The economic case for typhoid conjugate vaccines in countries with medium and high incidence of infection
Authors: Youngji Jo, David W Dowdy
Journal: The Lancet Infectious Diseases (2019)

Typhoid fever affects an estimated 11–20 million people globally, causing 128 000–161 000 deaths per year, many of which occur in young children living in resource-limited settings.1WHOTyphoid.https://www.who.int/mediacentre/factsheets/typhoid/en/Date: 2018Date accessed: January 11, 2019Google Scholar, 2Mogasale V Maskery B Ochiai RL et al.Burden of typhoid fever in low-income and middle-income countries: a systematic, literature-based update with risk-factor adjustment.Lancet Glob Health. 2014; 2: e570-e580Summary Full Text Full Text PDF PubMed Scopus (341) Google Scholar Newly developed typhoid conjugate vaccines (TCVs) are safe, efficacious, and offer durable protection, making TCVs compatible with WHO's Expanded Programme on Immunization (assuming routine vaccination at 9 months of age).3Andrews JR Baker S Marks F et al.Typhoid conjugate vaccines: a new tool in the fight against antimicrobial resistance.Lancet Infect Dis. 2019; 19: e26-e30Summary Full Text Full Text PDF PubMed Scopus (44) Google Scholar However, catch-up campaigns in children up to the age of 5 years or 15 years might also be appropriate, and cost-effectiveness is a critical consideration in choosing the ideal TCV strategy for a given setting.4Antillón M Bilcke J Paltiel AD Pitzer VE Cost-effectiveness analysis of typhoid conjugate vaccines in five endemic low- and middle-income settings.Vaccine. 2017; 35: 3506-3514Crossref PubMed Scopus (39) Google Scholar In their study published The Lancet Infectious Diseases, Joke Bilcke and colleagues5Bilcke J Antillón M Pieters Z et al.Cost-effectiveness of routine and campaign use of typhoid Vi-conjugate vaccine in Gavi-eligible countries: a modelling study.Lancet Infect Dis. 2019; (published online May 23.)http://dx.doi.org/10.1016/S1473-3099(18)30804-1Summary Full Text Full Text PDF PubMed Scopus (31) Google Scholar used a comprehensive model of typhoid transmission dynamics, vaccine costs, and epidemiological outcomes to evaluate the cost-effectiveness of alternative TCV delivery strategies in each of the 54 countries eligible for financial support from Gavi, The Vaccine Alliance. The authors concluded that a combined approach (routine immunisation of infants plus a catch-up campaign to the age of 15 years) is likely to be cost-effective in most high-incidence settings (>300 symptomatic cases per 100 000 people per year), whereas no TCV delivery strategy is likely to be cost-effective in low-incidence settings (<30 symptomatic cases per 100 000 annually). These findings are in broad agreement with those of a separate, independent cost-effectiveness analysis by Lo and colleagues,6Lo NC Gupta R Stanaway JD et al.Comparison of strategies and incidence thresholds for Vi conjugate vaccines against typhoid fever: a cost-effectiveness modeling study.J Infect Dis. 2018; 218: S232-S242Crossref PubMed Scopus (24) Google Scholar providing useful guidance to decision makers in high-incidence and low-incidence countries. In medium-incidence settings, however, the situation is less clear. Bilcke and colleagues suggest that the optimal TCV delivery strategy is likely to be all or none—routine immunisation plus a catch-up campaign to age 15 years in most medium-incidence countries and no TCV immunisation at all in a few. By contrast, Lo and colleagues suggest that routine immunisation without catch-up campaigns might be preferred in settings with medium incidence (50–130 symptomatic cases per 100 000 annually) and lower willingness to pay (<US$1000 per disability-adjusted life-year averted). Both analyses agree that the two most important factors in determining the optimal TCV strategy, from a health economic perspective, are typhoid-specific mortality and local willingness-to-pay thresholds, neither of which has been well defined in most countries with medium to high incidence of typhoid. In most medium-incidence countries, a key policy question will therefore be whether catch-up campaigns should be implemented, and if so, how? For example, such campaigns could be one-off or recurring, delivered at the national or sub-national level, and targeted at all children under a certain age or at specific age groups (eg, those entering elementary school). Importantly, as countries begin to implement TCV, the incidence of typhoid fever would be likely to fall, and the burden of morbidity and mortality would probably shift to older age groups. It might therefore also be important to account for any anticipated cessation of routine TCV immunisation, considering that many medium-incidence countries could become low-incidence within the foreseeable future as a result of TCV implementation and other intervention measures. For these and all other policy questions, cost-effectiveness is only one of many considerations, but it will be important to be forward-looking in future approaches to economic evaluation, moving on from questions of whether to implement TCV immunisation to how, where, and how frequently catch-up campaigns should be done. As Bilcke and colleagues showed, it is in medium-incidence countries that are increasingly willing to pay more for vaccination programmes that the value of additional information (in particular data on typhoid-specific mortality) is greatest. Efforts to implement TCV immunisation should therefore be combined with efforts to collect high-quality data on mortality due to typhoid fever, especially in medium-incidence settings. In summary, this rigorous model-based study, taken into account alongside other publications, provides strong evidence that TCV vaccines would be cost-effective in Gavi-eligible countries where incidence of typhoid fever is high, and is likely to be cost-effective in most medium-incidence countries. Policy decisions should consider regional variations in typhoid burden and access to care,7Antillón M Warren JL Crawford FW et al.The burden of typhoid fever in low- and middle-income countries: a meta-regression approach.PLoS Negl Trop Dis. 2017; 11: e0005376Crossref PubMed Scopus (159) Google Scholar how current interventions might affect the epidemiology of typhoid fever in the future, the feasibility of implementing specific catch-up vaccination strategies, and a careful assessment of willingness to pay. Systems for collecting better data on typhoid-specific mortality should also be prioritised. The high-level economic case for TCV immunisation in countries with medium and high incidence of typhoid fever has been made; it is now time to get down to the details of how to best deliver TCVs to save children's lives. The authors declare no competing interests. Cost-effectiveness of routine and campaign use of typhoid Vi-conjugate vaccine in Gavi-eligible countries: a modelling studyCountries 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. Full-Text PDF Open Access