Pathogenesis of tuberculosis Flashcards
Clinically relevant mycobacteria
M. tuberculosis - Tuberculosis
M. Bovis - Bovine tuberculosis
M. Leprae - Leprosy
M. Ulcerans - Buruli ulcer
Non-tuberculous mycobacteria (NTM) - environmental mycobacteria
M. avium/M. marinum/M. abscessus
–> Immunosuppression (HIV), cystic fibrosis
Features of mycobacterium tuberculosis
- Bacterium
- Hydrophobic - high lipid content of cell wall, gram stain difficult
- Slow-growing(generation time 22h)
- Special microscopy stains (ziehl-neelsen, auramine fluorescence, ‘acid-fast bacilli’)
Clinical presentation of TB
- Cough(>3wks)
- Weight loss
- Fatigue
- Fever
- Night sweats
- Hemoptysis (1/3rd)
- Difficulty breathing
Diagnosis of TB
Culture is standard but lengthy
- Liquid culture (MGIT) and MODS both culture based but quicker and can do resistance testing (days-weeks). Time to positivity
- Solid media (3-4 weeks)
Smear positive (AFB microscopy) Molecular methods including PCR increasingly used (GeneXpert MTB/RIF)
Need sputum
TB - Medical evaluation
- Anyone with TB symptoms or positive TST or IGRA result should be medically evaluated for TB disease
- Medical/family history
- Physical examination
- Test for TB infection
- Chest X-ray
- Bacteriological examination
Pathogenicity: Aerosol transmission
- Droplet nuclei containing 1-3 bacilli
- Reach alveolar space
- 5-200 bacilli required to establish infection
- Infection begins in the alveoli where bacilli are engulfed by macrophages
- M.tb bacilli able to survive phagocytosis
Granuloma formation - stalemate
- Granuloma forms protecting bacteria and host
- Latent infection - low number of bacteria, no clinical disease
- Granuloma breaks down - bacteria escape and replicate
- Active TB disease
Granuloma formation
- A dynamic process
- Caseous granuloma, non-necrotising granuloma and fibrotic granuloma
- Lesions may become active or dormant as infection controlled or spreads
TB and macrophages
M.tb able to survive within macrophages, which engulf and destroy most other bacteria
Cell-mediated immunity - TB
- Delayed type hypersensitivity key to controlling M.tb, interferon-gamma important, little role for antibodies
Sites of TB disease
Bacilli may reach any part of the body, but common sites include:
- Larynx
- Bone
- Kidney
- Brain (meningitis)
- Lymph node (scrotula)
- Pleura
- Lung
- Spine (pott’s disease)
Chest X-ray - TB
When a person has pulmonary TB disease, the chest x-ray usually appears abnormal
It may show:
- Infiltrates (collections of fluid and cells in lung tissue)
- Cavities (hollow spaces within lung)
TB meningitis features
- CNS TB is most serious complication - mortality up to 50%
- Commonest between 6 months and 4 yrs
- Rapid progression in yougner children
- 40% will have abnormal CXR
- Spread haematogenously
- Brain stem is the most common site, cranial nerves frequently involved
Gastrointestinal tuberculosis
- Primary infection due to unpasteurised milk
- Secondary infection
first degree complex elsewhere with reinfection, ingestion of expectorated, infected sputum, contiguous spread from organs
What is % extra pulmonary disease dependent on
- Ethnic background, HIV status and TB strain
Latent vs active TB infection
LTBI - Inactive, contained tubercle bacilli in the body Lungs - active, multiplying tubercle bacilli in the body
LTBI - TST or blood test results usually positive
Lungs - TST or blood test results usually positive
LTBI - Chest x-ray usually normal
Lungs - Chest x-ray usually abnormal
LTBI - Sputum smears and cultures negative
Lungs - Sputum smears and cultures may be positive
LTBI - No symptoms
Lungs - symptoms such as cough, fever, weight loss
LTBI - Not infectious
Lungs - Often infectious before treatment
LTBI - Not a case of TB
Lungs - A case of TB
Treatment of TB
Pulmonary TB, long therapy:
- 4 drugs (rifampicin, isoniazid, ethambutol and pyrazinamide) for 2 months, then
- Isoniazid and rifampicin continued for 4 months
Same regiment used for extra-pulmonary TB
However, bone, joint and miliary and TB meningitis are treated for 1 year
Monitor liver function
What does poor patient compliance lead to
Drug resistance
- MDR-TB/XDR-TB
New TB drugs under development
- Bedaquiline
- Delamanid
- Pretomanid
Why is TB still a problem
- Difficult to diagnose
- BCG vaccination efficacy 0%-80%
- Long treatment
- Poor patient compliance, need for directly observed therapy
- Drug resistance
- Latent infection (10% lifetime risk of reactivation of TB disease)
- Funding/profile/press
Leprosy
- Mycobacterium leprae
- Affects peripheral nerves
- > 50% of cases in India
- 2nd common mycobacterial disease
- Transmitted by respiratory droplets
- Not very contagious
- Leprosy is curable with drug treatment
Presentation of leprosy
Tuberculoid - hypopigmented skin patches
Lepromatous - skin nodules and lesions
Buruli ulcer
- Mycobacterium ulcerans
- Mainly in west africa
- 3rd common mycobacterial disease
- Necrotising ulceration (toxin-mediated - mycolactone) following water contact
- Surgical treatment
Non-tuberculous mycobacteria (NTM)
- Atypical, environmental, opportunistic
- > 125 identified species
- Not obligate pathogens i.e free living
- Usually harmless, part of normal flora
- Widely distributed in nature (water/soil/fomites/bronchoscopes)
- Granulomatous inflammation
M.marinum
- Fish tank granuloma - scratches from fish scales, abrasions in non-chlorinated swimming pools
- Inhabits water, causes systemic disease in fish
- Prognosis poor for fish, good for humans
Increasing NTM prevalence
- Increased identification
- Better clinical recognition
- Improvement in other treatments unmasking infection, or providing niche (M.abscessus in CF patients)
- Improved lab techniques for isolation and identification
- Infection acquired by inhalation(M.kansasii and M.avium infection of lungs), ingestion (disseminated M.avium disease via bowel), or direct contact(M.marinum)
