Polymorphisms in K13, pfcrt, pfmdr1, pfdhfr, and pfdhps in parasites isolated from symptomatic malaria patients in Burkina Faso.

Issaka Zongo,Frédéric Nikiéma,Yves-Daniel Compaoré,Thomas Bazié,Moussa Zongo,Amadé Sawadogo,Anyirékun Fabrice Somé,Hermann Sorgho,Jean-Bosco Ouédraogo

doi:10.1051/parasite/2016069

Issaka Zongo, Frédéric Nikiéma + Show 7 more

Open Access

https://doi.org/10.1051/parasite/2016069

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Abstract

Background: The emergence of resistance to artemisinin derivatives in western Cambodia is threatening to revert the recent advances made toward global malaria control and elimination. Known resistance-mediating polymorphisms in the K13, pfcrt, pfmdr1, pfdhfr, and pfdhps genes are of greatest importance for monitoring the spread of antimalarial drug resistance. Methods: Samples for the present study were collected from 244 patients with uncomplicated malaria in health centers of Bobo-Dioulasso, Burkina Faso. Blood sample was collected on filter paper before the subject received any treatment. The parasite DNA was then extracted and amplified by Polymerase Chain Reaction (PCR) to evaluate the prevalence of polymorphism of pfcrtK76T, pfmdr1 (N86Y, Y184F), and pfdhps (A437G, K540E). The K13 gene polymorphism was analyzed by nested PCR followed by sequencing. Results: The overall results showed 2.26% (5/221) of K13 synonymous mutant alleles (two C469C, one Y493Y, one G496G, and one V589V), 24.78%, 19.58%, 68.75%, 60.9%, 53.7%, 63.8%, and 64.28%, respectively, for mutant pfcrt 76T, pfmdr1-86Y, pfmdr1-184F, pfdhfr51I, pfdhfr59R, pfdhfr108N, and pfdhps 437G. We did not report any mutation at codon 540 of pfdhps. Conclusion: These results provide baseline prevalence of known drug resistance polymorphisms and suggest that artemisinin combination therapies may retain good efficacy in the treatment of uncomplicated malaria in Burkina Faso.

Highlights

In Burkina Faso, malaria is still the most important infectious disease with the highest rates of mortality and morbidity [17, 22]
We aimed to identify the baseline prevalence of known resistance-mediating mutations in the K13 propeller, pfcrt, pfmdr1, pfdhfr, and pfdhps genes in parasites isolated from symptomatic malaria patients in Bobo-Dioulasso, Burkina Faso
Our study aimed to evaluate the baseline prevalence of known resistance-mediating mutations in the k13 propeller, pfcrt, pfmdr1, pfdhfr, and pfdhps genes in parasites isolated from symptomatic malaria patients in Bobo-Dioulasso, Burkina Faso

Summary

Introduction

In Burkina Faso, malaria is still the most important infectious disease with the highest rates of mortality and morbidity [17, 22]. Several studies have since demonstrated the excellent efficacy of artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria in Burkina Faso [30, 37, 38]. The spread of parasite resistance to antimalarial drugs from Asia to Africa has already occurred with CQ and SP [35], suggesting the need for reinforced surveillance of artemisinin resistance in Africa. In early 2014, artemisinin-resistant phenotypes in Cambodia were associated with mutation in Pf3d7_1343700, one exon gene, which codes for a putative Kelch protein 13 [1]. The identified mutations were associated in vitro with an increased survival rate and in vivo with delayed parasite clearance after artemisinin treatment. The authors found that when a K13 mutant parasite was repaired to wild type, the artemisinin resistance was lost; and that sensitive parasites become more resistant to artemisinin once the wild-type K13 gene is converted to mutant [27]

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