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Typhoid and paratyphoid fever

Last updated: November 3, 2020

Summary

Typhoid and paratyphoid fever are infectious diseases caused by the bacteria Salmonella typhi and Salmonella paratyphi. Transmission occurs via the fecal-oral route. The incubation period is typically 7–21 days, although it may be as long as 30 days. Typhoid and paratyphoid fever classically have three clinical stages. In the first week of symptoms, body temperature rises gradually and relative bradycardia, as well as diarrhea or constipation, may occur. The second week of illness is characterized by persistent fever, rose-colored spots on the abdomen, nonspecific abdominal pain, and profuse diarrhea. During the third week, complications such as hepatosplenomegaly, intestinal bleeding, and/or perforation with secondary bacteremia and peritonitis may occur. Symptoms begin to subside in the fourth week. Pathogen detection in blood and stool cultures confirms the diagnosis. The treatment of choice includes fluoroquinolones such as ciprofloxacin. Up to 6% of patients become chronic Salmonella carriers after symptoms have resolved.

Epidemiology

  • There are an estimated 11–21 million cases per year worldwide.
  • Most prevalent in resource-limited regions with poor sanitation in East and Southeast Asia, Africa, and Central and South America
  • In the United States, approx. 300 culture-confirmed cases of typhoid fever and 100 cases of paratyphoid fever are reported annually, mostly in individuals who have traveled to endemic regions.

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • Pathogen
  • Reservoir
  • Transmission: fecal-oral
    • Direct: person-to-person contact; asymptomatic carriers frequently involved (e.g., the pathogen may be transferred from contaminated stool via handshake to the next person)
    • Indirect: contaminated food and water (e.g., if drinking water and sewage systems are not properly separated or a carrier prepares food)

Humans are the main reservoir for S. typhi.

Salmonella has flagella.

References:[3]

Pathophysiology

Lifecycle

  1. Oral uptake of pathogen: A relatively large number of organisms (∼ 105) is needed to cause infection (high infective dose), unlike, e.g., in Shigella infection, where as few as ∼ 10 organisms suffice to infect the host.
  2. Migration into the Peyer patches of the distal ileum; : If the pathogen manages to reach the distal ileum, it migrates via M cells through the epithelium and into the Peyer patches.
  3. Infection of macrophages → nonspecific symptoms
  4. Spread from macrophages to the bloodstream → septicemia → systemic disease
  5. Migration back to intestine excretion in feces

Virulence factors

The cell wall of the typhoid pathogens contains endotoxins; , which are responsible for the neurological symptoms associated with typhoid and paratyphoid fever (see the “Bacteria overview” article for more information).

References:[3][4]

Clinical features

General

  • Incubation period: 5–30 days (most commonly 7–14 days)
  • If left untreated, three different disease stages, each lasting a week, classically occur.
  • After 3 weeks of disease: slow regression of symptoms; patients may become chronic Salmonella carriers (see “Complications” below).

Typhoid fever is a systemic disease and it is not limited to the gastrointestinal system.

Typhoid fever must always be considered in cases of persistent fever of unknown origin and a history of travel to an endemic region.

Progression of illness

Week 1

Week 2

Week 3

References:[3]

Diagnostics

Blood culture is the most important diagnostic tool at disease onset, as stool cultures are often negative despite active infection.

Treatment

References:[8]

Complications

Chronic Salmonella carriage

References:[8]

We list the most important complications. The selection is not exhaustive.

Prevention

Food and water

Vaccination is not entirely effective. Measures must therefore be implemented to avoid exposure (see "Food and water safety").

Vaccination

Overcoming an infection with S. typhi or S. paratyphi does not confer lifelong immunity. Vaccination is not entirely protective.

Reporting requirements

Typhoid/paratyphoid fever are nationally notifiable diseases.

References:[2][8][11]

References

  1. Typhoid & Paratyphoid Fever. https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/typhoid-paratyphoid-fever. Updated: May 31, 2017. Accessed: December 18, 2017.
  2. Typhoid Fever. http://www.who.int/ith/vaccines/typhoidfever/en/. Updated: January 1, 2017. Accessed: December 18, 2017.
  3. Ryan ET, Andrews J. Epidemiology, Microbiology, Clinical Manifestations, and Diagnosis of Enteric (Typhoid and Paratyphoid) Fever. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/epidemiology-microbiology-clinical-manifestations-and-diagnosis-of-enteric-typhoid-and-paratyphoid-fever.Last updated: November 27, 2017. Accessed: December 15, 2017.
  4. Ryan ET, Andrews J. Pathogenesis of Enteric (Typhoid and Paratyphoid) Fever. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/pathogenesis-of-enteric-typhoid-and-paratyphoid-fever.Last updated: November 27, 2017. Accessed: December 29, 2017.
  5. Ishaq U, Malik J, Asif M, et al. Eosinopenia in Patients With Typhoid Fever: A Case-Control Study.. Cureus. 2020; 12 (9): p.e10359. doi: 10.7759/cureus.10359 . | Open in Read by QxMD
  6. Khan M, Coovadia YM, Connoly C, Sturm AW. The early diagnosis of typhoid fever prior to the Widal test and bacteriological culture results. Acta Trop. 1998; 69 (2): p.165-173. doi: 10.1016/s0001-706x(97)00139-3 . | Open in Read by QxMD
  7. Mogasale V, Ramani E, Mogasale VV, Park J. What proportion of Salmonella Typhi cases are detected by blood culture? A systematic literature review. Ann Clin Microbiol Antimicrob. 2016; 15 (1). doi: 10.1186/s12941-016-0147-z . | Open in Read by QxMD
  8. Ryan ET, Andrews J. Treatment and Prevention of Enteric (Typhoid and Paratyphoid) Fever. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/treatment-and-prevention-of-enteric-typhoid-and-paratyphoid-fever.Last updated: November 27, 2017. Accessed: December 18, 2017.
  9. Gunn JS, Marshall JM, Baker S, Dongol S, Charles RC, Ryan ET. Salmonella chronic carriage: epidemiology, diagnosis, and gallbladder persistence. Trends Microbiol. 2014; 22 (11): p.648-655. doi: 10.1016/j.tim.2014.06.007 . | Open in Read by QxMD
  10. Updated Recommendations for the Use of Typhoid Vaccine — Advisory Committee on Immunization Practices, United States, 2015. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6411a4.htm. Updated: March 27, 2015. Accessed: September 24, 2020.
  11. Typhoid Fever Vaccination. https://www.cdc.gov/vaccines/vpd/typhoid/hcp/index.html. Updated: September 30, 2010. Accessed: December 18, 2017.