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

Objectives: Updated estimates of the prevalence of complications and case fatality ratio (CFR) among typhoid fever patients are needed to understand disease burden. Methods: Articles published in PubMed and Web of Science from 1 January 1980 through 29 January 2020 were systematically reviewed for hospital or community-based non-surgical studies that used cultures of normally sterile sites, and hospital surgical studies of typhoid intestinal perforation (TIP) with intra- or post-operative findings suggestive of typhoid. Prevalence of 21 pre-selected recognized complications of typhoid fever, crude and median (interquartile range) CFR, and pooled CFR estimates using a random effects meta-analysis were calculated. Results: Of 113 study sites, 106 (93.8%) were located in Asia and Africa, and 84 (74.3%) were non-surgical. Among non-surgical studies, 70 (83.3%) were hospital-based. Of 10,355 confirmed typhoid patients, 2,719 (26.3%) had complications. The pooled CFR estimate among non-surgical patients was 0.9% for the Asia region and 5.4% for the Africa region. Delay in care was significantly correlated with increased CFR in Asia (r =0.84; p<0.01). Among surgical studies, the median CFR of TIP was 15.5% (6.7-24.1%) per study. Conclusions: Our findings identify considerable typhoid-associated illness and death that could be averted with prevention measures, including typhoid conjugate vaccine introduction. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association.