Drug-Resistance and Population Structure of Plasmodium falciparum Across the Democratic Republic of Congo Using High-Throughput Molecular Inversion Probes
A better understanding of the drivers of the spread of malaria parasites and drug resistance across space and time is needed. These drivers can be elucidated using genetic tools. Here, a novel molecular inversion probe (MIP) panel targeting all major drug-resistance mutations and a set of microsatel...
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| Veröffentlicht in: | The Journal of infectious diseases 2018-08, Vol.218 (6), p.946-955 |
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| creator | Aydemir, Ozkan Janko, Mark Hathaway, Nick J Verity, Robert Mwandagalirwa, Melchior Kashamuka Tshefu, Antoinette K Tessema, Sofonias K Marsh, Patrick W Tran, Alice Reimonn, Thomas Ghani, Azra C Ghansah, Anita Juliano, Jonathan J Greenhouse, Bryan R Emch, Michael Meshnick, Steven R Bailey, Jeffrey A |
| description | A better understanding of the drivers of the spread of malaria parasites and drug resistance across space and time is needed. These drivers can be elucidated using genetic tools. Here, a novel molecular inversion probe (MIP) panel targeting all major drug-resistance mutations and a set of microsatellites was used to genotype Plasmodium falciparum infections of 552 children from the 2013-2014 Demographic and Health Survey conducted in the Democratic Republic of the Congo (DRC). Microsatellite-based analysis of population structure suggests that parasites within the DRC form a homogeneous population. In contrast, sulfadoxine-resistance markers in dihydropteroate synthase show marked spatial structure with ongoing spread of double and triple mutants compared with 2007. These findings suggest that parasites in the DRC remain panmictic despite rapidly spreading antimalarial-resistance mutations. Moreover, highly multiplexed targeted sequencing using MIPs emerges as a cost-effective method for elucidating pathogen genetics in complex infections in large cohorts. |
| doi_str_mv | 10.1093/infdis/jiy223 |
| format | Article |
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These drivers can be elucidated using genetic tools. Here, a novel molecular inversion probe (MIP) panel targeting all major drug-resistance mutations and a set of microsatellites was used to genotype Plasmodium falciparum infections of 552 children from the 2013-2014 Demographic and Health Survey conducted in the Democratic Republic of the Congo (DRC). Microsatellite-based analysis of population structure suggests that parasites within the DRC form a homogeneous population. In contrast, sulfadoxine-resistance markers in dihydropteroate synthase show marked spatial structure with ongoing spread of double and triple mutants compared with 2007. These findings suggest that parasites in the DRC remain panmictic despite rapidly spreading antimalarial-resistance mutations. Moreover, highly multiplexed targeted sequencing using MIPs emerges as a cost-effective method for elucidating pathogen genetics in complex infections in large cohorts.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiy223</identifier><identifier>PMID: 29718283</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Child ; Democratic Republic of the Congo - epidemiology ; Drug Resistance ; Female ; High-Throughput Nucleotide Sequencing - methods ; Humans ; Major and Brief Reports ; Malaria, Falciparum - drug therapy ; Malaria, Falciparum - epidemiology ; Male ; Microsatellite Repeats ; Mutation ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - genetics ; Population Surveillance ; Sulfadoxine - pharmacology ; Surveys and Questionnaires</subject><ispartof>The Journal of infectious diseases, 2018-08, Vol.218 (6), p.946-955</ispartof><rights>The Author(s) 2018. 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These drivers can be elucidated using genetic tools. Here, a novel molecular inversion probe (MIP) panel targeting all major drug-resistance mutations and a set of microsatellites was used to genotype Plasmodium falciparum infections of 552 children from the 2013-2014 Demographic and Health Survey conducted in the Democratic Republic of the Congo (DRC). Microsatellite-based analysis of population structure suggests that parasites within the DRC form a homogeneous population. In contrast, sulfadoxine-resistance markers in dihydropteroate synthase show marked spatial structure with ongoing spread of double and triple mutants compared with 2007. These findings suggest that parasites in the DRC remain panmictic despite rapidly spreading antimalarial-resistance mutations. Moreover, highly multiplexed targeted sequencing using MIPs emerges as a cost-effective method for elucidating pathogen genetics in complex infections in large cohorts.</description><subject>Child</subject><subject>Democratic Republic of the Congo - epidemiology</subject><subject>Drug Resistance</subject><subject>Female</subject><subject>High-Throughput Nucleotide Sequencing - methods</subject><subject>Humans</subject><subject>Major and Brief Reports</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Malaria, Falciparum - epidemiology</subject><subject>Male</subject><subject>Microsatellite Repeats</subject><subject>Mutation</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium falciparum - genetics</subject><subject>Population Surveillance</subject><subject>Sulfadoxine - pharmacology</subject><subject>Surveys and Questionnaires</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU9v1DAQxS0EokvhyBX5yCXUjhOvc0GqtoVWKmJV2rPltSeJq8QO_lOpX4VPi7fbVnCakebNe6P5IfSRki-UdOzEut7YeHJnH-qavUIr2rJ1xTllr9GKkLquqOi6I_QuxjtCSMP4-i06qrs1FbVgK_TnLOShuoZoY1JOA1bO4K1f8qSS9Q7_SiHrlANg3-PtpOLsjc0z7tWk7aJCaU918DHiNAI-g9nrUDY1voYl76bSlL2Nd4PHt9G6AV_YYaxuxuDzMC454R9-Al3SAr509xDiPnQb_A7ie_SmpET48FSP0e2385vNRXX18_vl5vSq0kysUyXatiOGkr5p9rVrtTDEcGh5zQ1vGTeMg2p6wUTf7xhtytdAEQOioVqLHTtGXw--5eAZjAaXgprkEuyswoP0ysr_J86OcvD3khenhtbF4POTQfC_M8QkZxs1TJNy4HOUNWGMdQUGKdLqIH38WYD-JYYSuecpDzzlgWfRf_r3thf1M0D2F3w4opk</recordid><startdate>20180814</startdate><enddate>20180814</enddate><creator>Aydemir, Ozkan</creator><creator>Janko, Mark</creator><creator>Hathaway, Nick J</creator><creator>Verity, Robert</creator><creator>Mwandagalirwa, Melchior Kashamuka</creator><creator>Tshefu, Antoinette K</creator><creator>Tessema, Sofonias K</creator><creator>Marsh, Patrick W</creator><creator>Tran, Alice</creator><creator>Reimonn, Thomas</creator><creator>Ghani, Azra C</creator><creator>Ghansah, Anita</creator><creator>Juliano, Jonathan J</creator><creator>Greenhouse, Bryan R</creator><creator>Emch, Michael</creator><creator>Meshnick, Steven R</creator><creator>Bailey, Jeffrey A</creator><general>Oxford University Press</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180814</creationdate><title>Drug-Resistance and Population Structure of Plasmodium falciparum Across the Democratic Republic of Congo Using High-Throughput Molecular Inversion Probes</title><author>Aydemir, Ozkan ; Janko, Mark ; Hathaway, Nick J ; Verity, Robert ; Mwandagalirwa, Melchior Kashamuka ; Tshefu, Antoinette K ; Tessema, Sofonias K ; Marsh, Patrick W ; Tran, Alice ; Reimonn, Thomas ; Ghani, Azra C ; Ghansah, Anita ; Juliano, Jonathan J ; Greenhouse, Bryan R ; Emch, Michael ; Meshnick, Steven R ; Bailey, Jeffrey A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-85590d10f4490d195c8d0d6e5626d6536d36ea4f838ffb314093ea0de841cc8b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Child</topic><topic>Democratic Republic of the Congo - epidemiology</topic><topic>Drug Resistance</topic><topic>Female</topic><topic>High-Throughput Nucleotide Sequencing - methods</topic><topic>Humans</topic><topic>Major and Brief Reports</topic><topic>Malaria, Falciparum - drug therapy</topic><topic>Malaria, Falciparum - epidemiology</topic><topic>Male</topic><topic>Microsatellite Repeats</topic><topic>Mutation</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Plasmodium falciparum - genetics</topic><topic>Population Surveillance</topic><topic>Sulfadoxine - pharmacology</topic><topic>Surveys and Questionnaires</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aydemir, Ozkan</creatorcontrib><creatorcontrib>Janko, Mark</creatorcontrib><creatorcontrib>Hathaway, Nick J</creatorcontrib><creatorcontrib>Verity, Robert</creatorcontrib><creatorcontrib>Mwandagalirwa, Melchior Kashamuka</creatorcontrib><creatorcontrib>Tshefu, Antoinette K</creatorcontrib><creatorcontrib>Tessema, Sofonias K</creatorcontrib><creatorcontrib>Marsh, Patrick W</creatorcontrib><creatorcontrib>Tran, Alice</creatorcontrib><creatorcontrib>Reimonn, Thomas</creatorcontrib><creatorcontrib>Ghani, Azra C</creatorcontrib><creatorcontrib>Ghansah, Anita</creatorcontrib><creatorcontrib>Juliano, Jonathan J</creatorcontrib><creatorcontrib>Greenhouse, Bryan R</creatorcontrib><creatorcontrib>Emch, Michael</creatorcontrib><creatorcontrib>Meshnick, Steven R</creatorcontrib><creatorcontrib>Bailey, Jeffrey A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aydemir, Ozkan</au><au>Janko, Mark</au><au>Hathaway, Nick J</au><au>Verity, Robert</au><au>Mwandagalirwa, Melchior Kashamuka</au><au>Tshefu, Antoinette K</au><au>Tessema, Sofonias K</au><au>Marsh, Patrick W</au><au>Tran, Alice</au><au>Reimonn, Thomas</au><au>Ghani, Azra C</au><au>Ghansah, Anita</au><au>Juliano, Jonathan J</au><au>Greenhouse, Bryan R</au><au>Emch, Michael</au><au>Meshnick, Steven R</au><au>Bailey, Jeffrey A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Drug-Resistance and Population Structure of Plasmodium falciparum Across the Democratic Republic of Congo Using High-Throughput Molecular Inversion Probes</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2018-08-14</date><risdate>2018</risdate><volume>218</volume><issue>6</issue><spage>946</spage><epage>955</epage><pages>946-955</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><abstract>A better understanding of the drivers of the spread of malaria parasites and drug resistance across space and time is needed. 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| identifier | ISSN: 0022-1899 |
| ispartof | The Journal of infectious diseases, 2018-08, Vol.218 (6), p.946-955 |
| issn | 0022-1899 1537-6613 |
| language | eng |
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| source | MEDLINE; Jstor Complete Legacy; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Child Democratic Republic of the Congo - epidemiology Drug Resistance Female High-Throughput Nucleotide Sequencing - methods Humans Major and Brief Reports Malaria, Falciparum - drug therapy Malaria, Falciparum - epidemiology Male Microsatellite Repeats Mutation Plasmodium falciparum - drug effects Plasmodium falciparum - genetics Population Surveillance Sulfadoxine - pharmacology Surveys and Questionnaires |
| title | Drug-Resistance and Population Structure of Plasmodium falciparum Across the Democratic Republic of Congo Using High-Throughput Molecular Inversion Probes |
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