{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T22:48:01Z","timestamp":1780613281206,"version":"3.54.1"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"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":[[2015,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            There is considerable concern that malaria parasites are starting to evolve resistance to the current generation of antimalarial drugs, the artemisinin-based combination therapies (ACTs). We use pharmacological modeling to investigate changes in ACT effectiveness likely to occur if current regimens are extended from 3 to 5 days or, alternatively, given twice daily over 3 days. We show that the pharmacology of artemisinins allows both regimen changes to substantially increase the artemisinin killing rate. Malaria patients rarely contain more than 10\n            <jats:sup>12<\/jats:sup>\n            parasites, while the standard dosing regimens allow approximately 1 in 10\n            <jats:sup>10<\/jats:sup>\n            parasites to survive artemisinin treatment. Parasite survival falls dramatically, to around 1 in 10\n            <jats:sup>17<\/jats:sup>\n            parasites if the dose is extended or split; theoretically, this increase in drug killing appears to be more than sufficient to restore failing ACT efficacy. One of the most widely used dosing regimens, artemether-lumefantrine, already successfully employs a twice-daily dosing regimen, and we argue that twice-daily dosing should be incorporated into all ACT regimen design considerations as a simple and effective way of ensuring the continued long-term effectiveness of ACTs.\n          <\/jats:p>","DOI":"10.1128\/aac.00482-15","type":"journal-article","created":{"date-parts":[[2015,8,4]],"date-time":"2015-08-04T02:44:26Z","timestamp":1438656266000},"page":"6419-6427","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Altering Antimalarial Drug Regimens May Dramatically Enhance and Restore Drug Effectiveness"],"prefix":"10.1128","volume":"59","author":[{"given":"Katherine","family":"Kay","sequence":"first","affiliation":[{"name":"Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5821-1685","authenticated-orcid":false,"given":"Eva Maria","family":"Hodel","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Hastings","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314981"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2331"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1586\/ecp.13.17"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-187"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2007.03.006"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01712-10"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003151"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-13-138"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006113108"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0001-706X(96)00565-7"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1999.60.936"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2006.74.991"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.254"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)70049-6"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001564"},{"key":"e_1_3_3_18_2","volume-title":"Guidelines for the treatment of malaria","author":"World Health Organization","year":"2010","unstructured":"World Health Organization. 2010. 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