Mycobacterial diseases

Question 1

What shape are mycobacteria?

Answer 1

Slender bacillus

Question 2

In which 2 ways are mycobacteria different to other bacterial genera?

Answer 2

1) Unusual waxy cell wall - high lipid content

2) Slow growing - different media requirements

Question 3

Mycobacteria are ‘acid fast bacilli’ which have poor take up of gram’s stains, which 2 stains are used to identify mycobacteria?

Answer 3

1) Ziehl neelsen

2) Phenol auramine

Question 4

What kind of pathogens are mycobacteria?

Answer 4

Intracellular pathogens

Question 5

What kind of infections do mycobacteria tend to cause?

Answer 5

Chronic infections often with a latent phase of infection

Question 6

How are mycobacteria treated compared to other bacterial genera?

Answer 6

Different antimicrobial agents
Much longer courses of therapy
Combination of agents to prevent resistance emergence

Question 7

What mycobacteria causes TB?

Answer 7

Mycobacteria tuberculosis complex:
M. tuberculosis
M. bovis

Question 8

What mycobacteria causes leprosy?

Answer 8

M. leprae

Question 9

Name 3 atypical mycobacteria, which is associated with HIV and which is associated with fish tank granuloma?

Answer 9

1) M. avium complex - associated with HIV
2) M. kansasii
3) M. marinum - fish tank granuloma

Question 10

What fraction of the world population is affected by TB, how many deaths does it cause each year and what other condition is it associated with?

Answer 10

1/3 of the world population infected
2 million deaths per years
Co-infection with HIV - sub-Saharan Africa

Question 11

For what 4 reasons has TB infection become more common in the ‘developed world’?

Answer 11

1) HIV infection
2) Breakdown of control programmes
3) Increased migration from endemic areas
4) Increased travel

Question 12

What percentage of TB infected people in the UK were born abroad and 60% are from what age group?

Answer 12

70% born abroad

60% are young adults aged 15-44

Question 13

How is TB spread?

Answer 13

Person to person - inhalation of infected respiratory droplets

Question 14

What is the rough course of TB, at which stages are patients symptomatic?

Answer 14

1)Primary infection (usually pulmonary disease)
- Some patients will be symptomatic (flu like) and some completely asymptomatic
2) Latent infection period
3) Reactivation of TB (does not occur in all people some people it will remain latent forever)
4) Dissemination (doesn’t disseminate to affect other organs in all people who get reactivation)
NB. Primary infection may disseminate completely skipping the latent phase (this can happen in children)

Question 15

What is the most common site of primary TB infection?

Answer 15

Periphery of lung midzone

Question 16

What happens once TB is inhaled?

Answer 16

1) Inhaled bacilli is phagocytosed by macrophages and carried to the hilar lymph nodes - ghon focus (primary lesion caused by TB)
2) Get intracellular multiplication
3) In some patients can get dissemination at this point via the lymph system/ blood stream

Question 17

What is the bodies response to TB infection?

Answer 17

Tubercle formation (granuloma formation) via a cell mediated response

Question 18

What is the structure of the tubercles formed in TB, what happens to them and what is their function?

Answer 18

1) Central area of epitheloid cells and giant cells
2) Have a surrounding lymphocytic cell infiltration
3) Central area of necrosis
Eventually get fibrosis and calcification of the lesions
The tubercles aim to contain the infection
The bacilli slowly die but may remain viable for 20 years

Question 19

In what 2 ways could a primary TB infection be identified in a patient with some clinical symptoms?

Answer 19

1) CXR

2) Tuberculin skin test conversion

Question 20

In which 6 groups of people is reactivation of TB infection most likely to occur?

Answer 20

1) Lowered immunity
2) In western countries, males over 50
3) Malnutrition
4) Alcoholism
5) Debilitating illness
6) HIV infection

Question 21

People taking what drug are more likely to get a reactivation of TB and why?

Answer 21

Anti TNFa blockade

Role of TNFa is to maintain the granuloma thus harder to maintain in the presence of this drug

Question 22

Patients with what 3 conditions are more likely to get reactivation of TB?

Answer 22

1) Silicosis
2) Chronic renal failure
3) Gastrectomy

Question 23

Where does the pathogen tend to reside in reactivation of TB and why?

Answer 23

Lung apices: its an anaerobe and this is where the oxygen tension is highest

Question 24

What happens to the tubercles in reactivation of TB?

Answer 24

Tubercles coalesce and get caseous necrosis

Can also get cavitation - leading to a higher organism load so greater risk of transmission

Question 25

What are the 5 main symptoms in reactivation of TB?

Answer 25

1) Chronic productive cough 2) Haemoptysis 3) Weight loss 4) Fever 5) Night sweats

Question 26

What is the name for disseminated TB?

Answer 26

Miliary TB

Question 27

What 2 groups does disseminated TB tend to occur in (whether that be following primary infection or reactivation)?

Answer 27

1) Very young/very old | 2) Immunocompromised

Question 28

How does dissemination occur in secondary disease?

Answer 28

Erosion of necrotic tubercle into blood vessel

Question 29

What are the 8 common extra-pulmonary sights in military TB?

Answer 29

1) Pleura 2) Lymph nodes 3) Kidneys 4) Epididymis 5) Bone 6) Intestines 7) Brain/meninges (meningitis) 8) Pericardium

Question 30

What are the 5 main signs of TB meningitis?

Answer 30

1) Often insidious onset 2) Unidentified fever 3) Personality change 4) Focal neurological defect (basilar inflammation) 5) Mild headache/ meningism (May lack constitutional quartet - fever, anorexia, night sweats, weight loss)

Question 31

Other than microbiology what 4 other procedures lead to a diagnosis of TB?

Answer 31

1) CXR 2) Histology 3) Skin testing 4) Blood test: interfere gamma release assay: IGRA

Question 32

For what 3 reasons is microbiology necessary in a diagnosis of TB and what kind of sample is needed?

Answer 32

1) Confirmation of diagnosis 2) Drug sensitivities 3) Molecular typing profile:'MIRUs' Fresh sample - normally of sputum, 3 early morning specimens taken >8 hours apart

Question 33

How is a sample for TB used?

Answer 33

Direct microscopy for AFBs (acid fast bacilli) | >5000 organisms per ml of sputum is considered smear positive

Question 34

In which 2 ways can TB be cultured from a sample, how long does each take?

Answer 34

1) Lowenstein-Jensen solid media - 3-4 weeks | 2) Broth culture: automated - usually

Question 35

What 4 processes are carried out if a sputum sample is found to be AFB positive?

Answer 35

1) Referred to regional reference laboratory 2) Species identification 3) Sensitivites: within 2 weeks 4) Strain typing

Question 36

In children a sputum sample can be hard to obtain, what 3 procedures may be used to obtain one?

Answer 36

1) Induced sputa - nebulised saline 2) Bronchial aspirates 3) Gastric aspirates

Question 37

In suspected renal TB what sample would be needed?

Answer 37

Early morning urines x3

Question 38

How would CSF be analysed in suspected TB meningitis?

Answer 38

Cell count, protein, glucose, microscopy/culture | NB need an adequate volume - >6mls

Question 39

Other than culturing what other method can be used to identify TB, what are the 3 disadvantages and 1 advantage?

Answer 39

Nucleic acid amplification by PCR Advantage: rapid Disadvantage: less sensitive than culture, expensive and not 100% specific (false positives)

Question 40

The XPERT MTB/RIF test is a different method of testing for TB how? and where is it often used?

Answer 40

Direct to sputum test which is clinic based with a result in 2 hours Used in developing world where there is less access to cultures

Question 41

What are the 2 main difficulties with TB treatment?

Answer 41

Lengthy and involves combined tablets - can mean poor adherence

Question 42

What is the standard treatment for pulmonary TB?

Answer 42

2 months: Isoniazid, rifampicin, pyrazinamide, ethambutol | 4 months: isoniazid, rifampicin

Question 43

Why is combined therapy needed to treat TB?

Answer 43

Less chance of resistance, low chance of obtaining combined mutations

Question 44

How is TB in other sights (except meningeal) treated?

Answer 44

Standard 6 month regime used to treat TB

Question 45

How long does treatment for TB meningitis take?

Answer 45

12 months

Question 46

Other than length how does treatment for TB meningitis and pericarditis differ from treatment at other sights?

Answer 46

Initial treatment also with corticosteroids

Question 47

What are the 4 second line agents for drug resistant TB?

Answer 47

1) Amikacin 2) Ethionamide/prothionamide 3) Cycloserine 4) Fluoroquinolones: ciprofloxacin, moxifloxacin

Question 48

What are the 3 new drugs being used to treat TB?

Answer 48

1) Bedaloquine 2) Delamanid 3) Pa-824

Question 49

Why is it thought that shorter regimes for standard Rx would be good?

Answer 49

As it would improve completion rates

Question 50

What 5 things are put in place to try and control TB (ie. identify people with latent infection and prevent transmission)?

Answer 50

1) It is a notifiable disease 2) Contact tracing 3) Tuberculin skin test 4) Blood test: interferon gamma release assay 5) CXR

Question 51

How does the mantoux test work?

Answer 51

Inject purified protein derivative (MTB extract) subcutaneously Read at 48-72 hours observing skin reaction

Question 52

What do interferon gamma release assays measure?

Answer 52

Specific T cells: IFN gamma production | TB specific Ag (ESAT6, CFP10) - don't cross react with M bovis

Question 53

When can interferon gamma release assays be used to identify TB?

Answer 53

Both in latent TB (in new entrants, contacts, immunosuppressed people) and active disease

Question 54

What does the BCG vaccine contains?

Answer 54

Attenuated stain of mycobacteria bovis

Question 55

When is the BCG vaccine given in the UK?

Answer 55

Neonatal or occupational exposure risk

Question 56

What chemoprophylaxis can be used for TB?

Answer 56

1) 3 months of rifampicin/isoniazid or 6 months isoniazid

Question 57

Can the atypical mycobacteria 'non tuberculous mycobacteria' be transmitted from person to person?

Answer 57

No its an environmental organism

Question 58

What mycobacterium tends to cause disseminated disease in HIV infected people?

Answer 58

Mycobacterium avium complex

Question 59

What kind of disease does mycobacterium avium complex cause in non HIV infected adults and what in young children?

Answer 59

Non HIV infected: pulmonary TB like disease | Young children: cervical lymphadenitis

Question 60

How is mycobacterium avium diagnosed?

Answer 60

In a similar way, cultured, they are acid fast bacilli so can be stained in a similar way

Question 61

What is the treatment for mycobacterium avium complex?

Answer 61

Combined treatment, like TB is prolonged | Use a macrolide - clarithromycin or azithromycin

Question 62

What are the 2 possible immune responses to mycobacterium leprosy infection?

Answer 62

1) Tuberculoid - macules/plaques, can cluster around nerves (ulnar and common peroneal) - not severe 2) Lepromatous - subcutaneous tissue accumulation (disfiguring lesions), ear lobes , face - leonine facies - severe

Question 63

What are the 3 drugs used to treat leprosy?

Answer 63

1) Dapsone 2) Rifampicin 3) Clofazimine

Question 64

How does mycobacterium leprosy have to be identified, why?

Answer 64

Genomic analysis as non culturable in vitro

Question 65

What is the specific microbiology request for TB?

Answer 65

AFBs