Pertussis pathophysiology: Difference between revisions

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__NOTOC__
__NOTOC__
{{CMG}}; {{AE}} {{ADI}}
{{CMG}}; {{AE}} {{YD}}; {{SSK}}; {{ADI}}
{{Pertussis}}
{{Pertussis}}


== Overview ==
== Overview ==
Pertussis is primarily a toxin-mediated disease. ''Bordetella pertussis'' is usually tansmitted to the human host by direct contact with aerolized mucus of infected individials. ''B. pertussis'' attaches to the [[cilia]] of the respiratory [[epithelial cells]], proliferates and produces virulence factors that paralyze the cilia, and causes [[inflammation]] of the respiratory tract, which interferes with the clearing of pulmonary secretions. ''B. pertussis''  utilizes virulence factors, including pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae (FIM), adenylate cyclase toxin (ACT), trachael cytotoxin (TCT), lipooligosaccharide (LOS), and dermonecrotic toxin (DNT) to attach, proliferate, and and evade the host immune system.<ref name=CDC>[http://www.cdc.gov/pertussis/clinical/disease-specifics.html Pertussis (whooping cough). CDC.gov. Accessed on June 15th, 2014]</ref><ref name="pmid24626533">{{cite journal| author=Hewlett EL, Burns DL, Cotter PA, Harvill ET, Merkel TJ, Quinn CP et al.| title=Pertussis pathogenesis--what we know and what we don't know. | journal=J Infect Dis | year= 2014 | volume= 209 | issue= 7 | pages= 982-5 | pmid=24626533 | doi=10.1093/infdis/jit639 | pmc=PMC3952676 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24626533  }} </ref>
Pertussis is primarily a toxin-mediated disease. ''Bordetella pertussis'' is highly contagious and is usually transmitted to the human host by direct contact with aerolized mucus of infected individuals. ''B. pertussis'' attaches to the [[cilia]] of the respiratory [[epithelial cells]], proliferates and produces virulence factors that paralyze the cilia, and causes inflammation of the respiratory tract, which interferes with the clearing of pulmonary secretions. ''B. pertussis''  utilizes virulence factors - including pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae (FIM), adenylate cyclase toxin (ACT), tracheal cytotoxin (TCT), lipooligosaccharide (LOS), and dermonecrotic toxin (DNT) - to attach, proliferate, and and evade the host immune system.<ref name=CDC>[http://www.cdc.gov/pertussis/clinical/disease-specifics.html Pertussis (whooping cough). CDC.gov. Accessed on June 15th, 2014]</ref><ref name="pmid24626533">{{cite journal| author=Hewlett EL, Burns DL, Cotter PA, Harvill ET, Merkel TJ, Quinn CP et al.| title=Pertussis pathogenesis--what we know and what we don't know. | journal=J Infect Dis | year= 2014 | volume= 209 | issue= 7 | pages= 982-5 | pmid=24626533 | doi=10.1093/infdis/jit639 | pmc=PMC3952676 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24626533  }} </ref>


==Pathophysiology ==
==Pathophysiology ==
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*''Bordetella pertussis'' has tropism for pulmonary tissue and rarely disseminates to other organs.
*''Bordetella pertussis'' has tropism for pulmonary tissue and rarely disseminates to other organs.
*The steps involved in the pathogenesis of pertussis include the following:
*The steps involved in the pathogenesis of pertussis include the following:
:*Inoculation
:*[[Inoculation]]
:*Attachment to the respiratory epithelium
:*Attachment to the [[respiratory epithelium]]
:*Proliferation
:*Proliferation
:*Production of virulence factors (toxins)
:*Production of [[virulence factor]]s (toxins)
:*Evasion of host immune cells
:*Evasion of host [[immune cell]]s
:*Tissue destruction
:*Tissue destruction


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:*FHA is a component of the acellular DTaP vaccine.
:*FHA is a component of the acellular DTaP vaccine.
* '''Adenylate cyclase toxin (ACT)'''
* '''Adenylate cyclase toxin (ACT)'''
:*ACT delivers an adenylate cyclase domain into the host cell and increases the intracellular cAMP concentration.<ref name="pmid24626533">{{cite journal| author=Hewlett EL, Burns DL, Cotter PA, Harvill ET, Merkel TJ, Quinn CP et al.| title=Pertussis pathogenesis--what we know and what we don't know. | journal=J Infect Dis | year= 2014 | volume= 209 | issue= 7 | pages= 982-5 | pmid=24626533 | doi=10.1093/infdis/jit639 | pmc=PMC3952676 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24626533  }} </ref>
:*ACT delivers an [[adenylate cyclase]] domain into the host cell and increases the intracellular [[cAMP]] concentration.<ref name="pmid24626533">{{cite journal| author=Hewlett EL, Burns DL, Cotter PA, Harvill ET, Merkel TJ, Quinn CP et al.| title=Pertussis pathogenesis--what we know and what we don't know. | journal=J Infect Dis | year= 2014 | volume= 209 | issue= 7 | pages= 982-5 | pmid=24626533 | doi=10.1093/infdis/jit639 | pmc=PMC3952676 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24626533  }} </ref>
:*Following cAMP delivery, phagocyte activity is inhibited, and phagocytes undergo apoptosis.
:*Following cAMP delivery, phagocyte activity is inhibited, and phagocytes undergo apoptosis.
* '''Pertactin (PRN)'''
* '''Pertactin (PRN)'''
:* PRN defends ''Bordetella pertussis'' against the host neutrophil (immunomodulation).<ref name="pmid24626533">{{cite journal| author=Hewlett EL, Burns DL, Cotter PA, Harvill ET, Merkel TJ, Quinn CP et al.| title=Pertussis pathogenesis--what we know and what we don't know. | journal=J Infect Dis | year= 2014 | volume= 209 | issue= 7 | pages= 982-5 | pmid=24626533 | doi=10.1093/infdis/jit639 | pmc=PMC3952676 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24626533  }} </ref>
:* PRN defends ''Bordetella pertussis'' against the host [[neutrophils]] (immunomodulation).<ref name="pmid24626533">{{cite journal| author=Hewlett EL, Burns DL, Cotter PA, Harvill ET, Merkel TJ, Quinn CP et al.| title=Pertussis pathogenesis--what we know and what we don't know. | journal=J Infect Dis | year= 2014 | volume= 209 | issue= 7 | pages= 982-5 | pmid=24626533 | doi=10.1093/infdis/jit639 | pmc=PMC3952676 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24626533  }} </ref>
:*PRN is a component of the acellular DTaP vaccine.
:*PRN is a component of the acellular DTaP vaccine.
* '''Tracheal cytotoxin (TCT)'''
* '''Tracheal cytotoxin (TCT)'''
:*TCT is responsible for the death of host respiratory cells using intracellular IL-1 and nitric oxide.<ref name="pmid24626533">{{cite journal| author=Hewlett EL, Burns DL, Cotter PA, Harvill ET, Merkel TJ, Quinn CP et al.| title=Pertussis pathogenesis--what we know and what we don't know. | journal=J Infect Dis | year= 2014 | volume= 209 | issue= 7 | pages= 982-5 | pmid=24626533 | doi=10.1093/infdis/jit639 | pmc=PMC3952676 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24626533  }} </ref>
:*TCT is responsible for the death of host [[respiratory cell]]s using intracellular [[IL-1]] and [[nitric oxide]].<ref name="pmid24626533">{{cite journal| author=Hewlett EL, Burns DL, Cotter PA, Harvill ET, Merkel TJ, Quinn CP et al.| title=Pertussis pathogenesis--what we know and what we don't know. | journal=J Infect Dis | year= 2014 | volume= 209 | issue= 7 | pages= 982-5 | pmid=24626533 | doi=10.1093/infdis/jit639 | pmc=PMC3952676 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24626533  }} </ref>
*'''Lipooligoosaccharide (LOS)'''
*'''Lipooligoosaccharide (LOS)'''
:*Unique outer membrane component that is thought to play a role in clinical manifestations of pertussis.<ref name="pmid24626533">{{cite journal| author=Hewlett EL, Burns DL, Cotter PA, Harvill ET, Merkel TJ, Quinn CP et al.| title=Pertussis pathogenesis--what we know and what we don't know. | journal=J Infect Dis | year= 2014 | volume= 209 | issue= 7 | pages= 982-5 | pmid=24626533 | doi=10.1093/infdis/jit639 | pmc=PMC3952676 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24626533  }} </ref>
:*Unique outer membrane component that is thought to play a role in clinical manifestations of pertussis.<ref name="pmid24626533">{{cite journal| author=Hewlett EL, Burns DL, Cotter PA, Harvill ET, Merkel TJ, Quinn CP et al.| title=Pertussis pathogenesis--what we know and what we don't know. | journal=J Infect Dis | year= 2014 | volume= 209 | issue= 7 | pages= 982-5 | pmid=24626533 | doi=10.1093/infdis/jit639 | pmc=PMC3952676 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24626533  }} </ref>

Latest revision as of 23:14, 14 January 2016

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.; Aditya Govindavarjhulla, M.B.B.S. [2]

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Overview

Pertussis is primarily a toxin-mediated disease. Bordetella pertussis is highly contagious and is usually transmitted to the human host by direct contact with aerolized mucus of infected individuals. B. pertussis attaches to the cilia of the respiratory epithelial cells, proliferates and produces virulence factors that paralyze the cilia, and causes inflammation of the respiratory tract, which interferes with the clearing of pulmonary secretions. B. pertussis utilizes virulence factors - including pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae (FIM), adenylate cyclase toxin (ACT), tracheal cytotoxin (TCT), lipooligosaccharide (LOS), and dermonecrotic toxin (DNT) - to attach, proliferate, and and evade the host immune system.[1][2]

Pathophysiology

Transmission

  • Humans are the only reservoir for Bordatella pertussis, and the incubation period is approximately 10 days (range from 1 week to 3 weeks).
  • Infection occurs through direct contact with the aerosolized mucus of infected individuals, usually during coughing and sneezing. The bacterium adheres to the ciliated epithelium of the nasopharynx and proliferates in the lower respiratory system.

Pathogenesis

  • The bacterium produces toxins (virulence factors) that paralyze the cilia, and cause inflammation of the respiratory tract, which interferes with the clearing of pulmonary secretions.
  • Bordetella pertussis has tropism for pulmonary tissue and rarely disseminates to other organs.
  • The steps involved in the pathogenesis of pertussis include the following:

Virulence Factors

Bordetella pertussis produces multiple antigenic and biologically active virulence factors responsible for the clinical manifestations of pertussis. These virulence factors include:[1][2]

  • Pertussis toxin (PT)
  • PT undergoes ADP-ribosylation of G proteins to disrupt signal transduction in host cells.[2]
  • Filamentous hemagglutinin (FHA)
  • Suface protein responsible for the interaction and adhesion between host cells and Bordetella pertussis.[2]
  • FHA is a component of the acellular DTaP vaccine.
  • Adenylate cyclase toxin (ACT)
  • ACT delivers an adenylate cyclase domain into the host cell and increases the intracellular cAMP concentration.[2]
  • Following cAMP delivery, phagocyte activity is inhibited, and phagocytes undergo apoptosis.
  • Pertactin (PRN)
  • PRN defends Bordetella pertussis against the host neutrophils (immunomodulation).[2]
  • PRN is a component of the acellular DTaP vaccine.
  • Tracheal cytotoxin (TCT)
  • Lipooligoosaccharide (LOS)
  • Unique outer membrane component that is thought to play a role in clinical manifestations of pertussis.[2]
  • Unknown virulence mechanism.
  • Dermonecrotic toxin (DNT)
  • DNT de-aminates signaling proteins (similar mechanism to Pasteurella multicida leukotoxin).
  • Fimbriae (FIM)
  • Surface appendages to adhere to host cells and avoid host immune cells (immunomodulation).[2]
  • FIM is a component of the acellular DTaP vaccine.

References

  1. ↑ 1.0 1.1 Pertussis (whooping cough). CDC.gov. Accessed on June 15th, 2014
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Hewlett EL, Burns DL, Cotter PA, Harvill ET, Merkel TJ, Quinn CP; et al. (2014). "Pertussis pathogenesis--what we know and what we don't know". J Infect Dis. 209 (7): 982–5. doi:10.1093/infdis/jit639. PMC 3952676. PMID 24626533.

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