Complications and mortality of typhoid fever: an updated global systematic review and meta-analysis

Updated estimates of the prevalence of complications and case-fatality ratio (CFR) among patients with typhoid fever are needed to inform typhoid fever prevention and control. To support country-level decisions on typhoid prevention and control with contemporary estimates of morbidity and mortality, we updated our 2020 review.

We performed a systematic review and meta-analysis of non-surgical (typhoid fever) and surgical (typhoid intestinal perforation [TIP]) observational studies and control groups of vaccine trials that reported on typhoid fever complications or mortality. We searched PubMed, Web of Science, and eight preprint repositories using the keywords Salmonella Typhi, mortality, case fatality, died, death, complications, perforation, and haemorrhage, for reports published from Jan 1, 1980, to June 11, 2025, inclusive. Summary data were abstracted from published reports. We synthesised the prevalence of individual predefined complications, pooled CFR estimates using random-effects meta-analysis, and stratified prevalences by UN region, subregion, setting of recruitment, and age groups. This study was registered with PROSPERO (CRD42020166998).

Of 167 included reports, 106 (63%) were included from the 2020 review and 61 (37%) from the updated searches. 119 (71%) non-surgical reports provided data from 160 study sites among 29 933 patients with typhoid, and 48 (29%) surgical reports provided data from 62 study sites among 4486 patients with TIP. Delirium or confusion was the most prevalent typhoid fever complication, reported in 706 (26·5%) of 2662 typhoid cases. TIP was reported in 108 (1·7%) of 6362 typhoid cases. The overall pooled typhoid CFR was 2·1% (95% CI 1·7-2·7). The pooled typhoid CFR was 2·9% (1·1-7·1; I²=70·0%) in the Americas, 4·7% (3·1-6·8; I²=62·6%) in Africa, and 1·2% (1·0-1·7; I²=57·6%) in Asia; 2·3% (1·8-3·0; I²=77·7%) in facility-based recruitment sites; 0·9% (0·5-1·7; I²=0·0%) in community-based recruitment sites; and 2·7% (1·8-4·0; I²=73·4%) among patients aged 15 years or younger, and 1·8% (1·3-2·4; I²=70·6%) for mixed ages. The overall pooled TIP CFR was 16·3% (13·4-20·0).

We identified substantial ongoing morbidity and mortality due to typhoid fever in Africa and Asia, in facility-based sites, and across age groups. This updated evidence can be used to support decisions on vaccine and non-vaccine measures to prevent and control typhoid fever and TIP.

Gates Foundation.