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302/308 > Pathogenesis of tuberculosis > Flashcards

Pathogenesis of tuberculosis Flashcards

1
Q

Clinically relevant mycobacteria

A

M. tuberculosis - Tuberculosis
M. Bovis - Bovine tuberculosis
M. Leprae - Leprosy
M. Ulcerans - Buruli ulcer

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2
Q

Non-tuberculous mycobacteria (NTM) - environmental mycobacteria

A

M. avium/M. marinum/M. abscessus

–> Immunosuppression (HIV), cystic fibrosis

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3
Q

Features of mycobacterium tuberculosis

A
  • 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’)
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4
Q

Clinical presentation of TB

A
  • Cough(>3wks)
  • Weight loss
  • Fatigue
  • Fever
  • Night sweats
  • Hemoptysis (1/3rd)
  • Difficulty breathing
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5
Q

Diagnosis of TB

A

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

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6
Q

TB - Medical evaluation

A
  • Anyone with TB symptoms or positive TST or IGRA result should be medically evaluated for TB disease
  1. Medical/family history
  2. Physical examination
  3. Test for TB infection
  4. Chest X-ray
  5. Bacteriological examination
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7
Q

Pathogenicity: Aerosol transmission

A
  • 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
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8
Q

Granuloma formation - stalemate

A
  • 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
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9
Q

Granuloma formation

A
  • A dynamic process
  • Caseous granuloma, non-necrotising granuloma and fibrotic granuloma
  • Lesions may become active or dormant as infection controlled or spreads
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10
Q

TB and macrophages

A

M.tb able to survive within macrophages, which engulf and destroy most other bacteria

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11
Q

Cell-mediated immunity - TB

A
  • Delayed type hypersensitivity key to controlling M.tb, interferon-gamma important, little role for antibodies
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12
Q

Sites of TB disease

A

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)
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13
Q

Chest X-ray - TB

A

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)
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14
Q

TB meningitis features

A
  • 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
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15
Q

Gastrointestinal tuberculosis

A
  • Primary infection due to unpasteurised milk
  • Secondary infection
    first degree complex elsewhere with reinfection, ingestion of expectorated, infected sputum, contiguous spread from organs
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16
Q

What is % extra pulmonary disease dependent on

A
  • Ethnic background, HIV status and TB strain
17
Q

Latent vs active TB infection

A

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

18
Q

Treatment of TB

A

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

19
Q

What does poor patient compliance lead to

A

Drug resistance

- MDR-TB/XDR-TB

20
Q

New TB drugs under development

A
  • Bedaquiline
  • Delamanid
  • Pretomanid
21
Q

Why is TB still a problem

A
  • 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
22
Q

Leprosy

A
  • 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
23
Q

Presentation of leprosy

A

Tuberculoid - hypopigmented skin patches

Lepromatous - skin nodules and lesions

24
Q

Buruli ulcer

A
  • Mycobacterium ulcerans
  • Mainly in west africa
  • 3rd common mycobacterial disease
  • Necrotising ulceration (toxin-mediated - mycolactone) following water contact
  • Surgical treatment
25
Q

Non-tuberculous mycobacteria (NTM)

A
  • 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
26
Q

M.marinum

A
  • 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
27
Q

Increasing NTM prevalence

A
  • 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)

302/308 (22 decks)

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