigeria was investigated in this study. Regular surveillance is necessary to make a definite conclusion on the emergence and pattern of possible resistance to ART.MethodsThis cross-sectional study was carried out in the Southwestern and Southeastern geopolitical zones of Nigeria. A total of 150, 217, and 475 participants were enrolled for the study in the Southwest (2004_Group A), Southwest (2015_Group B), and southeast (2015_Group C), respectively. Blood samples were collected from the study participants for DNA extraction and a nested PCR for P. falciparum identification. Samples that were positive for P. falciparum were genotyped for the pfk13 gene using the Sanger sequencing method. The single nucleotide polymorphisms were analysed using the Bioedit software.ResultsA total of 116, 125, and 83 samples were positive for P. falciparum, respectively for the samples collected from the Southwest (2004 and 2015) and southeast (2015). Parasite DNA samples collected from febrile children in 2004 (Group A; n = 71) and 2015 (Group B; n = 73) in Osogbo Western Nigeria and 2015_Group C (n = 36) in southeast Nigeria were sequenced successfully. This study did not observe mutations associated with the in vitro resistance in southeast Asia, such as Y493H, R539T, I543T, and C580Y. Two new polymorphisms V520A and V581I were observed in two samples collected in Osogbo, Southwest Nigeria. These two mutations occurred in the year 2004 (Group A) before the introduction of ACT. Six mutations were identified in 17% of the samples collected in southeast Nigeria. One of these mutations (D547G) was non-synonymous, while the remaining (V510V, R515R, Q613Q, E688E, and N458N) were synonymous. Also, one (2%) heterozygote allele was identified at codon 458 in the 2015 (Group C) samples.ConclusionsNone of the mutations observed in this study were previously validated to be associated with ART resistance. These results, therefore, suggest that artemisinin is likely to remain highly effective in treating malaria in the study areas that are malarious zone.
Highlights
The occurrence of artemisinin resistance (ART)-associated polymorphism of Plasmodium falciparum K13-propeller gene before and after the introduction of artemisinin-based combination therapy (ACT) in two regions of Nigeria was investigated in this study
Implementing artemisinin-based combination therapy (ACT) as first-line chemotherapy for uncomplicated malaria treatment has led to a 10% reduction in the 1% symptomatic individuals that may progress to fatal severe malaria [1]
Regular surveillance is necessary to determine the emergence and pattern of possible resistance to ART. These facts motivated this study in which we investigated the presence of K13 mutant alleles in parasites collected before and after the introduction of ACT in two distinct geographical regions of Nigeria, where the incidence of malaria and delayed response to ART have been previously reported [17, 18]
Summary
The occurrence of artemisinin resistance (ART)-associated polymorphism of Plasmodium falciparum K13-propeller (pfk13) gene before and after the introduction of artemisinin-based combination therapy (ACT) in two regions of Nigeria was investigated in this study. Considerable progress was made in the control of malaria between 2000 and 2015, which was attributed to the massive rollout of mosquito nets, effective anti-malarial drugs, and the use of indoor residual spraying of insecticides resulting in the reduction of global malaria mortality and incidence rates by 62 and 41%, respectively [2]. This gain in malaria control is being threatened by the emergence of Plasmodium falciparum parasites resistant to artemisinin and its derivatives reported in Southeast Asia. Artemisinin monotherapies are still available as an over-the-counter medication in countries, where malaria is endemic, thereby increasing the likelihood of solo exposure and the development of resistance when any surviving parasites encounters sub-therapeutic levels [4]
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