Pertussis pathophysiology: Difference between revisions

	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

VisualWikitext

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]

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:

Inoculation
Attachment to the respiratory epithelium
Proliferation
Production of virulence factors (toxins)
Evasion of host immune cells
Tissue destruction

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)

TCT is responsible for the death of host respiratory cells using intracellular IL-1 and nitric oxide.^[2]

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

↑ ^1.0 ^1.1 Pertussis (whooping cough). CDC.gov. Accessed on June 15th, 2014
↑ ^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

[CDC-1] 1.0 ^1.1 Pertussis (whooping cough). CDC.gov. Accessed on June 15th, 2014

[pmid24626533-2] 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.

[1]

[2]

@@ Line 1: / Line 1: @@
 __NOTOC__
-{{CMG}}; {{AE}} {{ADI}}
+{{CMG}}; {{AE}} {{YD}}; {{SSK}}; {{ADI}}
 {{Pertussis}}
 == Overview ==
-Pertussis is primarily a toxin-mediated disease. ''Bordetella 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.<ref name=CDC>[http://www.cdc.gov/pertussis/clinical/disease-specifics.html Pertussis (whooping cough). CDC.gov. Accessed on June 15th, 2014]</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 ==
+===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:
-:*Inoculation
+:*[[Inoculation]]
-:*Attachment to the respiratory epithelium
+:*Attachment to the [[respiratory epithelium]]
 :*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
 ===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>
+''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>
 *'''Pertussis toxin (PT)'''
-:*PT undergoes ADP-ribosylation of G proteins to disrupt signal transduction in host cells.
+:*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''.
+:*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.
-* Agglutinogens
+* '''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.
+:*Following cAMP delivery, phagocyte activity is inhibited, and phagocytes undergo apoptosis.
-:*Following cAMP delivery, phagocyte activity is inhibited and undergo apoptosis.
 * '''Pertactin (PRN)'''
-:* PRN defends ''Bordetella pertussis'' against the host neutrophil (immunomodulation).
+:* 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'''
+* '''Tracheal cytotoxin (TCT)'''
-:*TCT is responsible for the death of host respiratory cells
+:*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).
+:*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.
-* 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.
-* 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.
-* 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.
 == References ==