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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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
. |
doi_str_mv | 10.1007/s12038-021-00200-3 |
format | Article |
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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
.</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 & 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. 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
.</description><subject>Animals</subject><subject>Antimalarial agents</subject><subject>Artemisinin</subject><subject>Artemisinins - administration & dosage</subject><subject>Artemisinins - therapeutic use</subject><subject>Biomarkers - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Chloroquine</subject><subject>Codons</subject><subject>Combination therapy</subject><subject>Drug resistance</subject><subject>Drug Resistance - genetics</subject><subject>Drug Therapy, Combination</subject><subject>Drugs</subject><subject>Erythrocytes</subject><subject>Genes</subject><subject>Genotypes</subject><subject>Haplotypes</subject><subject>Human diseases</subject><subject>India</subject><subject>Life Sciences</subject><subject>Malaria</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Markers</subject><subject>Microbiology</subject><subject>Multidrug resistance</subject><subject>Mutants</subject><subject>Mutation</subject><subject>Parasite resistance</subject><subject>Parasites</subject><subject>Plant Sciences</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium falciparum - enzymology</subject><subject>Plasmodium falciparum - genetics</subject><subject>Pyrimethamine</subject><subject>Sulfadoxine</subject><subject>Vector-borne diseases</subject><subject>Zoology</subject><issn>0250-5991</issn><issn>0973-7138</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc1u1TAQhSNERUvhBVggS2xY4Hb8k9heVlWBSpXooqwjx55cXBIn2MniPgmvi-9NAYkFK48135xjz6mqNwwuGIC6zIyD0BQ4owAcgIpn1RkYJahiQj8vNa-B1saw0-plzo8AzEgBL6pTIYWUWpqz6udVtMM-h0ymnvi07kjCcltsdEhGm75jIjuMeOzfDzaPkw_rSHo7uDDbVErbLwUK4zzgiHGxS5jigbZpwTHkEEOknc3oiZvGLsQNWL5hsvOehEju14jEF9MU3PKB3EYf7KvqpFhkfP10nldfP948XH-md18-3V5f3VEnVL3QxvvG1aC988o5bxpllTNOOm5rkA3WtldSst6LXnCDrsHD17XVvHPKdEqcV-833TlNP1bMS1ue7HAYbMRpzS2vaw1aA-iCvvsHfZzWVNZ3pJRhurCF4hvl0pRzwr6dUyiL3LcM2kNs7RZbW2Jrj7G1ogy9fZJeuxH9n5HfORVAbEAurbjD9Nf7P7K_AHcrpew</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>Ozarkar, Aarti</creator><creator>Kanyal, Abhishek</creator><creator>Dass, Swati</creator><creator>Deshpande, Prakash</creator><creator>Deobagkar, Deepti</creator><creator>Karmodiya, Krishanpal</creator><general>Springer India</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H99</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L.F</scope><scope>L.G</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5714-0587</orcidid></search><sort><creationdate>20210901</creationdate><title>Analysis of drug resistance marker genes of Plasmodium falciparum after implementation of artemisinin-based combination therapy in Pune district, India</title><author>Ozarkar, Aarti ; Kanyal, Abhishek ; Dass, Swati ; Deshpande, Prakash ; Deobagkar, Deepti ; Karmodiya, Krishanpal</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-6dd6c508dcd7ccd967a7c9c4c2a5046e5af7441fd3f329ec6e34348a82bc79b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Antimalarial agents</topic><topic>Artemisinin</topic><topic>Artemisinins - administration & dosage</topic><topic>Artemisinins - therapeutic use</topic><topic>Biomarkers - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Chloroquine</topic><topic>Codons</topic><topic>Combination therapy</topic><topic>Drug resistance</topic><topic>Drug Resistance - genetics</topic><topic>Drug Therapy, Combination</topic><topic>Drugs</topic><topic>Erythrocytes</topic><topic>Genes</topic><topic>Genotypes</topic><topic>Haplotypes</topic><topic>Human diseases</topic><topic>India</topic><topic>Life Sciences</topic><topic>Malaria</topic><topic>Malaria, Falciparum - drug therapy</topic><topic>Markers</topic><topic>Microbiology</topic><topic>Multidrug resistance</topic><topic>Mutants</topic><topic>Mutation</topic><topic>Parasite resistance</topic><topic>Parasites</topic><topic>Plant Sciences</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Plasmodium falciparum - enzymology</topic><topic>Plasmodium falciparum - genetics</topic><topic>Pyrimethamine</topic><topic>Sulfadoxine</topic><topic>Vector-borne diseases</topic><topic>Zoology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ozarkar, Aarti</creatorcontrib><creatorcontrib>Kanyal, Abhishek</creatorcontrib><creatorcontrib>Dass, Swati</creatorcontrib><creatorcontrib>Deshpande, Prakash</creatorcontrib><creatorcontrib>Deobagkar, Deepti</creatorcontrib><creatorcontrib>Karmodiya, Krishanpal</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ASFA: Marine Biotechnology Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Marine Biotechnology Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biosciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ozarkar, Aarti</au><au>Kanyal, Abhishek</au><au>Dass, Swati</au><au>Deshpande, Prakash</au><au>Deobagkar, Deepti</au><au>Karmodiya, Krishanpal</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of drug resistance marker genes of Plasmodium falciparum after implementation of artemisinin-based combination therapy in Pune district, India</atitle><jtitle>Journal of biosciences</jtitle><stitle>J Biosci</stitle><addtitle>J Biosci</addtitle><date>2021-09-01</date><risdate>2021</risdate><volume>46</volume><issue>3</issue><artnum>77</artnum><issn>0250-5991</issn><eissn>0973-7138</eissn><abstract>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
.</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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