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Immunol."],"abstract":"<jats:p>Malaria transmission depends on the presence of mature <jats:italic>Plasmodium<\/jats:italic> transmission stages (gametocytes) that may render blood-feeding <jats:italic>Anopheles<\/jats:italic> mosquitos infectious. Transmission-blocking antimalarial drugs and vaccines can prevent transmission by reducing gametocyte densities or infectivity to mosquitos. Mosquito infection outcomes are thereby informative biological endpoints of clinical trials with transmission blocking interventions. Nevertheless, trials are often primarily designed to determine intervention safety; transmission blocking efficacy is difficult to incorporate in sample size considerations due to variation in infection outcomes and considerable inter-study variation. Here, we use clinical trial data from studies in malaria naive and naturally exposed study participants to present an online sample size calculator tool. This sample size calculator allows studies to be powered to detect reductions in the proportion of infected mosquitos or infection burden (oocyst density) in mosquitos. The utility of this online tool is illustrated using trial data with transmission blocking malaria drugs.<\/jats:p>","DOI":"10.3389\/fimmu.2022.899615","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T13:00:04Z","timestamp":1654261204000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Quantifying Reductions in Plasmodium falciparum Infectivity to Mosquitos: A Sample Size Calculator to Inform Clinical Trials on Transmission-Reducing Interventions"],"prefix":"10.3389","volume":"13","author":[{"given":"Jordache","family":"Ramjith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Alkema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Bradley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alassane","family":"Dicko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Drakeley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Will","family":"Stone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teun","family":"Bousema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.30875\/6c551ba0-en","volume-title":"World Malaria Report 2021","author":"Organisation","year":"2021"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002456","article-title":"Malera: An Updated Research Agenda for Malaria Elimination and Eradication","volume":"14","author":"Rabinovich","year":"2017","journal-title":"PloS Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1051\/parasite\/2003104363","article-title":"Changes in Plasmodium Falciparum Gametocytaemia in Children With Chloroquine-Sensitive Asexual Infections","volume":"10","author":"Sowunmi","year":"2003","journal-title":"Parasite"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30044-6","article-title":"Efficacy and Safety of Primaquine and Methylene Blue for Prevention of Plasmodium Falciparum Transmission in Mali: A Phase 2, Single-Blind, Randomised Controlled Trial","volume":"18","author":"Dicko","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-017-0007-4","article-title":"Hexahydroquinolines Are Antimalarial Candidates With Potent Blood-Stage and Transmission-Blocking Activity","volume":"2","author":"Vanaerschot","year":"2017","journal-title":"Nat Microbiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01256","article-title":"Pfs230 and Pfs48\/45 Fusion Proteins Elicit Strong Transmission-Blocking Antibody Responses Against Plasmodium Falciparum","volume":"10","author":"Singh","year":"2019","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.08.033","article-title":"Safety and Immunogenicity of a Plant-Produced Pfs25 Virus-Like Particle as a Transmission Blocking Vaccine Against Malaria: A Phase 1 Dose-Escalation Study in Healthy Adults","volume":"36","author":"Chichester","year":"2018","journal-title":"Vaccine"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01222-13","article-title":"Antibodies to a Single, Conserved Epitope in Anopheles Apn1 Inhibit Universal Transmission of Plasmodium Falciparum and Plasmodium Vivax Malaria","volume":"82","author":"Armistead","year":"2014","journal-title":"Infect Immun"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2020.08.009","article-title":"Antibody Therapy Goes to Insects: Monoclonal Antibodies Can Block Plasmodium Transmission to Mosquitoes","volume":"36","author":"Coelho","year":"2020","journal-title":"Trends Parasitol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1038\/s41467-021-21955-1","article-title":"A Human Monoclonal Antibody Blocks Malaria Transmission and Defines a Highly Conserved Neutralizing Epitope on Gametes","volume":"12","author":"Coelho","year":"2021","journal-title":"Nat Commun"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.07.030","article-title":"Development of a Transmission-Blocking Malaria Vaccine: Progress, Challenges, and the Path Forward","volume":"32","author":"Nunes","year":"2014","journal-title":"Vaccine"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa157","article-title":"A Randomized Clinical Trial to Compare P. 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