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

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.

Micro-heterogeneity of transmission shapes the submicroscopic malaria reservoir in coastal Tanzania

“…Third, while we excluded those with recent antimalarial use, this was by self-report, and an unknown proportion of low-density infections may have resulted from prior partial treatment (Andagalu et al, 2022; Lindblade et al, 2013). Ultimately, it is hard to overcome heterogeneity in the etiology and prior duration or “age” of a submicroscopic infection without a longitudinal study design that allows one to capture incident infection (Andolina et al, 2023; Barry et al, 2021). Fourth, we did not perform molecular gametocyte detection on the large screening cohort to better understand their infectious potential; results of mosquito feeding studies in a subset of PCR-positive participants is forthcoming (“ASTMH-2022-Annual-Meeting-Program-Book_1.pdf,” n.d.).…”

“…Increasingly, as transmission declines, how best to identify and target pockets or hotspots of at-risk populations remains a key research question (Andolina et al, 2021; Bath et al, 2021; Bousema et al, 2016; Collins et al, 2019; Cotter et al, 2013; Dabira et al, 2022; Hsiang et al, 2020; Sturrock et al, 2013). Studying the submicroscopic reservoir is important both for the clinical implications of subclinical carriage (Chen et al, 2016; Lindblade et al, 2013; van Eijk et al, 2023) as well as the contribution of submicroscopic carriers to the infectious reservoir, i.e., their role in sustaining transmission (Andolina et al, 2023, 2021; Gonçalves et al, 2017; Lin et al, 2014). As more countries progress towards malaria elimination, a better understanding of the factors that shape the submicroscopic reservoir can help guide interventions to maintain progress towards healthy populations free of malaria.…”