{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T16:56:10Z","timestamp":1761929770863,"version":"3.37.3"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2015,12,31]],"date-time":"2015-12-31T00:00:00Z","timestamp":1451520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100007637","name":"Colciencias","doi-asserted-by":"crossref","award":["512-2010"],"award-info":[{"award-number":["512-2010"]}],"id":[{"id":"10.13039\/100007637","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["091625"],"award-info":[{"award-number":["091625"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["PA00P3-139723\/1"],"award-info":[{"award-number":["PA00P3-139723\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"The National Health and Medical Research Council (NHMRC) of the Australian Government","doi-asserted-by":"publisher","award":["1023438"],"award-info":[{"award-number":["1023438"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n Chloroquine (CQ)-resistant\n Plasmodium vivax<\/jats:named-content>\n is present in most countries where\n P. vivax<\/jats:named-content>\n infection is endemic, but the underlying molecular mechanisms responsible remain unknown. Increased expression of\n P. vivax<\/jats:named-content>\n crt-o<\/jats:italic>\n (\n pvcrt-o<\/jats:italic>\n ) has been correlated with\n in vivo<\/jats:italic>\n CQ resistance in an area with low-grade resistance. We assessed\n pvcrt-o<\/jats:italic>\n expression in isolates from Papua (Indonesia), where\n P. vivax<\/jats:named-content>\n is highly CQ resistant.\n Ex vivo<\/jats:italic>\n drug susceptibilities to CQ, amodiaquine, piperaquine, mefloquine, and artesunate were determined using a modified schizont maturation assay. Expression levels of\n pvcrt-o<\/jats:italic>\n were measured using a novel real-time quantitative reverse transcription-PCR method. Large variations in\n pvcrt-o<\/jats:italic>\n expression were observed across the 51 isolates evaluated, with the fold change in expression level ranging from 0.01 to 59 relative to that seen with the\n P. vivax<\/jats:named-content>\n \u03b2-tubulin gene and from 0.01 to 24 relative to that seen with the\n P. vivax<\/jats:named-content>\n aldolase gene. Expression was significantly higher in isolates with the majority of parasites at the ring stage of development (median fold change, 1.7) compared to those at the trophozoite stage (median fold change, 0.5;\n P<\/jats:italic>\n < 0.001). Twenty-nine isolates fulfilled the criteria for\n ex vivo<\/jats:italic>\n drug susceptibility testing and showed high variability in CQ responses (median, 107.9 [range, 6.5 to 345.7] nM). After controlling for the parasite stage, we found that\n pvcrt-o<\/jats:italic>\n expression levels did not correlate with the\n ex vivo<\/jats:italic>\n response to CQ or with that to any of the other antimalarials tested. Our results highlight the importance of development-stage composition for measuring\n pvcrt-o<\/jats:italic>\n expression and suggest that\n pvcrt-o<\/jats:italic>\n transcription is not a primary determinant of\n ex vivo<\/jats:italic>\n drug susceptibility. A comprehensive transcriptomic approach is warranted for an in-depth investigation of the role of gene expression levels and\n P. vivax<\/jats:named-content>\n drug resistance.\n <\/jats:p>","DOI":"10.1128\/aac.02207-15","type":"journal-article","created":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T01:35:21Z","timestamp":1446514521000},"page":"361-367","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Expression of Plasmodium vivax\n crt-o<\/i>\n Is Related to Parasite Stage but Not\n Ex Vivo<\/i>\n Chloroquine Susceptibility"],"prefix":"10.1128","volume":"60","author":[{"given":"Zuleima","family":"Pava","sequence":"first","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Handayuni","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grennady","family":"Wirjanata","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheren","family":"To","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leily","family":"Trianty","sequence":"additional","affiliation":[{"name":"Eijkman Institute for Molecular Biology, Jakarta, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rintis","family":"Noviyanti","sequence":"additional","affiliation":[{"name":"Eijkman Institute for Molecular Biology, Jakarta, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanne Rini","family":"Poespoprodjo","sequence":"additional","affiliation":[{"name":"Papuan Health and Community Development Foundation (PHCDF), Timika, Papua, Indonesia"},{"name":"Department of Paediatrics, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Auburn","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ric N.","family":"Price","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jutta","family":"Marfurt","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, 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