Tuberculosis ACTIVE VS. LATENT INFECTION & SCREENING MED STUDENT LECTURE SERIES UPDATED SEPTEMBER, 2019 Bacteriology of M. Tuberculosis Aerobic rod Cell wall with mycolic acid ◦ Gives the acid fast quality ◦ Weakly gram positive Source: Infected people Other bacteria in this genus: avum, intracellulare, leprae, bovus* *source of BCG vaccine Pathogenesis We rely on T-cell mediated immunity against M. tuberculosis Early in infection, M. tuberculosis replicates within macrophages (blocks phagolysosome fusion) Around 3 weeks after infection Th1 response activates macrophages via INF-gamma and formation of granulomas (caseating granulomas) to contain disease Any Th1 modulating therapy should have TB testing prior to administration Infection vs Active Disease INFECTION ACTIVE DISEASE In most immunocompetent hosts, Clinical tuberculosis generally asymptomatic Primary TB ◦ Often forms fibrocalcific pulm nodule ◦ After exposure, develop active disease ◦ May remain dormant (latent) and await immune insult to reactivate ◦ Occurs in ~5% of cases (active) Secondary TB 2-4 weeks after infection, can ◦ Infected host with prolonged latent develop (+)PPD infection that sustains immune insult, reactivating infection ~5% Primary TB Often resembles acute bacterial pneumonia ◦ Lobe consolidation, hilary adenopathy, pleural effusion ◦ May have lymphohematogenous spread Secondary TB Usually following latent infection and reactivation ◦ This is why we screen – to identify and treat latent TB before it becomes active disease More commonly has apical lung disease Symptoms concerning for TB infection ◦ Weight loss, FTT ◦ Night sweats ◦ Fever ◦ Fatigue ◦ Hemoptysis, cough or chest pain for pulmonary TB TB Infections by Tissue Meninges Meningitis Kidneys Renal tuberculosis Bones Osteomyelitis Adrenals Addison’s Disease Vertebrae Pott’s Disease Intestines Intestinal TB (more common in countries where M. bovis is in unpasturized milk) Screening for Latent TB Risk factors ◦ Born in high risk country ◦ Immunocompromised ◦ Travel to endemic countries ◦ Housing insecurity or lives in shelter ◦ Living with someone with TB ◦ Incarceration ◦ Having contact with someone who has been exposed to TB PPD vs IGRA (Quantiferon Gold) ◦ IDSA/CDC now recommends IGRA if >/= 5yo ◦ AAP even recommends IGRA as early as 2yo if concerns for follow-up or h/o BCG vaccination POSITIVE Tuberculin Skin Test 5mm induration if: • HIV-infected • Recent TB contact • Fibrotic changes on CXR c/w prior TB • Transplant patient • Immunosuppressed 10mm induration if: • Recent immigrant (<5yrs) from high prevalence country • IV drug user • Residents and employees of high-risk congregate setting • Mycobacteriology lab personnel • Children <4yo • Pediatric patient exposed to adult in high-risk category 15mm induration for everyone, even if no known risk factors, and including previous h/o BCG vaccination Treatment for Active TB Rifampin ◦ Hepatotoxic, stains secretions Isoniazid ◦ May cause transaminitis, B6 deficiency Pyrazinamide Ethambutol ◦ Optic toxicity Streptomycin ◦ Ototoxicity References CDC ◦ https://www.cdc.gov/tb/default.htm Hay, W, Levin, M, Deterding, R, & Abzug, M. (2016). Current Diagnosis & Treatment: Pediatrics (23rd ed.). Lange. Kumar, Abbas, & Aster. (2015). Robins and Cotran Pathologic Basis of Disease (9th ed.). Elsevier. Tuberculosis in Children. Pediatrics In Review. Apr 2019, Vol 40, Iss 4. https://pedsinreview.aappublications.org/content/40/4/168.