TOPLINE

A modeling study found that antiviral post-exposure prophylaxis (PEP) targeted to healthcare workers (HCWs) could reduce deaths significantly during orthoebolavirus outbreaks when delivered rapidly at high coverage. However, delayed deployment, operational disruption, and reduced coverage substantially eroded this benefit.

METHODOLOGY

• Researchers adapted a stochastic branching-process model of orthoebolavirus transmission across community, healthcare, and funeral settings. They used this model to estimate the impact of HCW-targeted antiviral PEP across calibrated outbreak archetypes, varying antiviral efficacy, coverage, deployment readiness, dosing delays, operational disruption, and allocation policies.
• Calibration was performed to define two outbreak archetypes: a West Africa-like high-burden scenario based on the 2013-2016 epidemic and a DR Congo-like scenario with prolonged transmission under conflict-related disruption based on the 2018-2020 North Kivu and Ituri outbreak.
• The analysis assessed three antiviral deployment-readiness scenarios (scenario 1: 100% PEP coverage; scenario 2: scaled to 80% coverage over 180 days; scenario 3: scaled to 50% coverage over 1 year). For the DR Congo-like archetype, the researchers simulated four disruption scenarios: no PEP, ideal delivery at 100% coverage with no dosing delay, delayed dosing with coverage preserved, and delayed dosing with delayed coverage.
• The primary outcome was the number of HCW deaths averted; secondary outcomes included reduction in HCW days lost and dose efficiency (the number of PEP doses required to avert one HCW death).
• Researchers tested antiviral efficacy ranging from 50% to 90%, with a central analysis assuming 80% efficacy and 80% coverage. They also compared two allocation policies: broad allocation to all eligible HCW exposures and targeted allocation to high-risk exposures (such as personal protective equipment breaches or direct contact with body fluids).

TAKEAWAY

• At baseline without antiviral PEP, the median cumulative number of HCW deaths was 553 by week 60 in the West Africa-like archetype, compared with 61 by week 80 in the DR Congo-like archetype. With 80% antiviral efficacy and 80% PEP coverage, HCW deaths fell to 200 and 22, respectively, over the same timeframes. The reduction in HCW workdays lost followed a similar percentage pattern to the reduction in HCW deaths across these scenarios.
• Under scenario 1 with immediate 100% coverage and 80% antiviral efficacy, the median reduction in HCW deaths compared with no PEP was 80% in both the West Africa-like archetype (95% credible interval [CrI], 79%-81%) and DR Congo-like archetype (95% CrI, 76%-84%). Under scenario 2, the reductions fell to 60% (95% CrI, 57%-62%) and 52% (95% CrI, 41%-58%), respectively. Under scenario 3, the respective reductions were 19% (95% CrI, 16%-22%) and 22% (95% CrI, 7%-29%).
• In the DR Congo-like disruption analysis, under the central delay-efficacy relationship, ideal PEP delivery at 100% coverage without delay averted 83% (95% CrI, 79%-87%) of HCW deaths and maintaining 100% coverage but delaying dosing averted 50% (95% CrI, 40%-55%) of HCW deaths compared with no antiviral PEP. Delaying coverage plus delayed dosing achieved only 35% (95% CrI, 25%-47%) of the ideal scenario’s impact.
• At 80% antiviral efficacy with same-day dosing, targeted allocation to high-risk exposures required 44 doses (95% CrI, 43-44) per HCW death averted, while broad allocation to all eligible HCW exposures required 109 doses (95% CrI, 85-161).

IN PRACTICE

"[O]ur results highlight the potential of HCW-targeted antiviral PEP in reducing occupational mortality and preserving clinical response capacity during orthoebolavirus outbreaks," the study authors wrote.

SOURCE

The study was led by Jacob N. Stapley, PhD, School of Public Health, University of California, Berkeley. It was published online on August 25, 2026, in The Lancet Infectious Diseases.

LIMITATIONS

No antiviral was approved for Ebola virus disease, so human efficacy, adherence, and optimal timing of PEP remained uncertain. The primary analysis assumed that PEP prevented infection and measured direct protection of HCWs without accounting for downstream transmission. The dose delay-efficacy curves came from nonhuman primate data and might not fully apply to human exposures.

DISCLOSURES

The study received funding from Gilead Sciences through a gift to the University of California, Berkeley School of Public Health, as well as grants from the UK National Institute for Health and Care Research, Oxford Martin School, Miller Institute, Coalition for Epidemic Preparedness Innovations, and EU Global Health EDCTP3. Two authors reported receiving grants, consulting fees, royalties, honoraria, and travel support from various organizations, as well as holding unpaid advisory or trustee roles with some of these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.