Persistent Malaria Transmission from Asymptomatic Children Despite Highly Effective Malaria Control in Eastern Uganda

Abstract

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 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 Statement: National institute of Health, Bill & Melinda Gates Foundation, European Research Council. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: 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.