Increased sensitivity of malaria parasites to common antimalaria drugs after the introduction of artemether-lumefantrine: Implication of policy change and implementation of more effective drugs in fight against malaria
Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multi-drug resistance protein 1 (Pfmrp1) gene have previously been reported to confer resistance to Artemisinin-based Combination Therapies (ACTs) in Southeast Asia. A total of 300 samples collected from six sites between 2008 and 2...
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| Veröffentlicht in: | PloS one 2024-06, Vol.19 (6), p.e0298585 |
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| creator | Okore, Winnie Ouma, Collins Okoth, Raphael O Yeda, Redemptah Ingasia, Luicer O Mwakio, Edwin W Ochora, Douglas O Wakoli, Duncan M Amwoma, Joseph G Chemwor, Gladys C Juma, Jackline A Okudo, Charles O Cheruiyot, Agnes C Opot, Benjamin H Juma, Dennis Egbo, Timothy E Andagalu, Ben Roth, Amanda Kamau, Edwin Akala, Hoseah M |
| description | Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multi-drug resistance protein 1 (Pfmrp1) gene have previously been reported to confer resistance to Artemisinin-based Combination Therapies (ACTs) in Southeast Asia. A total of 300 samples collected from six sites between 2008 and 2019 under an ongoing malaria drug sensitivity patterns in Kenya study were evaluated for the presence of SNPs at Pfmrp1 gene codons: H191Y, S437A, I876V, and F1390I using the Agena MassARRAY® platform. Each isolate was further tested against artemisinin (ART), lumefantrine (LU), amodiaquine (AQ), mefloquine (MQ), quinine (QN), and chloroquine (CQ) using malaria the SYBR Green I-based method to determine their in vitro drug sensitivity. Of the samples genotyped, polymorphism at Pfmrp1 codon I876V was the most frequent, with 59.3% (163/275) mutants, followed by F1390I, 7.2% (20/278), H191Y, 4.0% (6/151), and S437A, 3.3% (9/274). A significant decrease in median 50% inhibition concentrations (IC50s) and interquartile range (IQR) was noted; AQ from 2.996 ng/ml [IQR = 2.604-4.747, n = 51] in 2008 to 1.495 ng/ml [IQR = 0.7134-3.318, n = 40] (P |
| doi_str_mv | 10.1371/journal.pone.0298585 |
| format | Article |
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A total of 300 samples collected from six sites between 2008 and 2019 under an ongoing malaria drug sensitivity patterns in Kenya study were evaluated for the presence of SNPs at Pfmrp1 gene codons: H191Y, S437A, I876V, and F1390I using the Agena MassARRAY® platform. Each isolate was further tested against artemisinin (ART), lumefantrine (LU), amodiaquine (AQ), mefloquine (MQ), quinine (QN), and chloroquine (CQ) using malaria the SYBR Green I-based method to determine their in vitro drug sensitivity. Of the samples genotyped, polymorphism at Pfmrp1 codon I876V was the most frequent, with 59.3% (163/275) mutants, followed by F1390I, 7.2% (20/278), H191Y, 4.0% (6/151), and S437A, 3.3% (9/274). A significant decrease in median 50% inhibition concentrations (IC50s) and interquartile range (IQR) was noted; AQ from 2.996 ng/ml [IQR = 2.604-4.747, n = 51] in 2008 to 1.495 ng/ml [IQR = 0.7134-3.318, n = 40] (P<0.001) in 2019, QN from 59.64 ng/ml [IQR = 29.88-80.89, n = 51] in 2008 to 18.10 ng/ml [IQR = 11.81-26.92, n = 42] (P<0.001) in 2019, CQ from 35.19 ng/ml [IQR = 16.99-71.20, n = 30] in 2008 to 6.699 ng/ml [IQR = 4.976-9.875, n = 37] (P<0.001) in 2019, and ART from 2.680 ng/ml [IQR = 1.608-4.857, n = 57] in 2008 to 2.105 ng/ml [IQR = 1.266-3.267, n = 47] (P = 0.0012) in 2019, implying increasing parasite sensitivity to the drugs over time. However, no significant variations were observed in LU (P = 0.2692) and MQ (P = 0.0939) respectively, suggesting stable parasite responses over time. There was no statistical significance between the mutation at 876 and parasite sensitivity to selected antimalarials tested, suggesting stable sensitivity for the parasites with 876V mutations. These findings show that Kenyan parasite strains are still sensitive to AQ, QN, CQ, ART, LU, and MQ. Despite the presence of Pfmrp1 mutations in parasites among the population.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0298585</identifier><identifier>PMID: 38900782</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amodiaquine ; Amodiaquine - pharmacology ; Amodiaquine - therapeutic use ; Antimalarial agents ; Antimalarials - pharmacology ; Antimalarials - therapeutic use ; Antiparasitic agents ; Artemether ; Artemether, Lumefantrine Drug Combination - therapeutic use ; Artemisinin ; Artemisinins - pharmacology ; Artemisinins - therapeutic use ; Biology and Life Sciences ; Chloroquine ; Chloroquine - pharmacology ; Chloroquine - therapeutic use ; Chromosomes ; Codon ; Codons ; Coronaviruses ; COVID-19 ; Dihydrofolate reductase ; Disease transmission ; Drug dosages ; Drug resistance ; Drug Resistance - genetics ; Drug therapy ; Drugs ; Female ; Genes ; Humans ; In vitro methods and tests ; Kenya ; Malaria ; Malaria, Falciparum - drug therapy ; Malaria, Falciparum - parasitology ; Male ; Medical research ; Medicine and Health Sciences ; Mefloquine - pharmacology ; Mefloquine - therapeutic use ; Multidrug resistance ; Multidrug Resistance-Associated Proteins - genetics ; Mutation ; Nucleotides ; Pandemics ; Parasites ; People and Places ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - genetics ; Polymorphism ; Polymorphism, Single Nucleotide ; Pyrimethamine ; Quinine ; Quinine - pharmacology ; Quinine - therapeutic use ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Trends ; Vector-borne diseases</subject><ispartof>PloS one, 2024-06, Vol.19 (6), p.e0298585</ispartof><rights>Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c642t-ebdb40bb4af1cfdeebd0f252c8640ab1c24ccd6483ac22a5b8cb4f805ed066513</cites><orcidid>0000-0001-7406-7492 ; 0000-0002-6938-1150 ; 0000-0003-1536-968X ; 0000-0001-8584-2706 ; 0000-0003-2587-5375</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189199/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189199/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38900782$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Okore, Winnie</creatorcontrib><creatorcontrib>Ouma, Collins</creatorcontrib><creatorcontrib>Okoth, Raphael O</creatorcontrib><creatorcontrib>Yeda, Redemptah</creatorcontrib><creatorcontrib>Ingasia, Luicer O</creatorcontrib><creatorcontrib>Mwakio, Edwin W</creatorcontrib><creatorcontrib>Ochora, Douglas O</creatorcontrib><creatorcontrib>Wakoli, Duncan M</creatorcontrib><creatorcontrib>Amwoma, Joseph G</creatorcontrib><creatorcontrib>Chemwor, Gladys C</creatorcontrib><creatorcontrib>Juma, Jackline A</creatorcontrib><creatorcontrib>Okudo, Charles O</creatorcontrib><creatorcontrib>Cheruiyot, Agnes C</creatorcontrib><creatorcontrib>Opot, Benjamin H</creatorcontrib><creatorcontrib>Juma, Dennis</creatorcontrib><creatorcontrib>Egbo, Timothy E</creatorcontrib><creatorcontrib>Andagalu, Ben</creatorcontrib><creatorcontrib>Roth, Amanda</creatorcontrib><creatorcontrib>Kamau, Edwin</creatorcontrib><creatorcontrib>Akala, Hoseah M</creatorcontrib><title>Increased sensitivity of malaria parasites to common antimalaria drugs after the introduction of artemether-lumefantrine: Implication of policy change and implementation of more effective drugs in fight against malaria</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multi-drug resistance protein 1 (Pfmrp1) gene have previously been reported to confer resistance to Artemisinin-based Combination Therapies (ACTs) in Southeast Asia. A total of 300 samples collected from six sites between 2008 and 2019 under an ongoing malaria drug sensitivity patterns in Kenya study were evaluated for the presence of SNPs at Pfmrp1 gene codons: H191Y, S437A, I876V, and F1390I using the Agena MassARRAY® platform. Each isolate was further tested against artemisinin (ART), lumefantrine (LU), amodiaquine (AQ), mefloquine (MQ), quinine (QN), and chloroquine (CQ) using malaria the SYBR Green I-based method to determine their in vitro drug sensitivity. Of the samples genotyped, polymorphism at Pfmrp1 codon I876V was the most frequent, with 59.3% (163/275) mutants, followed by F1390I, 7.2% (20/278), H191Y, 4.0% (6/151), and S437A, 3.3% (9/274). A significant decrease in median 50% inhibition concentrations (IC50s) and interquartile range (IQR) was noted; AQ from 2.996 ng/ml [IQR = 2.604-4.747, n = 51] in 2008 to 1.495 ng/ml [IQR = 0.7134-3.318, n = 40] (P<0.001) in 2019, QN from 59.64 ng/ml [IQR = 29.88-80.89, n = 51] in 2008 to 18.10 ng/ml [IQR = 11.81-26.92, n = 42] (P<0.001) in 2019, CQ from 35.19 ng/ml [IQR = 16.99-71.20, n = 30] in 2008 to 6.699 ng/ml [IQR = 4.976-9.875, n = 37] (P<0.001) in 2019, and ART from 2.680 ng/ml [IQR = 1.608-4.857, n = 57] in 2008 to 2.105 ng/ml [IQR = 1.266-3.267, n = 47] (P = 0.0012) in 2019, implying increasing parasite sensitivity to the drugs over time. However, no significant variations were observed in LU (P = 0.2692) and MQ (P = 0.0939) respectively, suggesting stable parasite responses over time. There was no statistical significance between the mutation at 876 and parasite sensitivity to selected antimalarials tested, suggesting stable sensitivity for the parasites with 876V mutations. These findings show that Kenyan parasite strains are still sensitive to AQ, QN, CQ, ART, LU, and MQ. Despite the presence of Pfmrp1 mutations in parasites among the population.</description><subject>Amodiaquine</subject><subject>Amodiaquine - pharmacology</subject><subject>Amodiaquine - therapeutic use</subject><subject>Antimalarial agents</subject><subject>Antimalarials - pharmacology</subject><subject>Antimalarials - therapeutic use</subject><subject>Antiparasitic agents</subject><subject>Artemether</subject><subject>Artemether, Lumefantrine Drug Combination - therapeutic use</subject><subject>Artemisinin</subject><subject>Artemisinins - pharmacology</subject><subject>Artemisinins - therapeutic use</subject><subject>Biology and Life Sciences</subject><subject>Chloroquine</subject><subject>Chloroquine - pharmacology</subject><subject>Chloroquine - therapeutic use</subject><subject>Chromosomes</subject><subject>Codon</subject><subject>Codons</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Dihydrofolate reductase</subject><subject>Disease transmission</subject><subject>Drug dosages</subject><subject>Drug resistance</subject><subject>Drug Resistance - genetics</subject><subject>Drug therapy</subject><subject>Drugs</subject><subject>Female</subject><subject>Genes</subject><subject>Humans</subject><subject>In vitro methods and tests</subject><subject>Kenya</subject><subject>Malaria</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Malaria, Falciparum - parasitology</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Mefloquine - pharmacology</subject><subject>Mefloquine - therapeutic use</subject><subject>Multidrug resistance</subject><subject>Multidrug Resistance-Associated Proteins - genetics</subject><subject>Mutation</subject><subject>Nucleotides</subject><subject>Pandemics</subject><subject>Parasites</subject><subject>People and Places</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium falciparum - genetics</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Pyrimethamine</subject><subject>Quinine</subject><subject>Quinine - pharmacology</subject><subject>Quinine - therapeutic use</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Trends</subject><subject>Vector-borne diseases</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tu1DAQhiMEoqXwBggsISG42MVO4sThBlUVh5UqVeJ0a02ccdZVYm9tp6KvytPgZbNVF_UC5cLx-Pv_sceeLHvO6JIVNXt36SZvYVhunMUlzRvBBX-QHbOmyBdVTouHd_6PsichXFLKC1FVj7OjQjSU1iI_zn6vrPIIATsS0AYTzbWJN8RpMsIA3gDZgIcUx0CiI8qNo7MEbDT79c5PfSCgI3oS10iMjd51k4omgckHfMQR04pfDNOIOmm9sfierMbNYBTsuY1Lsxui1mB7TBk6YhKQpDbeMqPzSFBrTO7XOKc2lmjTryOBHowNcb_zp9kjDUPAZ_N4kv349PH72ZfF-cXn1dnp-UJVZR4X2HZtSdu2BM2U7jDNqc55rkRVUmiZykuluqoUBag8B94K1ZZaUI4drSrOipPs5c53M7gg52sJsqA15byuK56I1Y7oHFzKjU-18zfSgZF_A873MlXJqAFlwXkOADmjLOUt60a1tOFt3QpRU9bq5PVhzja1I3YqlcfDcGB6uGLNWvbuWjLGRMOaJjm8mR28u5owRDmaoHAYwKKbdhsXRV2yPKGv_kHvP95M9ZBOYKx2KbHamsrTuhEl46LYei3vodLX4WhUesTapPiB4O2BIDERf8UephDk6tvX_2cvfh6yr--wa4QhroMbpu0jC4dguQOVdyF41LdVZlRue3BfDbntQTn3YJK9uHtDt6J90xV_ACn_M30</recordid><startdate>20240620</startdate><enddate>20240620</enddate><creator>Okore, 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sensitivity of malaria parasites to common antimalaria drugs after the introduction of artemether-lumefantrine: Implication of policy change and implementation of more effective drugs in fight against malaria</title><author>Okore, Winnie ; Ouma, Collins ; Okoth, Raphael O ; Yeda, Redemptah ; Ingasia, Luicer O ; Mwakio, Edwin W ; Ochora, Douglas O ; Wakoli, Duncan M ; Amwoma, Joseph G ; Chemwor, Gladys C ; Juma, Jackline A ; Okudo, Charles O ; Cheruiyot, Agnes C ; Opot, Benjamin H ; Juma, Dennis ; Egbo, Timothy E ; Andagalu, Ben ; Roth, Amanda ; Kamau, Edwin ; Akala, Hoseah M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c642t-ebdb40bb4af1cfdeebd0f252c8640ab1c24ccd6483ac22a5b8cb4f805ed066513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Amodiaquine</topic><topic>Amodiaquine - pharmacology</topic><topic>Amodiaquine - therapeutic use</topic><topic>Antimalarial agents</topic><topic>Antimalarials - pharmacology</topic><topic>Antimalarials - therapeutic use</topic><topic>Antiparasitic agents</topic><topic>Artemether</topic><topic>Artemether, Lumefantrine Drug Combination - therapeutic use</topic><topic>Artemisinin</topic><topic>Artemisinins - pharmacology</topic><topic>Artemisinins - therapeutic use</topic><topic>Biology and Life Sciences</topic><topic>Chloroquine</topic><topic>Chloroquine - pharmacology</topic><topic>Chloroquine - therapeutic use</topic><topic>Chromosomes</topic><topic>Codon</topic><topic>Codons</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>Dihydrofolate reductase</topic><topic>Disease transmission</topic><topic>Drug dosages</topic><topic>Drug resistance</topic><topic>Drug Resistance - genetics</topic><topic>Drug therapy</topic><topic>Drugs</topic><topic>Female</topic><topic>Genes</topic><topic>Humans</topic><topic>In vitro methods and tests</topic><topic>Kenya</topic><topic>Malaria</topic><topic>Malaria, Falciparum - drug therapy</topic><topic>Malaria, Falciparum - parasitology</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Mefloquine - pharmacology</topic><topic>Mefloquine - therapeutic use</topic><topic>Multidrug resistance</topic><topic>Multidrug Resistance-Associated Proteins - genetics</topic><topic>Mutation</topic><topic>Nucleotides</topic><topic>Pandemics</topic><topic>Parasites</topic><topic>People and Places</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Plasmodium falciparum - genetics</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Pyrimethamine</topic><topic>Quinine</topic><topic>Quinine - pharmacology</topic><topic>Quinine - therapeutic use</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Trends</topic><topic>Vector-borne diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Okore, Winnie</creatorcontrib><creatorcontrib>Ouma, Collins</creatorcontrib><creatorcontrib>Okoth, Raphael O</creatorcontrib><creatorcontrib>Yeda, Redemptah</creatorcontrib><creatorcontrib>Ingasia, Luicer O</creatorcontrib><creatorcontrib>Mwakio, Edwin W</creatorcontrib><creatorcontrib>Ochora, Douglas O</creatorcontrib><creatorcontrib>Wakoli, Duncan M</creatorcontrib><creatorcontrib>Amwoma, Joseph G</creatorcontrib><creatorcontrib>Chemwor, Gladys C</creatorcontrib><creatorcontrib>Juma, Jackline A</creatorcontrib><creatorcontrib>Okudo, Charles O</creatorcontrib><creatorcontrib>Cheruiyot, Agnes C</creatorcontrib><creatorcontrib>Opot, Benjamin H</creatorcontrib><creatorcontrib>Juma, Dennis</creatorcontrib><creatorcontrib>Egbo, Timothy E</creatorcontrib><creatorcontrib>Andagalu, Ben</creatorcontrib><creatorcontrib>Roth, Amanda</creatorcontrib><creatorcontrib>Kamau, Edwin</creatorcontrib><creatorcontrib>Akala, Hoseah M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS 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UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</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>AIDS and Cancer Research 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Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</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 China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Okore, Winnie</au><au>Ouma, Collins</au><au>Okoth, Raphael O</au><au>Yeda, Redemptah</au><au>Ingasia, Luicer O</au><au>Mwakio, Edwin W</au><au>Ochora, Douglas O</au><au>Wakoli, Duncan M</au><au>Amwoma, Joseph G</au><au>Chemwor, Gladys C</au><au>Juma, Jackline A</au><au>Okudo, Charles O</au><au>Cheruiyot, Agnes C</au><au>Opot, Benjamin H</au><au>Juma, Dennis</au><au>Egbo, Timothy E</au><au>Andagalu, Ben</au><au>Roth, Amanda</au><au>Kamau, Edwin</au><au>Akala, Hoseah M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased sensitivity of malaria parasites to common antimalaria drugs after the introduction of artemether-lumefantrine: Implication of policy change and implementation of more effective drugs in fight against malaria</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2024-06-20</date><risdate>2024</risdate><volume>19</volume><issue>6</issue><spage>e0298585</spage><pages>e0298585-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multi-drug resistance protein 1 (Pfmrp1) gene have previously been reported to confer resistance to Artemisinin-based Combination Therapies (ACTs) in Southeast Asia. A total of 300 samples collected from six sites between 2008 and 2019 under an ongoing malaria drug sensitivity patterns in Kenya study were evaluated for the presence of SNPs at Pfmrp1 gene codons: H191Y, S437A, I876V, and F1390I using the Agena MassARRAY® platform. Each isolate was further tested against artemisinin (ART), lumefantrine (LU), amodiaquine (AQ), mefloquine (MQ), quinine (QN), and chloroquine (CQ) using malaria the SYBR Green I-based method to determine their in vitro drug sensitivity. Of the samples genotyped, polymorphism at Pfmrp1 codon I876V was the most frequent, with 59.3% (163/275) mutants, followed by F1390I, 7.2% (20/278), H191Y, 4.0% (6/151), and S437A, 3.3% (9/274). A significant decrease in median 50% inhibition concentrations (IC50s) and interquartile range (IQR) was noted; AQ from 2.996 ng/ml [IQR = 2.604-4.747, n = 51] in 2008 to 1.495 ng/ml [IQR = 0.7134-3.318, n = 40] (P<0.001) in 2019, QN from 59.64 ng/ml [IQR = 29.88-80.89, n = 51] in 2008 to 18.10 ng/ml [IQR = 11.81-26.92, n = 42] (P<0.001) in 2019, CQ from 35.19 ng/ml [IQR = 16.99-71.20, n = 30] in 2008 to 6.699 ng/ml [IQR = 4.976-9.875, n = 37] (P<0.001) in 2019, and ART from 2.680 ng/ml [IQR = 1.608-4.857, n = 57] in 2008 to 2.105 ng/ml [IQR = 1.266-3.267, n = 47] (P = 0.0012) in 2019, implying increasing parasite sensitivity to the drugs over time. However, no significant variations were observed in LU (P = 0.2692) and MQ (P = 0.0939) respectively, suggesting stable parasite responses over time. There was no statistical significance between the mutation at 876 and parasite sensitivity to selected antimalarials tested, suggesting stable sensitivity for the parasites with 876V mutations. These findings show that Kenyan parasite strains are still sensitive to AQ, QN, CQ, ART, LU, and MQ. Despite the presence of Pfmrp1 mutations in parasites among the population.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>38900782</pmid><doi>10.1371/journal.pone.0298585</doi><tpages>e0298585</tpages><orcidid>https://orcid.org/0000-0001-7406-7492</orcidid><orcidid>https://orcid.org/0000-0002-6938-1150</orcidid><orcidid>https://orcid.org/0000-0003-1536-968X</orcidid><orcidid>https://orcid.org/0000-0001-8584-2706</orcidid><orcidid>https://orcid.org/0000-0003-2587-5375</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2024-06, Vol.19 (6), p.e0298585 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_3070557765 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Amodiaquine Amodiaquine - pharmacology Amodiaquine - therapeutic use Antimalarial agents Antimalarials - pharmacology Antimalarials - therapeutic use Antiparasitic agents Artemether Artemether, Lumefantrine Drug Combination - therapeutic use Artemisinin Artemisinins - pharmacology Artemisinins - therapeutic use Biology and Life Sciences Chloroquine Chloroquine - pharmacology Chloroquine - therapeutic use Chromosomes Codon Codons Coronaviruses COVID-19 Dihydrofolate reductase Disease transmission Drug dosages Drug resistance Drug Resistance - genetics Drug therapy Drugs Female Genes Humans In vitro methods and tests Kenya Malaria Malaria, Falciparum - drug therapy Malaria, Falciparum - parasitology Male Medical research Medicine and Health Sciences Mefloquine - pharmacology Mefloquine - therapeutic use Multidrug resistance Multidrug Resistance-Associated Proteins - genetics Mutation Nucleotides Pandemics Parasites People and Places Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - genetics Polymorphism Polymorphism, Single Nucleotide Pyrimethamine Quinine Quinine - pharmacology Quinine - therapeutic use Single nucleotide polymorphisms Single-nucleotide polymorphism Trends Vector-borne diseases |
| title | Increased sensitivity of malaria parasites to common antimalaria drugs after the introduction of artemether-lumefantrine: Implication of policy change and implementation of more effective drugs in fight against malaria |
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