{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T23:02:45Z","timestamp":1770505365107,"version":"3.49.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2012,7,1]],"date-time":"2012-07-01T00:00:00Z","timestamp":1341100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The 4-aminoquinoline bisquinoline piperaquine is an important partner drug in one of the presently recommended artemisinin combination therapies. Recent clinical trials have confirmed its high efficacy in combination with dihydroartemisinin. Resistance to piperaquine alone has, however, been documented. Amplification in copy number of the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>\n            multidrug resistance locus on chromosome 5, containing the\n            <jats:italic>pfmdr1<\/jats:italic>\n            gene, has been shown to confer resistance to structurally unrelated antimalarials. Through the determination of the 50% inhibitory concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            s) and IC\n            <jats:sub>90<\/jats:sub>\n            s for piperaquine and chloroquine in a set of 46 adapted\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n            cultures originating from the Thai-Burmese border, we have characterized the regions around the\n            <jats:italic>pfmdr1<\/jats:italic>\n            gene and identified a significant association between the presence of\n            <jats:italic>pfmdr1<\/jats:italic>\n            duplications and enhanced sensitivity to piperaquine (\n            <jats:italic>P<\/jats:italic>\n            = 0.005 for IC\n            <jats:sub>50<\/jats:sub>\n            and\n            <jats:italic>P<\/jats:italic>\n            = 0.002 for IC\n            <jats:sub>90<\/jats:sub>\n            ) and chloroquine, reaching statistical significance at IC\n            <jats:sub>90<\/jats:sub>\n            s (\n            <jats:italic>P<\/jats:italic>\n            = 0.026). These results substantiate the potential importance of\n            <jats:italic>pfmdr1<\/jats:italic>\n            copy number amplifications in the efficacy of the combination therapy piperaquine-dihydroartemisinin. It supports the rational use of 4-aminoquinolines and artemisinin-based compounds, as they independently select for mutually incompatible combinations of mutations.\n          <\/jats:p>","DOI":"10.1128\/aac.06350-11","type":"journal-article","created":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T05:22:29Z","timestamp":1334640149000},"page":"3615-3619","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["<i>pfmdr1<\/i>\n            Amplification Is Related to Increased Plasmodium falciparum In Vitro Sensitivity to the Bisquinoline Piperaquine"],"prefix":"10.1128","volume":"56","author":[{"given":"M. I.","family":"Veiga","sequence":"first","affiliation":[{"name":"Malaria Research Lab, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"},{"name":"Microbiology and Infection Research Domain, Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal"},{"name":"Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York, USA"}]},{"given":"P. E.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Malaria Research Lab, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"},{"name":"Drug Resistance and Pharmacogenetics Group, Institute of Biotechnology and Bioengineering (IBB), Centre of Molecular and Structural Biomedicine (CBME), University of Algarve, Faro, Portugal"}]},{"given":"M.","family":"Malmberg","sequence":"additional","affiliation":[{"name":"Malaria Research Lab, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"}]},{"given":"L.","family":"J\u00f6rnhagen","sequence":"additional","affiliation":[{"name":"Malaria Research Lab, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"}]},{"given":"A.","family":"Bj\u00f6rkman","sequence":"additional","affiliation":[{"name":"Malaria Research Lab, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"}]},{"given":"F.","family":"Nosten","sequence":"additional","affiliation":[{"name":"Shoklo Malaria Research Unit, Mae Sot Tak, Thailand"},{"name":"Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"},{"name":"Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom"}]},{"given":"J. P.","family":"Gil","sequence":"additional","affiliation":[{"name":"Drug Resistance and Pharmacogenetics Group, Institute of Biotechnology and Bioengineering (IBB), Centre of Molecular and Structural Biomedicine (CBME), University of Algarve, Faro, Portugal"},{"name":"Drug Resistance Unit, Division of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden"},{"name":"Laboratory of Molecular Anthropology and Health, Department of Anthropology, Binghamton University, Binghamton, New York, USA"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1179\/136485910X12743554760144"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05378.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.4.1391-1394.2003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007871"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00183-10"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004551"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.3.1143"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.113.5.1033"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200565010-00004"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2331"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01793-10"},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/0092-8674(89)90330-9","article-title":"Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of P. falciparum","volume":"57","author":"Foote SJ","year":"1989","unstructured":"FooteSJ ThompsonJK CowmanAF KempDJ. 1989. 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