Quantifying the effect of threshold-triggered interventions on hepatitis E virus outbreaks.

Hepatitis E virus (HEV) presents a major public health threat in low-resource and displaced populations, where poor sanitation and limited access to healthcare facilitate transmission. Despite the availability of water, sanitation, and hygiene (WASH) programs and a licensed HEV vaccine for outbreak response, implementation challenges persist in terms of scaling, strategic use of resources, and timely deployment. To quantify the impact of these interventions, we developed a delay differential model of HEV transmission dynamics that incorporates the clinical status of infected individuals and delays associated with testing and isolation. Interventions were triggered by the cumulative number of confirmed symptomatic HEV cases, corresponding to either an early response after the first detected case or a delayed response after 25 cases. We found that when sanitation and water treatment were implemented individually, modest reductions were achieved in both overall and severe infections and were relatively insensitive to deployment timing. In contrast, combining them under WASH substantially amplified their impact, especially when deployed early. When vaccination and WASH were deployed together and implemented early, overall and severe infections were reduced by approximately 94%, whereas this reduction dropped to 67% under delayed deployment. Under early deployment, vaccination-, sanitation-, and water treatment-alone achieved comparable reductions in overall infections (26%-31%); however, vaccination produced a disproportionately larger reduction in severe disease (46%). The WASH intervention was more than twice as effective as vaccination alone in reducing total infections, although this effect was less pronounced for severe cases. Sensitivity analyses identified WASH-related parameters most strongly influenced outcomes. These findings highlight the importance of timely, integrated responses and emphasize the critical role of WASH-by reducing waterborne transmission-in mitigating HEV outbreaks in vulnerable populations.