Pertussis pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
 
(13 intermediate revisions by 2 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{CMG}}; {{AE}} {{ADI}}
{{CMG}}; {{AE}} {{YD}}; {{SSK}}; {{ADI}}
{{Pertussis}}
{{Pertussis}}


== Overview ==
== Overview ==
Pertussis is primarily a toxin-mediated disease caused by the bacterium [[Bordetella pertussis]]. The bacteria attach to the [[cilia]] of the respiratory [[epithelial cells]], produce toxins that paralyze the cilia, and cause [[inflammation]] of the respiratory tract, which interferes with the clearing of pulmonary secretions. Until recently, it was thought that Bordatella pertussis did not invade the tissues; however, recent studies have suggested that the bacteria are present in alveolar [[macrophage]]s.
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 ==
* Pertussis is an acute infectious disease caused by the bacterium Bordetella pertussis.
===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]].


* Humans are the only reservoir for Bordatella pertussis, and the [[incubation period]] varies from 1 to 3 weeks, and is usually about 10 days. Although asymptomatic carriers have been reported, they have a low probability of transmitting the disease as they are not actively [[coughing]]. [[Pertussis]] is highly contagious, and highest rates of transmission occurs with exposure to the infected individual at 5 feet or less.
===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:
:*[[Inoculation]]
:*Attachment to the [[respiratory epithelium]]
:*Proliferation
:*Production of [[virulence factor]]s (toxins)
:*Evasion of host [[immune cell]]s
:*Tissue destruction


* Infection occurs through direct contact with the aerosolized mucus of infected persons, usually during [[coughing]] and [[sneezing]]. The bacterium adheres to the ciliated epithelium of the [[nasopharynx]] and proliferates in the [[lower respiratory system]].  In addition, the bacterium produces toxins that paralyze the cilia, and cause inflammation of the respiratory tract, which interferes with the clearing of pulmonary secretions.
===Virulence Factors===
 
''Bordetella pertussis'' produces multiple antigenic and biologically active virulence factors responsible for the clinical manifestations of pertussis. These virulence factors include:<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>
* In a small number of cases, the bacteria may move further to the pulmonary [[alveoli]], causing Bordatella pneumonia. The bacteria does not however cross the respiratory epithelium to the bloodstream, and therefore [[sepsis]] is not seen.
*'''Pertussis toxin (PT)'''
:*PT undergoes ADP-ribosylation of G proteins to disrupt signal transduction in host cells.<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>
*'''Filamentous hemagglutinin (FHA)'''
:*Suface protein responsible for the interaction and adhesion between host cells and ''Bordetella 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>
:*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.<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.
* '''Pertactin (PRN)'''
:* 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.
* '''Tracheal cytotoxin (TCT)'''
:*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)'''
:*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>
:*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).<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>
:*FIM is a component of the acellular DTaP vaccine.


== References ==
== References ==
Line 24: Line 55:
[[Category:Emergency medicine]]
[[Category:Emergency medicine]]
[[Category:Pulmonology]]
[[Category:Pulmonology]]
[[Category:Needs content]]


{{WH}}
{{WH}}
{{WS}}
{{WS}}

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]

Pertussis Microchapters

Home

Patient Information

Overview

Historical Perspective

Pathophysiology

Causes

Differentiating Pertussis from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

Other Diagnostic Studies

Treatment

Medical Therapy

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Pertussis pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Pertussis pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Pertussis pathophysiology

CDC onPertussis pathophysiology

Pertussis pathophysiology in the news

Blogs on Pertussis pathophysiology

Directions to Hospitals Treating Type page name here

Risk calculators and risk factors for Pertussis pathophysiology

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.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Pertussis_pathophysiology&oldid=1202634"