Typhoid fever

Typhoid fever is an invasive bacterial disease associated with bloodstream infection caused by Salmonella enterica subsp. enterica serovar Typhi, which crosses the intestinal epithelium and disseminates to systemic and intracellular sites, causing an undifferentiated febrile illness ^[1]. Typhoidal serovars such as S. Typhi cause typhoid fever, the treatment of which is threatened by increasing drug resistance, and S. Typhi relies on type III secretion systems and specific virulence factors for invasion and intracellular replication ^[3].

Typhoid fever presents as an undifferentiated febrile illness, with the causative organism disseminating to systemic and intracellular sites ^[1]. S. Typhi has specific virulence factors including typhoid toxin and Vi antigen, which are involved in symptom development and immune evasion, respectively ^[3]. The Vi antigen contributes to immune evasion while typhoid toxin plays a role in symptom development ^[3].

Typhoid fever causes a high burden of disease in Africa and Asia, primarily affecting individuals ranging from infants through to young adults ^[1]. Analysis of 13,000 Salmonella Typhi genomes represents the largest Typhi genome sequence collection to date, revealing that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa, while distinct genotypes dominate and have independently evolved antimicrobial resistance in other regions ^[2]. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere ^[2]. Ciprofloxacin non-susceptibility is widespread across geographies and genotypes, with high-level ciprofloxacin resistance reaching 20% prevalence in South Asia ^[2].

Salmonella Typhi is transmitted via the faecal-oral route, crossing the intestinal epithelium and disseminating to systemic and intracellular sites ^[1]. Data gaps remain in many parts of the world, and travel-associated sequences can provide informal 'sentinel' surveillance for such locations ^[2].

Since 2017, remarkable progress has been made in advancing effective vaccination programmes through strategic multipartner collaboration and targeted clinical trials in multiple high-incidence priority settings ^[1].

GlobalID source-data note: German ‘Typhus’ and ‘Typhus abdominalis’ mean typhoid fever, not rickettsial typhus. Country series may be typhoid-only, paratyphoid-only, or a reported combined enteric-fever total; retain the source label before comparing or aggregating them.

1. 1Meiring JE et al. Typhoid fever. Nat Rev Dis Primers. 2023 Dec 14. PMID: 38097589. doi: 10.1038/s41572-023-00480-z.PubMed: https://pubmed.ncbi.nlm.nih.gov/38097589/
2. 2Carey ME et al. Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes. Elife. 2023 Sep 12. PMID: 37697804. doi: 10.7554/eLife.85867.PubMed: https://pubmed.ncbi.nlm.nih.gov/37697804/
3. 3Johnson R et al. Typhoidal Salmonella: Distinctive virulence factors and pathogenesis. Cell Microbiol. 2018 Sep. PMID: 30030897. doi: 10.1111/cmi.12939.PubMed: https://pubmed.ncbi.nlm.nih.gov/30030897/