{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:47:27Z","timestamp":1787312847650,"version":"build-2736575974"},"reference-count":22,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["AI127338"],"award-info":[{"award-number":["AI127338"]}]},{"name":"HHS | National Institutes of Health","award":["AI075045, AI139179"],"award-info":[{"award-number":["AI075045, AI139179"]}]},{"name":"HHS | National Institutes of Health","award":["AI173557"],"award-info":[{"award-number":["AI173557"]}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"crossref","award":["INV-035751"],"award-info":[{"award-number":["INV-035751"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,12,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Artemisinin partial resistance (ART-R) has emerged in eastern Africa, necessitating regular surveillance of susceptibility of\n                      <jats:italic>Plasmodium falciparum<\/jats:italic>\n                      to artemisinins. The microscopy-based ring-stage survival assay (RSA) provides a laboratory correlate of ART-R but is limited by low throughput and subjectivity of microscopic counts of viable parasites. The extended recovery ring-stage survival assay (eRRSA) replaces microscopy with efficient quantitative PCR (qPCR) readouts but has been studied only with culture-adapted\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      clones. We measured susceptibility to dihydroartemisinin (DHA) after a 6-h incubation with 700-nM DHA, followed by culture without drug, by comparing survival with that of untreated controls by microscopy (the RSA) or qPCR (the eRRSA) and also performed standard growth inhibition (half-maximal inhibitory concentration [IC\n                      <jats:sub>50<\/jats:sub>\n                      ]) assays for 122\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      isolates freshly collected in eastern and northern Uganda from March to July 2022. The median values for RSA survival, eRRSA fold change, and DHA IC\n                      <jats:sub>50<\/jats:sub>\n                      were 3.0%, 46.2, and 3.2 nM, respectively. RSA percent survival and eRRSA fold changes correlated strongly (Spearman correlation coefficient [\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>s<\/jats:italic>\n                      <\/jats:sub>\n                      ] = \u22120.7411,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.0001), with modest associations between the presence of validated\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      Kelch13 ART-R mutations (C469Y or A675V) and RSA (median survival 2.6% for wild type [WT] vs 4.1% for mutant,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.01), or eRRSA (median fold change 63.4 for WT vs 30.9 for mutant,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.003) results. Significant correlations were also observed between DHA IC\n                      <jats:sub>50<\/jats:sub>\n                      values and both RSA percent survival (\n                      <jats:italic>\n                        r\n                        <jats:sub>s<\/jats:sub>\n                      <\/jats:italic>\n                      = 0.4235,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.0001) and eRRSA fold changes (\n                      <jats:italic>\n                        r\n                        <jats:sub>s<\/jats:sub>\n                      <\/jats:italic>\n                      = \u22120.4116,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.0001). The eRRSA is a scalable alternative for phenotyping fresh\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      isolates, providing similar results with improved throughput.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01183-24","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T09:00:17Z","timestamp":1731661217000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["The extended recovery ring-stage survival assay is a scalable alternative for artemisinin susceptibility phenotyping of fresh\n                    <i>Plasmodium falciparum<\/i>\n                    isolates"],"prefix":"10.1128","volume":"68","author":[{"given":"Martin","family":"Okitwi","sequence":"first","affiliation":[{"name":"Infectious Diseases Research Collaboration","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4991-6039","authenticated-orcid":false,"given":"Douglas A.","family":"Shoue","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame","place":["Notre Dame, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2442-0301","authenticated-orcid":false,"given":"Lisa A.","family":"Checkley","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame","place":["Notre Dame, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Orena","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frida G.","family":"Ceja","sequence":"additional","affiliation":[{"name":"Dominican University of California","place":["San Rafael, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoweri","family":"Taremwa","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick K.","family":"Tumwebaze","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Katairo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oswald","family":"Byaruhanga","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie A.C.","family":"Sievert","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame","place":["Notre Dame, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreeya","family":"Garg","sequence":"additional","affiliation":[{"name":"University of California","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2026-345X","authenticated-orcid":false,"given":"Oriana K.","family":"Kreutzfeld","sequence":"additional","affiliation":[{"name":"University of California","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Legac","sequence":"additional","affiliation":[{"name":"University of California","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Brown University","place":["Providence, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam L.","family":"Nsobya","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9984-8030","authenticated-orcid":false,"given":"Melissa D.","family":"Conrad","sequence":"additional","affiliation":[{"name":"University of California","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7953-7622","authenticated-orcid":false,"given":"Philip J.","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"University of California","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3516-9829","authenticated-orcid":false,"given":"Michael T.","family":"Ferdig","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame","place":["Notre Dame, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8437-9382","authenticated-orcid":false,"given":"Roland A.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Dominican University of California","place":["San Rafael, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314981"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00362-1"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210956"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211803"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa687"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1005-2"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01008-2"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101746"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parint.2020.102277"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33873-x"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-339"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60484-X"},{"key":"e_1_3_4_15_2","volume-title":"Institute 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Ring\u2010stage survival assays (RSA) to evaluate the in\u2010vitro and ex\u2010vivo susceptibility of Plasmodium falciparum to artemisinins. In Institute Pasteur du Cambodge \u2013 National Institutes of Health Procedure RSAv1"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70252-4"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00921-15"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-020-3139-6"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02902-14"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70181-0"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-52414-8"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/s2666-5247(21)00085-9"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15779-8"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01183-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01183-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T09:04:20Z","timestamp":1733389460000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01183-24"}},"subtitle":[],"editor":[{"given":"Audrey","family":"Odom John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,12,5]]},"references-count":22,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12,5]]}},"alternative-id":["10.1128\/aac.01183-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.01183-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,5]]},"assertion":[{"value":"2024-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01183-24"}}