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{{Typhoid fever}}
{{Typhoid fever}}
 
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== Overview ==
== Overview ==
The sequence of events in the pathogenesis of typhoid fever include innoculation, [[gastrointestinal]] infection, systemic involvement and chronic carrier state.<ref name="pmid12456854">{{cite journal| author=Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ| title=Typhoid fever. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 22 | pages= 1770-82 | pmid=12456854 | doi=10.1056/NEJMra020201 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12456854  }} </ref><ref name="pmid7768613">{{cite journal| author=McCormick BA, Miller SI, Carnes D, Madara JL| title=Transepithelial signaling to neutrophils by salmonellae: a novel virulence mechanism for gastroenteritis. | journal=Infect Immun | year= 1995 | volume= 63 | issue= 6 | pages= 2302-9 | pmid=7768613 | doi= | pmc=173301 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7768613  }} </ref><ref name="pmid3553868">{{cite journal| author=Kohbata S, Yokoyama H, Yabuuchi E| title=Cytopathogenic effect of Salmonella typhi GIFU 10007 on M cells of murine ileal Peyer's patches in ligated ileal loops: an ultrastructural study. | journal=Microbiol Immunol | year= 1986 | volume= 30 | issue= 12 | pages= 1225-37 | pmid=3553868 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3553868  }} </ref><ref name="pmid8985935">{{cite journal| author=Kops SK, Lowe DK, Bement WM, West AB| title=Migration of Salmonella typhi through intestinal epithelial monolayers: an in vitro study. | journal=Microbiol Immunol | year= 1996 | volume= 40 | issue= 11 | pages= 799-811 | pmid=8985935 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8985935  }} </ref><ref name="pmid7752882">{{cite journal| author=Mills SD, Finlay BB| title=Comparison of Salmonella typhi and Salmonella typhimurium invasion, intracellular growth and localization in cultured human epithelial cells. | journal=Microb Pathog | year= 1994 | volume= 17 | issue= 6 | pages= 409-23 | pmid=7752882 | doi=10.1006/mpat.1994.1086 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7752882  }} </ref><ref name="pmid8514418">{{cite journal| author=Tartera C, Metcalf ES| title=Osmolarity and growth phase overlap in regulation of Salmonella typhi adherence to and invasion of human intestinal cells. | journal=Infect Immun | year= 1993 | volume= 61 | issue= 7 | pages= 3084-9 | pmid=8514418 | doi= | pmc=280966 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8514418  }} </ref><ref name="pmid4916913">{{cite journal| author=Hornick RB, Greisman SE, Woodward TE, DuPont HL, Dawkins AT, Snyder MJ| title=Typhoid fever: pathogenesis and immunologic control. | journal=N Engl J Med | year= 1970 | volume= 283 | issue= 13 | pages= 686-91 | pmid=4916913 | doi=10.1056/NEJM197009242831306 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4916913  }} </ref><ref name="pmid3523484">{{cite journal| author=Fields PI, Swanson RV, Haidaris CG, Heffron F| title=Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. | journal=Proc Natl Acad Sci U S A | year= 1986 | volume= 83 | issue= 14 | pages= 5189-93 | pmid=3523484 | doi= | pmc=323916 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3523484  }} </ref><ref name="pmid2674945">{{cite journal| author=Groisman EA, Chiao E, Lipps CJ, Heffron F| title=Salmonella typhimurium phoP virulence gene is a transcriptional regulator. | journal=Proc Natl Acad Sci U S A | year= 1989 | volume= 86 | issue= 18 | pages= 7077-81 | pmid=2674945 | doi= | pmc=297997 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2674945  }} </ref><ref name="pmid1519582">{{cite journal| author=Lai CW, Chan RC, Cheng AF, Sung JY, Leung JW| title=Common bile duct stones: a cause of chronic salmonellosis. | journal=Am J Gastroenterol | year= 1992 | volume= 87 | issue= 9 | pages= 1198-9 | pmid=1519582 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1519582  }} </ref><ref>Keuter, Monique, et al. "Patterns of proinflammatory cytokines and inhibitors during typhoid fever." Journal of Infectious Diseases 169.6 (1994): 1306-1311.</ref>
The sequence of events in the pathogenesis of typhoid fever include [[inoculation]], [[gastrointestinal]] infection, systemic involvement, and chronic carrier state.<ref name="pmid12456854">{{cite journal| author=Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ| title=Typhoid fever. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 22 | pages= 1770-82 | pmid=12456854 | doi=10.1056/NEJMra020201 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12456854  }} </ref><ref name="pmid7768613">{{cite journal| author=McCormick BA, Miller SI, Carnes D, Madara JL| title=Transepithelial signaling to neutrophils by salmonellae: a novel virulence mechanism for gastroenteritis. | journal=Infect Immun | year= 1995 | volume= 63 | issue= 6 | pages= 2302-9 | pmid=7768613 | doi= | pmc=173301 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7768613  }} </ref><ref name="pmid3553868">{{cite journal| author=Kohbata S, Yokoyama H, Yabuuchi E| title=Cytopathogenic effect of Salmonella typhi GIFU 10007 on M cells of murine ileal Peyer's patches in ligated ileal loops: an ultrastructural study. | journal=Microbiol Immunol | year= 1986 | volume= 30 | issue= 12 | pages= 1225-37 | pmid=3553868 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3553868  }} </ref><ref name="pmid8985935">{{cite journal| author=Kops SK, Lowe DK, Bement WM, West AB| title=Migration of Salmonella typhi through intestinal epithelial monolayers: an in vitro study. | journal=Microbiol Immunol | year= 1996 | volume= 40 | issue= 11 | pages= 799-811 | pmid=8985935 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8985935  }} </ref><ref name="pmid7752882">{{cite journal| author=Mills SD, Finlay BB| title=Comparison of Salmonella typhi and Salmonella typhimurium invasion, intracellular growth and localization in cultured human epithelial cells. | journal=Microb Pathog | year= 1994 | volume= 17 | issue= 6 | pages= 409-23 | pmid=7752882 | doi=10.1006/mpat.1994.1086 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7752882  }} </ref><ref name="pmid8514418">{{cite journal| author=Tartera C, Metcalf ES| title=Osmolarity and growth phase overlap in regulation of Salmonella typhi adherence to and invasion of human intestinal cells. | journal=Infect Immun | year= 1993 | volume= 61 | issue= 7 | pages= 3084-9 | pmid=8514418 | doi= | pmc=280966 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8514418  }} </ref><ref name="pmid4916913">{{cite journal| author=Hornick RB, Greisman SE, Woodward TE, DuPont HL, Dawkins AT, Snyder MJ| title=Typhoid fever: pathogenesis and immunologic control. | journal=N Engl J Med | year= 1970 | volume= 283 | issue= 13 | pages= 686-91 | pmid=4916913 | doi=10.1056/NEJM197009242831306 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4916913  }} </ref><ref name="pmid3523484">{{cite journal| author=Fields PI, Swanson RV, Haidaris CG, Heffron F| title=Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. | journal=Proc Natl Acad Sci U S A | year= 1986 | volume= 83 | issue= 14 | pages= 5189-93 | pmid=3523484 | doi= | pmc=323916 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3523484  }} </ref><ref name="pmid2674945">{{cite journal| author=Groisman EA, Chiao E, Lipps CJ, Heffron F| title=Salmonella typhimurium phoP virulence gene is a transcriptional regulator. | journal=Proc Natl Acad Sci U S A | year= 1989 | volume= 86 | issue= 18 | pages= 7077-81 | pmid=2674945 | doi= | pmc=297997 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2674945  }} </ref><ref name="pmid1519582">{{cite journal| author=Lai CW, Chan RC, Cheng AF, Sung JY, Leung JW| title=Common bile duct stones: a cause of chronic salmonellosis. | journal=Am J Gastroenterol | year= 1992 | volume= 87 | issue= 9 | pages= 1198-9 | pmid=1519582 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1519582  }} </ref><ref name="keuter">Keuter, Monique, et al. "Patterns of proinflammatory cytokines and inhibitors during typhoid fever." Journal of Infectious Diseases 169.6 (1994): 1306-1311.</ref>


==Pathogenesis==
==Pathogenesis==
The pathogenesis of typhoid fever consists of following sequence of events.<ref name="pmid12456854">{{cite journal| author=Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ| title=Typhoid fever. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 22 | pages= 1770-82 | pmid=12456854 | doi=10.1056/NEJMra020201 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12456854  }} </ref><ref name="pmid7768613">{{cite journal| author=McCormick BA, Miller SI, Carnes D, Madara JL| title=Transepithelial signaling to neutrophils by salmonellae: a novel virulence mechanism for gastroenteritis. | journal=Infect Immun | year= 1995 | volume= 63 | issue= 6 | pages= 2302-9 | pmid=7768613 | doi= | pmc=173301 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7768613  }} </ref><ref name="pmid3553868">{{cite journal| author=Kohbata S, Yokoyama H, Yabuuchi E| title=Cytopathogenic effect of Salmonella typhi GIFU 10007 on M cells of murine ileal Peyer's patches in ligated ileal loops: an ultrastructural study. | journal=Microbiol Immunol | year= 1986 | volume= 30 | issue= 12 | pages= 1225-37 | pmid=3553868 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3553868  }} </ref><ref name="pmid8985935">{{cite journal| author=Kops SK, Lowe DK, Bement WM, West AB| title=Migration of Salmonella typhi through intestinal epithelial monolayers: an in vitro study. | journal=Microbiol Immunol | year= 1996 | volume= 40 | issue= 11 | pages= 799-811 | pmid=8985935 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8985935  }} </ref><ref name="pmid7752882">{{cite journal| author=Mills SD, Finlay BB| title=Comparison of Salmonella typhi and Salmonella typhimurium invasion, intracellular growth and localization in cultured human epithelial cells. | journal=Microb Pathog | year= 1994 | volume= 17 | issue= 6 | pages= 409-23 | pmid=7752882 | doi=10.1006/mpat.1994.1086 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7752882  }} </ref><ref name="pmid8514418">{{cite journal| author=Tartera C, Metcalf ES| title=Osmolarity and growth phase overlap in regulation of Salmonella typhi adherence to and invasion of human intestinal cells. | journal=Infect Immun | year= 1993 | volume= 61 | issue= 7 | pages= 3084-9 | pmid=8514418 | doi= | pmc=280966 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8514418  }} </ref><ref name="pmid4916913">{{cite journal| author=Hornick RB, Greisman SE, Woodward TE, DuPont HL, Dawkins AT, Snyder MJ| title=Typhoid fever: pathogenesis and immunologic control. | journal=N Engl J Med | year= 1970 | volume= 283 | issue= 13 | pages= 686-91 | pmid=4916913 | doi=10.1056/NEJM197009242831306 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4916913  }} </ref><ref name="pmid3523484">{{cite journal| author=Fields PI, Swanson RV, Haidaris CG, Heffron F| title=Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. | journal=Proc Natl Acad Sci U S A | year= 1986 | volume= 83 | issue= 14 | pages= 5189-93 | pmid=3523484 | doi= | pmc=323916 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3523484  }} </ref><ref name="pmid2674945">{{cite journal| author=Groisman EA, Chiao E, Lipps CJ, Heffron F| title=Salmonella typhimurium phoP virulence gene is a transcriptional regulator. | journal=Proc Natl Acad Sci U S A | year= 1989 | volume= 86 | issue= 18 | pages= 7077-81 | pmid=2674945 | doi= | pmc=297997 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2674945  }} </ref><ref name="pmid1519582">{{cite journal| author=Lai CW, Chan RC, Cheng AF, Sung JY, Leung JW| title=Common bile duct stones: a cause of chronic salmonellosis. | journal=Am J Gastroenterol | year= 1992 | volume= 87 | issue= 9 | pages= 1198-9 | pmid=1519582 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1519582  }} </ref><ref>Keuter, Monique, et al. "Patterns of proinflammatory cytokines and inhibitors during typhoid fever." Journal of Infectious Diseases 169.6 (1994): 1306-1311.</ref>
The pathogenesis of typhoid fever consists of the following sequence of events.<ref name="pmid12456854">{{cite journal| author=Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ| title=Typhoid fever. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 22 | pages= 1770-82 | pmid=12456854 | doi=10.1056/NEJMra020201 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12456854  }} </ref><ref name="pmid7768613">{{cite journal| author=McCormick BA, Miller SI, Carnes D, Madara JL| title=Transepithelial signaling to neutrophils by salmonellae: a novel virulence mechanism for gastroenteritis. | journal=Infect Immun | year= 1995 | volume= 63 | issue= 6 | pages= 2302-9 | pmid=7768613 | doi= | pmc=173301 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7768613  }} </ref><ref name="pmid3553868">{{cite journal| author=Kohbata S, Yokoyama H, Yabuuchi E| title=Cytopathogenic effect of Salmonella typhi GIFU 10007 on M cells of murine ileal Peyer's patches in ligated ileal loops: an ultrastructural study. | journal=Microbiol Immunol | year= 1986 | volume= 30 | issue= 12 | pages= 1225-37 | pmid=3553868 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3553868  }} </ref><ref name="pmid8985935">{{cite journal| author=Kops SK, Lowe DK, Bement WM, West AB| title=Migration of Salmonella typhi through intestinal epithelial monolayers: an in vitro study. | journal=Microbiol Immunol | year= 1996 | volume= 40 | issue= 11 | pages= 799-811 | pmid=8985935 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8985935  }} </ref><ref name="pmid7752882">{{cite journal| author=Mills SD, Finlay BB| title=Comparison of Salmonella typhi and Salmonella typhimurium invasion, intracellular growth and localization in cultured human epithelial cells. | journal=Microb Pathog | year= 1994 | volume= 17 | issue= 6 | pages= 409-23 | pmid=7752882 | doi=10.1006/mpat.1994.1086 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7752882  }} </ref><ref name="pmid8514418">{{cite journal| author=Tartera C, Metcalf ES| title=Osmolarity and growth phase overlap in regulation of Salmonella typhi adherence to and invasion of human intestinal cells. | journal=Infect Immun | year= 1993 | volume= 61 | issue= 7 | pages= 3084-9 | pmid=8514418 | doi= | pmc=280966 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8514418  }} </ref><ref name="pmid4916913">{{cite journal| author=Hornick RB, Greisman SE, Woodward TE, DuPont HL, Dawkins AT, Snyder MJ| title=Typhoid fever: pathogenesis and immunologic control. | journal=N Engl J Med | year= 1970 | volume= 283 | issue= 13 | pages= 686-91 | pmid=4916913 | doi=10.1056/NEJM197009242831306 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4916913  }} </ref><ref name="pmid3523484">{{cite journal| author=Fields PI, Swanson RV, Haidaris CG, Heffron F| title=Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. | journal=Proc Natl Acad Sci U S A | year= 1986 | volume= 83 | issue= 14 | pages= 5189-93 | pmid=3523484 | doi= | pmc=323916 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3523484  }} </ref><ref name="pmid2674945">{{cite journal| author=Groisman EA, Chiao E, Lipps CJ, Heffron F| title=Salmonella typhimurium phoP virulence gene is a transcriptional regulator. | journal=Proc Natl Acad Sci U S A | year= 1989 | volume= 86 | issue= 18 | pages= 7077-81 | pmid=2674945 | doi= | pmc=297997 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2674945  }} </ref><ref name="pmid1519582">{{cite journal| author=Lai CW, Chan RC, Cheng AF, Sung JY, Leung JW| title=Common bile duct stones: a cause of chronic salmonellosis. | journal=Am J Gastroenterol | year= 1992 | volume= 87 | issue= 9 | pages= 1198-9 | pmid=1519582 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1519582  }} </ref><ref name="keuter">Keuter, Monique, et al. "Patterns of proinflammatory cytokines and inhibitors during typhoid fever." Journal of Infectious Diseases 169.6 (1994): 1306-1311.</ref>
 
===Innoculation===
===Innoculation===
*[[Orofecal]] transmission.
*Orofecal transmission
*Infective dose 1000 to 1 million organisms.
*Infective dose: 1000 to 1 million organisms


===Gastrointestinal Infection===
===Gastrointestinal Infection===
:'''Stomach'''
'''Stomach'''
:*Bacterium enters stomach.
*Bacterium enters stomach
:*Survives pH as low as 1.5
*Can survive a pH as low as 1.5
:'''Small intestine'''
'''Small intestine'''
:*Bacterium enters mucosa of the small intestine via [[M cells]] or direct penetration.
*Bacterium enters mucosa of the small intestine via [[M cells]] or direct penetration
:*Adherence to the mucosal cells via special proteins.
*Adherence to the mucosal cells via special proteins
:*Invade mucosal M cells overlying [[peyer's patches]]
*Invade mucosal M cells overlying [[peyer's patches]]
:*Internalisation in M cells of ileum.
*Internalisation in M cells of [[ileum]]
:*Translocation to underlying lymphoid tissue and draining lymph nodes.
*Translocation to underlying [[lymphoid tissue]] and draining [[lymph nodes]]


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


===Chronic carrier state===
===Chronic carrier state===
*Resides and multiplies in gall bladder
*Resides and multiplies in [[gall bladder]]
*Excretion in urine and stool infecting other individuals.
*Excretion in urine and stool may infect other individuals


== References ==
== References ==
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[[Category:Gastroenterology]]
[[Category:FinalQCRequired]]
[[Category:Emergency mdicine]]
[[Category:Disease]]
[[Category:Up-To-Date]]
[[Category:Infectious disease]]
[[Category:Infectious disease]]
[[Category:Gastroenterology]]

Latest revision as of 02:39, 18 July 2021

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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

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

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

Innoculation

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

Gastrointestinal Infection

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

Chronic carrier state

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

References

  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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