Abstract
Typhoid fever remains a major public health threat in low- and middle-income countries (LMICs), where inadequate access to clean water and sanitation drives recurrent outbreaks. With antimicrobial resistance on the rise, the urgency of deploying preventive strategies such as typhoid conjugate vaccines (TCVs) have grown. In this study, we developed a dynamic compartmental model calibrated to the 2015 typhoid outbreak in Kampala, Uganda, to assess the health and economic outcomes of various outbreak response immunization (ORI) strategies using TCVs. We aimed to identify optimal ORI strategies that minimize cases and typhoid-related deaths as well as the costs of implementation. Our model incorporated different phases of the outbreak, vaccine coverage levels (30%, 50%, 70%), timing (early, late, combined), and campaign duration. Cost-effectiveness was evaluated based on disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (ICERs), using World Health Organization (WHO) thresholds derived from Uganda's 2015 gross national income per capita. Early, high-coverage vaccination (Scenario 1) was most impactful reducing the effective reproduction number (Rt) below 1 during the epidemic peak and averting over 7,000 cases including 180 deaths. The timing of vaccine deployment was the most critical determinant of effectiveness, followed by coverage level and campaign duration. Our findings highlight the importance of rapid, high-coverage TCV deployment at the early stages of an outbreak. Strengthening disease surveillance and improving vaccine logistics are essential for a timely response. This modeling framework offers actionable evidence to support policy development and optimize outbreak preparedness in typhoid-endemic regions.