Prevalence and patterns of antifolate and chloroquine drug resistance markers in Plasmodium vivax across Pakistan

Malaria Journal

Research

Lubna Khatoon¹  Aamer A Khattak¹  Salman A Malik¹  Amed Ouattara²  Leo J Kenefic³  Christopher V Plowe⁴  Meera Venkatesan⁴  Farida Nighat⁵  Muhammad F Nadeem⁶ 

[1] Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan;Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA;Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA;Department of Medical and Research Technology, University of Maryland School of Medicine, Baltimore, MD, USA;Howard Hughes Medical Institute/Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA;Worldwide Antimalarial Resistance Network Molecular Module, University of Maryland School of Medicine, Baltimore, MD, USA;Islamic International Medical College, Rawalpindi, Pakistan;King Edward Medical University, Lahore, Pakistan;Department of Biochemistry and Molecular Biology, University of Gujrat, Gujrat, Pakistan;

关键词: Plasmodium vivax;    Malaria;    Pakistan;    Drug resistance;    Sulphadoxine-pyrimethamine;    Chloroquine;    Pvmdr1;    Pvdhfr;    Pvdhps;   

DOI  :  10.1186/1475-2875-12-310

 received in 2013-05-30, accepted in 2013-08-29,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundPlasmodium vivax is the most prevalent malaria species in Pakistan, with a distribution that coincides with Plasmodium falciparum in many parts of the country. Both species are likely exposed to drug pressure from a number of anti-malarials including chloroquine, sulphadoxine-pyrimethamine (SP), and artemisinin combination therapy, yet little is known regarding the effects of drug pressure on parasite genes associated with drug resistance. The aims of this study were to determine the prevalence of polymorphisms in the SP resistance-associated genes pvdhfr, pvdhps and chloroquine resistance-associated gene pvmdr1 in P. vivax isolates collected from across the country.MethodsIn 2011, 801 microscopically confirmed malaria-parasite positive filter paper blood samples were collected at 14 sites representing four provinces and the capital city of Islamabad. Species-specific polymerase chain reaction (PCR) was used to identify human Plasmodium species infection. PCR-positive P. vivax isolates were subjected to sequencing of pvdhfr, pvdhps and pvmdr1 and to real-time PCR analysis to assess pvmdr1 copy number variation.ResultsOf the 801 samples, 536 were determined to be P. vivax, 128 were P. falciparum, 43 were mixed vivax/falciparum infections and 94 were PCR-negative for Plasmodium infection. Of PCR-positive P. vivax samples, 372 were selected for sequence analysis. Seventy-six of the isolates (23%) were double mutant at positions S58R and S117N in pvdhfr. Additionally, two mutations at positions N50I and S93H were observed in 55 (15%) and 24 (7%) of samples, respectively. Three 18 base pair insertion-deletions (indels) were observed in pvdhfr, with two insertions at different nucleotide positions in 36 isolates and deletions in 10. Ninety-two percent of samples contained the pvdhps (S382/A383G/K512/A553/V585) SAKAV wild type haplotype. For pvmdr1, all isolates were wild type at position Y976F and 335 (98%) carried the mutation at codon F1076L. All isolates harboured single copies of the pvmdr1 gene.ConclusionsThe prevalence of mutations associated with SP resistance in P. vivax is low in Pakistan. The high prevalence of P. vivax mutant pvmdr1 codon F1076L indicates that efficacy of chloroquine plus primaquine could be in danger of being compromised, but further studies are required to assess the clinical relevance of this observation. These findings will serve as a baseline for further monitoring of drug-resistant P. vivax malaria in Pakistan.

【 授权许可】

Unknown   
© Khattak et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.