Mycobacterial diseases Flashcards

1
Q

What are mycobacterium?

A

Non motile rod shaped bacteria which are slow growing

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2
Q

What do mycobacteria have in their cell wall?

A

Long chain fatty (mycolic) acids, complex waves and glycolipids in cell wall

THEREFORE they are acid alcohol fast

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3
Q

What stain do you use for TB/ AFB?

A

Ziehl Neelson - Red on blue

Auramine - Yellow

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4
Q

How do you get non TB mycobacteria?

A

Environmental
Water
Soil

Atypical

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5
Q

What is non TB mycobacterium from?

A

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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6
Q

What are the slow growing NTM?

A

Mycobacterium avium intracellulare

M marinum

M ulcerans

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7
Q

What is MAI?

A
Mycobacterium avium intracellulare (MAI)
AKA M. avium complex (MAC)
Immunocompetent
May invade bronchial tree
Pre-existing bronchiectasis or cavities
Immunosuppressed
Disseminated infection
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8
Q

What is rapid growing NTM?

A

M. abscessus, M. chelonae, M. fortuitum

Skin & soft tissue infections

In hospital settings, isolated from BCs
Vascular catheters & other devices

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9
Q

What is the epidemiology of MTB?

A

Getting better

Endemic to asia and africa

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10
Q

What are the RFs of MTB?

A

COPD
Asthma
Previous MTB
Lung cancer

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11
Q

How do you diagnose lung MTB?

A

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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12
Q

How do you treat MTB?

A

Rifampicin (6 months)
Isoniazid (6 months)
Pyrazinamide (2 months)
Ethambutol (2 months)

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13
Q

How do you treat MAI?

A

Clarithromycin/azithromycin
Rifampicin
Ethambutol
+/- Amikacin/streptomycin

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14
Q

How do you treat rapid growing NTM?

A

Based on susceptibility testing, usually macrolide-based

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15
Q

What is mycobacterium leprae?

A

Paucibacillary tuberculoid

Multibacillary Lepromatous

Mostly in S America, Africa and Asia

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16
Q

What is the in depth epidemiology 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 kind of aerobe is MTB?

A

An obligate aerobe, generation time 15-20h

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18
Q

How is MTB transmitted?

A

Droplet/ Airborne

<10µm particles
Suspended in air
Reach lower airway macrophages

Infectious dose 1-10 bacilli

3000 infectious nuclei
Cough
Talking 5 mins

Air remains infectious 30 mins

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19
Q

How do you prevent MTB?

A

Detection of cases- treat index case

Prevent transmission- PPE, negative pressure isolation

Optimisation of susceptible contacts- Address RFs, Vaccinations

20
Q

What are the MTB vaccines?

A

Bacille Calmette-Guerin (BCG): live attenuated M. bovis strain
Given to babies in high prevalence communities only (since 2005)
70-80% effectiveness in preventing severe childhood TB
Protection wanes
Little evidence in adults

21
Q

What is the natural history of TB?

A
Primary TB
Usually asymptomatic
Ghon focus/complex
Limited by CMI
Rare allergic reactions include EN
Occasionally disseminated/miliary

Latent TB

Reactivation

22
Q

What is post primary TB?

A

Reactivation or exogenous re-infection

> 5 years after primary infection

5-10% risk per lifetime

Risk factors for reactivation
Immunosuppression
Chronic alcohol excess
Malnutrition
Ageing

Clinical presentation
Pulmonary or extra-pulmonary

23
Q

What is the most to least effective immune response to TB?

A
Healthy contact (LTBI)
Lymph node (Scrofula TB)
Localised Extrapulmonary

Pulmonary (localized)
Pulmonary (widespread)

Meningeal
Miliary

24
Q

What are the X-ray findings of MTB?

A

Caseating granulomata
Lung parenchyma
Mediastinal LNs

Commonly upper lobe

25
Q

What are some common extra pulmonary TB?

A

Lymphadenitis
AKA scrofula
Cervical LNs most commonly
Abscesses & sinuses

Gastrointestinal
Swallowing of tubercles

Peritoneal
Ascitic or adhesive

Genitourinary
Slow progression to renal disease
Subsequent spreading to lower urinary tract

26
Q

What is bone/joint and TB meningitis and miliary TB?

A

Bone & joint
Haematogenous spread
Spinal TB most common
Pott’s disease

Miliary TB
Millet seeds on CXR
Progressive disseminated haematogenous TB
Increasing due to HIV

Tuberculous meningitis

27
Q

What is the clinical approach to MTB?

A

Index of suspicion

Suggestive symptoms
Detailed history

Investigations

Treatment

Preventing onward transmission

28
Q

What are RFs for TB?

A

Non-UK born/recent migrants
South Asia 54.8%
Sub-Saharan Africa 29.5%

HIV
Other immunocompromise

Homeless

Drug users, prison

Close contacts

Young adults (also higher incidence in elderly)

29
Q

What is presentation of MTB?

A
FLAWS:
Fever
Lethargy/ Malaise 68%
Appetite loss/ Anorexia
Weight loss 74%
Sweats (Night) 55%

Pulmonary symptoms:
Cough 80%
Haemoptysis 6-37%

30
Q

What would you find on history and exam of MTB?

A
Other localising symptoms
Pulmonary 54.1%
Extra-pulmonary LN 20.4%
GI 4.1%
Spine 4.1%
Meningitis 2%
GU 1.3%

Ethnicity

Recent arrival or travel

Contacts with TB

BCG vaccination

Non-specific examination findings

31
Q

What investigations do you do for TB?

A

CXR & other radiology

Sputum x3
Induced sputum
Bronchoscopy
Biopsies
EMU

Stain for AAFBs (“smear”)
Culture
NAAT- Gene Xpert
Histology

Tuberculin skin test
IGRAs- e.g. T Spot

32
Q

What do you see on a sputum of TB?

A

Sputum
60% sensitivity
Increased 10% & 2% with 2nd & 3rd sputa

Gastric aspirates in kids

Other specimens centrifuged

Rapid

Operator dependent

33
Q

How do you do a TB culture?

A

Gold standard

Solid & liquid culture systems

Up to 6 weeks
1-3 weeks with modern automated systems

Further testing of cultured isolates

34
Q

What additional tests can you do for TB?

A

Speciation
NAAT
Chromatography
Drug sensitivity

Role of NAAT for primary samples?
Rapid diagnosis of smear +ve
Drug resistance mutations

35
Q

How good is the tuberculin skin test?

A

Previous exposure to Mycobacteria

2 units tuberculin

Delayed type hypersensitivity reaction

Cross-reacts with BCG

Poor sensitivity
HIV, age, immunosuppressants
Overwhelming TB

36
Q

What is an IGRA?

A

Detection of antigen-specific IFN-γ production

ELISpot
Quantiferon

No cross-reaction with BCG

Cannot distinguish latent & active TB

Similar problems with sensitivity & specificity

37
Q

What are anti TB drugs?

A

RHZE (RIPE)

+

Second line
Quinolones (Moxifloxacin)
Injectables
Capreomycin, kanamycin, amikacin
Ethionamide/Prothionamide
Cycloserine
PAS
Linezolid
Clofazamine
38
Q

What are the side affects of RHZE?

A

Rifampicin (R)
Raised transaminases & induces cytochrome P450
Orange secretions

Isoniazid (H)
Peripheral neuropathy (pyridoxine 10mg od)

Hepatotoxicity
Pyrazinamide (Z)
Hepatotoxicity

Ethambutol (E)
Visual disturbance

Vitamin D
Nutrition
Surgery

39
Q

How long do you give TB treatment?

A
Duration
3 or 4 drugs for 2/12 
Then Rifampicin & Isoniazid 4/12
10/12 if CNS TB
Cure rate 90%

Adherence
Directly observed therapy (DOT)
Video observed therapy (VOT)

40
Q

What is MDR TB?

A

Multi-drug resistant TB (MDR)
Resistant to rifampicin & isoniazid
Extremely drug-resistant TB (XDR)
Also resistant to fluoroquinolones & at least 1 injectable

Spontaneous mutation + inadequate treatment
Likelihood increased
Previous TB Rx
HIV+
Known contact of MDR TB
Failure to respond to conventional Rx
>4 months smear +ve/>5 months culture +ve

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

41
Q

What are the challenges in a TB history?

A

Clinical history
Less likely to be classical
Symptoms and signs often absent in population with low CD4 count (data from a number of cohorts starting HAART in Africa)

Chest X-ray
More likely extrapulmonary
X-ray changes variable

Smear microscopy & culture
Less sensitive

Tuberculin skin test
More likely to be negative

Sensitivity of IGRAs for active tuberculosis (Goletti et al PloS One 2008)
Quantiferon Gold 
78.1% (95% CI 70.7, 84.3)
T SPOT
85.1% (95% CI 79.2, 89.9)
42
Q

How many people have TB?

A

33%

43
Q

The laboratory calls you saying they have found Acid Fast Bacilli in a clinical sample. Which answer is most appropriate?

A

Recommend TB therapy

44
Q

A 23 year old male is a close contact of a person with smear positive pulmonary TB, What is his lifetime risk of developing active TB?

A

10%

HIV +ve, risk = 10% per year

45
Q

Which drug is the most important?

A

Rifampicin is the most important drug