Mycobacterial diseases Flashcards
What shape are mycobacteria?
Slender bacillus
In which 2 ways are mycobacteria different to other bacterial genera?
1) Unusual waxy cell wall - high lipid content
2) Slow growing - different media requirements
Mycobacteria are ‘acid fast bacilli’ which have poor take up of gram’s stains, which 2 stains are used to identify mycobacteria?
1) Ziehl neelsen
2) Phenol auramine
What kind of pathogens are mycobacteria?
Intracellular pathogens
What kind of infections do mycobacteria tend to cause?
Chronic infections often with a latent phase of infection
How are mycobacteria treated compared to other bacterial genera?
Different antimicrobial agents
Much longer courses of therapy
Combination of agents to prevent resistance emergence
What mycobacteria causes TB?
Mycobacteria tuberculosis complex:
M. tuberculosis
M. bovis
What mycobacteria causes leprosy?
M. leprae
Name 3 atypical mycobacteria, which is associated with HIV and which is associated with fish tank granuloma?
1) M. avium complex - associated with HIV
2) M. kansasii
3) M. marinum - fish tank granuloma
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?
1/3 of the world population infected
2 million deaths per years
Co-infection with HIV - sub-Saharan Africa
For what 4 reasons has TB infection become more common in the ‘developed world’?
1) HIV infection
2) Breakdown of control programmes
3) Increased migration from endemic areas
4) Increased travel
What percentage of TB infected people in the UK were born abroad and 60% are from what age group?
70% born abroad
60% are young adults aged 15-44
How is TB spread?
Person to person - inhalation of infected respiratory droplets
What is the rough course of TB, at which stages are patients symptomatic?
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)
What is the most common site of primary TB infection?
Periphery of lung midzone
What happens once TB is inhaled?
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
What is the bodies response to TB infection?
Tubercle formation (granuloma formation) via a cell mediated response
What is the structure of the tubercles formed in TB, what happens to them and what is their function?
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
In what 2 ways could a primary TB infection be identified in a patient with some clinical symptoms?
1) CXR
2) Tuberculin skin test conversion
In which 6 groups of people is reactivation of TB infection most likely to occur?
1) Lowered immunity
2) In western countries, males over 50
3) Malnutrition
4) Alcoholism
5) Debilitating illness
6) HIV infection
People taking what drug are more likely to get a reactivation of TB and why?
Anti TNFa blockade
Role of TNFa is to maintain the granuloma thus harder to maintain in the presence of this drug
Patients with what 3 conditions are more likely to get reactivation of TB?
1) Silicosis
2) Chronic renal failure
3) Gastrectomy
Where does the pathogen tend to reside in reactivation of TB and why?
Lung apices: its an anaerobe and this is where the oxygen tension is highest
What happens to the tubercles in reactivation of TB?
Tubercles coalesce and get caseous necrosis
Can also get cavitation - leading to a higher organism load so greater risk of transmission
What are the 5 main symptoms in reactivation of TB?
1) Chronic productive cough
2) Haemoptysis
3) Weight loss
4) Fever
5) Night sweats
What is the name for disseminated TB?
Miliary TB
What 2 groups does disseminated TB tend to occur in (whether that be following primary infection or reactivation)?
1) Very young/very old
2) Immunocompromised
How does dissemination occur in secondary disease?
Erosion of necrotic tubercle into blood vessel
What are the 8 common extra-pulmonary sights in military TB?
1) Pleura
2) Lymph nodes
3) Kidneys
4) Epididymis
5) Bone
6) Intestines
7) Brain/meninges (meningitis)
8) Pericardium
What are the 5 main signs of TB meningitis?
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)
Other than microbiology what 4 other procedures lead to a diagnosis of TB?
1) CXR
2) Histology
3) Skin testing
4) Blood test: interfere gamma release assay: IGRA
For what 3 reasons is microbiology necessary in a diagnosis of TB and what kind of sample is needed?
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
How is a sample for TB used?
Direct microscopy for AFBs (acid fast bacilli)
>5000 organisms per ml of sputum is considered smear positive
In which 2 ways can TB be cultured from a sample, how long does each take?
1) Lowenstein-Jensen solid media - 3-4 weeks
2) Broth culture: automated - usually
What 4 processes are carried out if a sputum sample is found to be AFB positive?
1) Referred to regional reference laboratory
2) Species identification
3) Sensitivites: within 2 weeks
4) Strain typing
In children a sputum sample can be hard to obtain, what 3 procedures may be used to obtain one?
1) Induced sputa - nebulised saline
2) Bronchial aspirates
3) Gastric aspirates
In suspected renal TB what sample would be needed?
Early morning urines x3
How would CSF be analysed in suspected TB meningitis?
Cell count, protein, glucose, microscopy/culture
NB need an adequate volume - >6mls
Other than culturing what other method can be used to identify TB, what are the 3 disadvantages and 1 advantage?
Nucleic acid amplification by PCR
Advantage: rapid
Disadvantage: less sensitive than culture, expensive and not 100% specific (false positives)
The XPERT MTB/RIF test is a different method of testing for TB how? and where is it often used?
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
What are the 2 main difficulties with TB treatment?
Lengthy and involves combined tablets - can mean poor adherence
What is the standard treatment for pulmonary TB?
2 months: Isoniazid, rifampicin, pyrazinamide, ethambutol
4 months: isoniazid, rifampicin
Why is combined therapy needed to treat TB?
Less chance of resistance, low chance of obtaining combined mutations
How is TB in other sights (except meningeal) treated?
Standard 6 month regime used to treat TB
How long does treatment for TB meningitis take?
12 months
Other than length how does treatment for TB meningitis and pericarditis differ from treatment at other sights?
Initial treatment also with corticosteroids
What are the 4 second line agents for drug resistant TB?
1) Amikacin
2) Ethionamide/prothionamide
3) Cycloserine
4) Fluoroquinolones: ciprofloxacin, moxifloxacin
What are the 3 new drugs being used to treat TB?
1) Bedaloquine
2) Delamanid
3) Pa-824
Why is it thought that shorter regimes for standard Rx would be good?
As it would improve completion rates
What 5 things are put in place to try and control TB (ie. identify people with latent infection and prevent transmission)?
1) It is a notifiable disease
2) Contact tracing
3) Tuberculin skin test
4) Blood test: interferon gamma release assay
5) CXR
How does the mantoux test work?
Inject purified protein derivative (MTB extract) subcutaneously
Read at 48-72 hours observing skin reaction
What do interferon gamma release assays measure?
Specific T cells: IFN gamma production
TB specific Ag (ESAT6, CFP10) - don’t cross react with M bovis
When can interferon gamma release assays be used to identify TB?
Both in latent TB (in new entrants, contacts, immunosuppressed people) and active disease
What does the BCG vaccine contains?
Attenuated stain of mycobacteria bovis
When is the BCG vaccine given in the UK?
Neonatal or occupational exposure risk
What chemoprophylaxis can be used for TB?
1) 3 months of rifampicin/isoniazid or 6 months isoniazid
Can the atypical mycobacteria ‘non tuberculous mycobacteria’ be transmitted from person to person?
No its an environmental organism
What mycobacterium tends to cause disseminated disease in HIV infected people?
Mycobacterium avium complex
What kind of disease does mycobacterium avium complex cause in non HIV infected adults and what in young children?
Non HIV infected: pulmonary TB like disease
Young children: cervical lymphadenitis
How is mycobacterium avium diagnosed?
In a similar way, cultured, they are acid fast bacilli so can be stained in a similar way
What is the treatment for mycobacterium avium complex?
Combined treatment, like TB is prolonged
Use a macrolide - clarithromycin or azithromycin
What are the 2 possible immune responses to mycobacterium leprosy infection?
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
What are the 3 drugs used to treat leprosy?
1) Dapsone
2) Rifampicin
3) Clofazimine
How does mycobacterium leprosy have to be identified, why?
Genomic analysis as non culturable in vitro
What is the specific microbiology request for TB?
AFBs
