Mycobacteria and Tuberculosis Flashcards
TB prevalence?
2nd most infectious killer worldwide
Mycobacterium tuberculosis features?
2-4 μ by 0.2-0.5 μ Obligate aerobe well-aerated upper lobes Facultative intracellular parasite usually macrophages Slow generation time 15-20 h
Where does tuberculosis most commonly affect? Where else can it effect?
Lungs - Pulmonary TB
Lymph nodes, bones, joints, kidneys and can cause meningitis
How do people catch TB?
Droplets from coughs or sneezes
Close/frequent prolonged contact with an infected person
Who is most at risk to TB?
Who else is at risk?
People with weakened immune systems
HIV infec Steroids, chemotherapy, transplants, elderly Unhealthy, overcrowded conditions High rate country - S.E Asia Exposed to TB in youth Prisoners, drug addicts, alcoholics Malnourished
How does primary TB occur?
Droplet nuclei inhaled = taken up by alveolar macrophages - not activated
Droplet nuclei reaches alveoli = infec begins
Granuloma in lung = Ghon focus
Enlarged lymph nodes + GF = primary complex
What causes secondary TB?
Reactivation of dormant mycobacteria - impaired immune func
Reinfec in a person previously sensitised to mycobacterial antigens
- occurs in months, yrs, decades after 1 infec
Where is reactivation of TB most common?
Apex of lungs - highly oxygenated
What occurs in secondary TB?
Caseous centres of tubercles liquefy = organisms grow very rapidly here
Large Ag load:
- Bronchi walls become necrotic and rupture
- Cavity formation
- Organisms spill into airways and spread to other areas of lung
Primary lesions heal - Ghon complex, Simon foci
How do TB infection and TB lung disease differ?
Infec TB: Chest x-ray normal Sputum smears negative putum culture negative No symptoms Not infectious Not defined as a case of TB
Lung disease TB Lesion on chest x-ray Sputum smear positive Sputum culture positive Symptoms Infectious Defined as TB case
What do TB infec and TB lung disease have in common?
Organism present
Tuberculin skin test positive
Most common symptoms of TB?
Cytokines causing: Persistent cough, +/- sputum Anorexia Weight loss Swollen glands Fever Night sweats Sense of tiredness Coughing blood
How to treat TB?
Isoniazid, rifampicin, pyrazinamide and ethambutol
for two months followed by isoniazid and rifampicin for four months
Non-infec after 2 weeks
Begin to feel better after 2-4 weeks
Treatment for 6+ months (prevent resistance)
Longer treatment for TB meningitis or if TB is resistant
How to prevent spread of MDR-TB? (multi-drug resistant)
Standardised drug regimens
Directly observed treatment
Good supply of high quality drugs
Isolation of infectious pts
What does vitamin D do?
Activates macrophages to destroy macrobacteria
TB fatality rates?
Untreated = 40-60% Treated = 5-50%, depending on nutrition; quality and availability of med care, HIV status
Name the vaccine for TB?
Bacille Calmette Guerin (BCG)
Features of BCG?
Protection restricted to childhood TB = rarely infectious
No impact on HIV related TB
Does not prevent infec - only disease
= Targeted vaccination, effective for 15yrs
How are HIV and TB linked?
HIV increases risk of TB - destroys immune system
TB makes HIV worse - increases replication rate of HIV
TB treatment slows down HIV and keeps pt alive to get HIV drugs
How are TB and animals linked?
TB common in cattle and humans infected with M.bovis
What are the obstacles of controlling TB?
Lack of money Social instability HIV epidemic Drug resistance Stigma
How to diagnose TB?
Suspicion
Chest x-ray
Tuberculin tests:
- Heaf, tine, mantoux
- May be negative in severe TB or concomitant HIV, malnutrition, steroids
- May be positive with BCG or after exposure to mycobacteria
T-SPOT TB and QuantiFeron Gold:
- Blood tests to replace tuberculin tests
- Detect reactive T cells
Specific for Mtb, not BCG
Microscopy:
- Ziehl-Neelsen stain
- 1/3 of pulmonary TB undiagnosed by microscopy
Sputum Culture:
- Homogenise
- Decontaminate
- Concentrate
- 4-6 weeks for visible colonies
Types of Multi/extensive drug resistance?
MDR TB - rifampicin and isoniazid
XDR TB - as above and aminoglucosides
Risk factors of MDR/XDR?
Previous treatment Current failure Contact with MDR TB HIV+ London resident Male 25-44yrs
MDR/EDR mortality?
25% MDR TB, 50% XDR TB
How does automated culture work?
MGIT 960:
Fluorescent reaction quenched by O2
Growth of mycobacteria lifts quenching and tubes fluoresce
10 days
Nucleic acid detection tests?
RFLP IS6110
Strand displacement – BD ProbeTec
Amplified Mycobacterium tuberculosis Direct Test - Gen-Probe (rRNA)
Enhanced Amplified Mycobacterium tuberculosis Direct Test - Gen-Probe
AMPLICOR Mycobacterium tuberculosis Test – Roche (DNA PCR)
Multiplex PCR assay for 23S rDNA
Typing?
Spoligotyping
Variable Number of Tandem Repeats
Mycobacterial Interspersed Repetitive Units - VNTR-MIRU
