To describe (1) the proportion of deaths that were in recently hospitalised children and (2) causes of mortality among deceased children aged 0–59 months with preceding hospitalisations who enrolled in a mortality surveillance programme.

Descriptive study using prospectively collected data.

Eight Child Health and Mortality Prevention Surveillance (CHAMPS) community and healthcare sites in sub-Saharan Africa and South Asia.

Deaths among children aged 0–59 months enrolled in CHAMPS 2016–2023.

None.

Deaths with antecedent hospitalisations within 180 days of death. Causes of death determined by expert panels who reviewed clinical data and histopathologic and microbiologic results from postmortem minimally invasive tissue sampling.

CHAMPS enrolled 8548 deaths; we excluded 3688 neonates who died before discharge or ≤24 hours of birth and 482 with unclear information on antecedent hospitalisations. Out of the 4378 remaining deaths, 16.7% (95% CI 15.7% to 17.9%) were deaths that occurred within 180 days of a hospitalisation (n=733/4378). Of these, 55.7% (95% CI 52.0% to 59.3%) occurred outside healthcare facilities. Among included deaths with minimally invasive tissue sampling completed (n=337), lower respiratory tract infections (41.2%, 95% CI 36.0% to 46.7%), sepsis (39.8%, 95% CI 34.5% to 45.2%) and undernutrition (n=92, 27.3%, 95% CI 22.7% to 32.4%) were most common causes of death among cases with antecedent hospitalisations. The greatest proportion of deaths with antecedent hospital admissions occurred among cases aged 1–11 months (48.0%, 95% CI 44.4% to 51.7%), compared with those aged 0–1 months (21.7%, 95% CI 18.8% to 24.9%) and those aged 1–5 years (30.3%, 95% CI 27.0% to 33.8%). Moreover, the greatest proportion of deaths with antecedent hospital admissions occurred among infants/children with weight-for-age Z-score of

We observed a high proportion of deaths with antecedent hospitalisations within 180 days among young children across eight sites in sub-Saharan Africa and Asia. Among those deaths, children aged 1–11 months and undernourished infants were over-represented, suggesting early follow-up as a potential point to focus targeted support and future research.

Enteric fever, primarily caused by Salmonella enterica Typhi and Salmonella enterica Paratyphi A (SPA), is endemic mainly in South Asia, disproportionately affecting school-age children. Although typhoid conjugate vaccines (TCVs) are effective and implemented in many countries, no licensed vaccine exists against paratyphoid A. Bivalent vaccines targeting both S. Typhi and SPA may address this gap. Although field efficacy trials are not considered feasible, controlled human infection models (CHIMs) offer an alternative pathway for evaluating vaccine efficacy. This will be the first efficacy study of a bivalent vaccine against typhoid and paratyphoid A using a paratyphoid CHIM.

This is a phase II multicentre, double-blind, randomised controlled trial assessing the efficacy and immunogenicity of a bivalent conjugate vaccine candidate, Serum Institute of India Typhoid Conjugate Vaccine (Bivalent) (SII-TCV(B)), against SPA using a CHIM in healthy UK adults aged 18–55 years. A total of 192 participants will be randomised 1:1 to receive either SII-TCV(B) or a licensed Vi-polysaccharide typhoid vaccine (Vi-PS). All participants will be orally challenged with S. Paratyphi A (strain NVGH308) 28 days postvaccination. Participants will be monitored closely for 14 days and treated at 14 days postchallenge or promptly on diagnosis, according to prespecified criteria. The primary objective is to evaluate vaccine efficacy of SII-TCV(B) against paratyphoid infection using a CHIM. The coprimary immunogenicity objective is to assess non-inferiority of the typhoid IgG response compared with a licensed Vi-PS control.

The study has received ethical approval from the Berkshire Research Ethics Committee (24/SC/0309) and regulatory approval from the UK Medicines and Healthcare products Regulatory Agency. Results will be disseminated via peer-reviewed publications and scientific meetings.

ISRCTN65855590.