Salmonella Typhi

Background: Salmonella enterica subsp. enterica serovar Typhi (antigenic formula: 9,12[Vi]:d:–) is a serovar of the O:9 (D1) serogroup. Serovar Typhi is one of the typhoidal Salmonella serovars that cause systemic infections (typhoid or enteric fever). In 1880, Karl Joseph Eberth became the first to observe Salmonella in specimens from typhoid fever patients. The term "typhoid" derives from the Greek "typhōdes" (meaning smoke-like or delirious), reflecting the disease's characteristic symptoms. In 1884, Georg Gaffky successfully isolated this bacillus, which subsequently became known as Salmonella Typhi. According to World Health Organization (WHO), as of 2019, approximately 9 million people contract typhoid annually, resulting in around 110,000 deaths. Common symptoms include persistent fever as high as 39-40°C (103-104°F), fatigue, headache, nausea, abdominal pain, and either constipation or diarrhea. Some individuals may develop a rash, while severe cases can lead to life-threatening complications or death. Although antibiotics such as fluoroquinolones, third-generation cephalosporins, macrolides, and carbapenems are effective for treatment, rising antimicrobial resistance has made managing the disease more challenging. To prevent infection, the typhoid conjugate vaccine (TCV) is recommended for children as young as six months and adults up to 45 or 65 years, depending on the vaccine. Since December 2017, the WHO has prequalified two TCVs, which are now being integrated into childhood immunization programs in typhoid-endemic regions. More specifically, two TCVs are: an inactivated (killed) vaccine given as an injection and a live, attenuated (weakened) vaccine taken orally. The inactivated vaccine is approved for individuals aged 2 years and older, while the oral vaccine is suitable for those 6 years and older. A healthcare provider can help determine the best option based on individual needs. Although routine typhoid vaccination is not advised in US, it is recommended for travelers visiting regions where typhoid fever is common. CDC stated that each year, an estimated 5,700 typhoid cases and 620 related hospitalizations occur in US, with the majority of infections acquired during international travel.

NCBI PD link for serovar Typhi: https://www.ncbi.nlm.nih.gov/pathogens/isolates/#(taxgroup_name:%22Salmonella%20enterica%22)%20AND%20computed_types:(%22serotype=Typhi%22)

Genetic characteristics: Parkhill et al. sequenced the complete genome (4,809,037 bp) of Salmonella Typhi (CT18) and found this isolate exhibited substantial genetic decay with over 200 pseudogenes, including homologs of key Salmonella Typhimurium virulence genes (e.g., sopE2 and fliB), potentially explaining its human-restricted host specificity. This isolate carries two plasmids: a 218,150 bp multidrug-resistant IncHI1 plasmid (pHCM1) and a 106,516 bp cryptic plasmid (pHCM2) phylogenetically linked to a virulence plasmid of Yersinia pestis. Additionally, it harbors up to 15 Salmonella pathogenicity islands (SPIs 1–7, 9, 11–13, and 15–18).

Comparative genomics and phylogenetic analyses have shown that S. Typhi (i) had a monophyletic origin approx. 50,000 years ago (ii) belongs to clade A, according to den Bakker et al. (2011) classification, and (iii) has 349 gene families unique to this serovar.

Animal reservoir: Salmonella Typhi is a human-restricted serovar.

Geographical distribution: Serovar Typhi is globally distributed; however, the prevalence of this serovar varies considerable. Crump et al. concluded that typhoid fever incidence is highest in south-central and southeast Asia, with over 100 cases per 100,000 people annually. Medium incidence rates (10–100 cases per 100,000 per year) are found in other parts of Asia, Africa, Latin America, the Caribbean, and Oceania (excluding Australia and New Zealand). In contrast, Europe, North America, and other developed regions report low typhoid fever rates, with fewer than 10 cases per 100,000 people each year.

Human outbreaks: Multiple human outbreaks linked to serovar Typhi has been reported. Below are some examples. 

¹ The outbreak was associated with travel to Kos, Greece. 

Border rejections: There have been no recent border rejections linked to this serovar. 

Recalls: 

¹ This recall was caused by a multistate outbreak described above. Goya Foods, Inc. and Montalvan’s Sales, Inc. issued voluntary recalls of their fruit pulp products.  

Relevant links:

1. https://pubmed.ncbi.nlm.nih.gov/25208300/
2. https://pmc.ncbi.nlm.nih.gov/articles/PMC7706954/
3. https://www.who.int/news-room/fact-sheets/detail/typhoid#:~:text=As%20of%202019%20estimates%2C%20there,children%20are%20at%20highest%20risk
4. https://www.cdc.gov/vaccines/hcp/current-vis/typhoid.html
5. https://www.cdc.gov/typhoid-fever/about/index.html
6. https://www.nature.com/articles/35101607

1. https://academic.oup.com/femsre/article/45/5/fuab014/6159486
2. https://pmc.ncbi.nlm.nih.gov/articles/PMC6128363/
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC2622843/
4. https://www.theguardian.com/world/2023/apr/02/typhoid-outbreak-on-refugee-ship-in-netherlands-traced-to-raw-sewage
5. https://archive.cdc.gov/www_cdc_gov/salmonella/2010/frozen-fruit-pulp-8-25-10.html#:~:text=Outbreak%20Investigation&text=Among%20interviewed%20ill%20persons%2C%207,brand%20frozen%20mamey%20fruit%20pulp.
6. https://pubmed.ncbi.nlm.nih.gov/15712078/
7. https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/216736
8. https://www.jstor.org/stable/30085190?seq=1
9. https://pubmed.ncbi.nlm.nih.gov/11092435/
10. https://pmc.ncbi.nlm.nih.gov/articles/PMC2490935/
11. https://ajph.aphapublications.org/doi/pdf/10.2105/AJPH.28.5.644
12. https://ajph.aphapublications.org/doi/10.2105/AJPH.2023.307434
13. https://pmc.ncbi.nlm.nih.gov/articles/PMC3959940/