Abstract
BackgroundEvidence for decreasing chloroquine (CQ) efficacy against Plasmodium vivax has been reported from many endemic countries in the world. In Ethiopia, P. vivax accounts for 40% of all malaria cases and CQ is the first-line drug for vivax malaria. Mutations in multidrug resistance 1 (pvmdr-1) and K10 insertion in the pvcrt-o genes have been identified as possible molecular markers of CQ-resistance (CQR) in P. vivax. Despite reports of CQ treatment failures, no data are currently available on the prevalence of molecular markers of P. vivax resistance in Ethiopia. The objective of this study was to determine the prevalence of mutations in the pvmdr-1 and K10 insertion in the pvcrt-o genes.MethodsA total of 36 P. vivax clinical isolates were collected from West Arsi district in Ethiopia. Sequencing was used to analyse polymorphisms of the pvcrt-o and pvmdr-1 genes.ResultsSequencing results of the pvmdr-1 fragment showed the presence of two non-synonymous mutations at positions 976 and 1076. The Y → F change at codon 976 (TAC → TTC) was observed in 21 (75%) of 28 the isolates while the F → L change (at codon 1076), which was due to a single mutation (TTT → CTT), was observed in 100% of the isolates. Of 33 samples successfully amplified for the pvcrt-o, the majority of the isolates (93.9%) were wild type, without K10 insertion.ConclusionsHigh prevalence of mutations in candidate genes conferring CQR in P. vivax was identified. The fact that CQ is still the first-line treatment for vivax malaria, the significance of mutations in the pvcrt-o and pvmdr-1 genes and the clinical response of the patients’ to CQ treatment and whether thus an association exists between point mutations of the candidate genes and CQR requires further research in Ethiopia.
Highlights
Evidence for decreasing chloroquine (CQ) efficacy against Plasmodium vivax has been reported from many endemic countries in the world
To unveil the current knowledge regarding the molecular mechanisms of P. vivax resistance to CQ and the prospects for developing and standardizing reliable molecular markers of drug resistance, Goncalves et al [13] reviewed the available data by combining published in vivo and in vitro studies
Unlike in P. falciparum, the molecular mechanism of P. vivax CQR remains elusive [7]. This is because, previous studies focusing on genes known to be main determinants of CQR in P. falciparum have failed to demonstrate a strong correlation between pvcrt-o and pvmdr-1 genotypes and the CQR phenotype in P. vivax
Summary
Evidence for decreasing chloroquine (CQ) efficacy against Plasmodium vivax has been reported from many endemic countries in the world. Mutations in multidrug resistance 1 (pvmdr-1) and K10 insertion in the pvcrt-o genes have been identified as possible molecular markers of CQ-resistance (CQR) in P. vivax. Despite reports of CQ treatment failures, no data are currently available on the prevalence of molecular markers of P. vivax resistance in Ethiopia. To unveil the current knowledge regarding the molecular mechanisms of P. vivax resistance to CQ and the prospects for developing and standardizing reliable molecular markers of drug resistance, Goncalves et al [13] reviewed the available data by combining published in vivo and in vitro studies. Unlike in P. falciparum, the molecular mechanism of P. vivax CQR remains elusive [7] This is because, previous studies focusing on genes known to be main determinants of CQR in P. falciparum have failed to demonstrate a strong correlation between pvcrt-o and pvmdr-1 genotypes and the CQR phenotype in P. vivax. Melo et al [14], on the other hand, showed the association of expression levels of pvcrt-o and pvmdr-1 with CQR and severe P. vivax malaria, because parasites from patients with CQR presented up to 6.1-fold and 2.4-fold increase in pvcrt-o and pvmdr-1 expression levels, respectively, compared to the susceptible group in the Brazilian Amazon
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