Evaluating the impact and cost-effectiveness of typhoid conjugate vaccine schedules across diverse settings: A multi-model comparison

Background: The typhoid conjugate vaccine (TCV) may lose effectiveness over time, prompting the World Health Organization (WHO) to commission a study comparing optimal vaccination schedules using agent-based and compartmental dynamic models of typhoid transmission. The models were calibrated using age-specific incidence data from areas with medium, high, and very high typhoid incidence rates.

Methods and Findings: Researchers evaluated two types of TCV schedules across different scenarios, assessing their public health and economic impacts using a net-monetary-benefit framework. The optimal routine vaccination schedule was found to be at 9 months, with a catch-up campaign for those aged 15 years and a booster dose at 5 years, resulting in a median reduction of 40%–68% in typhoid cases across all incidence settings.

TCV introduction with catch-up campaigns was cost-effective in medium incidence settings when illness costs and case fatality risk (CFR) are high, and in high incidence settings when costs and CFR are low.

In very high incidence areas, introducing TCV at 9 months or 2 years of age proved cost-saving, and adding a booster dose at 5 years maintained cost-effectiveness across most willingness-to-pay thresholds. However, the optimal schedule may vary depending on the typhoid incidence rate, case fatality rate, and the rate at which vaccine protection wanes. The study was limited by the data available on indirect vaccine protection and other simplifying assumptions made during analysis.