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The current burden of disease is estimated at 11\u201318 million infections annually, with the majority of infections located in Africa and South Asia. Data that have been used to estimate burden are limited to a small number of blood-culture surveillance studies, largely from densely populated urban centers. Extrapolating these data to estimate disease burden within and across countries highlights the lack of precision in global figures. A number of approaches have been developed, characterizing different geographical areas by water-based risk factors for typhoid infection or broader measures of health and development to more accurately extrapolate incidence. Recognition of the substantial disease burden is essential for policy-makers considering vaccine introduction. Typhoid vaccines have been in development for &amp;gt;100 years. The Vi polysaccharide (ViPS) and Ty21a vaccines have had a World Health Organization (WHO) recommendation for programmatic use in countries with high burden for 10 years, with 1 ViPS vaccine also having WHO prequalification. Despite this, uptake and introduction of these vaccines has been minimal. The development of a controlled human infection model (CHIM) enabled the accelerated testing of the newly WHO-prequalified ViPS\u2013tetanus toxoid protein conjugate vaccine, providing efficacy estimates for the vaccine, prior to larger field trials. There is an urgency to the global control of enteric fever due to the escalating problem of antimicrobial resistance. With more accurate burden of disease estimates and a vaccine showing efficacy in CHIM, that control is now a possibility.<\/jats:p>","DOI":"10.1093\/cid\/ciz630","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T11:25:44Z","timestamp":1563967544000},"page":"S402-S407","source":"Crossref","is-referenced-by-count":19,"title":["Generating the Evidence for Typhoid Vaccine Introduction: Considerations for Global Disease Burden Estimates and Vaccine Testing Through Human Challenge"],"prefix":"10.1093","volume":"69","author":[{"given":"James E","family":"Meiring","sequence":"first","affiliation":[{"name":"Oxford Vaccine Group, Department of Paediatrics, University of Oxford, United Kingdom"},{"name":"National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Giubilini","sequence":"additional","affiliation":[{"name":"Oxford Uehiro Centre for Practical Ethics, University of Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Savulescu","sequence":"additional","affiliation":[{"name":"Oxford Uehiro Centre for Practical Ethics, University of Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia E","family":"Pitzer","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J","family":"Pollard","sequence":"additional","affiliation":[{"name":"Oxford Vaccine Group, Department of Paediatrics, University of Oxford, United Kingdom"},{"name":"National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,10,15]]},"reference":[{"key":"2019121022405055900_CIT0001","doi-asserted-by":"crossref","first-page":"e0005376","DOI":"10.1371\/journal.pntd.0005376","article-title":"The burden of typhoid fever in low- and middle-income countries: a meta-regression approach","volume":"11","author":"Antill\u00f3n","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"2019121022405055900_CIT0002","doi-asserted-by":"crossref","first-page":"e570","DOI":"10.1016\/S2214-109X(14)70301-8","article-title":"Burden of typhoid fever in low-income and middle-income countries: a systematic, literature-based update with risk-factor adjustment","volume":"2","author":"Mogasale","year":"2014","journal-title":"Lancet Glob Health"},{"key":"2019121022405055900_CIT0003","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"},{"key":"2019121022405055900_CIT0004","first-page":"346","article-title":"The global burden of typhoid fever","volume":"82","author":"Crump","year":"2004","journal-title":"Bull World Health Organ"},{"key":"2019121022405055900_CIT0005","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/infdis\/7.4.489","article-title":"On the Mills-Reincke phenomenon and Hazen s theorem concerning the decrease in mortality from diseases other than typhoid fever following the purification of public water-supplies","volume":"7","author":"Sedgwick","year":"1910","journal-title":"J Infect Dis"},{"key":"2019121022405055900_CIT0006","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1353\/dem.2005.0002","article-title":"The role of public health improvements in health advances: the twentieth-century United States","volume":"42","author":"Cutler","year":"2005","journal-title":"Demography"},{"key":"2019121022405055900_CIT0007","volume-title":"WHO\/UNICEF Joint Monitoring Programme for Water Supply and Sanitation","author":"UN-Water"},{"key":"2019121022405055900_CIT0008","doi-asserted-by":"crossref","first-page":"5081","DOI":"10.1016\/j.vaccine.2017.08.001","article-title":"The Typhoid Vaccine Acceleration Consortium (TyVAC): vaccine effectiveness study designs: accelerating the introduction of typhoid conjugate vaccines and reducing the global burden of enteric fever. 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