Status of Artemisinin Resistance in Malaria Parasite Plasmodium falciparum from Molecular Analyses of the Kelch13 Gene in Southwestern Nigeria

Mary Aigbiremo Oboh,Hiasindh Ashmi Antony,Nazia Anwar Ali,Upasana Shyamsunder Singh,Aida Sadikh Badiane,Praveen Kumar Bharti,Aparup Das,Daouda Ndiaye

doi:10.1155/2018/2305062

Mary Aigbiremo Oboh, Hiasindh Ashmi Antony + Show 6 more

Open Access

https://doi.org/10.1155/2018/2305062

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Abstract

Evolution and spread of malaria parasite Plasmodium falciparum capable of evading antimalarials are the prime concern to malaria control. The currently effective drug, artemisinin (ART), is under threat due to detection of ART-resistant P. falciparum parasites in the Southeast Asian countries. It has been shown that amino acid (AA) mutations at the P. falciparum Kelch13 (Pfk13) gene provide resistance to ART. Nigeria, a part of the Sub-Saharan Africa, is highly endemic to malaria, contributing quite significantly to malaria, and resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) combination drugs has already been reported. Since artemisinin combined therapy (ACT) is the first-line drug for treatment of uncomplicated malaria in Nigeria and five amino acid mutations have been validated in the Pfk13 gene alongside with candidate mutations for ART resistance, we performed molecular surveillance for mutations (following PCR and DNA sequence analyses) in this gene from two southwestern states of Nigeria. Statistical analyses of DNA sequences were also performed following different evolutionary models. None of the different validated and candidate AA mutations of Pfk13 gene conferring resistance to ART could be detected in P. falciparum sampled in the two southwestern states of Nigeria. In addition, DNA sequencing and sequence analyses indicated neither evolutionary selection pressure on the Pfk13 gene nor association of mutations in Pfk13 gene with mutations of other three genes conferring resistance to CQ and SP. Therefore, based on the monomorphism at the Pfk13 gene and nonassociation of mutations of this gene with mutations in three other drug-resistant genes in malaria parasite P. falciparum, it can be proposed that malaria public health is not under immediate threat in southwestern Nigeria concerning ART resistance.

Highlights

Emergence and spread of drug resistance in malaria parasite, Plasmodium falciparum, are a severe public health concern all over the malaria endemic countries of the globe [1,2,3]
Patients with symptoms of malaria attending any of the four selected hospitals (Gbagada, Ikorodu, Akodo, and Ikate) in Lagos and two general hospitals (Central and Stella) in Edo were screened by rapid diagnostic test (RDT) kits and microscopy in the field
In order to identify if mutations in the amino acids at the Kelch13 protein of P. falciparum associated with ART are prevalent in Nigeria, we have generated sequences of the part of the P. falciparum Kelch13 (Pfk13) gene (831-nucleotide base pair, bearing ART-resistant single nucleotide polymorphisms (SNPs)) from 50 P. falciparum isolates in two southwestern Nigerian states (Lagos and Edo)

Summary

Introduction

Emergence and spread of drug resistance in malaria parasite, Plasmodium falciparum, are a severe public health concern all over the malaria endemic countries of the globe [1,2,3]. In order to discern molecular epidemiology of Pfk13 gene conferring resistance to ART in two southwestern states of Nigeria, we have collected field P. falciparum isolates to unravel (i) distributional prevalence of mutations in the part of the Pfk13 gene containing the five validated and other candidate mutations and (ii) the possible association of mutations detected in the Pfk13 gene with mutations in three other genes conferring resistance to CQ (Pfcrt) and SP (Pfdhfr and Pfdhps).

Results

Conclusion