MI: Mycobacterial Diseases Flashcards
How can mycobacteria be categorised?
Rapid-growing and slow-growing
List three types of mycobacterial complex.
Mycobacterium tuberculosis complex
- Mycobacterium tuberculosis
- Mycobacterium bovis
Mycobacterium avium complex
- Mycobacterium avium
- Mycobacterium intracellulare
Mycobacterium abscessus complex
- Mycobacterium abscessus
- Mycobacterium massiliense
- Mycobacterium bolletii
Describe the morphology of mycobacteria.
- Non-motile rod-shaped bacteria
- Relatively slow-growing
- Cell wall composed of mycolic acids, complex waxes and glycoproteins
- Acid-alcohol fast
What is used as a screening test for mycobacterial infections?
Auramine stain
How are non-tuberculous mycobacterial infections transmitted?
- NOT person-to-person
- From the environment
- May be colonising rather than infecting
List three examples of slow-growing non-tuberculous mycobacteria and the diseases that they cause.
Mycobacterium avium intracellulare
- May invade bronchial tree or pre-existing bronchiectasis/cavaties
- Disseminated infection in immunocompromised patients
Mycobacterium marinum
- Swimming pool granuloma
Mycobacterium ulcerans
- Skin lesions (e.g. Bairnsdale ulcer, Buruli ulcer)
- Chronic progressive painless ulcer
List three examples of rapid-growing non-tuberculous mycobacteria.
- Mycobacterium abscessus
- Mycobacterium chelonae
- Mycobacterium fortuitum
List some risk factors for NTM.
Age
Underlying lung disease
How is Mycobacterium avium intracellulare treated?
- Clarthromycin/azithromycin
- Rifampicin
- Ethambutol
- +/- streptomycin/amikacin
What are the two types of Mycobacterium leprae infection?
- Paucibacillary tuberculoid - few skin lesions (usually <5), robust T cell response, low number of bacteria in the body
- Multibacillary lepromatous - multiple skin lesions (usually >5), poor T cell response, high number of bacteria
What is the most common cause of death by infectious agent in the world?
- 1 = HIV
- 2 = TB (10% of world infected)
How many species are part of the Mycobacterium tuberculosis complex?
7 (including Mycobacterium tuberculosis, bovix and africanum)
What is the generation time of Mycobacterium tuberculosis?
15-20 hours
What is the infectious dose of Mycobacterium tuberculosis?
1-10 bacilli
What are the 2 types of primary TB infection
- Latent TB
- Asymptomatic
- Not contagious
- Active primary TB
- Symptomatic
- Infectious
- Can cause progessive disseminated disease
What is post-primary (secondary) TB?
Reactivation or exogenous re-infection
10% chance after primary infection
List some risk factors for reactivation of TB.
- Immunosuppression
- Chronic alcohol excess
- Malnutrition
- Ageing
List some types of extra-pulmonary TB.
- Lymphadenitis (scrofula) - cervical lymph nodes most commonly
- Gastrointestinal - due to swallowing of tubercle
- Peritoneal - ascitic or adhesive
- Genitourinary
- Bone and joint - due to haematogenous spread (e.g. Pott’s disease)
- Miliary TB
- Tuberculous meningitis
Why is it important to take 3 sputum samples when investigating suspected TB?
Increases the sensitivity of the smear microscopy
What is the turnaround time for smear microscopy and PCR?
2 hours
What is the issue with culturing TB?
It takes up to 6 weeks
What is the histological hallmark of TB?
Caseating granulomas
What is NAAT and why is it useful?
- Nucleic acid amplification test
- Allows speciation and the detection of drug resistance mutations
- Rapid
What are the screening tests for latent TB
Tuberculin skin test
Interferon gamma release assay
What is the tuberculin skin test (Mantoux test) and how does it work?
A sample of tuberculin is injected intradermally and left for 48-72 hours to observe the response
Type IV hypersensitivity (T cell) response to antigen
What are the disadvantages of the tuberculin skin test?
- Cross-reacts with BCG
- Cannot distinguish between active and latent TB
- False negative in immunosuppressed individuals
What is an IGRA assay?
- Uses M. tuberculosis specific antigens to stimulate T cell IFN-gamma production which is then measured using ELISA
What are the advantags and disadvantges of IGRA assay?
No cross reactivity with other strains
Does not distinguish between latent or active TB
What do you do if screening tests are positive?
CXR (looks for active TB)
if CXR normal - treat with latent TB protocol
What is the treatment of latent TB
- 3 months of isoniazid plus rifampicin
- Or 6 months of isoniazid
What is the treatment of active TB
- Initiation phase: rifampicin, isoniazid, pyrazinamide, ethambutol for 2 months
- Continuation phase: rifampicin plus isoniazid for 4 months
List some side-effects of:
- Rifampicin
- Isoniazid
- Pyrazinamide
- Ethambutol
-
Rifampicin
- Raised transaminases
- CYP450 induction
- Orange secretions
-
Isoniazid
- Peripheral neuropathy
- Hepatotoxicity
-
Pyrazinamide
- Hepatotoxicity
-
Ethambutol
- Visual disturbance
What drug is given to prevent peripheral neuropathy from isoniazid?
Pyridoxine
What is DOT?
Direct observation therapy
What is multi-drug resistant TB?
Resistant to rifampicin and isoniazid
What is extremely drug resistant TB?
Resistant to rifampicin, isoniazid, fluoroquinolones and at least 1 injectable
What are the diagnostic challenges of HIV and TB coinfection?
- Clinical presentation is less likely to be classical
- Symptoms may be absent if CD4+ count is low
- More likely to have extra-pulmonary manifestations
- Tuberculin skin test more likely to give false-negative
- Low sensitivity for IGRAs
What are the treatment challenges of HIV and TB coinfection?
- Timing of treatment
- Drug interactions
- Overlapping toxicities
- Duration of treatment
