Prevalence of molecular markers of anti-malarial drug resistance in <it>Plasmodium vivax </it>and <it>Plasmodium falciparum </it>in two districts of Nepal

<p>Abstract</p> <p>Background</p> <p>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) ag...

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Main Authors: Bygbjerg Ib C, Kapel Christian MO, Adhikari Madhav, Thomsen Thomas, Schousboe Mette L, Ranjitkar Samir, Alifrangis Michael
Format: Article
Language:English
Published: BMC 2011-04-01
Series:Malaria Journal
Online Access:http://www.malariajournal.com/content/10/1/75
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author Bygbjerg Ib C
Kapel Christian MO
Adhikari Madhav
Thomsen Thomas
Schousboe Mette L
Ranjitkar Samir
Alifrangis Michael
author_facet Bygbjerg Ib C
Kapel Christian MO
Adhikari Madhav
Thomsen Thomas
Schousboe Mette L
Ranjitkar Samir
Alifrangis Michael
author_sort Bygbjerg Ib C
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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 <it>Plasmodium falciparum </it>in highly endemic areas. However, SP is still used against <it>P. falciparum </it>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 <it>P. falciparum </it>and <it>Plasmodium vivax </it>to determine if high levels of <it>in vivo </it>resistance are reflected at molecular level as well.</p> <p>Methods</p> <p>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 <it>P. falciparum </it>and <it>P. vivax </it>for CQ (<it>Pfcrt, Pfmdr1, Pvmdr1</it>) and SP (<it>Pfdhfr, Pfdhps, Pvdhfr</it>), using various PCR-based methods.</p> <p>Results and discussion</p> <p>Positive <it>P. vivax </it>and <it>P. falciparum </it>infections were identified by PCR in 92 and 41 samples respectively. However, some of these were negative in subsequent PCRs. Based on a few <it>P. falciparum </it>samples, the molecular level of CQ resistance in <it>P. falciparum </it>was high since nearly all parasites had the <it>Pfcrt </it>mutant haplotypes CVIET (55%) or SVMNT (42%), though frequency of the <it>Pfmdr1 </it>wild type haplotype was relatively low (35%). Molecular level of SP resistance in <it>P. falciparum </it>was found to be high. The most prevalent <it>Pfdhfr </it>haplotype was double mutant CNRNI (91%), while frequency of <it>Pfdhps </it>double mutant SGEAA and AGEAA were 38% and 33% respectively. Combined, the frequency of quadruple mutations (CNRNI-SGEAA/AGEAA) was 63%. Based on <it>P. vivax </it>samples, low CQ and SP resistance were most likely due to low prevalence of <it>Pvmdr1 </it>Y976F mutation (5%) and absence of triple/quadruple mutations in <it>Pvdhfr</it>.</p> <p>Conclusions</p> <p>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 <it>P. falciparum </it>and low in <it>P. vivax</it>. Therefore, CQ could still be used in the treatment of <it>P. vivax </it>infections, but this remains to be tested <it>in vivo </it>while the change to ACT for <it>P. falciparum </it>seems justified.</p>
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spelling doaj.art-60af7b330d774262b077f9dd6e2a42dc2022-12-21T22:38:23ZengBMCMalaria Journal1475-28752011-04-011017510.1186/1475-2875-10-75Prevalence of molecular markers of anti-malarial drug resistance in <it>Plasmodium vivax </it>and <it>Plasmodium falciparum </it>in two districts of NepalBygbjerg Ib CKapel Christian MOAdhikari MadhavThomsen ThomasSchousboe Mette LRanjitkar SamirAlifrangis Michael<p>Abstract</p> <p>Background</p> <p>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 <it>Plasmodium falciparum </it>in highly endemic areas. However, SP is still used against <it>P. falciparum </it>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 <it>P. falciparum </it>and <it>Plasmodium vivax </it>to determine if high levels of <it>in vivo </it>resistance are reflected at molecular level as well.</p> <p>Methods</p> <p>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 <it>P. falciparum </it>and <it>P. vivax </it>for CQ (<it>Pfcrt, Pfmdr1, Pvmdr1</it>) and SP (<it>Pfdhfr, Pfdhps, Pvdhfr</it>), using various PCR-based methods.</p> <p>Results and discussion</p> <p>Positive <it>P. vivax </it>and <it>P. falciparum </it>infections were identified by PCR in 92 and 41 samples respectively. However, some of these were negative in subsequent PCRs. Based on a few <it>P. falciparum </it>samples, the molecular level of CQ resistance in <it>P. falciparum </it>was high since nearly all parasites had the <it>Pfcrt </it>mutant haplotypes CVIET (55%) or SVMNT (42%), though frequency of the <it>Pfmdr1 </it>wild type haplotype was relatively low (35%). Molecular level of SP resistance in <it>P. falciparum </it>was found to be high. The most prevalent <it>Pfdhfr </it>haplotype was double mutant CNRNI (91%), while frequency of <it>Pfdhps </it>double mutant SGEAA and AGEAA were 38% and 33% respectively. Combined, the frequency of quadruple mutations (CNRNI-SGEAA/AGEAA) was 63%. Based on <it>P. vivax </it>samples, low CQ and SP resistance were most likely due to low prevalence of <it>Pvmdr1 </it>Y976F mutation (5%) and absence of triple/quadruple mutations in <it>Pvdhfr</it>.</p> <p>Conclusions</p> <p>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 <it>P. falciparum </it>and low in <it>P. vivax</it>. Therefore, CQ could still be used in the treatment of <it>P. vivax </it>infections, but this remains to be tested <it>in vivo </it>while the change to ACT for <it>P. falciparum </it>seems justified.</p>http://www.malariajournal.com/content/10/1/75
spellingShingle Bygbjerg Ib C
Kapel Christian MO
Adhikari Madhav
Thomsen Thomas
Schousboe Mette L
Ranjitkar Samir
Alifrangis Michael
Prevalence of molecular markers of anti-malarial drug resistance in <it>Plasmodium vivax </it>and <it>Plasmodium falciparum </it>in two districts of Nepal
Malaria Journal
title Prevalence of molecular markers of anti-malarial drug resistance in <it>Plasmodium vivax </it>and <it>Plasmodium falciparum </it>in two districts of Nepal
title_full Prevalence of molecular markers of anti-malarial drug resistance in <it>Plasmodium vivax </it>and <it>Plasmodium falciparum </it>in two districts of Nepal
title_fullStr Prevalence of molecular markers of anti-malarial drug resistance in <it>Plasmodium vivax </it>and <it>Plasmodium falciparum </it>in two districts of Nepal
title_full_unstemmed Prevalence of molecular markers of anti-malarial drug resistance in <it>Plasmodium vivax </it>and <it>Plasmodium falciparum </it>in two districts of Nepal
title_short Prevalence of molecular markers of anti-malarial drug resistance in <it>Plasmodium vivax </it>and <it>Plasmodium falciparum </it>in two districts of Nepal
title_sort prevalence of molecular markers of anti malarial drug resistance in it plasmodium vivax it and it plasmodium falciparum it in two districts of nepal
url http://www.malariajournal.com/content/10/1/75
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