TB Flashcards
Is Mycobacterium tuberculosis aerobic or anaerobic?
Aerobic
Describe the features of Mycobacterium tuberculosis
- ?Gram positive (according to path guide, but can appear both due to unusual cell wall. Ziehl-Neelson staining used instead of Gram stain)
- Aerobic
- Acid alcohol fast
- Thick, waxy cell wall (complex, immunogenic)
- Intracellular rod
Describe the common presentation of TB
- Cough +/- haemoptysis
- Fever
- Night sweats
- Weight loss (?anorexia)
- Malaise
- Ethnicity also important factor
What is post-primary TB?
Re-activation/re-infection of latent TB following an earlier primary infection (usually in childhood).
List 4 clinical features of a post-primary TB infection
- Upper lobes affected
- May progress rapidly to cavitation
- Classic lesion: caseating granuloma
- Healing leads to fibrosis and calcification
What is miliary spread of TB?
- Progressive, disseminated haematogenous spread from the primary focus throughout the body.
- Occurs in ~10% of primary TB when infection is not controlled.
- Rare in post-primary.
- ‘Rich foci’
Is miliary spread more common in primary or post-primary TB?
Primary
What are the common clinical features of primary TB infection?
- Multiplies at pleural surface (Ghon focus)
- Taken by macrophages to lymph node (primary complex)
- Generalised lympho-haematogenous spread
- Characteristic lesion = granuloma (Langhan’s giant cells)
- Can be asymptomatic (esp in children)
What are the less common features of primary TB infection?
- Tuberculoma
- Miliary TB
- ‘Progressive primary’ - focus/node ulcerates into bronchus, leading to pneumonia / cavity formation / bronchiectasis / consolidation / collapse
What are the first line treatments for TB?
RIPE
- Rifampicin for 6 months
- Isoniazid for 6 months
- Pyrazinamide for 2 months
- Ethambutol for 2 months
- Adherence is key: observation of drug taking sometimes necessary for first 2 months (DOTS - directly observed treatment, short course)
- Vitamin D supplements
In which cases does standard first line treatment vary?
- TB meningitis and spinal TB: Rifampicin and isoniazid taken for 10-12 months. (Pyrazinamide and ethambutol as normal). Plus steroids in meningitis.
- Latent TB/prophylaxis: 6 months isoniazid only
What are the side effects of Rifampicin?
- Drug interactions (raised transaminases - CP450 induction)
- Orange secretions
- Hepatotoxicity
Bonus question: where does the word ‘miliary’ come from?
Hint: it’s not to do with hats
On CXR, the widely disseminated appearance of miliary TB lesions in the lungs looks like sprinkled milet seeds.
What are the side effects of isoniazid?
- Peripheral neuropathy (give B6/pyrodoxine)
- Hepatotoxicity
What are the side effects of Pyrazinamide?
- Hyperuricaemia
- Hepatotoxicity
What are the side effects of ethambutol?
- Optic neuritis
- Visual disturbances
What are the second line treatments for TB?
- Injectables (capreomycin, kanamycin, amikacin)
- Quinolones (moxifloxacin)
- Cycloserine
- Ethionamide/Protionamide
- PAS (P-aminosalicylic acid)
- Linezolid
- Clofazamine
What are the drug resistant strains of TB?
- Mono - resistant to one drug only
- MDRTB - resistant to Rifampicin and isoniazid
- XDRTB - resistant to Rifampicin, isoniazid, Injectables (kanamycin/amikacin) and Quinolones
Which investigations are necessary for TB?
- Imaging: CXR (upper lobe cavitation - post primary) and CT
- Cultures: sputum x3, bronchoalveloar lavage (BAL), urine (EMU), pus in “Lowenstein-Jensen medium” (gold standard)
- Tuberculin skin tests (TSTs): Mantoux/Heaf using PPD
Heaf = 6 skin pricks, discontinued in 2005
Mantoux = manual, more accurate - Interferon Gamma Release assays (IGRAs): eg Elispot, Quantiferon - bloods taken, alternative to TST
- Nucleic acid amplification tests (NAATs): PCR line probe assays, tests for sensitivities
- Other: liquid culture mediums
What imaging is needed to diagnose TB?
CXR (upper lobe cavitation seen in post-primary) and CT
What cultures should be taken to diagnose TB?
- Sputum x3
- Bronchoalveloar lavage (BAL)
- Urine (EMU)
- Pus (in Lowenstein-Jensen medium)
What is the “gold standard” test for TB?
Culture in Lowenstein-Jensen medium
Which staining techniques can be used for TB microscopy?
- Ziehl-Neelsen (aka acid fast)
- Auramine-rhodamine
What is seen in TB microscopy?
Gram positive, acid fast, aerobic, intracellular rods
What are the two tuberculin skin tests (TSTs) and what is the difference between them?
- Mantoux and Heaf tests
- Both involve introducing a purified protein derivative (PPD) of TB intradermally and assessing the reaction (size of induration) to determine any previous TB exposure.
- Heaf test (6 pricks) used a special automated device which was discontinued in 2005.
- The Mantoux test is an older, manual version which is now preferred and thought to be more accurate.
What is an IGRA?
Interferon-gamma release assay.
Eg Elispot or Quantiferon. The standard blood test for TB and an alternative to the TST (Mantoux).
What is a NAAT?
Nucleic acid amplification test.
A PCR-line probe assay, used to determine TB sensitivities (ie whether it is a resistant strain)
What percentage of TB cases are extrapulmonary?
20%
What are the sites/types of extrapulmonary TB?
Meningitis Spinal Lymphadenitis Pericarditis Abdominal (peritonitis, ileitis) Genito-urinary Renal Testicular Skin Liver
What percentage of all TB cases are TB meningitis?
2%
Describe the features of TB meningitis presentation
Subacute Weight loss Fever Night sweats Headache Neck stiffness Reduced GCS Focal neurological deficit
How is TB meningitis diagnosed?
Tuberculomata on CT and lymphocytic LP
What is the treatment for TB meningitis?
12 months of RIPE and steroids
What percentage of all TB cases are spinal TB?
4%
What are the characteristic presenting features of spinal TB?
Fever
Sweats
Weight loss
Back pain
What are the main steps in the pathogenesis of spinal TB?
1) Haematogenous spread
2) Initial discitis
3) Vertebral destruction and collapse +/- anterior extension (causing iliopsoas abscess)
Describe the epidemiology and risk factors for TB in the UK
Increasing incidence, currently around 15/100,000 UK wide but as high as 150/100,000 in some London boroughs.
More common in young and elderly.
RFs: recent migrant, HIV+, homeless, prisoners, close contacts with TB.
What are the risk factors for reactivation of latent TB?
Immunosuppression
Malnutrition
Ageing
Chronic alcohol excess
What does the BCG stand for and what does the vaccination contain?
Bacille Calmette-Guerin
Contains an attenuated strain of Mycobacterium Bovis.
What is the efficacy of the BCG vaccine?
Very variable: 0-80%
Good at protecting against TB meningitis, disseminated TB and leprosy but bad for pulmonary TB.
Who should receive the BCG vaccination?
Babies born in or with parents/grandparents from areas with incidence >40/100,000
Previously unvaccinated new immigrants from high prevalence countries.
In which group is the BCG vaccination contraindicated?
HIV patients
What is the chance of latent TB becoming reactived in an HIV +ve patient?
5-10% Yearly risk (contrast with 5-10% lifetime risk if HIV -ve)