Comparison of Strategies for Typhoid Conjugate Vaccine Introduction in India: A Cost-Effectiveness Modeling Study

Abstract

Background: Typhoid fever causes substantial global mortality, with almost half occurring in India. New typhoid vaccines are highly effective and recommended by the World Health Organization for high-burden settings. There is a need to determine whether and which typhoid vaccine strategies should be implemented in India.

Methods: We assessed typhoid vaccination using a dynamic compartmental model, parameterized by and calibrated to disease and costing data from a recent multisite surveillance study in India. We modeled routine and 1-time campaign strategies that target different ages and settings. The primary outcome was cost-effectiveness, measured by incremental cost-effectiveness ratios (ICERs) benchmarked against India's gross national income per capita (US$2130).

Results: Both routine and campaign vaccination strategies were cost-saving compared to the status quo, due to averted costs of illness. The preferred strategy was a nationwide community-based catchup campaign targeting children aged 1-15 years alongside routine vaccination, with an ICER of $929 per disability-adjusted life-year averted. Over the first 10 years of implementation, vaccination could avert 21-39 million cases and save $1.6-$2.2 billion. These findings were broadly consistent across willingness-to-pay thresholds, epidemiologic settings, and model input distributions.

Conclusions: Despite high initial costs, routine and campaign typhoid vaccination in India could substantially reduce mortality and was highly cost-effective.

Keywords: India; cost-effectiveness; enteric fever; model; typhoid; vaccines.

Figure 1.

Typhoid infection and natural history. Boxes indicate compartments and arrows indicate transitions between compartments (new infections are further delineated via dashed arrows). Compartment abbreviations are as follows: C, carrier; I_C, clinically infected; I_S, subclinically infected; R, recovered; S, susceptible; V, vaccinated. New infections (transitions to the I_C or I_S compartments) are designated with dashed lines. Details are shown in the Supplementary Technical Appendix.

Figure 2.

Typhoid outcomes over the next 10 years under the status quo. Left panel displays projected incidence after 10 years of the status quo of no national vaccination strategy, stratified by age group and urban-rural setting. Middle panel displays projected cumulative cases (left axis) and cumulative typhoid deaths (right axis) over the next 10 years, also stratified by age group and urban-rural setting. Right panel shows cumulative costs over the next 10 years, stratified by age group and medical vs nonmedical (out of pocket and productivity) costs. Costs broken down by urban-rural setting are available in Supplementary Figure 3. Abbreviations: cum., cumulative; USD, United States dollars.

Figure 3.

Typhoid incidence and costs over the next 10 years with typhoid vaccination. Left 2 panels show annual incidence (top) and cumulative costs (bottom) by time and strategy over 10 years of implementation. Right 2 panels show annual incidence (top) and cumulative costs (bottom) after 10 years. In the left 2 panels, school-based strategies are shown with dashed lines. Error bars reflect model parameter uncertainty and were calculated based on the 2.5th and 97.5th quantiles of costs and cases across 10 000 simulations. Error bars do not reflect correlation in outcomes across strategies for a given simulation (eg, high cost ranges for 1 strategy typically correlate with high cost ranges for the remaining 8 strategies). Abbreviations: cum., cumulative; USD, United States dollars.

Figure 4.

Cost-effectiveness analysis sensitivity over parameter uncertainty and willingness to pay (WTP). Figure shows the proportion of 10 000 probabilistic sensitivity analysis runs for which a given strategy was considered the preferred strategy (nondominated with the highest incremental cost-effectiveness ratio below the WTP threshold) over a range of WTP thresholds. Abbreviation: USD, United States dollars.

Figure 5.

One-way sensitivity analysis. Figure depicts the preferred strategy when all parameters are held at their mean values and a single parameter is adjusted over its full range. Thick black lines indicate the mean values for each parameter. The x-axis indicates the parameter value when it is scaled from 0% to 100%, with 0% representing the minimum, 100% representing the maximum, 50% representing the median, and so on. The x-axis locations where the graph changes color indicate the threshold of that parameter value at which the optimal strategy changes. Parameter minima and maxima are displayed on the plot margins.