Impact of asymptomatic Plasmodium falciparum infection on the risk of subsequent symptomatic malaria in a longitudinal cohort in Kenya.

Background Asymptomatic Plasmodium falciparum infections are common in sub-Saharan Africa, but their effect on subsequent symptomaticity is incompletely understood. Methods In a 29-month cohort of 268 people in Western Kenya, we investigated the association between asymptomatic P. falciparum and subsequent symptomatic malaria with frailty Cox models. Results Compared to being uninfected, asymptomatic infections were associated with an increased 1 month likelihood of symptomatic malaria (adjusted hazard ratio [aHR]: 2.61, 95% CI: 2.05 to 3.33), and this association was modified by sex, with females (aHR: 3.71, 95% CI: 2.62 to 5.24) at higher risk for symptomaticity than males (aHR: 1.76, 95% CI: 1.24 to 2.50). This increased symptomatic malaria risk was observed for asymptomatic infections of all densities and in people of all ages. Long-term risk was attenuated but still present in children under age 5 (29-month aHR: 1.38, 95% CI: 1.05 to 1.81). Conclusions In this high-transmission setting, asymptomatic P. falciparum can be quickly followed by symptoms and may be targeted to reduce the incidence of symptomatic illness. Funding This work was supported by the National Institute of Allergy and Infectious Diseases (R21AI126024 to WPO, R01AI146849 to WPO and SMT).