Pulmonary · PANCE / PANRE

Tuberculosis (Active and Latent)

Mycobacterium tuberculosis infection — active disease or asymptomatic latent infection (LTBI).

Also known as: TB, tuberculosis, latent TB, LTBI, active TB, Mycobacterium tuberculosis, miliary TB

Overview

Infection with Mycobacterium tuberculosis complex. Latent TB infection (LTBI): asymptomatic, non-contagious, positive immunologic test, no clinical/radiographic disease. Active TB: symptomatic disease, often pulmonary, contagious; may be primary or reactivation.

Epidemiology

Globally ~10 million new cases and ~1.3 million deaths annually. In the US, >85% of cases occur in non-US-born persons or those born in high-burden countries. HIV coinfection accelerates progression. Drug-resistant TB (MDR, XDR) is a global challenge.

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Risk factors

Birth or residence in high-prevalence country, recent travel
Close contact with active pulmonary TB case
HIV/AIDS, immunosuppression (TNF-alpha inhibitors, transplant, chemotherapy, chronic corticosteroids)
Diabetes mellitus, end-stage renal disease, silicosis
Healthcare workers, prison/shelter exposure, IV drug use
Children <5 years and elderly
Malnutrition, alcohol use disorder, smoking

Pathophysiology

Inhaled aerosolized droplet nuclei reach alveoli, ingested by alveolar macrophages. Most contain infection in granulomas (latent). With reduced immunity, dormant bacilli reactivate → caseating granulomas, cavitation, hematogenous spread (miliary). Lifetime reactivation risk ~5-10% (general), ~10%/year with untreated HIV.

Clinical presentation

Symptoms

LTBI: asymptomatic by definition
Active pulmonary TB: chronic cough >3 weeks (productive, may be hemoptysis), drenching night sweats, fevers, weight loss, anorexia, fatigue
Pleuritic chest pain if pleural involvement
Extrapulmonary TB: lymphadenitis (scrofula), TB meningitis, Pott disease (spinal), genitourinary, peritoneal, miliary

Signs / physical exam

Often nonspecific exam early in disease
Fever, cachexia, post-tussive crackles, amphoric breath sounds over cavities
Lymphadenopathy, hepatosplenomegaly (miliary)

Classic findings

Apical/posterior upper lobe or superior segment of lower lobe cavitary disease (reactivation); hilar lymphadenopathy + middle/lower lobe infiltrate (primary); miliary nodules (2-3 mm) on CXR (disseminated).

Differential diagnosis

Community-acquired pneumonia — Acute onset, lobar consolidation, responds to standard antibiotics within days
Lung cancer — Mass lesion in smoker, weight loss, hemoptysis; biopsy distinguishes
Non-tuberculous mycobacteria (M. avium complex, M. kansasii) — Older women with bronchiectasis ('Lady Windermere'), cavitary disease in COPD; AFB+ but TB-specific NAAT negative
Fungal pneumonia (histoplasmosis, coccidioidomycosis, blastomycosis) — Geographic exposure (Mississippi/Ohio valley, Southwest, Great Lakes); serology and fungal cultures
Sarcoidosis — Bilateral hilar lymphadenopathy without parenchymal cavitation, non-caseating granulomas, elevated ACE
Lung abscess — Air-fluid level on CXR, putrid sputum, polymicrobial flora
Pulmonary aspergillosis — Aspergilloma in pre-existing cavity (often TB), positive Aspergillus IgG/galactomannan

Diagnostic workup

Diagnostic criteria

LTBI: positive TST (induration ≥5/10/15 mm cutoff based on risk) or positive IGRA + no active disease on imaging/clinical evaluation. Active TB: clinical findings + positive AFB smear/NAAT/culture from respiratory or other site.

Labs

LTBI: tuberculin skin test (TST/PPD) OR interferon-gamma release assay (IGRA — QuantiFERON, T-SPOT)
Active TB: 3 sputum samples for AFB smear, culture (gold standard, 6-8 weeks), and NAAT (Xpert MTB/RIF, rapid)
HIV test on every TB patient
CBC, CMP, hepatitis serologies, baseline LFTs before treatment
Drug susceptibility testing on positive culture

Imaging

CXR — primary: hilar adenopathy, middle/lower infiltrate, Ghon complex; reactivation: apical/posterior cavitary lesions; miliary: 2-3 mm nodules diffuse
CT chest if CXR equivocal or to characterize disease
MRI brain/spine if neurologic/spinal TB suspected

Diagnostic algorithm

TST Induration	Considered Positive If…
≥5 mm	HIV+, recent contact with active TB, fibrotic CXR consistent with prior TB, organ transplant, immunosuppression (≥15 mg/d prednisone × 1 mo, TNF inhibitors)
≥10 mm	Recent immigrant (<5 y) from high-prevalence country, IVDU, healthcare workers, prison/shelter residents, children <5, mycobacterial lab workers, diabetes/CKD/silicosis
≥15 mm	Any person with no known risk factors

Mantoux tuberculin skin test (TST) cutoffs for positivity by risk category (CDC).

Treatment

First-line

LTBI (CDC 2020 preferred shorter regimens): isoniazid + rifapentine weekly × 12 weeks (3HP, DOT); OR rifampin daily × 4 months (4R); OR isoniazid + rifampin daily × 3 months (3HR)
LTBI alternative: isoniazid daily × 6 or 9 months (older standard; longer, more hepatotoxicity)
Active drug-susceptible TB (RIPE × 2 months intensive phase): rifampin (R) + isoniazid (H/INH) + pyrazinamide (Z/PZA) + ethambutol (E)
Continuation phase × 4 months: rifampin + isoniazid (HR) — total 6 months
Always add pyridoxine (vitamin B6) 25-50 mg daily with isoniazid to prevent peripheral neuropathy
Directly observed therapy (DOT) recommended to ensure adherence and prevent resistance
Report all cases to public health department; contact tracing

Second-line / adjunct

Drug-resistant TB: MDR (resistant to INH + RIF) — bedaquiline-containing regimens (BPaL: bedaquiline + pretomanid + linezolid × 6 months, per 2022 WHO update)
XDR (additional resistance to fluoroquinolones and a second-line injectable): individualized regimens with newer agents
TB meningitis: extend therapy to 9-12 months + adjunctive corticosteroids (dexamethasone) to reduce mortality and neurologic sequelae
Pott disease (spinal TB): 6-9 months + surgical consultation for spinal instability or cord compression
HIV coinfection: start ART within 2-8 weeks of TB therapy (sooner if CD4 <50); watch for IRIS
Drug toxicities: hepatotoxicity (especially INH, RIF, PZA — monitor LFTs), optic neuritis (ethambutol — baseline and monthly vision), hyperuricemia/gout (PZA), orange body fluids (rifampin), drug-drug interactions (rifampin is potent CYP3A4 inducer)

Complications

Cavitary disease, hemoptysis (Rasmussen aneurysm), pneumothorax
Miliary/disseminated TB, TB meningitis, Pott disease
Multidrug-resistant and extensively drug-resistant TB
Aspergilloma formation in old cavities
Constrictive pericarditis, bronchiectasis (post-TB)
Drug toxicities — DILI, peripheral neuropathy, optic neuritis

PANCE pearls

Reactivation TB favors apical/posterior segments (higher O2 tension); primary TB favors middle/lower lobes with hilar adenopathy.
Mantoux interpretation: ≥5 mm positive if HIV, recent contact, immunosuppressed, fibrotic CXR; ≥10 mm if high-risk demographic; ≥15 mm for low-risk patients.
IGRA preferred over TST in BCG-vaccinated individuals (BCG can cause false-positive TST).
Rifampin turns body fluids orange and is a potent CYP3A4 inducer — reduces efficacy of OCPs, warfarin, ART, statins, and many others.
Pregnancy: use RIPE without streptomycin (ototoxic to fetus); pyridoxine essential. Treat LTBI in pregnant women only if recent infection or HIV+; otherwise defer postpartum.

References

CDC/IDSA/NTCA 2020 — Guidelines for the Treatment of Latent Tuberculosis Infection (Sterling et al., MMWR 2020)
ATS/CDC/IDSA 2016 — Treatment of Drug-Susceptible Tuberculosis (Nahid et al., Clin Infect Dis 2016)
WHO 2022 — WHO Consolidated Guidelines on Tuberculosis: Drug-Resistant TB Treatment (2022 Update)
Nix-TB / ZeNix Trials — Bedaquiline-Pretomanid-Linezolid for Highly Drug-Resistant TB (Conradie et al., NEJM 2020/2022)

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