Mycobacterial Diseases (TB) Flashcards by Katerina Fernandez

What two terms are important for TB

Non-tuberculosis mycobacteria (NTM)

M. tuberculosis (MTB) - pathological form

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What is the microbiology of tuberculosis (4)

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

Auramine

Ziehl Neelsen

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What are the features fo NTM (6)

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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What are some examples of slow growing NTM (3)

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

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

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

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Where does m. marinum cause

Swimming pool granuloma

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What does m ulcerans cause (2)

Skin lesions (bairnsdale ulcer, buruli ulcer) 
Chronic progressive painless ulcer

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What are some fast growing NTM (3)

M abscessus
M chelonae
M fortuitum

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What do fast growing NTMs cause

Skin and soft tissue infections

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What are the typical sources of fast growing NTMs

Hospital settings - vascular catheters and other devices

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What are some risk factors for NTM infection (4)

COPD
Asthma
Previous MTB
Bronchiectasis

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What is in the diagnostic criteria for NTM (3)

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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What is the treatment of NTM

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

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

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What are the subtypes of m. leprae (2)

Paucibacillary tuberculoid

Multibacillary lepromatous

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What are the features of MTB

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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What are the disease states for MTB (5)

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

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How is MTB transmitted

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

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What dose is required for MTB infection

1-10 bacilli

3000 infectious nuclei - cough, talking for 5 mins

Air remains infectious for 30mins

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How is TB prevented (4)

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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What type of vaccine is the BCG

Live attenuated M bovis strain

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What is the natural history of TB (3)

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

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What is post-primary TB

Reactivation or exogenous re-infection

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When does post-primary TB occur

> 5 years after primary infection

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What is the lifetime risk of post-primary TB

5-10% per lifetime

What are the risk factors for TB reactivation (4)

Immunosuppression Chronic alcohol excess Malnutrition Ageing

What is the clinical presentation of post-primary TB

Pulmonary or extra-pulmonary

How does the immune system affect the clinical outcome of TB

From more effective to less effective immune response: Healthy contact (LTBI) Lymph node Localised extrapulmonary Pulmonary (localised) Pulmonary (widespread) Meningeal Miliary

What is the typical presentation of pulmonary TB (2)

``` Caeseating granulomatoma (lung parenchyma, mediastinal lymph nodes) Commonly in the upper lobe ```

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

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

What is the most common form of spinal TB

Pott's disease

What is a risk factor for milliary TB

HIV

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

``` Index of suspicion Suggestive of symptoms? (detailed history) Investigations Treatment Preventing onward transmission ```

What are the geographical demographics of TB (2)

Non-UK born/recent migrants. | South Asia, Sub-Saharan Africa

What are the risk factors for TB (6)

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

How does TB present (6)

``` Fever Weight loss Night sweats Pulmonary symptoms (cough, haemoptyisis) Malaise Anorexia ```

What are important questions in a TB history (5)

``` Ethnicity Recent arrival or travel Contacts with TB BCG vaccine Non-specific examination findings ```

What systems must be considered when assessing TB (6)

``` Pulmonary (most common) Extra-pulmonary LN GI Spine Meningitis GU ```

What are the important investigations for TB (5)

``` CXR and other radiology Sputum x 3 (induced sputum) Bronchoscopy Biopsies EMU ```

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

``` Stain for AAFBs (smear) Culture NAAT Histology Tuberculin skin test IGRAs ```

What is needed for a diagnosis of TB (5)

Microbiology Radiology Histology Epidemiology

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

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

What is the gold standard to diagnose TB

Culture

What are the key features of TB culture (4)

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

Histology features of TB (6)

``` Granulomatous Epithelious macrophages Langerhans giant cells Lymphocytes Plasma cells Caeseous necrosis in teh centre ```

How does TB appear with Ziehl Neelsen stain

Thin red rods

How is species determined in TB infection (2)

NAAT | Chromatography

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

Rapid diagnosis of smear positive | Drug resistance mutations

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

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)

What is IGRAs for TB detection (6)

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

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

Rifampicin and isoniazid and pyrazinamide and ethambutol

What are the second line drugs for TB (7)

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

How is TB treated (4)

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

What is the MOA of rifampicin

Raised transaminiases and induced cytochrome p450

What is a side effect of rifampicin

Orange secretions

Side effects of isoniazid (2)

``` Hepatotoxicity Peripheral neuropathy (pyridoxine 10mg OD) ```

Side effects of pyrazinamide

Hepatotoxicity

Side effect of ethambutol

Visual disturbance

What are the treatment regimens for TB (3)

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

What is the cure rate for TB

90%

How is adherence monitored for TB (2)

Directly observed therapy (DOT) | Video observed therapy (DOT)

What are the main features of MRD TB (2)

Resistant to rifampicin and isoniazid

What is extremely drug resistant TB resistant to (4)

Rifampicin Isoniazid Fluoroquinolones And at least 1 injectable

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

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

How is MDR TB treated (5)

4/5 drug regimen for a longer duration | Quinolones, aminoglycosides, PAS, cycloserine, ethionamide

What are the WHO recommendations for MDR TB shorter duration treatment

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

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

2nd line drug resistance Extrapulmonary TB Pregnancy

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

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

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

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

Mycobacterial Diseases (TB) Flashcards

(69 cards)