Tuberculosis Overview 10 million new M. tuberculosis infections/year Facultative intracellular rod-shaped bacteria Multidrug-resistant tuberculosis (MDR-TB) accounts for 4.6% of new infections Mycobacteria Species: • Mycobacterium tuberculosis • Mycobacterium africanum • Mycobacterium bovis Most infected with Mycobacterium tuberculosis - asymptomatic (90%) & develop latent tuberculosis (LTBI) Pathophysiology: 1. Droplets that contain bacilli 2. Inhaled droplet nuclei reach the terminal alveoli and are taken up by the alveolar macrophages 3. Replication within macrophages 4. IFN-γ-activated macrophages secrete TNF-α. TNF-α promotes the aggregation of macrophages and T cells to form granulomas affecting the lungs and regional lymph nodes Risk Factors For Active TB: • HIV • Recent infection • Pulmonary fibrotic lesions • Malnutrition • Immunosuppression • Tumor necrosis factor-α inhibitors • Injection drug use • Silicosis • Chronic kidney disease • DM DDX: • Nontuberculous mycobacterial infection (NTM) • Fungal infection • Sarcoidosis • Lymphoma • Lung cancer • Septic emboli • Lung abscess Primary Tuberculosis: 1. Latent: Asymptomatic 2. Active: Symptomatic Primary Tuberculosis Disease Progression: (+) Immune Response: • Most bacteria killed - rest LTBI (-) Immune Response: • Granulomas unable to limit infection • Progressive lung disease, bacteremia, and miliary TB Secondary Tuberculosis: • Endogenous reactivation of a latent infection • Mostly due to immunosuppression • 75% are pulmonary • HIV: 2/3 pulmonary & extrapulmonary Secondary Tuberculosis Disease Progression: • Upper lobe lung involvement • Other organ involvement - seeding • Caseating granulomas with central necrosis and Langerhans giant cells are characteristic features Clinical Presentation: Latent TB: • Asymptomatic Active TB: • Fever • Weight loss (Anorexia) • Night sweats • Productive cough Pleuritic CP • +/- hemoptysis • Dyspnea • Lymphadenopathy Immunosuppressed Active Disease: Hematogenous spread -> Miliary TB Can involve any organ system: • Pleura • Lymph nodes • Central nervous system • Skeletal system • Pericardium • GU system Complications: Hemoptysis, pneumothorax, bronchiectasis, extensive pulmonary destruction (including pulmonary gangrene), fistula, tracheobronchial stenosis, malignancy, and chronic pulmonary aspergillosis, Broncholithiasis Tuberculosis Diagnosis: Latent TB: • Tuberculin skin test (TST) • Interferon-γ release assay (IGRA) • PPD (TST) and quantiferon-gold (IGRA) have no role in assessing for active TB - Only latent Active TB: • Acid-fast staining, NAA (PCR) and Culture • CXR Tuberculosis Treatment: Active TB: • (RIPE) isoniazid, rifampin, ethambutol and pyrazinamide for two months • Followed by rifampin and isoniazid for an additional four months Latent TB: • Isoniazid + rifapentine weekly for 3 months • Isoniazid + rifampin daily for 3 months • Rifampin daily X 4 months • INH daily X 6 or 9 months Initiating Treatment With TNF Inhibitor: • Risk of reactivation TB and death from disseminated disease • Check CXR and simultaneous TST or IGRA HIV: • HIV-infected patients should be screened for latent TB with TST or IGRA #Tuberculosis #TB #Diagnosis #Management #Treatment #ActiveTB #LatentTB
