Tuberculosis, 5TH MBBS, By 0.A. Adeleke (Principles of Internal Medicine) & Dr Aneke Sunny, M2

Textbook Source: Principles of Internal Medicine by O.A. Adeleke (Chapter 22) Basics Caused by Mycobacterium tuberculosis complex (MTC): M. tuberculosis, M. bovis, M. africanum, M. microti, M. canetti. M. tuberculosis: non-spore-forming, nonmotile, weakly Gram-positive, obligate aerobe, acid-fast (due to mycolic acids). Epidemiology 9 million new cases (2013), 1.5 million deaths; 95% in developing countries. 24% of deaths in HIV-coinfected. Transmission Inhalation of infected droplet nuclei (main). Also ingestion, skin/mucosa penetration, placental. Pathogenesis – Primary TB Ghon focus (subpleural) → spreads to hilar/mediastinal LNs → Ghon complex (primary complex). Type IV hypersensitivity; T-cells release IFN-γ and IL-2. Erythema nodosum & phlyctenular conjunctivitis = mucocutaneous manifestations. Post-primary (Secondary) TB Reactivation or reinfection; apical seeding (Simon foci); cavities, caseation, fibrosis. Pulmonary TB – Clinical Features Constitutional: fever, night sweats, weight loss, anorexia, malaise. Pulmonary: chronic cough (>3 wk), haemoptysis, dyspnoea, chest pain. Signs: tachypnoea, dull percussion, reduced breath sounds, crepitations, wheeze. CXR Findings Hilar/paratracheal lymphadenopathy (primary TB); upper lobe infiltrates with cavities (post-primary). Extrapulmonary TB (in order of frequency) Lymph node TB (most common) : posterior cervical/supraclavicular; painless → matted → draining sinus. Pleural effusion: straw-coloured fluid, low ADA excludes TB; pleural biopsy better than fluid. Skeletal TB: Pott's disease (spine – lower thoracic/upper lumbar) → back pain, gibbus (kyphosis), cold abscess. TB meningitis: basal exudates, CN II affected; CSF: clear/xanthochromic, elevated pressure, WBC 10-500, glucose 20-40, protein 400-5000. Miliary TB: choroid tubercles (pathognomonic); hepatosplenomegaly. Diagnosis Culture (gold standard) : Lowenstein-Jensen, Middlebrook 7H10, BACTEC. AFB staining: Ziehl-Neelsen; cannot differentiate species. NAAT/Gene Xpert MTB/RIF: detects TB + rifampin resistance in <2 hr (WHO recommended). TST (Mantoux) : 5 TU PPD intradermal, read 48-72 hr; cannot distinguish latent vs active. False negatives: malnutrition, immunosuppression, overwhelming TB. False positives: non-tuberculous mycobacteria, BCG. IGRAs: measure IFN-γ; more specific than TST (no BCG cross-reaction); also cannot distinguish latent vs active. Treatment – First-line drugs H (isoniazid) : 5 mg/kg daily – hepatitis, peripheral neuropathy (give pyridoxine 10-25 mg/d). R (rifampin) : 10 mg/kg – orange urine, hepatitis, contraceptive failure. Z (pyrazinamide) : 25 mg/kg – hepatotoxicity, hyperuricaemia, arthralgias. E (ethambutol) : 15 mg/kg – optic neuritis, red-green colour blindness. Regimen for drug-susceptible TB Initial phase (2 months): HRZE Continuation phase (4 months): HR Drug-resistant TB MDR-TB : resistant to H+R. Initial phase 8 months (fluoroquinolone + injectable + ethionamide + cycloserine/PAS + Z), continuation up to 12 months. XDR-TB : resistant to H+R + fluoroquinolone + at least one injectable (amikacin, kanamycin, capreomycin). Poor prognosis. TDR-TB (totally drug-resistant): resistant to almost all drugs. Corticosteroid indications in TB TB meningitis, pericardial effusion, severe miliary TB, large pleural effusion, IRIS. PowerPoint Supplement (Dr. Aneke Sunny) Additional facts TB is 13th leading cause of death globally; 2nd leading infectious killer after COVID-19 (above HIV/AIDS). 2020: 10 million ill; 1.5 million deaths. 8 high-burden countries: India, China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh, South Africa. Survival strategies of M. tb: cell wall lipids prevent phagosome-lysosome fusion; blocks EEA1; neutralizes reactive oxygen/nitrogen intermediates. Newer diagnostics: LED fluorescence microscopy, MODS, TLA, NRA (Griess method), Line probe assays (GenoType MTBDR). BCG vaccine: variable efficacy (0-80%); also used for bladder cancer (immunotherapy), leprosy protection, multiple sclerosis. TB/HIV co-infection: start TB treatment first, then ART within 2-4 weeks; rifampin interacts with PIs and NNRTIs (CYP450 inducer).