Lower Respiratory Tract infection Part A (bacterial) Flashcards
What is Whooping Cough?
Causative organism - Bordetella pertussis •
- Small Gram-negative, aerobic bacillus
- obligate aerobe
- pleomorphic
Transmission
- Highly infectious respiratory infection
- Spread by airborne droplets
Clinical features – Life threatening in infants
- Characterised by violent coughing fits, due to narrow ariways
- Clinical disease has three stages: catarrhal, paroxysmal, and convalescent
What are the clinical features of whoopig cough? What are its virulence factors
Catarrhal – symptoms usually develop within 5–10 days
- symptoms similar to minor upper respiratory tract infections
- inflammation of mucous membrane
Paroxysmal
- numerous, rapid coughs due to difficulty expelling thick mucus
- characteristic “whoop” at the end of the paroxysms
- Cyanosis (bluish colour of the skin and the mucous membranes due to an insufficient level of oxygen in the blood), vomiting and exhaustion, dehydration
- Less severe in older children, adults or immunised
Convalescent
- Less persistent, paroxysmal coughs that disappear in 2-3 week
Bordetalla Pertussis has multiple virulence factors
- Pertussis toxin = main pathogen mechanism
- FHA
- PRN
- Endotoxin = LPS
What is the pathogenic mechanism for whooping cough
- Pertussis pathogenesis is complex and not fully understood
- Primarily a toxin-mediated disease
- Antibodies against pertussis toxin are protective •
- Bacteria attach to cilia of respiratory epithelial cells (trachea, bronchi and bronchioles)
- Toxins paralyse the cilia
- Inflammation occurs which interferes with clearance of pulmonary secretions
- Pertussis virulence factors allow evasion of host defences
What is the epidemiology of whooping cough?
- Despite vaccination pertussis is prevalent in Australia
- Epidemics occur every 3-4 years
- Waning immunity in adults and adolescents contributes
- Maternal antibodies do not give adequate protection
- Vaccine schedule has been modified to improve protection
- Additional boosters and new vaccines
- Current strategy – minimise exposure of vulnerable infants
Booster immunisation of pregnant women –> Improves maternal antibodies
- Booster immunisation for adult family members
- Improved surveillance
What is the treatment and vaccine?
- Early antibiotic therapy is recommended –> Prophylaxis is used for exposed individuals
- Current pertussis vaccines are acellular (since 1999) – > They contain purified antigens from B. pertussis and previous whole cell vaccine had adverse reactions
- Usually combined with diphtheria/tetanus vaccines
>Improves immunity to tetanus and diphtheria toxoids
>Children given Intanrix Hexa vaccine (see Vaccine lecture)
>Contains 3 antigens: toxoid, haemagglutinin, pertactin
>Administration: 6-8 wks, 4, 6 and 18 months, 4 yrs
- Protective against severe disease but may not prevent mild illness
What is tuberculosis?
- Caused by Mycobacterium tuberculosis
- Aerobic, slender straight or curved bacilli
- Obligate pathogen – man is the principal host
- There are >50 species of Mycobacteria which are environmental organisms
- MOTTS: Mycobacteria Other Than Tuberculosis
> MOTT organisms can be responsible for opportunistic infections, especially in people with AIDS
- Transmission – through inhalation of respiratory droplets
- Mycobacteria in droplet nuclei –> very small and stay suspended in the air for several hours
- Tuberculosis is not highly infectious and usually requires prolonged close proximity to an individual with active disease
What is the shape/characteristics of Tuberculosis?
- Aerobic slender straight or curved bacilli
>Usually straight in tissue specimens (more variable in culture) •
- Very resistant to drying, most disinfectants, acids and alkalis
- Sensitive to heat (Pasteurization) and UV light
Mycobacterial culture
- Complex and highly enriched media
- Slow growth-doubling time 15-24 hrs
- Colonies after several weeks!
- Float on the surface of liquid broths forming clumps due to their hydrophobic nature
Describe the features of the mycobacterial cell wall (tuberculosis)
- Distinctive cell wall structure with a very high lipid content
>Impermeable to stains and dyes
>Resistance to many antibiotics
>Resistance to killing by acidic and alkaline compounds
- Resistance to osmotic lysis via complement deposition
- Resistance to lethal oxidation and can survive inside macrophages
- Sensitive to heat (Pasteurization) and UV light
- Mycolic acids – survival in macrophages
- Cord factor – multiple functions, inhibits immune cells, stops lysosome fusing with phagosome
- Does not stain with Gram stain
- Stain with Acid Fast stain
What is the pathogenesis of tuberculosis?
- Mycobacterium tuberculosis is inhaled as airborne droplets into the lungs
- The bacilli enter the alveolus
- The bacilli are taken up and multiply within alveolar macrophages; cannot be killed by macrophage. The body’s immune system dispatches other specialized macrophages and T lymphocytes to the site.
- Multinucleated giant cells develop as the cells join together
- Forms giant cell called granuloma
- Forms tubercles in lungs that can act as future reservoir for reactivation when immune system is weak –> tubercles encased by macrophages (granulamos)
Discuss the primary and progressive clinical features of tuberculosis?
- TB infection is generally asymptomatic and noninfectious –> May become a latent infection (common)
- A person may be infected in the early decades of life and remain healthy and free of disease for decades –> some bacilli remain viable in tubercules
- Disease may be activated by malignancy, immune suppression, old age or chronic ill-health
- Infected general population – a 5-10% life-long risk of developing disease
- Higher for HIV/AIDS patients – have a 10% annual risk of developing disease
Primary tuberculosis
- Disease is chronic pneumonia with a gradual onset
Symptoms:
- Bad cough that last 3 weeks or longer, chest pain,coughing up blood or sputum, weakness/fatigue, weight loss
Symptoms due to to the immune response
- M.tuberculosis doesnt produce any toxin
- Overproduction of tumour necrosis factor (TNF) by immune cells
Progressive infection
- Results from a number of early lesions eroding into bronchioles
- Subsequent cavitation and dissemination to other sites in the lung
- Access to lymphatics and bloodstream may lead to miliary (systemic) tuberculosis, infecting other organs such as liver and spleen
Discuss the reactivation (secondary) clinical features and causes
5-15% of infected patients
- Balance between infection and immunity is tipped
> triggered by underlying conditions such as alcoholism, diabetes, old age, steroid use or therapy and AIDS
- Usually in apical portions of lung (most oxygenated site) – leading to chronic pulmonary disease with one or two productive lesions
- Tubercles – Double edged sword –> contains the infection but may provide a reservoir
Explain the clinical diagnosis of tuberculosis
- Clinical signs and symptoms, including chest x-ray
- Positive skin reactivity to tuberculosis antigen –> Tuberculin (Mantaux) test – takes up to 3 days
- Presence of M. tuberculosis in a clinical specimen e.g. sputum –> Microscopy: Acid Fast stain (Ziehl-Neelsen), takes only 1 hour
- Culture for definitive confirmation, but may take 6 weeks for growth
- Molecular diagnosis - demonstration of MT DNA or RNA in the specimen.
Discuss the therapy and vaccine for tuberculosis
Therapy: – Tuberculosis requires long term therapy which must be supervised to ensure compliance
- Slow replication and dormant state: treatment is for 6 months to ensure sterilisation of lesion
- Combination of at least 3 anti-tuberculous drugs are used
Vaccine:
- A live, attenuated M. bovis strain (Bacillus Calmette-Guérin - BCG) is used for vaccination.
- BCG vaccine is effective in some populations but not in others –> Not very effective in Africa – where major disease burden is
- Protects against disseminated disease (spread through body) –> Useful in high risk groups i.e. immunocompromised
- Newer vaccines are being developed- these may be attenuated M. tuberculosis strains or subunit vaccines presented as naked DNA
Discuss the epidemiology of tuberculosis
- TB is responsible for ~25% of adult deaths in the developing world – more than those caused by diarrhoea, malaria and AIDS combined •
- TB was considered eradicated in developed countries but is now viewed as a re-emerging disease
- Emergence of multi-drug resistant strains of TB
- TB infections have continued in the developing world and increased population mobility means it can spread
- People with HIV are very susceptible to TB
- Australia has one of the lowest rates in the world
