{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:26:51Z","timestamp":1785407211732,"version":"3.56.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T00:00:00Z","timestamp":1585785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["ERC-2014-StG 639776"],"award-info":[{"award-number":["ERC-2014-StG 639776"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>For malaria elimination efforts, it is important to better understand parasite transmission to mosquitoes and develop models for early-clinical evaluation of transmission-blocking interventions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In a randomized open-label trial, 24 participants were infected by bites from Plasmodium falciparum 3D7-infected mosquitoes (mosquito bite [MB]; n\u2005=\u200512) or by induced blood-stage malaria (IBSM) with the same parasite line (n\u2005=\u200512). After subcurative piperaquine treatment, asexual parasite and gametocytes kinetics were assessed, and mosquito feeding experiments were performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Study procedures were well tolerated. The median peak gametocyte density was 1304\/mL (interquartile range, 308\u20131607\/mL) after IBSM, compared with 14\/mL (10\u201364\/mL) after MB inoculation (P\u2005&amp;lt;\u2005.001), despite similar peak asexual parasite densities (P\u2005=\u2005.48). Peak gametocyte density was correlated with preceding pfap2-g transcripts, indicative of gametocyte commitment (\u03c1\u2005=\u20050.62; P\u2005=\u2005.002). Direct feeding assays resulted in mosquito infections from 9 of 12 participants after IBSM versus 0 of 12 after MB inoculation (P\u2005&amp;lt;\u2005.001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We observed a striking effect of inoculation method on gametocyte production, suggesting higher gametocyte commitment after IBSM. Our direct comparison of MB and IBSM establishes the controlled human malaria infection transmission model, using intravenous administration of P. falciparum\u2013infected erythrocytes as a model for early-clinical evaluation of interventions that aim to interrupt malaria transmission.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trial Registration<\/jats:title>\n                  <jats:p>NCT03454048<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaa157","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T19:10:38Z","timestamp":1585681838000},"page":"1257-1265","source":"Crossref","is-referenced-by-count":27,"title":["A Randomized Clinical Trial to Compare <i>Plasmodium falciparum<\/i> Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite\u2013Induced Controlled Malaria Infection"],"prefix":"10.1093","volume":"224","author":[{"given":"Manon","family":"Alkema","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaie J","family":"Reuling","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerdie M","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, University Medical Center Rotterdam, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjerstin","family":"Lanke","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinout","family":"van Crevel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Ivinson","sequence":"additional","affiliation":[{"name":"PATH Malaria Vaccine Initiative, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian F","family":"Ockenhouse","sequence":"additional","affiliation":[{"name":"PATH Malaria Vaccine Initiative, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, 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