What are the stages of tuberculosis (TB) and their clinical signs and symptoms?

Stages of Tuberculosis and Their Clinical Manifestations

Tuberculosis exists along a clinical spectrum from latent infection to active disease, with distinct intermediate stages that have specific diagnostic and clinical features.

Stage 1: Latent Tuberculosis Infection (LTBI)

LTBI represents subclinical infection with immune responses to Mycobacterium tuberculosis without any clinical, bacteriological, or radiographic evidence of active disease. 1

• Patients are completely asymptomatic with no signs or symptoms of TB disease 1
• Positive tuberculin skin test (TST) or interferon-gamma release assay (IGRA) 1, 2
• Normal chest radiography with no active lesions 1
• Negative bacteriologic studies (if performed) 1
• Not infectious to others 1
• Lifetime reactivation risk of 5-15%, with majority occurring within first 5 years after initial infection 1
• Without treatment, approximately 5-10% will progress to active TB disease 3

Stage 2: Incipient Tuberculosis

Incipient TB describes early, contained disease in asymptomatic, relatively immunocompetent individuals who are progressing from LTBI toward active disease. 4, 5

• Patients remain asymptomatic with no clinical symptoms 4, 5
• Represents early disease with detectable manifestations but effective immune containment 4
• May show subtle radiographic changes not yet meeting criteria for active TB 5
• Occurs in immunocompetent hosts with intact immune responses 4
• Represents a critical window for intervention before progression to active disease 5

Stage 3: Subclinical Tuberculosis

Subclinical TB refers to disease in asymptomatic individuals (often immunocompromised) with loss of effective containment, who have radiographic or bacteriologic evidence of TB but no recognized symptoms. 4, 5, 6

• Patients lack recognized clinical symptoms but have detectable disease 4, 5
• Chest radiography shows abnormalities consistent with TB 5, 6
• May have positive sputum cultures despite absence of symptoms 5
• Can transmit M. tuberculosis to others 6
• More common in immunocompromised individuals, particularly HIV-infected patients 4, 5
• Represents failure of immune containment without symptom development 4

Stage 4: Active Tuberculosis Disease (Clinically Active TB)

Active TB includes all patients with clinical, bacteriological, and/or radiographic evidence of current tuberculosis disease. 1, 7

Primary Tuberculosis (within 1 year of exposure):

• Lobar pneumonia pattern on chest radiography 1
• Mediastinal and hilar lymphadenopathy 1
• Most commonly seen in children and severely immunocompromised individuals 1

Reactivation Tuberculosis (>1 year after initial exposure):

• Apical posterior upper lobe or superior-segment lower lobe fibrocavitary disease 1
• Endobronchial spread through airways with tree-in-bud nodules on CT 1

Common Clinical Signs and Symptoms:

• Cough lasting ≥2-3 weeks (cardinal symptom requiring TB evaluation) 7, 8, 2
• Fever, particularly evening fever 8, 2
• Night sweats 8, 2
• Weight loss and anorexia 8, 2
• Hemoptysis (suggests cavitary disease) 8, 2
• Fatigue and malaise 7

Diagnostic Features:

• Positive AFB smear microscopy (though negative smears do not exclude TB) 7, 2
• Positive mycobacterial culture (gold standard for diagnosis) 7, 2
• Chest radiography showing infiltrates, cavitations, or lymphadenopathy 1, 7
• Patients are infectious and require isolation until three consecutive negative sputum smears on different days 7

Stage 5: Previously Treated/Inactive Tuberculosis

This classification includes individuals with history of previous TB episode(s) or abnormal stable radiographic findings without current clinical or bacteriologic evidence of active disease. 1

• Positive TST with stable radiographic abnormalities 1
• Negative bacteriologic studies 1
• No clinical or radiographic evidence of current disease 1
• Upper lobe fibronodular infiltrations on chest radiography (typical of old TB) 1
• Requires evaluation to exclude active disease, particularly if no previous radiographs available for comparison 1

Critical Clinical Pitfalls to Avoid:

• Never exclude TB based on negative AFB smears alone—culture is required 2
• Never assume non-infectiousness immediately after starting treatment—isolation continues until three negative sputums 7, 2
• Never use TST/IGRA to diagnose active TB—these tests only indicate infection, not active disease 2
• Maintain high suspicion in HIV-infected patients who may have atypical presentations or false-negative skin tests 8, 2
• In immunocompromised hosts, chest radiography may appear deceptively normal despite active disease 1