Assessment of drug resistance associated genetic diversity in Mauritanian isolates of Plasmodium vivax reveals limited polymorphism

Jemila Mint Deida,Ali Ould Mohamed Salem Boukhary,Emal Mint Semane,Leonardo Basco,Yacoub Ould Khalef,Rachida Tahar,Hervé Bogreau,Mohamed Salem Ould Ahmedou Salem

doi:10.1186/s12936-018-2548-2

Abstract

BackgroundPlasmodium vivax is the predominant malaria species in northern Mauritania. Molecular data on P. vivax isolates circulating in West Africa are scarce. The present study analysed molecular markers associated with resistance to antifolates (Pvdhfr and Pvdhps), chloroquine (Pvmdr1), and artemisinin (Pvk12) in P. vivax isolates collected in two cities located in the Saharan zone of Mauritania.MethodsBlood samples were obtained from P. vivax-infected patients recruited for chloroquine therapeutic efficacy study in 2013 and febrile patients spontaneously consulting health facilities in Nouakchott and Atar in 2015–2016. Fragments of Pvdhfr (codons 13, 33, 57, 58, 61, 117, and 174), Pvdhps (codons 382, 383, 512, 553, and 585), Pvmdr1 (codons 976 and 1076) and Pvk12 (codon 552) genes were amplified by PCR and sequenced.ResultsMost of the isolates in Nouakchott (126/154, 81.8%) and Atar (44/45, 97.8%) carried the wild-type Pvdhfr allelic variant (IPFSTSI). In Nouakchott, all mutants (28/154; 18.2%) had double Pvdhfr mutations in positions 58 and 61 (allelic variant IPFRMSI), whereas in Atar only 1 isolate was mutant (S117N, allelic variant IPFSTNI). The wild-type Pvdhps allelic variant (SAKAV) was found in all tested isolates (Nouakchott, n = 93; Atar, n = 37). Few isolates in Nouakchott (5/115, 4.3%) and Atar (3/79, 3.8%) had the mutant Pvmdr1 allele 976F or 1076L, but not both, including in pre-treatment isolates obtained from patients treated successfully with chloroquine. All isolates (59 in Nouakchott and 48 in Atar) carried the wild-type V552 allele in Pvk12.ConclusionsPolymorphisms in Pvdhfr, Pvdhps, Pvmdr1, and Pvk12 were limited in P. vivax isolates collected recently in Nouakchott and Atar. Compared to the isolates collected in Nouakchott in 2007–2009, there was no evidence for selection of mutants. The presence of one, but not both, of the two potential markers of chloroquine resistance in Pvmdr1 in pre-treatment isolates did not influence the clinical outcome, putting into question the role of Pvmdr1 mutant alleles 976F and 1076L in treatment failure. Molecular surveillance is an important component of P. vivax malaria control programme in the Saharan zone of Mauritania to predict possible emergence of drug-resistant parasites.

Highlights

Plasmodium vivax is the predominant malaria species in northern Mauritania
Among blood samples collected in Nouakchott and confirmed positive by rapid diagnostic test, the molecular markers of drug resistance were analysed for the following numbers of isolates: 154 for Plasmodium vivax dihydrofolate reductase (Pvdhfr), 93 for Plasmodium vivax dihydropteroate synthase (Pvdhps), 115 for Plasmodium vivax multidrug resistance 1 (Pvmdr1), and 59 for Plasmodium vivax Kelch 12 (Pvk12) (Table 2)
The results of the present study showed that mutations in Pvdhfr, Pvdhps, Pvmdr1 and Pvk12 occur in some P. vivax isolates collected recently in the Saharan zone of Mauritania

Summary

Introduction

Plasmodium vivax is the predominant malaria species in northern Mauritania. Molecular data on P. vivax isolates circulating in West Africa are scarce. The present study analysed molecular markers associated with resistance to antifolates (Pvdhfr and Pvdhps), chloroquine (Pvmdr1), and artemisinin (Pvk12) in P. vivax isolates collected in two cities located in the Saharan zone of Mauritania. Both Plasmodium falciparum and Plasmodium vivax are endemic in Mauritania with approximately 300,000 malaria cases reported in 2017 [1]. In the northern Saharan zone of Mauritania, in Nouakchott, the capital city of the country, and Atar, the provincial capital of Adrar region, malaria transmission is seasonal, and P. vivax has been shown to be the main causative species of malaria parasite [2,3,4]. Delay, and overcome the emergence of multidrug-resistant parasites, ACT has been recommended since 2001 for the treatment of uncomplicated malaria in endemic countries [11]

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