{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:14:08Z","timestamp":1790738048275,"version":"4.1.0"},"reference-count":48,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T00:00:00Z","timestamp":1519689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T00:00:00Z","timestamp":1519689600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T00:00:00Z","timestamp":1519689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005624","name":"PATH","doi-asserted-by":"publisher","award":["Malaria Vaccine Initiative"],"award-info":[{"award-number":["Malaria Vaccine Initiative"]}],"id":[{"id":"10.13039\/100005624","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["Fellowship"],"award-info":[{"award-number":["Fellowship"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","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\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Malaria elimination strategies require a thorough understanding of parasite transmission from human to mosquito. A clinical model to induce gametocytes to understand their dynamics and evaluate transmission-blocking interventions (TBI) is currently unavailable. Here, we explore the use of the well-established Controlled Human Malaria Infection model (CHMI) to induce gametocyte carriage with different antimalarial drug regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In a single centre, open-label randomised trial, healthy malaria-naive participants (aged 18\u201335 years) were infected with Plasmodium falciparum by bites of infected Anopheles mosquitoes. Participants were randomly allocated to four different treatment arms (n = 4 per arm) comprising low-dose (LD) piperaquine (PIP) or sulfadoxine-pyrimethamine (SP), followed by a curative regimen upon recrudescence. Male and female gametocyte densities were determined by molecular assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Mature gametocytes were observed in all participants (16\/16, 100%). Gametocytes appeared 8.5\u201312 days after the first detection of asexual parasites. Peak gametocyte densities and gametocyte burden was highest in the LD-PIP\/SP arm, and associated with the preceding asexual parasite biomass (p=0.026). Male gametocytes had a mean estimated circulation time of 2.7 days (95% CI 1.5\u20133.9) compared to 5.1 days (95% CI 4.1\u20136.1) for female gametocytes. Exploratory mosquito feeding assays showed successful sporadic mosquito infections. There were no serious adverse events or significant differences in the occurrence and severity of adverse events between study arms (p=0.49 and p=0.28).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The early appearance of gametocytes indicates gametocyte commitment during the first wave of asexual parasites emerging from the liver. Treatment by LD-PIP followed by a curative SP regimen, results in the highest gametocyte densities and the largest number of gametocyte-positive days. This model can be used to evaluate the effect of drugs and vaccines on gametocyte dynamics, and lays the foundation for fulfilling the critical unmet need to evaluate transmission-blocking interventions against falciparum malaria for downstream selection and clinical development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>Funded by PATH Malaria Vaccine Initiative (MVI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs6\">\n                    <jats:title>Clinical trial number:<\/jats:title>\n                    <jats:p>\n                      <jats:related-object document-id=\"NCT02836002\" document-id-type=\"clinical-trial-number\" id=\"RO1\" source-id=\"ClinicalTrials.gov\" source-id-type=\"registry-name\" source-type=\"clinical-trials-registry\" xlink:href=\"https:\/\/clinicaltrials.gov\/show\/NCT02836002\">NCT02836002<\/jats:related-object>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.31549","type":"journal-article","created":{"date-parts":[[2018,2,26]],"date-time":"2018-02-26T19:00:25Z","timestamp":1519671625000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.31549","source":"Crossref","is-referenced-by-count":66,"title":["A randomized feasibility trial comparing four antimalarial drug regimens to induce Plasmodium falciparum gametocytemia in the controlled human malaria infection model"],"prefix":"10.7554","volume":"7","clinical-trial-number":[{"clinical-trial-number":"nct02836002","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1783-0735","authenticated-orcid":true,"given":"Isaie J","family":"Reuling","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Radboud university medical 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