Evaluating the impact of antiviral post-exposure prophylaxis for health-care workers during ebolavirus outbreaks: a modelling study

Background Ebolavirus outbreaks place health-care workers (HCWs) at substantial risk, and HCW illness or death can weaken response capacity. The 2026 Bundibugyo virus disease outbreak in the DRC highlights the need for deployable countermeasures where species-specific vaccines are unavailable. With candidate antivirals under evaluation, but limited evidence on how best to use them if they become available, we assessed HCW-targeted antiviral post-exposure prophylaxis (PEP) across deployment and disruption scenarios. Methods We developed a stochastic branching-process model of ebolavirus transmission, representing health-care, community, and funeral transmission, time-varying non-pharmaceutical interventions and HCW-targeted PEP. Calibrated to previous outbreaks (a high-burden West Africa-like scenario and a DRC-like scenario with conflict-disrupted response) we estimated HCW deaths and capacity loss averted by PEP, varying antiviral efficacy, coverage, deployment readiness, dosing delay, disruption, and allocation policy. Findings At 80% efficacy and 80% coverage, PEP averted approximately 64% of HCW deaths across both archetypes. Under low readiness, where clinical evaluation and access expansion occurred during the outbreak and coverage reached only 50% over one year, reductions fell to 19% and 22% in the West Africa-like and DRC-like archetypes. In disruption scenarios, delayed dose receipt reduced HCW deaths averted from 83% to 50%; combined dosing delay and coverage loss retained only 35% of achievable impact. Dose efficiency varied by allocation: targeting recognised highest-risk exposures required 44 doses per HCW death averted, compared with 109 under broad allocation. Interpretation HCW-targeted antiviral PEP could reduce occupational mortality and preserve clinical capacity during ebolavirus epidemics where vaccines are unavailable, but realising this benefit depends on implementation readiness, rapid delivery, operational coverage and efficient allocation. Funding Gilead Sciences; UK NIHR; Oxford Martin School; Miller Institute; EDCTP; CEPI