Comparison of model predictions of typhoid conjugate vaccine public health impact and cost-effectiveness

Abstract

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.

Keywords: Economic evaluation; Mathematical modeling; Model comparison; Typhoid conjugate vaccines; Typhoid fever.

Fig. 1

Model fits to the incidence of blood-culture-confirmed typhoid fever during a population-based surveillance study in Kolkata, India. The black bars represent the observed incidence , while the colored bars represent the fitted models. Note that Model C is a static model that uses the observed age-specific incidence as an input.

Fig. 2

Model predictions for the percent reduction in the incidence of typhoid fever cases over 10 years. We examined two different vaccination strategies (routine or routine plus a catch-up campaign) and three different assumptions for the relative infectiousness of chronic carriers (r); the base-case scenario assumes r = 0.1 (outlined). Results are shown for each of the five models (colored bars) and for each combination of assumptions regarding the initial vaccine efficacy (95 % or 82 %) and average duration of protection (19 years or 6 years) (horizontal axis groups).

Fig. 3

Time series of annual model-predicted cases per 100,000 population for 10 years after vaccine introduction. Projected cases are shown for different assumptions of initial vaccine efficacy (95 % or 82 %) and average duration of protection (19 years or 6 years), and for each vaccination strategy: no vaccination, routine vaccination, and routine vaccination plus a catch-up campaign. Results shown are for the base-case scenario assuming the relative infectious of chronic carriers is 0.1.

Fig. 4

Cost-effectiveness planes. Incremental costs compared to a no vaccination strategy (in thousands of 2016 USD) vs benefits (DALYs averted) for five scenarios of initial vaccine efficacy (VE), average duration of protection (yrs), and case fatality risk (CFR).