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]

## Overview

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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]

## Pathogenesis

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

### Innoculation

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

### Gastrointestinal Infection

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Stomach

* 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

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* Dissemination of S.typhi to reticuloendothelial system
* Spreads via lymph and blood
* Replication within reticuloendothelial system such as spleen, liver, bone marrow
* Evades immune system by hiding intracellularly within macrophages

### Chronic carrier state

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

## References

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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.CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Multiple names: authors list (link)
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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