Prevalence of molecular markers of anti-malarial drug resistance in Plasmodium vivaxand Plasmodium falciparumin two districts of Nepal

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Sulphadoxine-pyrimethamine (SP) and chloroquine (CQ) have been used in treatment of falciparum and vivax malaria in Nepal. Recently, resistance to both drugs have necessitated a change towards artemisinin combination therapy (ACT) against Plasmodium falciparum in highly endemic areas. However, SP is still used against P. falciparum infections in low endemic areas while CQ is used in suspected cases in areas with lack of diagnostic facilities. This study examines the prevalence of molecular markers of CQ and SP resistance in P. falciparum and Plasmodium vivax to determine if high levels of in vivo resistance are reflected at molecular level as well. Methods Finger prick blood samples (n = 189) were collected from malaria positive patients from two high endemic districts and analysed for single nucleotide polymorphisms (SNPs) in the resistance related genes of P. falciparum and P. vivax for CQ ( Pfcrt, Pfmdr1, Pvmdr1 ) and SP ( Pfdhfr, Pfdhps, Pvdhfr ), using various PCR-based methods. Results and discussion Positive P. vivax and P. falciparum infections were identified by PCR in 92 and 41 samples respectively. However, some of these were negative in subsequent PCRs. Based on a few P. falciparum samples, the molecular level of CQ resistance in P. falciparum was high since nearly all parasites had the Pfcrt mutant haplotypes CVIET (55%) or SVMNT (42%), though frequency of the Pfmdr1 wild type haplotype was relatively low (35%). Molecular level of SP resistance in P. falciparum was found to be high. The most prevalent Pfdhfr haplotype was double mutant CNRNI (91%), while frequency of Pfdhps double mutant SGEAA and AGEAA were 38% and 33% respectively. Combined, the frequency of quadruple mutations (CNRNI-SGEAA/AGEAA) was 63%. Based on P. vivax samples, low CQ and SP resistance were most likely due to low prevalence of Pvmdr1 Y976F mutation (5%) and absence of triple/quadruple mutations in Pvdhfr . Conclusions Based on the limited number of samples, prevalence of CQ and SP resistance at molecular levels in the population in the study area were determined as high in P. falciparum and low in P. vivax . Therefore, CQ could still be used in the treatment of P. vivax infections, but this remains to be tested in vivo while the change to ACT for P. falciparum seems justified.

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Publié le 01 janvier 2011
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Ranjitkaret al.Malaria Journal2011,10:75 http://www.malariajournal.com/content/10/1/75
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Open Access
Prevalence of molecular markers of antimalarial drug resistance inPlasmodium vivaxand Plasmodium falciparumin two districts of Nepal 1 1 1 2 3 Samir Ranjitkar , Mette L Schousboe , Thomas Thyge Thomsen , Madhav Adhikari , Christian MO Kapel , 1 1* Ib C Bygbjerg and Michael Alifrangis
Abstract Background:Sulphadoxinepyrimethamine (SP) and chloroquine (CQ) have been used in treatment of falciparum and vivax malaria in Nepal. Recently, resistance to both drugs have necessitated a change towards artemisinin combination therapy (ACT) againstPlasmodium falciparumin highly endemic areas. However, SP is still used againstP. falciparum infections in low endemic areas while CQ is used in suspected cases in areas with lack of diagnostic facilities. This study examines the prevalence of molecular markers of CQ and SP resistance inP. falciparumandPlasmodium vivaxto determine if high levels ofin vivoresistance are reflected at molecular level as well. Methods:Finger prick blood samples (n = 189) were collected from malaria positive patients from two high endemic districts and analysed for single nucleotide polymorphisms (SNPs) in the resistance related genes ofP. falciparumand P. vivaxfor CQ (Pfcrt, Pfmdr1, Pvmdr1) and SP (Pfdhfr, Pfdhps, Pvdhfr), using various PCRbased methods. Results and discussion:PositiveP. vivaxandP. falciparuminfections were identified by PCR in 92 and 41 samples respectively. However, some of these were negative in subsequent PCRs. Based on a fewP. falciparumsamples, the molecular level of CQ resistance inP. falciparumwas high since nearly all parasites had thePfcrtmutant haplotypes CVIET (55%) or SVMNT (42%), though frequency of thePfmdr1wild type haplotype was relatively low (35%). Molecular level of SP resistance inP. falciparumwas found to be high. The most prevalentPfdhfrhaplotype was double mutant CNRNI (91%), while frequency ofPfdhpsdouble mutant SGEAA and AGEAA were 38% and 33% respectively. Combined, the frequency of quadruple mutations (CNRNISGEAA/AGEAA) was 63%. Based onP. vivax samples, low CQ and SP resistance were most likely due to low prevalence ofPvmdr1Y976F mutation (5%) and absence of triple/quadruple mutations inPvdhfr. Conclusions:Based on the limited number of samples, prevalence of CQ and SP resistance at molecular levels in the population in the study area were determined as high inP. falciparumand low inP. vivax. Therefore, CQ could still be used in the treatment ofP. vivaxinfections, but this remains to be testedin vivowhile the change to ACT forP. falciparumseems justified.
Background Malaria is one of the major health problems in South East Asia where 1.3 billion people (76% of total popula tion) are at risk, causing around 120,000 deaths yearly [1].Plasmodium vivaxmalaria is the most widespread and prevalent in this region but large knowledge gaps
* Correspondence: micali@sund.ku.dk 1 Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark Full list of author information is available at the end of the article
still exits that preventing the assessment of the technical feasibility of its elimination still exist [2]. In Nepal, roughly 80% (22.5 million) of the population lives in malaria endemic areas of which seven million reside in highly endemic areas [3].P. vivaxis the predominant species that causes around 8090% of the total malaria cases whilePlasmodium falciparumis the main cause of malaria epidemics in Nepal [4]. Malaria transmission may occur throughout the year but mostly from March to November with peaks in June, July and August [5].
© 2011 Ranjitkar et al; licensee 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.