{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:34:29Z","timestamp":1785429269439,"version":"3.56.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K24AI144048, U01AI184646"],"award-info":[{"award-number":["K24AI144048, U01AI184646"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-048214, INV-067310, INV-081860"],"award-info":[{"award-number":["INV-048214, INV-067310, INV-081860"]}],"id":[{"id":"10.13039\/100000865","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":[[2026,5,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Reliable assessment of antimalarial drug efficacy is crucial for an effective response to emerging drug resistance, and therapeutic efficacy studies (TESs) are the primary means of estimating\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      efficacy. The accuracy of such estimates rests on correctly classifying recurrent infections developed during follow-up as recrudescences or new infections. Genotyping is used to guide classification, but polyclonal infections and alleles matching by chance make classification challenging, especially in high transmission settings. Match-counting algorithms currently recommended by the World Health Organization are unreliable and produce biased results, necessitating the development of principled statistical approaches. Modern genotyping methods, such as multiplexed amplicon sequencing, hold great potential for resolving recurrences and motivate the need for corresponding statistical methods able to utilize the rich data they provide. We propose an Adaptive Statistical framework for Therapeutic Efficacy and Recrudescence (Aster) that delivers accurate and consistent results by explicitly incorporating the complexity of infection, population allele frequencies, and imperfect detection of alleles in minority strains. Using an identity-by-descent approach, Aster accounts for alleles matching by chance and for a background infection relatedness structure that can otherwise lead to misclassification. The flexible framework can also use external information, such as parasite density and performance characteristics of a genotyping panel. Using simulations, we show that Aster dramatically outperforms match-counting algorithms in a wide variety of transmission settings and demonstrates consistently balanced performance that improves with more informative genotyping panels. Aster is implemented in a fast, fully scalable, and user-friendly R software package,\n                      <jats:italic toggle=\"yes\">asterTES,<\/jats:italic>\n                      and provides accurate estimates of treatment failure for TES with any type of genotyping data, facilitating reliable evaluation of drug efficacy and effective management of malaria.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01411-25","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T14:50:17Z","timestamp":1776091817000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Classification of outcomes in antimalarial therapeutic efficacy studies with Aster"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7772-7473","authenticated-orcid":true,"given":"Inna","family":"Gerlovina","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"EPPIcenter Research Program, Division of HIV, ID and Global Medicine, Department of Medicine, University of California","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Berube","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02y3ad647","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biostatistics, University of Florida","place":["Gainesville, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Briggs","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"EPPIcenter Research Program, Division of HIV, ID and Global Medicine, Department of Medicine, University of California","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Murie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"EPPIcenter Research Program, Division of HIV, ID and Global Medicine, Department of Medicine, University of California","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxwell","family":"Murphy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"EPPIcenter Research Program, Division of HIV, ID and Global Medicine, Department of Medicine, University of California","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6320-3575","authenticated-orcid":true,"given":"Amy","family":"Wesolowski","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0287-9111","authenticated-orcid":true,"given":"Bryan","family":"Greenhouse","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"EPPIcenter Research Program, Division of HIV, ID and Global Medicine, Department of Medicine, University of California","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15535"},{"key":"e_1_3_3_3_2","unstructured":"World Health Organization. 2023. 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Methods and techniques for clinical trials on antimalarial drug efficacy: Genotyping to identify parasite populations. Informal consultation organized by the Medicines for Malaria Venture and cosponsored by the World Health Organization 29-31 May 2007 Amsterdam The Netherlands"},{"key":"e_1_3_3_21_2","unstructured":"World Health Organization. 2021. Informal consultation on methodology to distinguish reinfection from recrudescence in high malaria transmission areas. Report of a virtual meeting 17--18 May 2021"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","unstructured":"Mehra S Taylor AR Imwong M White NJ Watson JA. 2025. Probabilistic classification of late treatment failure in uncomplicated malaria. 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