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Kat's Pathology > Mycobacterial Diseases (TB) > Flashcards

Mycobacterial Diseases (TB) Flashcards

1
Q

What two terms are important for TB

A

Non-tuberculosis mycobacteria (NTM)

M. tuberculosis (MTB) - pathological form

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2
Q

What is the microbiology of tuberculosis (4)

A

Non-motile rod-shaped bacteria
Relatively slow-growing compared to other bacteria
Long-chain fatty (mycolic) acids, complex waxes & glycolipids in (cell wall, Structural rigidity, Complete Freund’s adjuvant, Staining characteristics_
Acid alcohol fast

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3
Q

What are the two stains used for acid alcohol fast bacilli detection (2)

A

Auramine

Ziehl Neelsen

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4
Q

What are the features fo NTM (6)

A 
AKA (Environmental, Atypical)
Ubiquitous in nature
Varying spectrum of pathogenicity
No person-to-person transmission
Commonly resistant to classical anti-TB Rx
May be found colonising
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5
Q

What are some examples of slow growing NTM (3)

A

Mycobacterium avium intracellulare (MAI)
M. marinum
M. ulcerans

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6
Q

What are the pathologies of m. avium intracellulare (2)

A

Immunocompetent: may invade bronchial tree, pre-existing bronchectasis or cavities.
Immunosuppressed: Disseminated infection

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7
Q

Where does m. marinum cause

A

Swimming pool granuloma

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8
Q

What does m ulcerans cause (2)

A 
Skin lesions (bairnsdale ulcer, buruli ulcer) 
Chronic progressive painless ulcer
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9
Q

What are some fast growing NTM (3)

A

M abscessus
M chelonae
M fortuitum

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10
Q

What do fast growing NTMs cause

A

Skin and soft tissue infections

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11
Q

What are the typical sources of fast growing NTMs

A

Hospital settings - vascular catheters and other devices

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12
Q

What are some risk factors for NTM infection (4)

A

COPD
Asthma
Previous MTB
Bronchiectasis

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13
Q

What is in the diagnostic criteria for NTM (3)

A

Lung disease: Clinical: pulmonary symptoms, nodular/cavitary opacities, multifocal bronchiectasis with multiple small nodules

Exclusion of other diagnoses

Microbiologic: Positive culture >1 sputum samples, OR +ve BAL, OR +ve biopsy with granulomata

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14
Q

What is the treatment of NTM

A

MAI: clarithromycin/asithromycin, rifampicin, ethambutol, +/- amikacin/stretpomycin

Rapid-growing NTM: based on susceptibility testing, usually macrolide based.

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15
Q

What are the subtypes of m. leprae (2)

A

Paucibacillary tuberculoid

Multibacillary lepromatous

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16
Q

What are the features of MTB

A

Multisystem disease

Common worldwide
2nd most common cause of death by infectious agent (after HIV)
~2 million deaths each year

Increasing incidence since 1980s: Most common opportunistic infection in HIV, Immigration

9000 cases reported p.a. in UK

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17
Q

What are the disease states for MTB (5)

A 
Exposed individual can develop: 
Uninfected - insufficiency dose
Cleared - innate response/resistance 
Contained - localised immune response 
Active TB
Latent TB
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18
Q

How is MTB transmitted

A

Droplet nuclei/airborne
<10microm particles
Suspended in air
Reach lower airway macrophages

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19
Q

What dose is required for MTB infection

A

1-10 bacilli

3000 infectious nuclei - cough, talking for 5 mins

Air remains infectious for 30mins

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20
Q

How is TB prevented (4)

A

Detection of cases
Treatment of index cases
Prevention of transmission (PPE, negative pressure isolation)
Optimisation of susceptible contacts (address risk factors, BCG)

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21
Q

What type of vaccine is the BCG

A

Live attenuated M bovis strain

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22
Q

What is the natural history of TB (3)

A

Primary TB - usually asymptomatic, ghon focus/complex, limited by CMI, rare allergic reactions, occasionally disseminated/milliary.
Latent TB
Reactivation

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23
Q

What is post-primary TB

A

Reactivation or exogenous re-infection

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24
Q

When does post-primary TB occur

A

> 5 years after primary infection

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25
Q

What is the lifetime risk of post-primary TB

A

5-10% per lifetime

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26
Q

What are the risk factors for TB reactivation (4)

A

Immunosuppression
Chronic alcohol excess
Malnutrition
Ageing

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27
Q

What is the clinical presentation of post-primary TB

A

Pulmonary or extra-pulmonary

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28
Q

How does the immune system affect the clinical outcome of TB

A

From more effective to less effective immune response:

Healthy contact (LTBI)
Lymph node
Localised extrapulmonary

Pulmonary (localised)
Pulmonary (widespread)

Meningeal
Miliary

29
Q

What is the typical presentation of pulmonary TB (2)

A 
Caeseating granulomatoma (lung parenchyma, mediastinal lymph nodes) 
Commonly in the upper lobe
30
Q

What are the extra-pulmonary manifestations of TB (6)

A

Lymphadenitis (AKA scrofula, cervical lymph nodes most commonly, abscesses and sinuses)
GI (swallowing or tubercles)
Peritoneal (ascitic or adhesive)
GU (slow progression to renal disease, subsequent spreading to lower urinary tract)
Bone and joints (haematogenous spread, spinal TB most common, Pott’s disease)
Miliary TB (millet seeds on CXR, progressive disseminated haematogenous TB, increasing due to HIV)
Tuberculosis meningitis

31
Q

What is the most common form of spinal TB

A

Pott’s disease

32
Q

What is a risk factor for milliary TB

A

HIV

33
Q

What are the steps involved in the clinical approach to suspected TB (5)

A 
Index of suspicion 
Suggestive of symptoms? (detailed history) 
Investigations 
Treatment 
Preventing onward transmission
34
Q

What are the geographical demographics of TB (2)

A

Non-UK born/recent migrants.

South Asia, Sub-Saharan Africa

35
Q

What are the risk factors for TB (6)

A 
Non-UK born/recent migrants
HIV
Other immunocompromise
Homeless
Drug users, prison
Close contacts
Young adults (also higher incidence in elderly)
36
Q

How does TB present (6)

A 
Fever
Weight loss
Night sweats 
Pulmonary symptoms (cough, haemoptyisis) 
Malaise
Anorexia
37
Q

What are important questions in a TB history (5)

A 
Ethnicity
Recent arrival or travel 
Contacts with TB 
BCG vaccine 
Non-specific examination findings
38
Q

What systems must be considered when assessing TB (6)

A 
Pulmonary (most common)
Extra-pulmonary LN 
GI
Spine 
Meningitis 
GU
39
Q

What are the important investigations for TB (5)

A 
CXR and other radiology
Sputum x 3 (induced sputum) 
Bronchoscopy 
Biopsies
EMU
40
Q

What are some analyses that can be done on samples in a patient suspected of TB (6)

A 
Stain for AAFBs (smear) 
Culture 
NAAT
Histology 
Tuberculin skin test
IGRAs
41
Q

What is needed for a diagnosis of TB (5)

A

Microbiology
Radiology
Histology
Epidemiology

42
Q

What are the key features of a smear for TB (5)

A 
Sputum (60% sensitive, increased 10% and 2% with 2nd and 3rd sputa) 
Gastric aspirates in kids 
Other specimens centrifuged 
Rapid 
Operator dependent
43
Q

What is the gold standard to diagnose TB

A

Culture

44
Q

What are the key features of TB culture (4)

A

Gold standard for diagnosis
Solid and liquid culture systems
Up to 6 weeks (1-3 weeks with modern automated systems)
Further testing of cultured isolates

45
Q

Histology features of TB (6)

A 
Granulomatous 
Epithelious macrophages 
Langerhans giant cells
Lymphocytes
Plasma cells
Caeseous necrosis in teh centre
46
Q

How does TB appear with Ziehl Neelsen stain

A

Thin red rods

47
Q

How is species determined in TB infection (2)

A

NAAT

Chromatography

48
Q

What is the role of NAAT for primary samples of TB (2)

A

Rapid diagnosis of smear positive

Drug resistance mutations

49
Q

What are the key features of tuberculin skin tests (5)

A

Identifies previous exposure to mycobacteria
Uses 2 units of tuberculin
Delayed type hypersensitivity reaction
Cross-reacts with BCG
Poor sensitivity (HIV, age, immunosuppressants, overwhelming TB)

50
Q

What is IGRAs for TB detection (6)

A

Detection of antigen specific IFNgamma production
ELISpot
Quantiferon
No cross-reaction with BCG
Cannot distinguish latent and active TB
Similar problems with sensitivity and specificity

51
Q

What is the first-line treatment for TB (4)

A

Rifampicin and isoniazid and pyrazinamide and ethambutol

52
Q

What are the second line drugs for TB (7)

A

Quinolones (moxifloxacin), injectables (capreomycin, kanamycin, amikacin), ethionamide/prothionamide, cycloserine, PAS, linezolid, clofazamine

53
Q

How is TB treated (4)

A

Multi-drug therapy (rifampicin, isoniazid, pyrazinamide, ethambutol)
Vitamin D
Nutrition
Surgery

54
Q

What is the MOA of rifampicin

A

Raised transaminiases and induced cytochrome p450

55
Q

What is a side effect of rifampicin

A

Orange secretions

56
Q

Side effects of isoniazid (2)

A 
Hepatotoxicity
Peripheral neuropathy (pyridoxine 10mg OD)
57
Q

Side effects of pyrazinamide

A

Hepatotoxicity

58
Q

Side effect of ethambutol

A

Visual disturbance

59
Q

What are the treatment regimens for TB (3)

A

3 or 4 drugs for 2 months
Then rifampicin and isoniazid for 4 months.
Treatment for 10 months if CNS TB

60
Q

What is the cure rate for TB

A

90%

61
Q

How is adherence monitored for TB (2)

A

Directly observed therapy (DOT)

Video observed therapy (DOT)

62
Q

What are the main features of MRD TB (2)

A

Resistant to rifampicin and isoniazid

63
Q

What is extremely drug resistant TB resistant to (4)

A

Rifampicin
Isoniazid
Fluoroquinolones
And at least 1 injectable

64
Q

What increases the risk of MDR and XDR TB (5)

A 
Previous TB Rx
HIV
Known contact with MDR TB
Failure to respond to conventional Rx
>4 months smear +ve/>5 months culture +ve
65
Q

How is MDR TB treated (5)

A

4/5 drug regimen for a longer duration

Quinolones, aminoglycosides, PAS, cycloserine, ethionamide

66
Q

What are the WHO recommendations for MDR TB shorter duration treatment

A

7 drugs and a treatment duration of 9-12 months.

67
Q

What is the exclusion criteria for shorter MDR-TB treatment (3)

A

2nd line drug resistance
Extrapulmonary TB
Pregnancy

68
Q

What are the challenges in TB diagnosis in HIV+ve patients (5)

A

Clinical history (less likely to be classical, symptoms and signs often absent in populations with low CD4 count)
CXR (more likely extrapulmonary, X-ray changes variable)
Smear microscopy and culture less sensitive
Tuberculin skin test more likely to be negative
IGRA sensitivity reduced

69
Q

What are the challenges in TB treatment in HIV+ve patients (5)

A 
Timing of treatment initiation 
Drug interactions 
Overlapping toxicity 
Duration of treatment - adherence 
Health care resources

Kat's Pathology (105 decks)

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