Persistent malaria transmission from asymptomatic children despite highly effective malaria control in eastern Uganda

Summary Background Persistent asymptomatic Plasmodium falciparum infections are common in malaria-endemic settings, but their contribution to transmission is poorly understood. Methods A cohort of children and adults from Tororo, Uganda was closely followed for 24 months by continuous passive surveillance and routine assessments. P. falciparum parasite density, gametocyte density and genetic composition were determined molecularly; mosquito membrane feeding assays were performed on samples from participants with symptomatic and asymptomatic infections. Findings From October 2017 to October 2019, we followed all 531 residents from 80 households. Parasite prevalence was 5·8% by microscopy and 17·3% by PCR at enrolment and declined thereafter. We conducted 538 mosquito feeding experiments on samples from 107 individuals. Mosquito infection rates were strongly associated with gametocyte densities of participants. Considering both transmissibility of infections and their relative frequency, the estimated human infectious reservoir was primarily asymptomatic microscopy-detected infections (83·8%), followed by asymptomatic submicroscopic (15·6%) and symptomatic (0·6%) infections. Over half of the infectious reservoir was children aged 5-15 years (56·8%); individuals <5 years (27·5%) and > 16 years (15·7%) contributed less. Four children were responsible for 62·6% (279/446) of infected mosquitos and were infectious at multiple timepoints. Interpretation Individuals with asymptomatic infections were important drivers of malaria transmission. School-aged children were responsible for over half of all mosquito infections, with a small minority of asymptomatic children highly infectious. Demographically targeted interventions, aimed at school-aged children, could further reduce transmission in areas under effective vector control. Funding National institute of Health, Bill & Melinda Gates Foundation, European Research Council.