Tuberculosis

Chronic infectious disease caused by Mycobacterium tuberculosis (acid-fast bacillus), transmitted via airborne droplet nuclei.

Primary infection often contained by cell-mediated immunity forming granulomas (latent TB infection), with ~5-10% lifetime risk of reactivation to active disease, significantly higher with immunosuppression (especially HIV co-infection).

Classified by:

• Latent TB infection (LTBI): asymptomatic, non-infectious, positive immune sensitization test, no active disease

• Active TB: symptomatic, infectious (if pulmonary/laryngeal with cavitation), further divided:

• Pulmonary TB: most common site, may be primary (initial infection) or post-primary/reactivation (classically upper lobe cavitary disease)

• Extrapulmonary TB: lymph nodes (most common extrapulmonary site), pleura, bone/joint (Pott's disease of spine), miliary/disseminated, CNS (meningitis, tuberculoma), genitourinary, gastrointestinal, pericardial

• Drug-resistant TB: MDR-TB (resistant to isoniazid + rifampicin), XDR-TB (MDR plus resistance to fluoroquinolone + additional second-line agent)

• Pulmonary TB: chronic cough (>2-3 weeks, classic screening threshold), hemoptysis, night sweats, fever, weight loss, anorexia, fatigue, chest pain

• Symptoms typically insidious, progressive over weeks-months (contrast with acute bacterial pneumonia)

• Examination: often unremarkable early; may have crackles/signs of consolidation/cavitation, reduced breath sounds if effusion, cachexia in advanced disease

• Extrapulmonary presentations:

• Lymphadenitis (scrofula): painless, matted cervical lymphadenopathy, may develop sinus tracts

• Pleural TB: pleuritic chest pain, dyspnea, exudative effusion

• Spinal TB (Pott's disease): back pain, kyphotic deformity, may cause cord compression/neurological deficit

• TB meningitis: subacute headache, fever, meningism, cranial nerve palsies, altered consciousness — high mortality/morbidity if diagnosis delayed

• Miliary TB: disseminated, non-specific febrile illness, hepatosplenomegaly, can affect any organ, higher risk in immunocompromised/very young/elderly

• HIV co-infection: atypical presentations common (lower lobe disease, less cavitation, higher extrapulmonary rates, higher smear-negative rates) — TB is leading cause of death in HIV-positive individuals globally

• Sputum microscopy: acid-fast bacilli (AFB) smear (Ziehl-Neelsen or fluorescence staining):rapid, widely available, but lower sensitivity, requires ≥2 samples

• GeneXpert MTB/RIF (or Ultra): rapid PCR-based test: detects M. tuberculosis DNA and rifampicin resistance simultaneously within hours; now recommended as initial diagnostic test where available (WHO)

• Sputum culture (liquid — MGIT, or solid — Löwenstein-Jensen media): gold standard, allows full drug susceptibility testing, but slow (weeks)

• Chest X-ray: upper lobe infiltrates/cavitation (post-primary/reactivation pattern), or lower lobe/hilar lymphadenopathy (primary pattern, more common in children/HIV); miliary pattern in disseminated disease

• Latent TB testing: tuberculin skin test (TST/Mantoux — induration measured, cutoffs vary by risk category) or interferon-gamma release assay (IGRA — more specific, unaffected by prior BCG vaccination)

• Extrapulmonary diagnosis: site-specific sampling (lymph node biopsy/FNA, pleural fluid analysis, exudative, lymphocyte-predominant, elevated ADA; CSF analysis for TB meningitis, lymphocytic pleocytosis, elevated protein, low glucose; imaging (MRI/CT) for spinal/CNS disease)

• HIV testing: offer to all patients diagnosed with TB (bidirectional screening recommended given strong association)

• Drug susceptibility testing: essential given rising drug resistance, especially in retreatment cases or high MDR-TB prevalence settings

Differentials: pulmonary — lung cancer (especially with hemoptysis/weight loss in older/smoking history), other chronic pneumonias, sarcoidosis, fungal infection (histoplasmosis, especially in endemic areas), lymphoma; extrapulmonary — malignancy, other granulomatous diseases, chronic osteomyelitis (spinal TB), bacterial meningitis (TB meningitis).

Standard first-line treatment (drug-sensitive TB): WHO regimen:

• Intensive phase (2 months): isoniazid + rifampicin + pyrazinamide + ethambutol (RIPE/HRZE), daily dosing

• Continuation phase (4 months): isoniazid + rifampicin

Total standard duration: 6 months for most pulmonary/extrapulmonary TB

Extended duration (9-12 months) for: TB meningitis, bone/joint TB (some guidelines extend to 9-12 months given poorer drug penetration/higher relapse risk)

Fixed-dose combination tablets preferred (improves adherence, reduces risk of selective drug resistance from partial adherence)

Directly observed therapy (DOT) recommended, especially in high-burden/resource-limited settings, to ensure adherence

Key drug doses (adult, weight-based per WHO):

• Isoniazid: 5mg/kg (max 300mg) od — pyridoxine (vitamin B6) 10-25mg od co-administered to prevent peripheral neuropathy, especially in malnourished, pregnant, HIV-positive, diabetic, or alcohol-dependent patients

• Rifampicin: 10mg/kg (max 600mg) od — potent CYP450 inducer, major drug interactions (reduces efficacy of oral contraceptives, warfarin, many antiretrovirals — requires ART regimen adjustment); causes orange discoloration of body fluids (expected, reassure)

• Pyrazinamide: 25mg/kg od

• Ethambutol: 15mg/kg od — risk of optic neuritis (dose-dependent), baseline and monitoring visual acuity/color vision recommended, discontinue if visual symptoms occur

Baseline and monitoring: LFTs (isoniazid/rifampicin/pyrazinamide hepatotoxicity risk — monitor clinically, formal LFT monitoring for those with risk factors: pre-existing liver disease, alcohol use, HIV, pregnancy), renal function, HIV test, visual acuity (ethambutol), sputum smear/culture conversion monitoring (repeat at 2 months to confirm response, guides extension decisions if still positive)

Drug-resistant TB (MDR/XDR): managed per WHO guidelines with longer, individualized regimens using second-line agents (bedaquiline, linezolid, clofazimine, later-generation fluoroquinolones such as levofloxacin/moxifloxacin) — specialist TB service management essential, treatment duration 9-18+ months depending on regimen and resistance pattern.

HIV co-infection: start TB treatment first, initiate/continue ART within 2-8 weeks of TB treatment start (earlier in more immunosuppressed patients, e.g., CD4 <50 — within 2 weeks) — balance against risk of immune reconstitution inflammatory syndrome (IRIS, can cause paradoxical worsening of TB symptoms); rifampicin interacts significantly with many ART regimens, requires careful selection (e.g., dolutegravir dose adjustment, avoid certain protease inhibitors).

Latent TB treatment (for those testing positive without active disease, particularly high-risk, HIV, recent close contact, immunosuppression, young children): isoniazid monotherapy 6-9 months, or rifampicin 4 months, or isoniazid+rifapentine weekly for 3 months (shorter regimens increasingly preferred for adherence) always exclude active disease first before starting LTBI treatment.

Public health measures: mandatory notification, contact tracing and screening (household/close contacts), infection control (airborne precautions — negative pressure isolation for infectious pulmonary/laryngeal TB until smear-negative/clinically improved on treatment), BCG vaccination (variable efficacy, mainly protects against severe childhood disease — miliary TB, TB meningitis — rather than reliably preventing pulmonary TB in adults).

Monitoring for cure: clinical response, sputum smear/culture conversion, completion of full treatment course — treatment success defined by WHO criteria (cured/completed); default/interruption significantly increases resistance risk and requires regimen reassessment.