Gametocyte production in incident P. falciparum infections: a longitudinal study in a low transmission setting under intensive vector control

Malaria transmission depends on the presence of Plasmodium gametocytes that are the only parasite life stage that can infect mosquitoes. Gametocyte production varies between infections and over the course of infections. Infection duration is influenced by host and parasite characteristics, and is highly important for gametocyte production but poorly quantified. Between 2017-2019 an all-age cohort from Tororo, eastern Uganda was followed by continuous passive and routine assessments. Among 104 longitudinally monitored incident infections coming from 98 individuals, we observed that nearly all infections lasting 3 or more months initiated gametocyte production prior to clearance. However, the majority of infections were of shorter duration (<28 days) and were cleared before gametocytes were detectable. Infections in individuals with sickle-cell trait were more likely to produce gametocytes and produced gametocytes at higher densities. Our findings suggest that a large proportion of infections may be too short in duration and of too low density to contribute to onward transmission. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding was provided by the National Institutes of Health as part of the International Centers of Excellence in Malaria Research (ICEMR) program (AI089674) and another program (AI075045), the Bill & Melinda Gates Foundation (INDIE OPP1173572) and a fellowship from the European Research Council to TB (ERC-CoG 864180; QUANTUM). BG is a Chan Zuckerberg Biohub investigator. The ClinEpiDB platform is supported by the Bill & Melinda Gates Foundation (OPP1169785). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for the study was received from the Uganda National Council of Science and Technology (HS119ES), Makerere University School of Medicine, the University of California, San Francisco and the London School of Hygiene & Tropical Medicine I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data from the PRISM2 cohort study is available through a novel open-access clinical epidemiology database resource .