7. Mycobacterial diseases Flashcards
What percentage of world’s population is infected with TB?
About 30%
What are examples of mycobacterium tuberculosis complex?
Mycobacterium tuberculosis and Mycobacterium bovis (BCG).
What are examples of mycobacterium avium complex?
Mycobacterium avium and mycobacterium intracellulare
What are examples of mycobacterium abscessus complex?
Mycobacterium abscessus, mycobacterium massiliense, mycobacterium bolletii
What are examples of ungrouped mycobacteria?
Mycobacterium leprae
What is the shape of mycobacteria?
Non-motile rod-shaped bacteria
How quickly do mycobacteria grow?
Relatively slow-growing compared to other bacteria
How is mycobacteria characterised?
Long-chain fatty (mycolic) acids, complex waxes and glycoproteins in the cell wall. Structural rigidity. Makes up complete Freund’s adjuvant. Has specific staining characteristics. Acid-alcohol fast.
What staining is used to detect mycobacteria?
Auramine is usually used as a screening test.
What are 5 features of non-tuberculous mycobacteria?
Ubiquitous, environmental, atypical, varying spectrum of pathogenicity, and may be colonising rather than infecting.
How is non-tuberculous mycobacteria transmitted?
NO person-to-person transmission
What is non-tuberculous mycobacteria resistant to?
Commonly resistant to the usual anti-TB therapy.
What are examples of slow-growing NTM?
Mycobacterium avium intracellulare, mycobacterium marinum and mycobacterium ulcerans.
How does mycobacterium avium intracellulare infect people?
Immunocompetent - may invade bronchial tree; pre-existing bronchiectasis or cavities. Immunosuppressed - disseminated infection
What causes swimming pool granuloma?
Mycobacterium marinum
What causes skin lesions (e.g. Bairnsdale ulcer, Buruli ulcer) and/or a chronic progressive painless ulcer?
Mycobacterium ulcerans
What are examples of rapid-growing non-tuberculous mycobacteria?
Mycobacterium abscessus, Mycobacterium chelonae, Mycobacterium fortuitum
How does non-tuberculous mycobacteria present?
Causes skin and soft tissue infections, may be found in hospital settings and isolated from blood cultures (especially when devices such as vascular catheters are being used).
What are risk factors for NTM?
Age and underlying lung disease
How is NTM diagnosed?
Combines clinical findings with microbiology findings (blood culture, bronchoalveolar lavage, biopsy). It is important to exclude other diagnoses.
What is the treatment for Mycobacterium avium intracellulare (NTM)?
Clarithromycin/azithromycin, rifampicin, ethambutol, with or without streptomycin/amikacin.
How is rapid-growing NTM treated?
Based on susceptibility testing and usually macrolide based.
What are the two types of Mycobacterium leprae?
Paucibacillary tuberculoid and multibacillary lepromatous
How is paucibacillary tuberculoid (Mycobacterium leprae) characterised?
Few skin lesions and robust T cell response
How is multibacillary lepromatous characterised?
Abundance of bacilli, multiple skin lesions, poor T cell response
What is the 2nd most common cause of death by infectious agent (after HIV)?
Mycobacterium tuberculosis (TB) - it is a multisystem disease
How many deaths per year due to TB?
2 million
What is the incidence of mycobacterium tuberculosis?
Increasing incidence since the 1980s. 9000 per year in the UK.
TB Disease States
After contact with a person with TB you could become infected, become latently infected or not become infected at all.
MTB complex involves 7 closely related species. What are the 3 main ones?
Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium africanum.
What kind of aerobe is MTB?
Obligate aerobe
What is the generation time of MTB complex?
Generation time 15-20 hours
How is MTB transmitted?
Droplet/airborne, suspended in air. Reaches the lower airway macrophages. Infectious dose is 1-10 bacilli and air remains infectious for 30 mins.
How can MTB be prevented?
Detecting cases; treating cases; preventing transmission (protective equipment, negative pressure isolation); optimisation of susceptible contacts, and vaccination (BCG).
How does primary TB present?
Usually asymptomatic, Ghon focus on X-ray (granuloma in the lungs)
What can be be seen in imaging in primary TB?
Ghon focus (granuloma in the lungs)
What is primary TB controlled by?
Cell-mediated immunity
What is an example of a rare allergic reaction caused by primary TB?
Erythema nodosum
What does primary TB occasionally cause?
Disseminated/miliary TB
What is post-primary TB?
This is reactivation or exogenous re-infection. Happens > 5 years after initial infection.
What is the risk of post-primary TB?
5-10% lifetime risk
What are risk factors for reactivation?
Immunosuppression, chronic alcohol excess, malnutrition and ageing
Is the clinical presentation of post-primary TB pulmonary or extra-pulmonary?
Both. The host immune response determines the clinical outcome.
What are some pulmonary effects of post-primary TB?
Caseating granuloma. Can be found in lung parenchyma and mediastinal lymph nodes. Commonly found in upper lobes.
What are some extra-pulmonary effects of post-primary TB?
Lymphadenitis (AKA scrofula); gastrointestinal (swallowing of tubercles); peritoneal (ascitic or adhesive), genitourinary (slow progression to renal disease and subsequent spreading to lower urinary tract); bone and joint (haematogenous spread and spine - Pott’s disease), miliary TB; and tuberculous meningitis
How does miliary TB present?
Millet seeds on CXR; progressive disseminated haematogenous TB; increasing due to HIV
What are risk factors for post-primary TB?
Non-UK born; HIV or other immunocompromise; homeless; drug users; close contacts; and young adults
How does post-primary TB present?
Fever, weight loss, night sweats, pulmonary (cough, haemoptysis), malaise and anorexia
What investigations for TB?
CXR and other radiology; sputum x 3; bronchoscopy; biopsies; early morning urine; stains for acid-fast bacilli; culture; histology; tuberculin skin test; IGRA assay; and NAAT (nucleic acid amplification test)
How is smear done for TB?
Sputum: sensitivity increases with additional samples, hence why 3 samples should be collected. Gastric aspirated in children.
What bacteriological examinations are there?
Smear microscopy, culture solid medium, culture liquid medium, culture microcolonies, LPA, automated real-time PCR.
What is the sensitivity for each of the bacteriological examinations?
Smear microscopy (highest): >5000 AFB/ml. Culture solid medium: +/- 100. Culture liquid medium, culture microcolonies, and automated real-time PCR: +/-10. LPA: only on positive smear.
What is the median turn-around time for each of the bacteriological examinations?
Smear microscopy: 2 hours. Culture solid medium: 16 days (smear+), 29 days (smear-). Culture liquid medium: 8 days (smear+), 16 days (smear-). Culture microcolonies: 14 days. LPA: 1 day (direct testing). Automated real-time PCR: 2 hours.
What is the additional turn-around time with DST?
Culture solid medium: 6 weeks. Culture liquid medium: 2 weeks (smear+) and 2 weeks (smear-). Culture microcolonies: 0 (H and R). LPA: 0 (H and R), and 21 days (indirect testing). Automated real-time PCR: 0 (R only).
What is the gold-standard investigation for MTB?
Culture. (Can be done with liquid or solid systems).
How long does culture take for MTB?
Up to 6 weeks. Further testing for culture isolates.
What is the histological hallmark of TB?
Caseating granuloma
What additional tests can be done for MTB?
- Speciation: NAAT - rapid diagnosis of smear positive samples and identified drug resistance mutations.
- Speciation: chromatography
- Drug sensitivity
What does the Tuberculin Skin Test (TST) do?
Looks fore previous exposure to Mycobacteria
How is the TST carried out?
2 units of tuberculin are injected intradermally. It is examined after 48-72 hours looking for a reaction. It is a delayed-type hypersensitivity reaction.
What can TST cross react with?
This cross-reacts with BCG so can confuse the interpretation.
What is the sensitivity of TST?
POOR sensitivity. May produce false negative if: HIV, age, immunosuppression and overwhelming TB.
What does IGRAs do?
Investigation - detection of antigen-specific IFN-gamma production
What are examples of IGRAs?
ELISpot and Quantiferon
Any cross-reactions with IGRAs?
NO cross-reaction with BCG
What are issues with IGRAs?
Cannot distinguish latent and active TB. Issues with sensitivity and specificity.
What is the first-line treatment of TB?
As standard treatment for individuals with active tuberculosis, offer rifampicin, isoniazid (with pyridoxine hydrochloride), pyrazinamide and ethambutol hydrochloride in the initial phase of therapy; modified according to drug susceptibility testing; and continued for 2 months. After the initial phase, offer standard continuation treatment with rifampicin and isoniazid (with pyridoxine hydrochloride) for a further 4 months in individuals with active tuberculosis without central nervous system involvement. (10 months of treatment needed for CNS involvement)
What are second-line medications for MTB?
Quinolones (Moxifloxacin), injectables (capreomycin, kanamycin, amikacin), ethionamide/prothionamide, cycloserine, PAS, linezolid, clofazamine.
What are side effects of rifampicin?
Raised transaminases; induces CYP450; orange secretions
What are side-effects of isoniazid?
Peripheral neurotoxicity (give with pyridoxine)
What are side-effects of pyrazinamide?
Hepatotoxicity
What are side-effects of ethambutol?
Visual disturbance
What are other treatments for TB?
Vitamin D, nutrition, and surgery
What is the cure rate of TB?
90%
How can adherence to TB treatment be checked?
Direct observation therapy or video observed therapy
What is multi-drug resistant TB resistant to?
Rifampicin and isoniazid
What is extremely drug resistant TB resistant to?
Rifampicin, isoniazid and fluoroquinolones, and at least 1 injectable
How may drug resistant TB arise?
These may arise due to spontaneous mutation or due to inadequate treatment
How does risk of drug-resistant TB increase?
If previous TB treatment, HIV+, known contact with MDR TB, failure to respond to conventional TB.
What treatment do those with drug resistant TB require?
They require 4/5 drug regimen with a longer duration: quinolones + aminoglycosides + para-aminosalicylic acid (PAS) + cycloserine + ethionamide. Current WHO recommendations state that 7 drugs should be used for 9-12 months.
What are diagnostic challenges of HIV and TB coinfection?
Coinfection is common. Clinical presentation is less likely to be classical. Symptoms and signs might be absent if low CD4+. More likely to have extra-pulmonary manifestations (i.e. normal CXR). Smear microscopy and culture is less sensitive. Tuberculin skin test is more likely to be negative. Low sensitivity of IGRAs.
What are treatment challenges of TB and HIV coinfection?
Timing of treatment initiation; drug interactions; overlapping toxicity; duration of treatment (adherence); healthcare resources.
