Incidence of symptomatic Lassa virus infection in West African countries (Enable 1.0 Lassa Research Study): a prospective, multisite, cohort study

BACKGROUND: Lassa fever vaccine trials are hampered by knowledge gaps on disease incidence, at-risk populations, sequelae, and transmission risks. We aimed to estimate symptomatic Lassa virus infection incidence in endemic areas and determine community Lassa fever case fatality risk (CFR), malaria co-infection, hearing loss in survivors, and household risk factors. METHODS: The Enable 1.0 Lassa Research Study was a prospective, multisite, cohort study conducted in 111 rural communities across Benin, Liberia, Nigeria, and Sierra Leone, with documented Lassa fever transmission. Households were identified using country-specific random sampling approaches, and eligible household members aged at least 2 years were invited to participate following community engagement and informed consent. Eligibility required participants to be afebrile at enrolment, resident in the community for at least 6 months, intending to remain for the study duration, and able and willing to comply with study procedures. Participants were monitored for suspected Lassa fever symptoms over 18-30 months. The blood samples of people with suspected Lassa fever were evaluated for Lassa virus by RT-PCR and malaria by rapid diagnostic test. The hearing status of people who survived Lassa fever was tested at the hospital before discharge and 4 months later. Crude Lassa fever incidence rates (IRs) and rate ratios (IRRs) were estimated using Poisson regressions. Household risk factors were analysed using mixed-effect logistic models. FINDINGS: Between Nov 30, 2020 and Nov 20, 2023, among 20 131 participants, 8183 people with suspected Lassa fever were evaluated, revealing 39 people with Lassa fever, representing an overall Lassa fever IR of 1·27 people with Lassa fever per 1000 person-years (95% CI 0·88-1·84). Lassa fever risk was higher in children aged 2-17 years than in adults (adjusted IRR 1·96, 95% CI 1·04-3·72) but did not differ by sex. CFR was 13% (five of 39). 27 (69%) of 39 people with Lassa fever had malaria co-infection, nine (32%) of 28 had hearing loss at discharge, and 14 (48%) of 29 had hearing loss 4 months after discharge. No household-level characteristics were significantly associated with Lassa fever. INTERPRETATION: Symptomatic Lassa virus infection occurs infrequently in West Africa, meaning large vaccine trials are required to measure efficacy. Trials should target children, who are at higher risk of Lassa fever, alongside the further development of targeted school-based health education and household-level risk communication programmes in endemic communities. The high prevalences of malaria co-infection and hearing loss after infection warrant further exploration in future trials and reinforce the need for integrated community fever management strategies that include Lassa fever as a differential diagnosis. FUNDING: The Coalition for Epidemic Preparedness Innovations.