Age distribution of typhoid fever, paratyphoid fever, and non-typhoidal Salmonella invasive disease: a secondary analysis of global epidemiologic data

Background Policy decisions on the timing of initial and booster doses of typhoid conjugate vaccines (TCVs) and the development and deployment of combination Salmonella vaccines require a robust understanding of disease occurrence by age. We aimed to generate highly age-resolved evidence on the occurrence of invasive salmonelloses.Methods We conducted a secondary analysis of deidentified individual participant-level data from studies reporting culture-confirmed invasive salmonelloses identified by our recent systematic reviews. Age-specific data were obtained from investigators, pooled, and analysed using hierarchical Bayesian models to derive high-resolution age-occurrence estimates.Findings We included data from 13 studies done at 37 sites collected from 1993 through 2025 comprising 34 966 participants across 20 countries in Asia, Africa, the Americas, and Oceania. In relation to potential vaccine programme contact points for typhoid, paratyphoid, and iNTS, respectively, 1·3% (95% CrI 1·0–1·7)%, 1·0% (0·7–1·5)%, and 12·8% (9·6–16·5)% of illnesses occurred by 6 months; 2·0% (1·5–2·4)%, 1·6% (1·0–2·2)%, and 19·9% (15·9–24·6)% by 9 months; 3·6% (3·0–4·4)%, 3·0% (2·1–3·9)%, and 35·4% (29·7–41·1)% by 15 months; 18·5% (15·4–21·8)%, 17·7% (14·4–21·3)%, and 65·4% (58·0–72·2)% by 5 years; and 55·0% (50·4–58·8)%, 47·0% (42·6–51·3)%, and 77·9% (72·3–82·8)% by 15 years.Interpretation We found that enteric fever and iNTS disease exhibit distinct age patterns with notable implications for TCV vaccine policy and Salmonella combination vaccines. From an age-occurrence perspective, vaccines combining Salmonella Typhi and Salmonella Paratyphi A antigens seem rational, while inclusion of iNTS antigens would involve trade-offs in timing for epidemiology and duration of protection.