5. Tuberculosis Flashcards
What is Tuberculosis?
- 1.4 millions deaths in developing nations
- Respiratory TB/ Non-respiratory TB
- caused by Mycobacterium Tuberculosis; M.africanum, M. bovis, M.microti, M.absessus, M.canetii
How can you get TB?
- close contacts of infected cases
- travelling to endemic regions
- immuno-compromised immune system; HIV
- elderly
- homeless, drug abusers, alcoholics
What mycobacteria species are in humans and what does it cause?
M. tuberculosis
M. africanum
M. microti
M. canetii
- Tuberculosis
What mycobacterium resides in animals?
M. bovis
- Bovine TB
What bacterium resides insides in humans ad armadillos?
M. leprae
- Leprosy
What mycobacterium resides in environment and water systems?
M. absessus
- only affects those with fibrosis/ bronchiectasis
What mycobacterium is present in birds?
M. avium-intracellulare
- TB-like lung infection/ disseminated in AIDS patients
What are characteristics for the Mycobacterium species?
- Phylum: Actinobacteria; filamentous
- Acid fast: cell envelope contains 60% long chain branched hydrocarbons
- has a virulence factor: mycolic acid
- has a cord factor: Trehalose dimycolate (TDM)
What are the roles of Mycobacterium?
- reduce permeability to other molecules; confers resistance to chemicals, stains, antibiotics
- confers resistance to drying
- intracellular survival
- slow growing: generation time 15-22 hours (cf 1 hour staphylococci)
What is stage 1 of tuberculosis pathogenesis?
Inhalation of infectious particles: droplet nuclei (5micrometers, approx 3 bai=cilli)
What is stage 2 of tuberculosis pathogenicity?
- after 7-21 days. MTB multiplies with macrophages intracellularly
- Macrophages secrete IL-2 and present MTB antigen on their surface
- they eventually burst liberating MTB
What is the third stage of tuberculosis pathogenicity?
- IL-2 stimulates T-lymphocytes (CD4+8) to infiltrate, recognise MTB antigen and become sensitised
- CD4 release inflammatory cytokines, IFN-gamma resulting in tubercle formation (primary lesion)
What is the fourth stage of M. tuberculosis pathogenesis?
- MTB continues to multiply within inactivated/ poorly activated macrophages and tubercle expands
What is the fifth stage of M. tuberculosis pathogenesis?
The primary lesion heals: forming GHON focus- type of granuloma
How does latency to infection occur?
Bacteria ceases to grow and lesion calcifies (90%) and this causes reactivation
What happens in active TB infection?
- the lesion liquifies and bacteria spreads to lungs/organs
- bacteria coughed up in sputum
What is primary tuberculosis?
can be:
-immunocompetent host:
CMI prevents spread of M. tuberculosis, so no symptoms.
latent TB, reactivation may occur
-immunocompromised host:
primary focus worsens; pneumonia develops to LRTI. systemic dissemination.
symptoms result from CMI response: chronic inflammation (has no endotoxin/exotoxin).
What is secondary TB?
endogenous- reactivation of initial infection (within 2 years)
- associated with impairments in CMI and local disturbance of dormant tubercles
- caseous necrotic lesions develop which liquify and leave discharge into bronchi
How does mycobacteria affects AIDS patients?
- 2/3 AIDS patients in sub-saharan Africa develop TB
- prone to rapid primary infection and reactivation of previous infection
- prone to disseminated MAC (M.avium complex) infection
- AIDS patients are very susceptible to M.avium intracellulare
What are the symptoms of tuberculosis?
- 90% of TB patients asymptomatic
- 10% leads to primary TB
- LRTI; cough, fever, weight loss, faitgue
- Military TB: meningitis, septicaemia, kidney infection, joint infection (Pott disease)
What is the clinical diagnosis of TB?
- presenting symptoms
- radiological changes on chest xray
- Tuberculin skin test (TST); Mantoux test, injection with purified protein derivative (PPD)
What is the laboratory diagnosis of TB?
Non-culture techniques:
- IGRA: interferon gamma release assay
- molecular detection in clinical samples, eg..Nucleic acid amplification, PCR
- Microscopy
Culture techniques:
- culture; gold standard method MGIT
What is the diagnostic microbiology of TB?
- early morning sputum x3
- renal TB; complete EMU x3
- CSF; meningitis
- lymph node biopsy
- blood/ bone marrow aspirate
- whole blood; IGRA
How would you use IGRA for TB diagnosis?
- patient sample with possible active or latent TB is re-exposed to specific mycobacterial antigens
- antigens utilised are encoded in region of difference (RD)1
- RD1 encoded antigens are; early secretary antigenic target ESAT-6 and culture filtrate protein CFP-10
can use commercial kits
