Analysis of drug resistance marker genes of Plasmodium falciparum after implementation of artemisinin-based combination therapy in Pune district, India

The global emergence and spread of malaria parasites resistant to antimalarial drugs is a major problem in malaria control and elimination. In this study, samples from Pune district were characterized to determine prevalence of molecular markers of resistance to chloroquine ( pfcrt codons C72S, M74I...

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Veröffentlicht in:Journal of biosciences 2021-09, Vol.46 (3), Article 77
Hauptverfasser: Ozarkar, Aarti, Kanyal, Abhishek, Dass, Swati, Deshpande, Prakash, Deobagkar, Deepti, Karmodiya, Krishanpal
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Kanyal, Abhishek
Dass, Swati
Deshpande, Prakash
Deobagkar, Deepti
Karmodiya, Krishanpal
description The global emergence and spread of malaria parasites resistant to antimalarial drugs is a major problem in malaria control and elimination. In this study, samples from Pune district were characterized to determine prevalence of molecular markers of resistance to chloroquine ( pfcrt codons C72S, M74I, N75E, K76T and pfmdr-1 N86Y, Y184F), pyrimethamine ( pfdhfr C50R, N51I, C59R, S108N), sulfadoxine (pfdhps, S436A, A437G, K540E, A581G), and artemisinin ( pfkelch13, C580Y, R539T). The pfcrt K76T mutation was found in 78% samples as CVMNT, SVMNT and CVIET haplotype. The pfmdr-1 N86Y and Y184F mutations were found in 54% of samples. The pfdhfr double mutation C59R + S108N was present in 67% of samples, while the pfdhfr triple mutation (N51I + C59R + S108N) was not detected. The pfdhps mutations A437G and K540E were found in 67% of samples. Single mutants of pfdhps were rare, with K540E detected in only 6 patient samples. Similarly, pfdhps A581G was found in 13 of the isolates. The molecular markers associated with artemisinin resistance (mutations in pfkelch13 C580Y, R539T) were not detected in any of the isolates. These results suggest an emerging problem with multidrug-resistant P. falciparum . Though the genotype conventionally associated with artemisinin resistance was not observed, chloroquine-resistant genotype has reached complete fixation in the population. Moreover, the prevalence of mutations in both pfdhfr and pfdhps , with the presence of the quadruple mutant, indicates that continued monitoring is required to assess whether sulfadoxine-pyrimethamine can be used efficiently as a partner drug for artemisinin for the treatment of P. falciparum .
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In this study, samples from Pune district were characterized to determine prevalence of molecular markers of resistance to chloroquine ( pfcrt codons C72S, M74I, N75E, K76T and pfmdr-1 N86Y, Y184F), pyrimethamine ( pfdhfr C50R, N51I, C59R, S108N), sulfadoxine (pfdhps, S436A, A437G, K540E, A581G), and artemisinin ( pfkelch13, C580Y, R539T). The pfcrt K76T mutation was found in 78% samples as CVMNT, SVMNT and CVIET haplotype. The pfmdr-1 N86Y and Y184F mutations were found in 54% of samples. The pfdhfr double mutation C59R + S108N was present in 67% of samples, while the pfdhfr triple mutation (N51I + C59R + S108N) was not detected. The pfdhps mutations A437G and K540E were found in 67% of samples. Single mutants of pfdhps were rare, with K540E detected in only 6 patient samples. Similarly, pfdhps A581G was found in 13 of the isolates. The molecular markers associated with artemisinin resistance (mutations in pfkelch13 C580Y, R539T) were not detected in any of the isolates. 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Moreover, the prevalence of mutations in both pfdhfr and pfdhps , with the presence of the quadruple mutant, indicates that continued monitoring is required to assess whether sulfadoxine-pyrimethamine can be used efficiently as a partner drug for artemisinin for the treatment of P. falciparum .</description><identifier>ISSN: 0250-5991</identifier><identifier>EISSN: 0973-7138</identifier><identifier>DOI: 10.1007/s12038-021-00200-3</identifier><identifier>PMID: 34344849</identifier><language>eng</language><publisher>New Delhi: Springer India</publisher><subject>Animals ; Antimalarial agents ; Artemisinin ; Artemisinins - administration &amp; dosage ; Artemisinins - therapeutic use ; Biomarkers - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Chloroquine ; Codons ; Combination therapy ; Drug resistance ; Drug Resistance - genetics ; Drug Therapy, Combination ; Drugs ; Erythrocytes ; Genes ; Genotypes ; Haplotypes ; Human diseases ; India ; Life Sciences ; Malaria ; Malaria, Falciparum - drug therapy ; Markers ; Microbiology ; Multidrug resistance ; Mutants ; Mutation ; Parasite resistance ; Parasites ; Plant Sciences ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - enzymology ; Plasmodium falciparum - genetics ; Pyrimethamine ; Sulfadoxine ; Vector-borne diseases ; Zoology</subject><ispartof>Journal of biosciences, 2021-09, Vol.46 (3), Article 77</ispartof><rights>Indian Academy of Sciences 2021</rights><rights>Indian Academy of Sciences 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-6dd6c508dcd7ccd967a7c9c4c2a5046e5af7441fd3f329ec6e34348a82bc79b73</citedby><cites>FETCH-LOGICAL-c375t-6dd6c508dcd7ccd967a7c9c4c2a5046e5af7441fd3f329ec6e34348a82bc79b73</cites><orcidid>0000-0002-5714-0587</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12038-021-00200-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12038-021-00200-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34344849$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ozarkar, Aarti</creatorcontrib><creatorcontrib>Kanyal, Abhishek</creatorcontrib><creatorcontrib>Dass, Swati</creatorcontrib><creatorcontrib>Deshpande, Prakash</creatorcontrib><creatorcontrib>Deobagkar, Deepti</creatorcontrib><creatorcontrib>Karmodiya, Krishanpal</creatorcontrib><title>Analysis of drug resistance marker genes of Plasmodium falciparum after implementation of artemisinin-based combination therapy in Pune district, India</title><title>Journal of biosciences</title><addtitle>J Biosci</addtitle><addtitle>J Biosci</addtitle><description>The global emergence and spread of malaria parasites resistant to antimalarial drugs is a major problem in malaria control and elimination. 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In this study, samples from Pune district were characterized to determine prevalence of molecular markers of resistance to chloroquine ( pfcrt codons C72S, M74I, N75E, K76T and pfmdr-1 N86Y, Y184F), pyrimethamine ( pfdhfr C50R, N51I, C59R, S108N), sulfadoxine (pfdhps, S436A, A437G, K540E, A581G), and artemisinin ( pfkelch13, C580Y, R539T). The pfcrt K76T mutation was found in 78% samples as CVMNT, SVMNT and CVIET haplotype. The pfmdr-1 N86Y and Y184F mutations were found in 54% of samples. The pfdhfr double mutation C59R + S108N was present in 67% of samples, while the pfdhfr triple mutation (N51I + C59R + S108N) was not detected. The pfdhps mutations A437G and K540E were found in 67% of samples. Single mutants of pfdhps were rare, with K540E detected in only 6 patient samples. Similarly, pfdhps A581G was found in 13 of the isolates. The molecular markers associated with artemisinin resistance (mutations in pfkelch13 C580Y, R539T) were not detected in any of the isolates. These results suggest an emerging problem with multidrug-resistant P. falciparum . Though the genotype conventionally associated with artemisinin resistance was not observed, chloroquine-resistant genotype has reached complete fixation in the population. Moreover, the prevalence of mutations in both pfdhfr and pfdhps , with the presence of the quadruple mutant, indicates that continued monitoring is required to assess whether sulfadoxine-pyrimethamine can be used efficiently as a partner drug for artemisinin for the treatment of P. falciparum .</abstract><cop>New Delhi</cop><pub>Springer India</pub><pmid>34344849</pmid><doi>10.1007/s12038-021-00200-3</doi><orcidid>https://orcid.org/0000-0002-5714-0587</orcidid></addata></record>
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subjects Animals
Antimalarial agents
Artemisinin
Artemisinins - administration & dosage
Artemisinins - therapeutic use
Biomarkers - metabolism
Biomedical and Life Sciences
Biomedicine
Cell Biology
Chloroquine
Codons
Combination therapy
Drug resistance
Drug Resistance - genetics
Drug Therapy, Combination
Drugs
Erythrocytes
Genes
Genotypes
Haplotypes
Human diseases
India
Life Sciences
Malaria
Malaria, Falciparum - drug therapy
Markers
Microbiology
Multidrug resistance
Mutants
Mutation
Parasite resistance
Parasites
Plant Sciences
Plasmodium falciparum
Plasmodium falciparum - drug effects
Plasmodium falciparum - enzymology
Plasmodium falciparum - genetics
Pyrimethamine
Sulfadoxine
Vector-borne diseases
Zoology
title Analysis of drug resistance marker genes of Plasmodium falciparum after implementation of artemisinin-based combination therapy in Pune district, India
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