Respiratory tract infections: TB Flashcards
TB and HIV
HIV infection has caused much of recent increase in TB in developing countries
TB in humans is caused by
mycobacterium TB
M. bovis known to have caused TB in cattle (M. tuberculosis is human-adapted farm)
many harmless species of mycobacteria in environment
M. kansasii and M. abscessus:
uncommon cause of respiratory infection esp those with compromised lung function (eg. CF)
M. avium-intracellulare
causes disseminated disease in AIDS patients (only in immune compromised)
M. marinum
uncommon cause of skin infections (‘fish-tank granuloma’)
M. chelonei
rapid growing ‘environmental’ species: may contaminate bronchoscopes!(water, can cause confusion in diagnosis when they grow bacteria in lab)
M. leprae
cause of Leprosy (cannot be grown in vitro)- only survives inside cells
Tuberculoid leprosy
common
strong cellular IR
few bacilli in lesions
depigmented anaesthetic lesions
Lepromatous leprosy
uncommon
weak cellular IR
many bacilli lesions
thick granulomatous lesions
M. tuberculosis
- Obligate aerobes - grow in tissues with a high O2 content (i.e. the lungs).
- Facultative intracellular pathogens - usually infecting mononuclear phagocytes (e.g. macrophages).
- Slow-growing - slow signs and symptoms
- Hydrophobic - high lipid content in the cell wall. Less permeable to usual bacterial stains (e.g. Gram stain).
- Known as “acid-fast bacilli” because, once stained, the cells resist decolourisation.
pathophysiology of M. tuberculosis
- Active TB is spread by airborne droplet nuclei
- Nuclei can remain airborne after coughing for several hours.
- Droplets are inhaled, lodge in alveoli and the organism is taken up by alveolar macrophages.
- Slow replication and spread (via lymphatic system) to hilar lymph nodes.
- In most individuals – cell-mediated immunity (CMI) develops 2-8 weeks after infection (associated with the development of a positive tuberculin skin test).
- Activated T lymphocytes and macrophages form granulomas that limit further replication and spread.
- Bacterial cells remain (sometimes viable) in centre of necrotic ‘caseating’ granulomas.
- Most individuals are asymptomatic (latent infection) and never develop active disease (unless a subsequent defect in CMI occurs).
are extra-pulmonary contagious?
No
it is more common in HIV+
Tuberculous ‘caseous’ granuloma
Langhan’s giant cell
epithelioid cells
central necrosis
surrounded by lymphocytes
Clinical features of TB: non specific B symptoms
fever
weight loss
night sweats
clinical features of TB: respiratory symptoms
cough
SoB
haemoptysis
chest pain
chest radiograph
upper zone cavitating lesions most common
most serious form of TB
CNS disease:
TB meningitis
space-occupying lesions (tuberculomas)
cerebral tuberculoma
other sites of infection: skin/ soft tissue infection
commonest type of non-pulmonary disease cervical lymphadenitis (firm, discrete, painless lymph nodes) diffuse swelling in neck as doesnt cause inflammation
other sites of infection
bones and joints (Pott’s disease- TB in spine)
disseminated disease
many organs involved simultaneously
- primary progressive disease or reactivation of latent infection
- miliary pattern on CXR
other sites of infections: genitourinary tract
prostatitis orchitis renal lesions may cause infertility in women sterile pyuria (WBC in urine but no growth)
Diagnosis
- Early diagnosis improves survival and prevents spread of TB.
- Category 3 pathogen (potential for laboratory-acquired infection).
- Only handled in a designated containment level 3 (Category 3) laboratory.
- Samples from patients suspected of having TB labelled accordingly.
- All sputum samples handled in a Category 3 lab.
samples
• Sputum - decontamination required • Bronchoalveolar lavage (BAL) • Pus / Tissue • Urine - 3 x24 hour collections o NB M. smegmatis may contaminate urine and cause confusion. • Cerebrospinal fluid (CSF)
Ziehl- Neelsan stain
• Remains crucial to TB diagnosis and control
• Rapid, cheap, simple, robust
• Moderate specificity & sensitivity
• Treated for active until know otherwise
(acid fast stays red as opposed to blue)
Microscopy for TB
- Auramine staining (UV microscopy) - sensitive but not highly specific
- ZN stain may be used to confirm auramine positive samples
Culture of Mycobacterium tuberculosis
Slow (2-8 weeks)
• Requires specialised media: Löwenstein-Jensen slopes in ‘shatter-proof’ glass containers
• Culture performed in a Category 3 facility
• Grow to see whether they are resistant stains
cauliflower or verrucose colonies
‘Rapid’ culture of M. tuberculosis
- 1-2 weeks
- Liquid media e.g. Kirchner’s liquid medium
- Automated system – Mycobacteria Growth Indicator Tube (MGIT)
Antibiotic sensitivity tests
to detect resistance
especially in multi drug resistant TB= resistant to rifampicin and isoniazid- longer courses
(MDR-TB)
must treat with multiple agents
extensively drug resistant TB (XDR-TB) definition
tuberculosis that is resistant to rifampicin and isoniazid AND to any member of the quinolone family and at least one second-line anti-TB agents: kanamycin, capreomycin, or amikacin
other countries where treatment isnt monitored- cannot afford resistance
Genomic tests for Mycobacteria
- Polymerase chain reaction (PCR)
- DNA probes - allows speciation
- Rapid detection of Rifampicin resistance
- Increasing use of whole-genome sequencing (WGS) for species identification and typing
Treatment of pulmonary TB
– Initial phase: 2 months of 4 drugs (rifampicin, isoniazid, pyrazinamide, ethambutol)
– Continuation phase: 4 months of rifampicin and isoniazid
– If resistance is suspected, 5 drugs may be used initially. For confirmed resistant strains, longer courses are required with second line agents.
Prevention of tuberculosis
• Early diagnosis and treatment:
– ‘Open’ (ZN stain positive) pulmonary disease usually rendered non-infectious after 2 weeks of effective therapy.
– Contact tracing and detection of latent infection:
• Tuberculin skin test
• Chest radiography
• In vitro Interferon-gamma release tests (T SPOT-TB or QuantiFERON-TB Gold)
– Contacts treated if evidence of infection.
– TB is a formally notifiable disease (HPE co-ordinates contact tracing and investigation of outbreaks in the community).
Vaccination
- Bacillus Calmette-Guerin (BCG)
- Live attenuated M. bovis strain.
- Main role is protecting children against severe disease (meningitis & miliary disease) doesn’t prevent pulmonary TB asia ad Africa shows no effect
