Global Trends, Inequalities, and Projections of Typhoid Fever Burden Among Children and Adolescents, 1990–2045: A Global Burden of Disease 2021 Analysis with a Focus on South Asia

Typhoid fever remains a vaccine-preventable cause of childhood and adolescent morbidity in settings with limited water, sanitation, diagnostic capacity, and treatment capacity. We used Global Burden of Disease Study 2021 estimates to assess typhoid fever burden among individuals aged 0-19 years in 204 countries and territories from 1990 to 2021, with projections to 2045. We analyzed prevalence, incidence, deaths, and disability-adjusted life-years (DALYs); estimated average annual percentage changes using joinpoint regression; decomposed changes into epidemiological and demographic components; assessed Sociodemographic Index (SDI)-related inequality using the Slope Index of Inequality and Concentration Index; benchmarked countries against SDI-adjusted incidence frontiers; and projected future burden using Bayesian age-period-cohort models. Globally, the age-standardized incidence rate declined from 653.07 per 100,000 population in 1990 to 194.81 in 2021, while incident cases decreased from 14.76 million to 4.98 million. Deaths declined from 152,567 to 69,364, and DALYs from 12.93 million to 5.86 million. Despite these reductions, the burden remained concentrated in South Asia, sub-Saharan Africa, Oceania, and low- and low-middle-SDI settings. In 2021, South Asia accounted for 3.37 million incident cases, 44,095 deaths, and 3.74 million DALYs. Decomposition showed that declining age-specific rates drove global reductions, whereas population growth partly offset gains in lower-DI settings. Negative inequality indices indicated persistent concentration of burden among lower-SDI countries. Frontier analysis identified large excess-incidence gaps in South Asia, Oceania, Southeast Asia, and parts of sub-Saharan Africa. Projections suggested continued global reductions under historical-trend assumptions but persistent concentration in South Asia and widening uncertainty. Integrated typhoid conjugate vaccine scale-up, water and sanitation investment, diagnostic strengthening, and antimicrobial-resistance surveillance remain priorities for equitable typhoid control.