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



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