Plasmodium falciparum gametocyte production in longitudinally monitored incident infections is associated with duration of infection and human host factors

Abstract

Abstract 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 highly important for gametocyte production but poorly quantified. Between 2017–2019 an all-age cohort of individuals from Tororo, eastern Uganda was followed by continuous passive and routine assessments. We longitudinally monitored 104 incident infections from 98 individuals. Among infections that lasted ≥ 3 months, gametocyte production was near-universal with 96% of infections producing gametocytes prior to clearance. However, most infections were of much shorter duration; 55.7% of asymptomatic infections were detected only once. When considering all asymptomatic infections, regardless of their duration, only 36.3% initiated gametocyte production prior to clearance. Infections in individuals with sickle-cell trait (HbAS) were more likely to produce gametocytes (Hazard Rate (HR) = 2.68, 95% CI: 1.12, 6.38; p = 0.0231) and produced gametocytes at higher densities (Density Ratio (DR) = 9.19, 95% CI: 2.79–30.23; p = 0.0002) compared to wildtype (HbAA) individuals. Our findings suggest that a large proportion of incident infections is too short in duration and of too low density to contribute to onward transmission.