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Typhoid fever is an acute systemic infectious disease responsible for an estimated 12–20 million illnesses and over 150 000 deaths annually. In March, 2018, a new recommendation was issued by WHO for the programmatic use of typhoid conjugate vaccines in endemic countries. Health economic analyses of typhoid vaccines have informed funding decisions and national policies regarding vaccine rollout. However, by focusing only on averted typhoid cases and their associated costs, traditional cost-effectiveness analyses might underestimate crucial benefits of typhoid vaccination programmes, because the potential effect of typhoid vaccines on the treatment of patients with non-specific acute febrile illnesses is not considered. For every true case of typhoid fever, three to 25 patients without typhoid disease are treated with antimicrobials unnecessarily, conservatively amounting to more than 50 million prescriptions per year. Antimicrobials for suspected typhoid might therefore be an important selective pressure for the emergence and spread of antimicrobial resistance globally. We propose that large-scale, more aggressive typhoid vaccination programmes—including catch-up campaigns in children up to 15 years of age, and vaccination in lower incidence settings—have the potential to reduce the overuse of antimicrobials and thereby reduce antimicrobial resistance in many bacterial pathogens. Funding bodies and national governments must therefore consider the potential for broad reductions in antimicrobial use and resistance in decisions related to the rollout of typhoid conjugate vaccines.

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. 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. 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. 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. Bill & Melinda Gates Foundation, Research Foundation–Flanders, and the Belgian–American Education Foundation.

A novel typhoid conjugate vaccine (TCV) presentation, the microarray patch (MAP), is in early-stage development and could potentially help to increase coverage in hard-to-reach populations beyond what is being achieved with the current TCV in a vial presentation administered with a needle and syringe (TCV-N&S). However, TCV-MAPs may come at a higher price per dose than TCV-N&S. Our analysis evaluated the potential cost-effectiveness of TCV-MAPs alongside TCV-N&S compared to TCV-N&S alone. A global extended cost-effectiveness analysis, taking a health care perspective, was conducted for 133 low- to upper-middle-income countries for a time horizon of 20 years (2033–2052). Health outcomes were expressed in disability-adjusted life years (DALYs) and costs in 2021 US dollars, both discounted at 3 %. We assumed TCV-MAP would cost 1.33 to 3 times the price of the TCV-N&S vaccine. We calculated incremental cost-effectiveness ratios and evaluated them against various cost-effectiveness thresholds. For five selected countries, we conducted an additional subnational analysis to understand the potential value of a district-specific TCV-MAP implementation instead of a national rollout. Across the 133 low- to upper-middle-income countries, national rollout of TCV-MAPs could avert an additional 5.2 million cases, 47,000 deaths, and 2.4 million DALYs compared to TCV-N&S only, at an additional cost of US$3.5 billion over 20 years. The largest proportion of the averted burden would be in the sub-Saharan African region. TCV-MAPs could be cost-effective in 33 % of the countries but in 78 % of sub-Saharan African countries. A subnational implementation could benefit some countries for which a national implementation may not be cost-effective, averting 2–15 % of cases for less than 1–3 % of the additional cost as compared to a national rollout. MAP price was a key driver of the results. Regional or subnational implementation, coupled with a lower price point, could significantly improve the TCV-MAP value proposition.

Typhoid fever remains a major public health threat in low- and middle-income countries (LMICs), where inadequate access to clean water and sanitation drives recurrent outbreaks. With antimicrobial resistance on the rise, the urgency of deploying preventive strategies such as typhoid conjugate vaccines (TCVs) have grown. In this study, we developed a dynamic compartmental model calibrated to the 2015 typhoid outbreak in Kampala, Uganda, to assess the health and economic outcomes of various outbreak response immunization (ORI) strategies using TCVs. We aimed to identify optimal ORI strategies that minimize cases and typhoid-related deaths as well as the costs of implementation. Our model incorporated different phases of the outbreak, vaccine coverage levels (30%, 50%, 70%), timing (early, late, combined), and campaign duration. Cost-effectiveness was evaluated based on disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (ICERs), using World Health Organization (WHO) thresholds derived from Uganda’s 2015 gross national income per capita. Early, high-coverage vaccination (Scenario 1) was most impactful reducing the effective reproduction number ( R t ) below 1 during the epidemic peak and averting over 7,000 cases including 180 deaths. The timing of vaccine deployment was the most critical determinant of effectiveness, followed by coverage level and campaign duration. Our findings highlight the importance of rapid, high-coverage TCV deployment at the early stages of an outbreak. Strengthening disease surveillance and improving vaccine logistics are essential for a timely response. This modeling framework offers actionable evidence to support policy development and optimize outbreak preparedness in typhoid-endemic regions.

Typhoid fever remains endemic in low- and middle-income countries. Programmatic use of existing vaccines is limited, but upcoming typhoid conjugate vaccines (TCVs) could warrant wider use. We evaluated the cost-effectiveness of five TCV delivery strategies in three urban areas (Delhi and Kolkata, India and Nairobi, Kenya) and two rural settings (Lwak, Kenya and Dong Thap, Vietnam) with varying incidence. We evaluated routine infant vaccination with and without catch-up campaigns among older individuals. We used a dynamic model of typhoid transmission to simulate cases, hospitalizations, deaths, disability-adjusted life-years (DALY) lost, treatment and intervention costs. We estimated cost-effectiveness (in terms of cost in international dollars (I$) per DALY averted) from the healthcare payer perspective, and assessed how it was influenced by uncertain model parameters. Compared to no vaccination, routine infant vaccination at I$1/dose was cost-saving in Delhi and Dong Thap, “very cost-effective” in Kolkata and Nairobi, and “cost-effective” in Lwak according to World Health Organization thresholds. However, routine vaccination was not the optimal strategy compared to strategies that included a catch-up campaign, which yielded the highest probability of being cost-saving in Delhi and Dong Thap and were most likely to provide a return on investment above a willingness-to-pay threshold of I$1440 in Kolkata, I$2300 in Nairobi, and I$5360 in Lwak. Vaccine price impacted the optimal strategy, and the number of doses required and rate of hospitalization were the primary sources of uncertainty. Routine vaccination with TCV would be cost-effective in most settings, and additional one-time catch-up campaigns would also be economically justified.

Typhoid places a substantial economic burden on low- and middle-income countries. We performed a literature review and critical overview of typhoid-related economic issues to inform vaccine introduction. We searched 4 literature databases, covering 2000–2017, to identify typhoid-related cost-of-illness (COI) studies, cost-of-delivery studies, cost-effectiveness analyses (CEAs), and demand forecast studies. Manual bibliographic searches of reviews revealed studies in the gray literature. Planned studies were identified in conference proceedings and through partner organization outreach. We identified 29 published, unpublished, and planned studies. Published COI studies revealed a substantial burden in Asia, with hospitalization costs alone ranging from $159 to $636 (in 2016 US$) in India, but there was less evidence for the burden in Africa. Cost-of-delivery studies are largely unpublished, but 1 study found that $671 000 in government investments would avert $60 000 in public treatment costs. CEA evidence was limited, but generally found targeted vaccination programs to be cost-effective. This review revealed insufficient economic evidence for vaccine introduction. Countries considering vaccine introduction should have access to relevant economic evidence to aid in decision-making and planning. Planned studies will fill many of the existing gaps in the literature.

The World Health Organization now recommends the use of typhoid conjugate vaccines (TCVs) in typhoid-endemic countries, and Gavi, the Vaccine Alliance, added TCVs into the portfolio of subsidized vaccines. Data from the Severe Typhoid Fever in Africa (SETA) program were used to contribute to TCV introduction decision-making processes, exemplified for Ghana and Madagascar. Data collected from both countries were evaluated, and barriers to and benefits of introduction scenarios are discussed. No standardized methodological framework was applied. The Ghanaian healthcare system differs from its Malagasy counterpart: Ghana features a functioning insurance system, antimicrobials are available nationwide, and several sites in Ghana deploy blood culture-based typhoid diagnosis. A higher incidence of antimicrobial-resistant Salmonella Typhi is reported in Ghana, which has not been identified as an issue in Madagascar. The Malagasy people have a low expectation of provided healthcare and experience frequent unavailability of medicines, resulting in limited healthcare-seeking behavior and extended consequences of untreated disease. For Ghana, high typhoid fever incidence coupled with spatiotemporal heterogeneity was observed. A phased TCV introduction through an initial mass campaign in high-risk areas followed by inclusion into routine national immunizations prior to expansion to other areas of the country can be considered. For Madagascar, a national mass campaign followed by routine introduction would be the introduction scenario of choice as it would protect the population, reduce transmission, and prevent an often-deadly disease in a setting characterized by lack of access to healthcare infrastructure. New, easy-to-use diagnostic tools, potentially including environmental surveillance, should be explored and improved to facilitate identification of high-risk areas.

With a newly World Health Organization (WHO)–prequalified typhoid conjugate vaccine (TCV), Gavi funding for eligible countries, and a WHO policy recommendation for TCV use, now is the time for countries to introduce TCVs as part of an integrated typhoid control program, particularly in light of the increasing burden of antimicrobial resistance. Continued vaccine development efforts will lead to secure supply of low-cost vaccines, and ongoing vaccine studies will provide critical vaccine performance data and inform optimal deployment strategies, in both routine use and in outbreak settings. TCV programs should include thoughtful communication planning and community engagement to counter vaccine hesitancy.

Typhoid fever is responsible for a substantial health burden in low- and middle-income countries (LMICs). New means of prevention became available with the prequalification of typhoid conjugate vaccines (TCV) by the World Health Organization (WHO) in 2018. Policymakers require evidence to inform decisions about TCV. The economic burden related to typhoid fever can be considerable, both for healthcare providers and households, and should be accounted for in the decision-making process. We aimed to understand the breadth of the evidence on the cost of typhoid fever by undertaking a scoping review of the published literature. We searched scientific databases with terms referring to typhoid fever cost of illness to identify published studies for the period January 1st 2000 to May 24 th 2024. We also conferred with stakeholders engaged in typhoid research to identify studies pending completion or publication. We identified 13 published studies reporting empirical data for 11 countries, most of them located in Asia. The total cost of a typhoid episode ranged from$23 in India to $ 884 in Indonesia (current 2022 United States Dollar [USD]). Household expenditures related to typhoid fever were characterized as catastrophic in 9 studies. We identified 5 studies pending completion or publication, which will provide evidence for 9 countries, most of them located in Africa. Alignment in study characteristics and methods would increase the usefulness of the evidence generated and facilitate cross-country and regional comparison. The gap in evidence across regions should be mitigated when studies undertaken in African countries are published. There remains a lack of evidence on the cost to treat typhoid in the context of increasing antimicrobial resistance. Decision-makers should consider the available evidence on the economic burden of typhoid, particularly as risk factors related to antimicrobial resistance and climate change increase typhoid risk. Additional studies should address typhoid illness costs, using standardized methods and accounting for the costs of antimicrobial resistance.

In the United States, typhoid vaccination is recommended for international travelers to areas with a recognized risk of typhoid exposure. Using MarketScan® Commercial Database from 2016 through 2022, we estimated typhoid vaccination costs by route (injectable vs. oral) and provider setting (clinic vs. pharmacy). Of 165,930 vaccinated individuals, 99,471 received injectable and 66,459 received oral typhoid vaccines, with 88 % and 17 % respectively administered at clinics. Average costs for injectable vaccination were $132.91 per person [95 % confidence interval (CI): $132.68–$133.13], with clinic and pharmacy costs at $136.38 [95 % CI: $136.14–$136.63] and $107.45 [95 % CI: $107.13–$107.77], respectively. Oral vaccination costs averaged $81.23 per person [95 % CI: $81.14–$81.33], encompassing $86.61 [95 % CI: $86.13–$87.10] at clinics and $80.14 [95 % CI: $80.09–$80.19] at pharmacies. Out-of-pocket costs comprised 21 % and 33 % of total costs for injectable and oral vaccinations. These findings may inform clinical decision-making to protect international travelers’ health.