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. 2018 Mar 27;17(1):130.
doi: 10.1186/s12936-018-2286-5.

Simultaneous detection of Plasmodium vivax dhfr, dhps, mdr1 and crt-o resistance-associated mutations in the Colombian Amazonian region

Juan Ricardo Cubides  1 , Paola Andrea Camargo-Ayala  1 , Carlos Hernando Niño  1 , Diego Garzón-Ospina  1   2 , Anggie Ortega-Ortegón  1 , Estefany Ospina-Cantillo  1 , María Fernanda Orduz-Durán  1 , Manuel Elkin Patarroyo  1   3 , Manuel Alfonso Patarroyo  4   5
Affiliations

Simultaneous detection of Plasmodium vivax dhfr, dhps, mdr1 and crt-o resistance-associated mutations in the Colombian Amazonian region

Juan Ricardo Cubides et al. Malar J. .

Abstract

Background: Malaria continues being a public health problem worldwide. Plasmodium vivax is the species causing the largest number of cases of malaria in Asia and South America. Due to the lack of a completely effective anti-malarial vaccine, controlling this disease has been based on transmission vector management, rapid diagnosis and suitable treatment. However, parasite resistance to anti-malarial drugs has become a major yet-to-be-overcome challenge. This study was thus aimed at determining pvmdr1, pvdhfr, pvdhps and pvcrt-o gene mutations and haplotypes from field samples obtained from an endemic area in the Colombian Amazonian region.

Methods: Fifty samples of parasite DNA infected by a single P. vivax strain from symptomatic patients from the Amazonas department in Colombia were analysed by PCR and the pvdhfr, pvdhps, pvmdr1 and pvcrt-o genes were sequenced. Diversity estimators were calculated from the sequences and the haplotypes circulating in the Colombian Amazonian region were obtained.

Conclusion: pvdhfr, pvdhps, pvmdr1 and pvcrt-o genes in the Colombian Amazonian region are characterized by low genetic diversity. Some resistance-associated mutations were found circulating in this population. New variants are also being reported. A selective sweep signal was located in pvdhfr and pvmdr1 genes, suggesting that these mutations (or some of them) could be providing an adaptive advantage.

Keywords: Amazonian region; Antimalarial drug resistance; Colombia; Malaria; Plasmodium vivax; pvdhfr; pvdhps; pvmdr1 and pvcrt-o.

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Figures

Fig. 1
Fig. 1
DNA haplotypes found in the Colombian Amazon region. a Aligning pvmdr1 gene non-conserved residues. b Aligning pvdhps non-conserved residues. c Aligning pvdhfr non-conserved residues. Dots indicate conserved residues. Nucleotide positions are indicated according to the P. vivax Sal-I strain numbering (PlasmoDB accession PVX_089950 for pvmdr1, PVX_123230 for pvdhps and PVX_080100 for pvdhfr)
Fig. 2
Fig. 2
Amino acid haplotypes found in the Colombian Amazon region. a PvMDR1 alignment. b PvDHPS alignment. c PvDHFR alignment. Dots indicate conserved residues. Amino acid positions are indicated according to P. vivax Sal-I strain numbering (PlasmoDB accession PVX_089950 for PvMDR1, PVX_123230 for PvDHPS and PVX_080100 for PvDHFR)
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