Cost-effectiveness of routine and campaign use of typhoid Vi-conjugate vaccine in Gavi-eligible countries: a modelling study

Abstract

Background: Typhoid fever is a major cause of morbidity and mortality in low-income and middle-income countries. In 2017, WHO recommended the programmatic use of typhoid Vi-conjugate vaccine (TCV) in endemic settings, and Gavi, The Vaccine Alliance, has pledged support for vaccine introduction in these countries. Country-level health economic evaluations are now needed to inform decision-making.

Methods: In this modelling study, we compared four strategies: no vaccination, routine immunisation at 9 months, and routine immunisation at 9 months with catch-up campaigns to either age 5 years or 15 years. For each of the 54 countries eligible for Gavi support, output from an age-structured transmission-dynamic model was combined with country-specific treatment and vaccine-related costs, treatment outcomes, and disability weights to estimate the reduction in typhoid burden, identify the strategy that maximised average net benefit (ie, the optimal strategy) across a range of country-specific willingness-to-pay (WTP) values, estimate and investigate the uncertainties surrounding our findings, and identify the epidemiological conditions under which vaccination is optimal.

Findings: The optimal strategy was either no vaccination or TCV immunisation including a catch-up campaign. Routine vaccination with a catch-up campaign to 15 years of age was optimal in 38 countries, assuming a WTP value of at least US$200 per disability-adjusted life-year (DALY) averted, or assuming a WTP value of at least 25% of each country's gross domestic product (GDP) per capita per DALY averted, at a vaccine price of $1·50 per dose (but excluding Gavi's contribution according to each country's transition phase). This vaccination strategy was also optimal in 48 countries assuming a WTP of at least $500 per DALY averted, in 51 with assumed WTP values of at least $1000, in 47 countries assuming a WTP value of at least 50% of GDP per capita per DALY averted, and in 49 assuming a minimum of 100%. Vaccination was likely to be cost-effective in countries with 300 or more typhoid cases per 100 000 person-years. Uncertainty about the probability of hospital admission (and typhoid incidence and mortality) had the greatest influence on the optimal strategy.

Interpretation: Countries should establish their own WTP threshold and consider routine TCV introduction, including a catch-up campaign when vaccination is optimal on the basis of this threshold. Obtaining improved estimates of the probability of hospital admission would be valuable whenever the optimal strategy is uncertain.

Funding: Bill & Melinda Gates Foundation, Research Foundation-Flanders, and the Belgian-American Education Foundation.

Figure 1

Predicted impact of typhoid Vi-conjugate vaccine use in Gavi-eligible countries Predicted percentage reduction in symptomatic typhoid cases over 10 years in 54 Gavi-eligible countries when introducing (A) routine vaccination at 9 months of age alone, (B) a routine vaccination programme with a catch-up campaign up to the age of 5 years, and (C) a routine vaccination programme with a catch-up campaign up to the age of 15 years, compared with no vaccination. Vaccine coverage in each country is based on the Gavi demand forecast. Results shown are not discounted.

Figure 2

Optimal intervention strategy and its estimated certainty for each country for a range of willingness-to-pay values per disability-adjusted life-year averted The optimal strategy is defined as the strategy that yields the highest average net monetary benefit and hence is preferable over the three other strategies on the basis of cost-effectiveness alone. Shading shows the preferred strategy: no vaccination (white) or routine immunisation with a catch-up campaign up to age 15 years (shaded). The percentages indicate certainty about the optimal strategy, estimated by the percentage of parameter samples in which the strategy yielded the highest net benefit. The degree of uncertainty influences the value of obtaining more evidence to make a future decision but should not influence the choice of strategy given the current evidence.

Figure 3

Optimal intervention strategy and its estimated certainty for each country for a range of willingness-to-pay values (0–4 times GDP per capita per disability-adjusted life-year averted) The optimal strategy is defined as the strategy that yields the highest average net monetary benefit and hence is preferable over the three other strategies on the basis of cost-effectiveness alone. Shading shows the preferred strategy: no vaccination (white) or routine immunisation with a catch-up campaign up to age 15 years (shaded). Certainty is indicated by the percentage of parameter samples in which the strategy yielded the highest net benefit. The degree of uncertainty influences the value of obtaining more evidence to make a future decision but should not influence the choice of strategy given the current evidence. No gross domestic product per capita was available for North Korea. GDP=gross domestic product.