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Models are useful to inform policy decisions on typhoid conjugate vaccine (TCV) deployment in endemic settings. However, methodological choices can influence model-predicted outcomes. To provide robust estimates for the potential public health impact of TCVs that account for structural model differences, we compared four dynamic and one static mathematical model of typhoid transmission and vaccine impact. All models were fitted to a common dataset of age-specific typhoid fever cases in Kolkata, India. We evaluated three TCV strategies: no vaccination, routine vaccination at 9 months of age, and routine vaccination at 9 months with a one-time catch-up campaign (ages 9 months to 15 years). The primary outcome was the predicted percent reduction in symptomatic typhoid cases over 10 years after vaccine introduction. For three models with economic analyses (Models A-C), we also compared the incremental cost-effectiveness ratios (ICERs), calculated as the incremental cost (US$) per disability-adjusted life-year (DALY) averted. Routine vaccination was predicted to reduce symptomatic cases by 10-46 % over a 10-year time horizon under an optimistic scenario (95 % initial vaccine efficacy and 19-year mean duration of protection), and by 2-16 % under a pessimistic scenario (82 % initial efficacy and 6-year mean protection). Adding a catch-up campaign predicted a reduction in incidence of 36-90 % and 6-35 % in the optimistic and pessimistic scenarios, respectively. Vaccine impact was predicted to decrease as the relative contribution of chronic carriers to transmission increased. Models A-C all predicted routine vaccination with or without a catch-up campaign to be cost-effective compared to no vaccination, with ICERs varying from $95-789 per DALY averted; two models predicted the ICER of routine vaccination alone to be greater than with the addition of catch-up campaign. Despite differences in model-predicted vaccine impact and cost-effectiveness, routine vaccination plus a catch-up campaign is likely to be impactful and cost-effective in high incidence settings such as Kolkata.

Typhoid conjugate vaccine (TCV) has been shown to be costeffective in some settings, but to make the most of limited healthcare funds, the WHO recommends that decisions about when and where to introduce TCV should be based on local evidence of transmission. Further, Gavi, The Vaccine Alliance, recommends that countries request TCV funding based on epidemiological data from within-country. Since few countries have reliable case reporting, we considered environmental surveillance as a decision-support tool for vaccine introduction choices. Environmental surveillance methods are still in development and this analysis assesses its potential as a decision support tool. We combined a disease transmission simulation model with an economic model, to quantify the value of surveillance. The disease transmission model is fit to historical case reporting from Blantyre, Malawi. The economic model takes a social perspective and incorporates the cost of environmental surveillance, vaccination, and both direct and indirect cost of care for acute typhoid cases. We find that the use of time-limited environmental surveillance to differentiate low- from high-endemicity areas is low cost relative to potential savings, especially if it is paired with a locally targeted vaccination campaign. These findings are robust to the uncertainty of cost model parameters and underlying endemicity.