Typhoid fever pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aysha Aslam, M.B.B.S[2]


The sequence of events in the pathogenesis of typhoid fever include inoculation, gastrointestinal infection, systemic involvement, and chronic carrier state.[1][2][3][4][5][6][7][8][9][10][11]


The pathogenesis of typhoid fever consists of the following sequence of events.[1][2][3][4][5][6][7][8][9][10][11]


  • Orofecal transmission
  • Infective dose: 1000 to 1 million organisms

Gastrointestinal Infection


  • Bacterium enters stomach
  • Can survive a pH as low as 1.5

Small intestine

  • Bacterium enters mucosa of the small intestine via M cells or direct penetration
  • Adherence to the mucosal cells via special proteins
  • Invade mucosal M cells overlying peyer's patches
  • Internalisation in M cells of ileum
  • Translocation to underlying lymphoid tissue and draining lymph nodes

Systemic spread

Chronic carrier state

  • Resides and multiplies in gall bladder
  • Excretion in urine and stool may infect other individuals


  1. 1.0 1.1 Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ (2002). "Typhoid fever". N Engl J Med. 347 (22): 1770–82. doi:10.1056/NEJMra020201. PMID 12456854.
  2. 2.0 2.1 McCormick BA, Miller SI, Carnes D, Madara JL (1995). "Transepithelial signaling to neutrophils by salmonellae: a novel virulence mechanism for gastroenteritis". Infect Immun. 63 (6): 2302–9. PMC 173301. PMID 7768613.
  3. 3.0 3.1 Kohbata S, Yokoyama H, Yabuuchi E (1986). "Cytopathogenic effect of Salmonella typhi GIFU 10007 on M cells of murine ileal Peyer's patches in ligated ileal loops: an ultrastructural study". Microbiol Immunol. 30 (12): 1225–37. PMID 3553868.
  4. 4.0 4.1 Kops SK, Lowe DK, Bement WM, West AB (1996). "Migration of Salmonella typhi through intestinal epithelial monolayers: an in vitro study". Microbiol Immunol. 40 (11): 799–811. PMID 8985935.
  5. 5.0 5.1 Mills SD, Finlay BB (1994). "Comparison of Salmonella typhi and Salmonella typhimurium invasion, intracellular growth and localization in cultured human epithelial cells". Microb Pathog. 17 (6): 409–23. doi:10.1006/mpat.1994.1086. PMID 7752882.
  6. 6.0 6.1 Tartera C, Metcalf ES (1993). "Osmolarity and growth phase overlap in regulation of Salmonella typhi adherence to and invasion of human intestinal cells". Infect Immun. 61 (7): 3084–9. PMC 280966. PMID 8514418.
  7. 7.0 7.1 Hornick RB, Greisman SE, Woodward TE, DuPont HL, Dawkins AT, Snyder MJ (1970). "Typhoid fever: pathogenesis and immunologic control". N Engl J Med. 283 (13): 686–91. doi:10.1056/NEJM197009242831306. PMID 4916913.
  8. 8.0 8.1 Fields PI, Swanson RV, Haidaris CG, Heffron F (1986). "Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent". Proc Natl Acad Sci U S A. 83 (14): 5189–93. PMC 323916. PMID 3523484.
  9. 9.0 9.1 Groisman EA, Chiao E, Lipps CJ, Heffron F (1989). "Salmonella typhimurium phoP virulence gene is a transcriptional regulator". Proc Natl Acad Sci U S A. 86 (18): 7077–81. PMC 297997. PMID 2674945.
  10. 10.0 10.1 Lai CW, Chan RC, Cheng AF, Sung JY, Leung JW (1992). "Common bile duct stones: a cause of chronic salmonellosis". Am J Gastroenterol. 87 (9): 1198–9. PMID 1519582.
  11. 11.0 11.1 Keuter, Monique, et al. "Patterns of proinflammatory cytokines and inhibitors during typhoid fever." Journal of Infectious Diseases 169.6 (1994): 1306-1311.

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