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All models were fitted to harmonized age-specific incidence data from medium, high, and very high incidence settings. We assessed different TCV schedules under slow- and fast-waning scenarios to evaluate the best age for routine vaccination and the potential need for booster doses and catch-up campaigns. We evaluated the public health and economic impact predicted for each model and scenario using the net-monetary-benefit framework to determine cost-effectiveness under two representative scenarios for the health outcomes and costs of vaccination and treatment. Over a 10-year time horizon, routine vaccination at 9 months with a catch-up campaign to 15 years and a booster dose at 5 years was predicted to have the greatest impact, reducing cases by a median of 40%\u201368% across the incidence settings. Across all four models, TCV introduction with a catch-up campaign was cost-effective above willingness-to-pay (WTP) thresholds of $1,250 per disability-adjusted life-year (DALY) averted in medium incidence settings when costs of illness and case fatality risk (CFR) are high and in high incidence settings when costs and CFR are low. The optimal strategy was to delay vaccination to 2 or 5 years of age if waning is fast, depending on the age of peak incidence. In very high incidence settings, TCV introduction at 9 months or 2 years of age was cost-saving, and adding a booster dose at 5 years was cost-effective at most WTP values across all scenarios. The study findings are limited by the data available to inform indirect vaccine protection and other simplifying assumptions made in this analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Model predictions for the impact and cost-effectiveness of different TCV schedules were fairly robust to uncertainty in parameter values and model structure, but the optimal strategy depends on the typhoid incidence rate, CFR, and waning rate of vaccine protection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1005280","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:43:49Z","timestamp":1791913429000},"page":"e1005280","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating the impact and cost-effectiveness of typhoid conjugate vaccine schedules across diverse settings: A multi-model comparison"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5564-0630","authenticated-orcid":true,"given":"Catherine G. 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M.","family":"Kraay","sequence":"additional","affiliation":[{"name":"Institute for Disease Modeling, Gates Foundation","place":["Seattle, Washington, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9213-0798","authenticated-orcid":true,"given":"Nick","family":"Scott","sequence":"additional","affiliation":[{"name":"Burnet Institute","place":["Melbourne, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9618-6457","authenticated-orcid":true,"given":"Romesh G.","family":"Abeysuriya","sequence":"additional","affiliation":[{"name":"Burnet Institute","place":["Melbourne, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5967-251X","authenticated-orcid":true,"given":"Jason R.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Stanford University","place":["Stanford, California, United States of America"],"department":["Division of Infectious Diseases and Geographic Medicine, Department of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian","family":"Gauld","sequence":"additional","affiliation":[{"name":"Institute for Disease Modeling, Gates Foundation","place":["Seattle, Washington, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5407-2005","authenticated-orcid":true,"given":"Nathan C.","family":"Lo","sequence":"additional","affiliation":[{"name":"Stanford University","place":["Stanford, California, United States of America"],"department":["Division of Infectious Diseases and Geographic Medicine, Department of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-2289","authenticated-orcid":true,"given":"Virginia E.","family":"Pitzer","sequence":"additional","affiliation":[{"name":"Yale University","place":["New Haven, Connecticut, United States of America"],"department":["Department of Epidemiology of Microbial Diseases, Yale School of Public Health"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"pmed.1005280.ref001","doi-asserted-by":"crossref","first-page":"102883","DOI":"10.1016\/j.eclinm.2024.102883","article-title":"The global burden of enteric fever, 2017\u20132021: A systematic analysis from the global burden of disease study 2021","volume":"77","author":"D Piovani","year":"2024","journal-title":"EClinicalMedicine"},{"issue":"4","key":"pmed.1005280.ref002","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S1473-3099(18)30685-6","article-title":"The global burden of typhoid and paratyphoid fevers: A systematic analysis for the Global Burden of Disease Study 2017","volume":"19","author":"GBD 2017 Typhoid and Paratyphoid Collaborators","year":"2019","journal-title":"Lancet Infect Dis"},{"issue":"3","key":"pmed.1005280.ref003","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/S1473-3099(25)00551-1","article-title":"Complications and mortality of typhoid fever: an updated global systematic review and meta-analysis","volume":"26","author":"S Murthy","year":"2026","journal-title":"Lancet Infect Dis"},{"issue":"4","key":"pmed.1005280.ref004","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1128\/CMR.00002-15","article-title":"Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive Salmonella infections","volume":"28","author":"JA Crump","year":"2015","journal-title":"Clin Microbiol Rev"},{"issue":"2","key":"pmed.1005280.ref005","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.vaccine.2018.04.022","article-title":"Typhoid vaccines: WHO position paper, March 2018 - 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