Modeling the drivers of differential Typhoid Conjugate Vaccine (TCV) impact in Pakistan: force of infection and age-specific duration of protection

BackgroundWhile trials have demonstrated high efficacy of typhoid conjugate vaccine (TCV), data on effectiveness are limited. We report initial impacts and predict future benefits of TCV from two provinces in Pakistan. MethodsWe used blood culture-confirmed typhoid cases from the Surveillance for Enteric Fever in Asia Project (SEAP) and Impact assessment of Typhoid conjugate vaccine following introduction in Routine Immunization Program of Pakistan (ITRIPP) to estimate the population-level impact of vaccination (2018-2023). We used regression models to estimate initial impacts and an agent-based model to predict future benefits. FindingsIn Sindh, typhoid incidence was higher and cases were younger compared with Punjab. TCV reduced incidence by 48.9% in Sindh (95% CI: 47.3-50.3%) and 66.2% in Punjab (95% CI: 64.7%, 67.6%) over the first 2 years after vaccine rollout but declined each year. In Sindh, waning was quicker and models predicted that population incidence would stabilize near pre-vaccine levels in 2024. An additional campaign could provide short-term, but not long-term, benefits. In contrast, in Punjab, incidence is projected to remain low for several years, and the standard vaccine program may be sufficient. However, follow up data from Punjab are needed to better characterize waning immunity. InterpretationTCV has reduced incidence in Pakistan, but protection varies by site. Standard vaccine policy may be sufficient to control incidence in settings with moderate transmission. However, in settings with particularly high incidence and/or short duration of protection, alternative strategies to reduce the force of infection may be needed. FundingBill & Melinda Gates Foundation