The global burden of enteric fever, 2017-2021: a systematic analysis from the global burden of disease study 2021.

Background: Enteric fever is a major public health challenge in developing countries. We conducted a systematic analysis from the Global Burden of Diseases 2021 Study to provide updated estimates of enteric fever's burden. Methods: We presented estimates for incident cases and deaths, age-standardized incidence and mortality rates, years of life lost (YLLs), and case-fatality rates spanning the study period of 2017-2021, stratified by region, country, socio-demographic index (SDI), and age group. Random-effects Poisson regression for longitudinal data was used to estimate the association between SDI and case-fatality rates, adjusting for antimicrobial resistance patterns. Findings: In 2021, there were 9.3 million global cases of enteric fever (95% uncertainty interval: 7.3-11.9) and 107.5 thousand deaths (56.1-180.8). The age-standardized incidence rate decreased from 152/100,000 person-years (118-195) in 2017 to 128/100,000 person-years (100-163) in 2021, and the mortality rate decreased from 1.87/100,000 person-years (0.95-3.18) to 1.50/100,000 person-years (0.78-2.54). There were wide geographical differences, with South Asia contributing the most cases and deaths. Age-standardized incidence exceeded the threshold for "high burden" of enteric fever (100/100,000 person-years) in 23 countries in 2021.Children under five accounted for 40% of deaths and 47% of YLLs, with incidence and mortality peaking during the second year. Case-fatality was highest in low SDI countries and showed a global trend toward reduction, except among children aged 1-4 years. After adjusting for the prevalence of multidrug resistance, fluoroquinolone non-susceptibility, and third-generation cephalosporin resistance, a higher SDI was associated with a lower case-fatality rate, with a 1.1% (0.7-1.7) reduction for each percentage point increase in SDI. Interpretation: Despite notable improvements, several countries still showed a high burden of enteric fever, which remains a significant global health concern, especially among children under five. Although enhancing water and sanitation systems is crucial, the most significant reductions in the global disease burden are likely to be achieved through broader vaccine coverage. This includes the use of typhoid conjugate vaccines, which are effective in infants and young children and offer extended protection, along with improved data collection and surveillance to guide vaccine distribution efforts across high-incidence areas. Funding: This work was partially supported by "Ricerca Corrente" funding from Italian Ministry of Health to IRCCSHumanitas Research Hospital.