Which bacterium causes TB?
mycobacterium tuberculosis
What disease does M. Bovis cause?
Bovine TB in animals
What is the reservoirs for M. Leprae?
humans
armadillos - in the lab
What are some characteristics of the mycobacterium species?
1) mycolic acid virulence factor in cell walls - makes mycobacterium resistant to chemicals, stains and antibiotics, increases survival
2) intracellular survival
3) slow growing (15-22 hrs) and NOT fastidious
What is the pathogenesis for M TB?
- it has 5 stages
- it replicates in macrophages when engulfed by them, MO secrete IL-12 and present MTB antigen on surface -> MO eventually bursts
- IL-12 triggers T cell infiltration -> recognise MTB ag and become activated when APCs process the bacterial antigens and presents them on the cell surface via MHC II
- CD4 T cell release gamma interferon = tubercle formation (primary lesion)
- MTB multiplies within inactivated and poor MO’s = tubercle expands
- primary lesion heals: ghon focus (dormant lesion) forms
What happens in a latent TB infection?
bacteria cease to grow and lesion calcifies
What happens in an active TB infection?
lesion liquifies and bacteria spread to blood and organs
bacteria spreads to blood and organs
bacteria is coughed up in sputum
What is a ghon focus?
lesion found in lungs of individuals with M TB
localised area of inflammation
can undergo caseous necrosis over time
What occurs to a healthy host in TB?
-cell mediated immunity prevents spread of TB
-TB remains latent
-however reactivation may occur
What occurs to an immunocompromised host? (children, elderly,HIV patient/transplant patient)
pneumonia can develop
chronic inflammation
systemic dissemination to the lymph nodes, meninges, upper parts of lung
What is secondary TB?
- reactivation of the initial infection
- associated with the impairment of the cell mediated immune response
- cheesy necrotic lesions develop which discharge contents into the bronchi -> contents of lesions are coughed up and become infective nuclei droplet
-TB pneumonia can occur
What are the symptoms for TB?
lower respiratory tract infection: cough, sputum, weight loss, fatigue, fever
miliary TB where it spreads to other parts of the body: meningitis, septicaemia, kidney infection
How would you diagnose TB?
- can do an x ray to identify ghon focus etc
-tuberculin skin test/ Mantoux test
What are some non culture techniques to detect tuberculosis?
Interferon Gamma Release Assay - uses blood sample from patient with active/latent TB
PCR
Microscopy
Which stain would you use on a microscope to identify TB?
ziehl-neelson stain/ fluorescent auramine stain
NO GRAM STAINING EVER
What are the treatments for respiratory TB?
-isoniazid (inhibits cell wall formation), rifampicin (inhibits nucleic acid synthesis), pyrazinamide (cell acidification), ethambutol (inhibits cell wall formation)
for active TB: first 2 months: isoniazid, rifampicin and continuation phase the same
What are some side effects of the TB drugs?
- Isoniazid: hepatitis, peripheral neuropathy
- Rifampicin: hepatitis, stains bodily fluids orange
- pyrazinamide: hepatitis
Why are mycobacterium acid fast?
their cell envelope contains long chain hydrocarbon
What is the cord factor for mycobacterium TB and what does it do?
trehalose dimycolate (TDM) - toxic to mammalian cells and inhibits migration of neutrophils
What is the tuberculin skin test?
Mantoux test - injection with purified protein derivative (PPD)
which clinical samples establish a lab diagnosis of tb?
- early morning sputum
- early morning urine for renal TB
- CSF for meningitis
- blood/ bone marrow aspirate
