7. Whooping Cough Flashcards
Similarities between Cholera and Whooping Cough (pertussis)
Both Gram neg
Both colonise
Both produce complex A-B toxin
Both have ADP-ribosylase activity (acts on G protein to increase cAMP)
Differences between Cholera and Whooping Cough
Cholera: tropism for GI cells
Whooping cough: tropism for respiratory tract cells
Cholera: diarrhoea
Whooping cough: coughing
Similarities but have different target sites in the body → different primary symptoms
What bacterium causes whooping cough?
Bordetella pertussis
Features of Bordetella pertussis
Gram neg
Coccobacillus
Fastidious
Humans only reservoir
What part of the body becomes infected by Bordetella pertussis?
Respiratory tract
How is B. pertussis spread?
Spread by aerosols, direct contact e.g. coughing into hands & not washing hands
What does initial whooping cough infection resemble?
The common cold
What are the symptoms of whooping cough that begin to develop?
Severe paroxysmal (short & frequent, stereotyped symptom) cough, excess mucous & vomiting, can progress to irreversible neurological damage
What are the 3 stages of whooping cough disease?
- Catarrhal (7-10 days after exposure) - cold-like symptoms with hacking cough, fever rare
- Paroxysmal (10-14 days after exposure) - fits of consecutive coughs followed by gasps for air (‘whoop’ noise)
- Convalescent (4-6 weeks after exposure) - coughing fits gradually decrease although can recur for months when triggered by a respiratory infection
Is whooping cough primarily a disease of children or adults? Why?
Primarily children since most adults have been exposed to the organism as children
What lead to a decrease in vaccine uptake & resurgence of whooping cough?
Perceived risk of side effects i.e. brain bleeds
What type of vaccine for pertussis was created after the brain bleed scare?
An acellular vaccine (aPV), which is not as effective as the host cell vaccine
Who are more commonly associated with severe pertussis?
Naive infants
Inhalation
Colonisation
Toxin production
Pathogenesis of pertussis in 3 steps?
What is the main issue with animal models of pertussis?
Very poor symptom mimicry
What cells are B. pertussis highly specific for?
Ciliated respiratory mucosal cells (alcohol paralyses these cilia)
What happens after colonisation by B. pertussis?
The ciliated respiratory cells die - prevents removal in the normal manner (involves several adhesins)
What is Fha?
FHa is filamentous haemagglutinin. It is a very elongated single surface protein which forms loose filamentous structures on the cell surface. It binds to sulfatide, found on the surface of tracheal cells
To what does filamentous haemagglutinin bind?
Sulfatide
What do Fha mutants exhibit?
Reduced colonisation
What are the 2 roles of the pertussis toxin?
- As an adhesin
- As a toxin
Pertussis toxin mutants are…
avirulent
What type of toxin is the pertussis toxin?
A complex A-B toxin, composed of S subunits
S1 = A subunit
S2, 3, x2 S4, S5 = equivalent to 5B subunits
S2 and S3 subunits of pertussis toxin mediate binding to?
Lactosylceramide (a glycolipid)
What is the active subunit of the pertussis toxin?
S1 subunit - an ADP-ribosylase that acts on host G protein to affect cAMP levels
How do the cholera toxin and pertussis toxin slightly differ in mode of action?
Ptx prevents release of GDP (by targeting Gi protein) → AC complex permanently switched on
Cholera toxin permanently switches on AC complex by targeting the Gs protein
What bacterium also causes the cough but does not produce Ptx?
Bordetella parapertussis
What are 3 other toxins produced by B. pertussis?
- Invasive adenylate cyclase (AMP is converted to cAMP via ACase (+calmodulin) to open ion channels)
- Tracheal cytotoxin (kills ciliated cells in tracheal rings, stimulates IL-1 release - fever)
- Dermonecrotic toxin (causes skin lesions (necrosis) at low concentrations, role in whooping cough is unclear)
What host protein does invasive adenylate cyclase (ACT) require for full activity?
Calmodulin
ACase mutants are?
avirulent
Expression of virulence genes (pertussis) enhanced in what conditions?
High temp., low magnesium conc., low nicotinamide
Treatment for pertussis?
Antibiotics do not influence the duration of the illness but may limit the infectivity. Best solution would be the development of better vaccines. Current best aPV not as effective as whole cells (in terms of duration of protection).
