Predicting the Impact of Vaccination on the Transmission Dynamics of Typhoid in South Asia: A Mathematical Modeling Study.

Background: Modeling of the transmission dynamics of typhoid allows for an evaluation of the potential direct and indirect effects of vaccination; however, relevant typhoid models rooted in data have rarely been deployed. Methodology/Principal Findings: We developed a parsimonious age-structured model describing the natural history and immunity to typhoid infection. The model was fit to data on culture-confirmed cases of typhoid fever presenting to Christian Medical College hospital in Vellore, India from 2000–2012. The model was then used to evaluate the potential impact of school-based vaccination strategies using live oral, Vi-polysaccharide, and Vi-conjugate vaccines. The model was able to reproduce the incidence and age distribution of typhoid cases in Vellore. The basic reproductive number (R0) of typhoid was estimated to be 2.8 in this setting. Vaccination was predicted to confer substantial indirect protection leading to a decrease in the incidence of typhoid in the short term, but (intuitively) typhoid incidence was predicted to rebound 5–15 years following a one-time campaign. Conclusions/Significance: We found that model predictions for the overall and indirect effects of vaccination depend strongly on the role of chronic carriers in transmission. Carrier transmissibility was tentatively estimated to be low, consistent with recent studies, but was identified as a pivotal area for future research. It is unlikely that typhoid can be eliminated from endemic settings through vaccination alone. Author Summary: We developed a mathematical model for the transmission dynamics of typhoid in order to evaluate the potential direct and indirect (i.e. herd immunity) effects of vaccination. The model was fit to data from Vellore, India and validated against the results of cluster randomized vaccine trials. We evaluated a variety of school-based vaccination strategies and found that typhoid vaccination is expected to lead to short-term indirect protection and a decrease in typhoid incidence, but vaccination alone is unlikely to lead to elimination. The level of indirect protection was found to depend on assumptions about the role of chronic carriers, identifying an important area for future research. [ABSTRACT FROM AUTHOR]