{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:42:11Z","timestamp":1784166131688,"version":"3.55.0"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"51","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["093956\/Z\/10\/C"],"award-info":[{"award-number":["093956\/Z\/10\/C"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["223253\/Z\/21\/Z"],"award-info":[{"award-number":["223253\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["FL130100039"],"award-info":[{"award-number":["FL130100039"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,12,17]]},"abstract":"<jats:p>\n                    <jats:italic>Plasmodium vivax<\/jats:italic>\n                    parasites can lie dormant in the liver as hypnozoites, activating weeks to months after sporozoite inoculation to cause relapsing malarial illness. It is not known what biological processes govern hypnozoite activation. We use longitudinal data from the most detailed cohort study ever conducted in an area where both\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    and\n                    <jats:italic>P. vivax<\/jats:italic>\n                    were endemic to fit a simple within-host mathematical model of\n                    <jats:italic>P. vivax<\/jats:italic>\n                    hypnozoite activation. 1,344 children living on the Thailand\u2013Myanmar border were followed daily for 21 mo. There were 2,504 vivax and 1,164 falciparum malaria symptomatic episodes recorded over 1988 person-years. The model assumes that hypnozoites activate independently at a constant rate (\u201cexponential clock model\u201d). When this model was embedded in a stochastic framework for repeated infectious mosquito bites, with seasonality inferred from the incidence of clinical falciparum malaria episodes, it explained the observed temporal patterns of multiple (up to 13) recurrent vivax malaria episodes. Under this model, we estimate the mean dormancy period for a single hypnozoite to be 6 mo (i.e., a half-life of 4 mo). We use the calibrated within-host model to characterize population-level overdispersion in the risk of relapse, and assess the potential utility of a serological test for radical cure in low transmission settings. We show that mefloquine treatment of falciparum malaria eliminates early vivax relapses; and that there are substantially more\n                    <jats:italic>P. vivax<\/jats:italic>\n                    recurrences than expected under the model following artesunate monotherapy treatment for falciparum malaria. These results suggest that hypnozoites can be activated by symptomatic malarial illness.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2401024121","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T11:16:51Z","timestamp":1733829411000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["Modeling the within-host dynamics of\n                    <i>Plasmodium vivax<\/i>\n                    hypnozoite activation: An analysis of the SPf66 vaccine trial"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0507-3204","authenticated-orcid":false,"given":"Somya","family":"Mehra","sequence":"first","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit","place":["Bangkok, Thailand"]},{"name":"Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]},{"name":"School of Mathematics and Statistics","place":["Parkville, Australia"]},{"name":"The University of Melbourne","place":["Parkville, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7951-0745","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Nosten","sequence":"additional","affiliation":[{"name":"Shoklo Malaria Research Unit","place":["Mae Sot, Tak, Thailand"]},{"name":"Centre for Tropical Medicine and Global Health","place":["Oxford, United Kingdom"]},{"name":"Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Luxemburger","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit","place":["Bangkok, Thailand"]},{"name":"Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]},{"name":"Shoklo Malaria Research Unit","place":["Mae Sot, Tak, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-1978","authenticated-orcid":false,"given":"Nicholas J.","family":"White","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit","place":["Bangkok, Thailand"]},{"name":"Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]},{"name":"Centre for Tropical Medicine and Global Health","place":["Oxford, United Kingdom"]},{"name":"Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5524-0325","authenticated-orcid":false,"given":"James A.","family":"Watson","sequence":"additional","affiliation":[{"name":"Centre for Tropical Medicine and Global Health","place":["Oxford, United Kingdom"]},{"name":"Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]},{"name":"Infectious Diseases Data Observatory, Big Data Institute","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2016.08.014"},{"key":"e_1_3_4_2_2","unstructured":"World Health Organization WHO Guidelines for Malaria (World Health Organization 2023)."},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-297"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-032421-061155"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.01.002"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1144453"},{"key":"e_1_3_4_7_2","first-page":"55","article-title":"Relapses and latency in malaria","volume":"2","author":"Garnham P.","year":"1967","unstructured":"P. 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