title: Burden of typhoid fever in low-income and middle-income countries: a systematic, literature-based update with risk-factor adjustment.
abstract: BACKGROUND
  No access to safe water is an important risk factor for typhoid fever, yet risk-level heterogeneity is unaccounted for in previous global burden estimates. Since WHO has recommended risk-based use of typhoid polysaccharide vaccine, we revisited the burden of typhoid fever in low-income and middle-income countries (LMICs) after adjusting for water-related risk.
  
  
  METHODS
  We estimated the typhoid disease burden from studies done in LMICs based on blood-culture-confirmed incidence rates applied to the 2010 population, after correcting for operational issues related to surveillance, limitations of diagnostic tests, and water-related risk. We derived incidence estimates, correction factors, and mortality estimates from systematic literature reviews. We did scenario analyses for risk factors, diagnostic sensitivity, and case fatality rates, accounting for the uncertainty in these estimates and we compared them with previous disease burden estimates.
  
  
  RESULTS
  The estimated number of typhoid fever cases in LMICs in 2010 after adjusting for water-related risk was 11·9 million (95% CI 9·9-14·7) cases with 129 000 (75 000-208 000) deaths. By comparison, the estimated risk-unadjusted burden was 20·6 million (17·5-24·2) cases and 223 000 (131 000-344 000) deaths. Scenario analyses indicated that the risk-factor adjustment and updated diagnostic test correction factor derived from systematic literature reviews were the drivers of differences between the current estimate and past estimates.
  
  
  CONCLUSIONS
  The risk-adjusted typhoid fever burden estimate was more conservative than previous estimates. However, by distinguishing the risk differences, it will allow assessment of the effect at the population level and will facilitate cost-effectiveness calculations for risk-based vaccination strategies for future typhoid conjugate vaccine.
authors.affiliation: International Vaccine Institute, Seoul, South Korea. Electronic address: vmogasale@ivi.int.
authors.forename: Vittal
authors.initials: V
authors.lastname: Mogasale
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Brian
authors.initials: B
authors.lastname: Maskery
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: R Leon
authors.initials: RL
authors.lastname: Ochiai
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Jung Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Vijayalaxmi V
authors.initials: VV
authors.lastname: Mogasale
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Enusa
authors.initials: E
authors.lastname: Ramani
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Young Eun
authors.initials: YE
authors.lastname: Kim
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Park
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wierzba
mesh_terms: D001431:Bacteriological Techniques; D003906:Developing Countries; D014943:Global Health; D006801:Humans; D011159:Population Surveillance; D012307:Risk Factors; D014435:Typhoid Fever / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage; D014881:Water Supply
chemical_list: D014436:Typhoid-Paratyphoid Vaccines