Pulmonary TB03/05/12

TB

2004 14.6 million people worldwide had active TB, 1.7 million deaths mostly developing countries. When TB meds misused/mismanagedemergence of resistance ~10% of all new TB cases are resistant to at least one drug, if more than one = MDR TB

XDR TB-resistant to fluoroquinolone & at least one of injectable agents

AFB = bacilli that resist acid-alcohol decolourization under auramine/ZN staining.

TB Primary TB: Initial infxn usually pulmonary (droplet spread). Peripheral lesion forms (Ghon focus) & its draining nodes infected (Ghon complex). Often asymptomatic or fever, lassitude, night sweats, anorexia, cough, sputum, erythema nodosum. AFB may be in sputum. Commonest non-pulmonary primary infxn is GI (affecting ileocaecal junction & its LNs)

TB Post-primary TB: Any form of immunocompromise may reactivate TB e.g. malignancy, DM, steroids, debilitation (HIV, elderly). Lung lesions (usually upper lobe) progress & fibrose. Tuberculomas contain few AFB unless erode into bronchus, where can rapidly multiply & make pt highly contagious (open TB). In elderly, immunocompromised, 3rd world, dissemination of multiple foci throughout body results in miliary TB.

TB Pulmonary TB: silent or cough, sputum, malaise, weight loss, night sweats, haemoptysis, pleural effusion

TB Miliary TB: following haematogenous dissemination. Clinical features non-specific. CXR: reticulonodular shadowing. Bx of lung, liver, LN or marrow may give AFB/granulomata. Meningeal TB: Subacute onset meningitic symptoms: fever, headache, n&v, neck stiffness, photophobia GU TB: frequency, dysuria, loin/back pain, haematuria, sterile pyuria. 3 EMU for AFB. Renal US. Renal TB may spread to bladder, seminal vesicles, epididymis or fallopian tubes.

TB Bone TB: vertebral collapse adjacent to paravertebral abscess (Potts vertebra). X-rays & biopsies (for AFB & culture) Skin TB (lupus vulgaris): jelly-like nodules, e.g. face/neck Acute TB pericarditis: primary exudative allergic lesion Chronic pericardial effusion & constrictive pericarditis: reflect chronic granulomata. Fibrosis & calcification may be prominent with spread to myocardium (Steroids for 11 wks with anti-TB meds need for pericardiectomy)

TB Advise HIV & hepatitis testing (with consent & counselling) Notify public health to arrange contact tracing & screening Prolonged tx necessary & adherence NB. DOT may be required if non-adherence issue Diagnosis Relevant clinical samples (sputum, pleural fluid, pleura, urine, ascites, peritoneum or CSF) for culture Microbiology: 3 EMS for AFB (smear & culture), pleural aspiration & biopsy (if effusion). If sputum neg/unable to expectorate bronchoscopy for biopsy & BAL. Biopsy if suspicious lesion in liver, LN, bone marrow. TB PCR: rapid id of rifampicin resistance.

TB Histology: caseating granulomata

Radiology CXR = consolidation, cavitation, fibrosis & calcification in pulmonary TB, usually upper lobes

Immunological

Tuberculin skin test/Mantoux: tuberculin purified protein derivative (PPD) injected intradermally & cell-mediated response at 48-72h . +ve 5-14mm induration, strongly +ve >15mm +ve test indicated immunity (may be previous exposure, BCG) Strong +ve test = active infxn. False neg tests in immunosuppression (miliary TB, sarcoid, AIDS, lymphoma)

Treatment of pulmonary TB NB of compliance (helps cure pt & prevents spread of resistance) Before tx baseline FBC, LFTs (incl alt), RP Isoniazid, rifampicin & pyrazinamide all hepatotoxic Test colour vision (Ishihara chart) & acuity (Snellen chart) before & after tx (ethambutol may cause (reversible) ocular toxicity TB treated in 2 phases initial phase using at least 3-4 drugs & continuation phase using 2 drugs in fully sensitive cases

Treatment of pulmonary TB Initial phase (2/12 on 3-4 drugs) designed to bacterial population asap & prevent resistance. Rifampicin: MOA - Inhibits bacterial RNA synthesis by binding to the beta subunit of RNA polymerase, blocking RNA transcription. Isoniazid: MOA - Unknown, but may include the inhibition of myocolic acid synthesis resulting in disruption of the bacterial cell wall. Most effective Bactericidal agent Pyrazinamide (bactericidal active against intracellular dividing forms of M. tuberculosis, main effect only in 1st 2/12, useful in TB meningitis as good meningeal penetration) [Combination=RIFATER] If resistance likely add ethambutol (if previous TB, immunosuppressed, in contact with organism likely to be drug resistant) Streptomycin rarely used (given if resistance to isoniazid established)

Treatment of pulmonary TB Continuation phase (4/12 on 2 drugs) Rifampicin + isoniazid. [Combination RIFINAH] If resistance problem use ethambutol. Drugs best given as combination preparations unless one of components cannot be given (resistance/intolerance) Monitor LFTs. If pre-existing liver disease/alcohol abuse need frequent LFTs esp in initial phase. If no liver problem further checks necessary only if sx fever, malaise, n&v, jaundice, deterioration. If AST/ALT 2 times normal monitor LFTs until normal If AST/ALT 5 times normal or bilirubin stop anti-TB meds -if pt not unwell & non-infectious TB no tx until LFTs normal -if pt unwell/smear positive need inpt tx until LFTs normal, eg with streptomycin/ethambutol -once LFTs normal challenge doses of original drugs sequentially in order: isoniazid, rifampicin, pyrazinamide with monitoring pts clinical condition & LFTs

Treatment of pulmonary TB RP checked prior to tx. Streptomycin & ethambutol best avoided if renal impairment, but if used need to dose & monitor drug levels. If +ve culture for M. tuberculosis but susceptibility results not available after 2/12 then tx with pyrazinamide (& ethambutol if appropriate) should continue until susceptibilities confirmed Longer tx for meningitis (~ 12 mths) & resistant organisms NB Give pyridoxine 10 mg OD (Vit B6 ) throughout tx in high risk pts Steroids indicated in meningeal & pericardial disease Relapse uncommon if good compliance with tx

- Rifater [rifampicin, isoniazid, pyrazinamide] ( for 2/12 initial phase)Adults 65kg 6 tablets/d - Ethambutol (for 2/12 initial phase) 15mg/kg OD -

Recommended dosage for standard unsupervised 6-mth tx of Pulmonary TB

Rifinah/Rimactazid [rifampicin & isoniazid] (for 4/12 continuation phase following initial tx with Rifater) Adults 10mm, if recent exposure to active TB) Isoniazid (e.g. 300mg/d PO, children 5mg/kg, max 300mg given with pyroxidine) for 9 mths. If known isoniazidresistant TB contact give rifampicin

Chemoprophylaxis for asymptomatic TB infxn Immigrant/contact screening may id pts with no symptoms/no CXR findings, but +mantoux In LTBI ~10% will go onto develop active disease Chemoprophylaxis useful to kill organisms & prevent disease progression Chemoprophylaxis may be required in latent disease & receiving tx with immunosuppressants (eg cytotoxics, TNF blockers, long term tx with steroids) 1 or 2 anti-TB agents used for shorter period than with symptomatic disease (e.g. rifampicin 600mg OD PO & isoniazid 300mg OD PO [Rifinah] for 4 mths or isoniazid 300mg OD PO alone for 9 mths) Standard anti-TB tx should be initiated once any evidence active disease (clinical/radiological)

BCG vaccine BCG is live attenuated strain derived from M. bovis stimulates development of hypersensitivity to M. tuberculosis Within 2-4wks swelling at injection site, progresses to papule about 10mm diam & heals in 6-12 wks BCG recommended if immunisation not previously carried out & neg for tuberculoprotein hypersensitivity Infants in area of TB incidence > 40/100,000 Infants with parent/grandparent born in country with incidence of TB >40/100,000 Contacts of pts with active pulmonary TB Health care staff Veterinary staff Prison staff If intending to stay for >1 mth in country with high incidence TB

BCG vaccine Live vaccines CI if: -acute infxn -pregnant women -pts with impaired immune fn -BCG also CI if generalised septic skin conditions