Tuberculosis Flashcards
Challenges of managing TB in HK
Aging population
Immigrants from countries with hier risk and incidence of TB
Diagnosis and Treatment of LTBI
Disease course (exposure, infection, disease). strongest risk factors
Exposure
- contact with individuals with active TB (airborne transmission with high infectivity)
- risk of infection after exposure depends on closeness of contact and infectiousness of source (50% infected if spend 8hr/day for 6mnths with infectious patient)
Infection
- 5-10% lifetime risk of progression to disease after infection
- > 50% active TB occur within 1st 2 yrs of infection
- STRONGEST RISK FACTOR = HIV (5-10% annual risk of progression); other risks e.g. DM, smoking, silicosis, age, co-morbidities
Disease
- progressive primary disease or endogenous reactivation
- pulmonary or extra-pulmonary
Mycobacteria general properties - cell wall, staining technique, growth characteristics, molecular methods advantage/disadvantages
Aerobic, non-spore forming, non-motile bacillus
High lipid content in cell wall (mycolic acids, glycolipids etc)
–> thick wall, resistant to chemical agents, drying, very hydrophobic, resistant to lysis and cellular reactions
but sensitive to heat, UV
==> acid-fast
Staining:
- Ziehl-Neelsen staining - Carbol fuschin (red) heated for 5 min –> 3% acid alcohol washing for 2 min –> counterstain with methylene blue for 30 sec –> wash/dry
==> MTB complex resists decolourisation by acid alcohol
Growth characteristics:
- slow growing (3-8 wks)
- special culture required: LOWENSTEIN-JENSON medium (egg based) – gold standard showing morphology, allowing quantification, speciation, susceptibility testing
- rapid culture medium available with radiometric substrate - broth (1-3 wks) with similar sensitivity and specificity to solid media but no quantification/morphology
Nucleic acid amplification:
- TB PCR quick but culture still needed for speciation/susceptibility testing
- Gene Xpert very high sensitivity, detects MTB and rifampicin resistance; limitations as with PCR
Pathogenesis of TB
Droplet nuclei as source of infection
1. inhaled bacteria implant in alveolus with subsequent multiplication: primary infection
2. organisms migrate to hilar LN and enter blood to reach other organs
3. subsequent clinical course depends on host immunity
–> absence of response e.g infants, HIV = infection progress to involve more lung parenchyma –> rapid acute disease leading to disseminated infection
–> cell-mediated immunity = halt disease and cause chronic inflammatory reactions with local destruction and necrosis – ASYMPTOMATIC
(–> or organism completely killed by immune response)
4. develop granuloma (caseous necrosis) with fibrosis and calcification to contain organisms
5. mycobacteria remain DORMANT BUT VIABLE and potentially pathogenic for years
6. breakdown of host defenses e.g. age, cancer, HIV = rupture of tubercles and reactivation (usually start at apex-posterior aspect with cavitation)
7. disease can occur in any organ seeded during primary infection
–> local symptoms + general malaise, LOW, night sweats, fever
Immunity and Hypersensitivity
CELL MEDIATED immunity (humoural no role)
Host acquires hypersensitivity to tubercle bacilli in the course of primary infection resulting in positive tuberculin reaction
Latent TB infection - definition, diagnosis
State of persistent immune response to stimulation by MTB antigens without evidence of clinically manifested active TB
Diagnosis:
- tuberculin skin test
- IFN-gamma release assay
==> doesn’t detect active/latent - judge clinically
Recommend for persons at high risk of developing TB and those with possible latent infection who will require treatment
Tuberculin/Mantoux Test - concept, definition of positive test, interpretation of results
Immunological skin test eliciting response by injecting mycobacterial protein into skin of sensitised individuals
- use purified protein derivative; 0.1 ml injected (2TU) intradermally
- delayed HSR
Positive test = INDURATION with edema/erythema 48-72hrs after injection
- different sizes of cut-off based on risk
- —> >5mm if HIV infected; >10 mm for silicosis, on anti-TNF; >15 mm for immunocompetent household contact >1 yrs old
Interpretation of positive results
- within 4-6 wks after infection
- history of infection
- after BCG vaccination or non-TB mycobacteria (false positive)
Negative results:
- very recent infection (<3wks)
- “anergy” with lack of normal cell mediated immunity due to steroids, AIDS, malnutrition, measles
- after elimination of infection by chemotherapy
CAN’T TELL IMMUNITY VS ACTIVE INFECTION
IFN-gamma release assay (IGRA) - method, concept
Quantitative measurement of interferon-gamma in blood
– incubate patient’s blood with MTB antigens and monitor IFN-gamma release
- more sensitive and specific than skin test
Symptoms of Pulmonary TB
Early TB: asymptomatic, incidental finding on CXR (Gohn focus, hilar LN)
Non-specific constitutional symptoms e.g. LOW, fever, chills, night sweats
Productive cough +/- other respiratory symptoms e.g. SOB, sputum, chest pain (if extend to parietal pleura)
Haemoptysis from caseous sloughing is minor but suggests advanced disease
Primary TB in childhood - symptoms, progression
Diagnosis relies on symptoms, positive tuberculin skin test/IFN-g, hx of contact with active disease and CXR
Gastric aspirate for AFB smear and culture
Initial focus MC as mid-lung zones
CXR: regional lymphadenitis
–> compress central bronchi (brassy cough) or atelectasis or may rupture into a bronchus and seed infection distally to cause pneumonia
<5 yrs old: progressive lymphato-haematogenous dissemination with miliary meningeal disease
5-12 yrs: relatively disease resistant period, usually non-progressive
Diagnosis of TB infection - clinical, lab 1st line, other additional methods
Clinical signs and symptoms, history
Radiological (CXR)
- primary: hilar LN, generally normal
- secondary: apical-posterior segment of lung, cavitation, patchy pneumonitis, fibrosis
1st line: EARLY MORNING SPUTUM
- microscopy (AFB)
- culture (LJ media/ rapid)
[- molecular (PCR)]
If patient can’t produce sputum or AFB negative but still suspect clinically:
- sputum induction by hypertonic saline aerosols
- fiberoptic bronchoscopy with biopsy and BAL
- granuloma formation on histological exam of biopsy
Extra-pulmonary TB - possible manifestations, diagnosis
Local symptoms pertaining to site of disease - can occur in any organ seeded
Meningitis
Lymphadenitis (MC non-pul TB; cervical LN more involved - painless, slowly progressive)
Genitourinary - sterile pyuria
Skeletal - osteomyelitis, arthritis; >50% in spine leading to back pain (destroy IVD and then adjacent vertebral bodies - Pott’s disease)
GI - caecum MC, enteric ulceration/perforation/mass formation
Peritonitis (in AIDS)
Percarditis, laryngeal, anal etc
Miliary TB if severely immunocompromised
- numerous millet seeds in lungs and organs
- usually tuberculin negative
Diagnosis: PET-CT aids in diagnosis
Treatment - aims
Aims:
- reduce number of ACTIVELY growing bacilli –> decrease severity of disease and halt transmission
- eradicate PERSISTING bacilli to prevent relapse after completion of therapy
- prevent acquisition of drug resistance during therapy
Overall:
- combination therapy (prevent MDR)
- prolonged course (6-9 mths; up to 2 yrs)
- directly observed therapy (DOT) to ensure compliance and lower risk of MDR
Treatment regimen - drugs and duration
Intensive phase for 2 months:
- Isoniazid
- Rifampicin (KEY DRUG)
- Pyrazinamide
- Ethambutol (or streptomycin IM)
Continuation phase for 6 months:
- Isoniazid
- Rifampicin
Can check for sputum smear/culture conversion after 2 months and 6 months of therapy
Extension of therapy may be needed:
- e.g. additional 3 months continuation if positive culture after 2 months + cavitation on initial CXR or DM or HIV
- 3 HRZE + 9 HR if CNS involvement, miliary
- 10 month continuation if bone/joint
Use of Dexamethasone in TB treatment
Suppress inflammation which may be caused by TB treatment initially –> more neurological damage with raised ICP/ hearing loss etc
