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YR5 Microbiology > Mycobacterial diseases > Flashcards

Mycobacterial diseases Flashcards

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1
Q

What species causes the most TB cases?

A

M. tuberculosis (MTB)

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2
Q

List 5 Mycobacteria that can cause TB

A

M. tuberculosis

M. bovis

M. africanum

M. microti

M. canetti

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3
Q

Name 4 non-TB Mycobacteria and which populations are most susceptible

A

M. avium complex: untreated HIV

M chelonae: Salmon farmers

M abscessus: CF

M chimaera: vascular bypass device

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4
Q

How is TB transmitted?

A

Aerosol

Infectious expulsion on: coughing, sneezing, speaking, singing

Droplet nuclei suspended in air for up to 30min

Inhalation of droplet nuclei, reach lower airway macrophages

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5
Q

What percentage of the world’s population have latent TB infection? How many go on to develop active TB?

A

¼ to ⅓

~10% lifetime risk of progression to active TB

~30-50% if HIV +ve

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6
Q

What can be used to diagnose latent TB infection?

A

Mantoux with PPD

Gamma Interferon Release Assays (IGRA)

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7
Q

What is the normal incubation period of active TB? What may have happened if active TB occurs later?

A

3-9m

Almost always <2y

Most are endogenously reinfected with TB (not TB activation)

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8
Q

What drugs are used in treatment of TB?

A

Rifampicin: 6m

Isoniazid: 6m

Pyrazinamide: 2m

Ethambutol: 2m

Directly observed therapy (DOTs)

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9
Q

Name the side effects of each TB drug

A

Rifampicin: orange secretions, raised transaminases, induces CYP450

Isoniazid: peripheral neuropathy, hepatoxicity

Pyrazinamide: hepatotoxic

Ethambutol: optic neuritis

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10
Q

What drug can be given to prevent the peripheral neuropathy caused by Isoniazid?

A

Pyridoxine

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11
Q

What is the natural clinical course of TB?

A

Infection usually asymptomatic, controlled by cell mediated immunity: becomes latent in Gohn focus/ caeseating granuloma

Upon reactivation (e.g. immunosuppression) becomes symptomatic

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12
Q

Which baseline investigations must be made before commencing anti-TB treatment?

A

FBC, LFT, U+Es, CRP

CXR

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13
Q

What is the duration of treatment for TB meningitis?

A

12m

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14
Q

What is the microbiology of Mycobacteria?

A

Non-motile rod-shaped bacteria

Relatively slow-growing cf. other bacteria

Long-chain fatty (mycolic) acids, complex waxes + glycolipids in cell wall giving structural rigidity

Acid alcohol fast

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15
Q

What are tests for acid alcohol fast bacilli (AAFBs)? What is the turn around time? Which is more sensitive?

A

Auramine 20-30m (more sensitive)

Ziehl-Neelsen 30m

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16
Q

What is this?

A

Auramine staining

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17
Q

What is this?

A

Ziehl-Neelson staining

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18
Q

Name 3 slow growing non tuberculous mycobacterium

A

Mycobacterium avium-intracellulare complex (MAC)

Mycobacterium marinarum

Mycobacterium ulcerans

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19
Q

Describe the pathology of mycobacterium avium intracellulare complex

A

RF: pre-existing lung disease, heavy smoking/ drinking, HIV

Immunocompetent: invades bronchial tree

Immunocompromised: disseminated infection

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20
Q

Describe the pathology of mycobacterium marinarum

A

“Fish tank/ Swimming pool granuloma”

Swimmers/ Aquarium owners

Plaques/ papules- granulomatous ulcers

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21
Q

Describe the pathology of mycobacterium ulcerans

A

aka. Buruli ulcer

Tropical: S America, Australia, Africa

Painless nodule/ induration/ swelling progressing to ulceration, scarring + contractures

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22
Q

Where are non-tuberculous mycobacteria found?

A

Water

Soil

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23
Q

Explain the aetiology/pathophysiology of non-tuberculous mycobacteria.

A

AKA Environmental or Atypical Mycobacteria

Ubiquitous in nature. Varying spectrum of pathogenicity.

Little risk of person-to-person transmission. Commonly resistant to classical anti-TB Rx. May be found colonizing humans.

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24
Q

List 3 fast-growing non-tuberculous mycobacteria

A

M. abscessus

M. chelonae

M. fortuitum

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25
Q

What are fast-growing non-tuberculous mycobacteria outbreaks associated with?

A

Skin + soft tissue infections

Tattoo assaociated outbreaks

In hospital settings from BCs: Vascular catheters, Plastic surgery

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26
Q

Give 2 broad risk factors for NTM.

A

Age

Underlying lung disease: COPD, Asthma, Bronchiectasis, CF, cancer

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27
Q

What is the diagnostic criteria for Mycobacterial diseases?

A

Clinical: Pulmonary Sx, nodular/cavitary opacities, multifocal bronchiectasis with multiple small nodules.

Exclusion of other dx.

Microbiologic:

  • +ve culture >1 sputum samples
  • OR +ve BAL
  • OR +ve biopsy with granulomata
28
Q

What is the treatment of MAC/ slow growing non tuberculous Mycobacterial diseases?

A

Rifampicin

Clarithromycin/ azithromycin

Ethambutol

+/- Amikacin/streptomycin

“RiCES”

29
Q

What is the treatment for fast growing non tuberculous mycobacterial diseases?

A

Based on susceptibility testing, usually macrolide-based

30
Q

What is Leprosy? What is it caused by?

A

aka Hansen disease

Chronic infectious disease caused by prolonged exposure to Mycobacterium Leprae

31
Q

Give 3 cardinal clinical manifestations of Leprosy

A

Hypopigmented skin lesions

Nerve thickening

Peripheral nerve palsies +/- repeated injury due to sensory loss

32
Q

Compare the two types of Mycobacterium leprae

A

Paucibacillary/ Tuberculoid

  • Few bacilli
  • Strong Th1 response
  • Less destruction of structures- skin, nerves, bones

Multibacillary/ Lepromatous

  • Abundance of bacilli
  • Th2 response
  • Multiple skin lesions + joint infiltration
33
Q

What is Mycobacterium tuberculosis? Summarise the epidemiology of TB.

A

Multisystem disease.

Obligate aerobe

  • Common worldwide
  • Most common cause of death by infectious agent, pre COVID: ~2 million deaths each year
  • Increasing incidence since 80s
  • Most common opportunistic infection in HIV
34
Q

What vaccination is given to protect against TB?

A

BCG

Attenuated strain of M. bovis

Given to infants + high risk

CI in immunosuppressed (live vaccine)

35
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 TB?

A

10% for immunocompetent hosts

36
Q

What are the 3 possible outcomes after exposure to TB?

A
  • Nothing
  • Mild febrile disease
  • Straight progression to clinical TB

Majority control 1st exposure, go into state of latent TB infection, may remain like this for many years until something affects their immune system, causing re-activation.

New evidence is going against this current paradigm.

37
Q

List 5 clinical investigations for TB

A

CXR: predilection to apices, mediastinal LNs, miliary TB

Sputum x 3

EBUS TBNA (endobronchial US transbronchial needle aspiration)

Bronchoscopy

Early morning urine

38
Q

What tests are performed on broncho-alveolar lavage for TB?

A

Check for acid fast bacilli on smear

Culture on Lowenstein-Jenson medium, stain with auramine/ Ziehl-Neelson

39
Q

How is an endobronchial ultrasound transbronchila needle aspiration utilised in diagnosis of TB?

A

Histology- caseating granuloma

40
Q

What is the tuberculin skin test?

A

aka. Mantoux

Intradermal tuberculin purified protein derivative (PPD)

Examine induration 48-72h later

Indicates previous exposure- BCG, active, latent

41
Q

List 3 disadvantages of the tuberculin skin test

A

No differentiation of vaccination, latent or active

Poor sensitivity (HIV, age, immunosuppression, overwhelming TB)

Risk of delayed type hypersensitivity reaction from PPD

42
Q

What is an IGRA test?

A

Interferon gamma release assay

e.g. Elispot, Quantiferon

Detects antigen-specific IFNg production

No cross reaction with BCG

43
Q

Give 2 disadvantages of IGRAs

A

Can’t distinguish latent + active TB

Issues with sensitivity + specificity

44
Q

How is TB prevented?

A

Detection + Tx of index case

Prevention of transmission:

  • PPE
  • -ve pressure isolation

Optimisation of susceptible contacts

Address RFs

Bacille Calmette-Guerin (BCG): live attenuated M. bovis strain.

45
Q

What is post-primary TB and how does this present?

A

Reactivation or exogenous re-infection: 10% risk per lifetime

Clinical presentation: Pulmonary or extra-pulmonary depending on host immune response

46
Q

List 4 risk factors for reactivation of latent TB

A

Immunosuppression

Chronic alcohol excess

Malnutrition

Ageing

47
Q

In order of most effective to least effective immune response, what are the outcomes of TB?

A

Healthy contact (LTBI)

Lymph node

Localised Extrapulmonary

Pulmonary (localized)

Pulmonary (widespread)

Meningeal

Miliary

48
Q

What is pulmonary TB?

A

Caseating granulomata in lung parenchyma + mediastinal LNs

Commonly upper lobe

49
Q

Give 5 systems affected by extra-pulmonary TB. What are the features of involvement in each?

A

Lymphadenitis: aka scrofula

Cervical LNs most commonly

Abscesses + sinuses

GI: May present like IBD, due to swallowing of tubercles

Peritoneal: Ascitic or adhesive

GU: slow progression to renal disease

Subsequent spreading to lower urinary tract

Bone + joint: Haematogenous spread

Spine (Pott’s disease)

50
Q

What is miliary TB?

A

Disseminated haematogenous spread

Millet seeds on CXR

Increasing due to HIV

51
Q

Give 4 features of presentation of tuberculosis meningitis. How is it diagnosed?

A

Headaches

Personality change

Meningism

Confusion

Ix: LP- turbid

52
Q

What are 8 risk factors for TB?

A

Non-UK born/recent migrants

South Asia

SS Africa

HIV/ Other immunocompromise

Homeless

IVDU, prison

Close contacts

YA (also higher in elderly)

53
Q

List 8 signs/ symptoms of TB

A

Cough 80%

Weight loss 74%

Night sweats 55%

Fever

Pulmonary Sx

Haemoptysis 6-37%

Malaise 68%

Anorexia

54
Q

What is this?

A

Milliary TB

55
Q

What is this?

A

Milliary TB

56
Q

What is this?

A

Mediastinal lymph nodes

57
Q

List 7 second line medications for drug resistant TB

A
  • Quinolones (Levofloxacin)
  • Bedaquiline
  • Linezolid
  • Clofazimine
  • Injectables: kanamycin, amikacin
  • Ethionamide/ Prothionamide
58
Q

List 4 risk factors for drug resistant TB

A

Previous TB Rx

HIV+

Known contact of MDR TB

Failure to respond to conventional

59
Q

What test can be used to determine TB drug sensitivity?

A

Molecular line-probe assays

Whole genome sequencing on culture

Next gen sequencing

60
Q

What are the forms of resistant TB?

A

Multidrug resistant (MDR): resistant to Rifampicin + Isoniazid

Extremely drug resistant (XDR): resistant to rifampicin, isoniazid, fluoroquinolones + at least 1 injectable

61
Q

What is drug resistant TB though to be due to?

A

Spontaneous mutation

Inadequate tx

62
Q

What is the treatment for drug resistant TB?

A

>,4 drugs for 9-12m

Levofloxacin/ Moxifloxacin

Bedaquiline

Linezolid

Clofazimine

Pretomanid

63
Q

List 5 diagnostic challenges of HIV and TB coinfection

A
  1. Clinical presentation less likely to be classical, Sx + signs absent if low CD4
  2. CXR may be normal (more likely extra pulmonary manifestations)
  3. Smear microscopy + culture less sensitive
  4. Tuberculin skin test more likely to be -ve
  5. Low sensitivity of IGRAs
64
Q

List 5 treatment challenges of HIV and TB coinfection

A

Timing of tx initiation

Drug interactions

Overalapping toxicity

Duration of tx ?adherence

Healthcare resources

65
Q

What is the MTB complex? List 3 important members

A

Genetically related group of mycobacterium that can cause TB

Mycobacterium tuberculosis

Mycobacterium bovis

Mycobacterium africanum

YR5 Microbiology (23 decks)

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