Modeling the impact of outbreak response immunization on typhoid fever using data from 19 outbreaks between 2000-2022.

Typhoid fever remains endemic in many low- and middle-income countries, with antimicrobial-resistant S. Typhi increasingly triggering outbreaks in previously unaffected regions. While typhoid conjugate vaccines (TCVs) offer a means of outbreak control, the potential impact of outbreak response immunization (ORI) -- and how coverage, timing, and outbreak characteristics shape that impact -- remains poorly characterized. We evaluated single-dose TCV ORI strategies using a time series dataset of 19 typhoid outbreaks reported between 2000 and 2022. A static model was applied to each outbreak, incorporating direct and indirect vaccine effectiveness, immunological delay, and cost-effectiveness analyses across a range of timing and coverage scenarios. The 19 outbreaks had a median duration of 27.5 weeks and median size of 805.5 cases. At an 8-week ORI delay and 80% vaccine coverage, outbreaks reporting weekly incidence showed a median case reduction of 30.0% (95%CI: 0%-68.5%), corresponding to a median of 275 cases averted (95%CI: 0-2,787). The median cost per DALY averted was $82,756 (95%CI: 0-618,927) and median cases averted per 1,000 doses was 0.63 (95%CI: 0.06-8.76). ORI timing, vaccine coverage, and outbreak characteristics -- particularly duration and size -- were key determinants of impact. ORI is a valuable strategy for mitigating typhoid fever outbreaks. Timely deployment substantially reduces case burden, particularly in larger or longer outbreaks, and is most effective when integrated with water, sanitation, and hygiene interventions in resource-limited settings.