What are the signs and symptoms that indicate latent tuberculosis (TB) has progressed to active TB?

Signs and Symptoms of Latent TB Progressing to Active TB

The key signs and symptoms that indicate latent tuberculosis (TB) has progressed to active TB include persistent cough (lasting ≥3 weeks), bloody sputum, night sweats, weight loss, fever, anorexia, and fatigue. 1

Clinical Presentation of Active TB

Active TB typically presents with the following symptoms:

• Respiratory symptoms:

  • Persistent cough lasting ≥3 weeks (most common presenting symptom)
  • Bloody sputum (hemoptysis)
  • Chest pain
  • Dyspnea (shortness of breath)

• Systemic symptoms:

  • Fever (often low-grade and occurring in the evening)
  • Night sweats
  • Weight loss
  • Anorexia (loss of appetite)
  • Fatigue
  • Malaise

The presence of these symptoms, especially in combination, should prompt immediate evaluation for active TB disease 1, 2.

Risk Factors for Progression from Latent to Active TB

Certain populations have a higher risk of progression from latent to active TB:

• Immunocompromised individuals (HIV infection, organ transplant recipients)
• Patients on immunosuppressive medications (especially anti-TNF therapy)
• Recent TB contacts
• Persons with fibrotic changes on chest radiograph
• Patients with chronic conditions (diabetes, silicosis, end-stage renal disease)
• Individuals with a history of inadequately treated TB
• Persons with malnutrition or low body weight

The lifetime risk of progression from latent to active TB is approximately 5-10% in the general population, with most cases occurring within the first 2-5 years after infection 3, 4.

Diagnostic Approach for Suspected Active TB

When latent TB is suspected of progressing to active disease:

1. Chest radiography: Look for infiltrates in upper lobes, cavitary lesions, consolidations, centrilobular nodules, or miliary pattern 2

2. Microbiological confirmation:

   • Sputum collection for acid-fast bacilli (AFB) smear
   • Culture for Mycobacterium tuberculosis
   • Molecular testing (e.g., nucleic acid amplification tests)

3. Additional testing based on suspected site of disease:

   • CT scan for equivocal chest radiographs
   • Bronchoscopy for patients unable to produce sputum
   • Appropriate sampling of suspected extrapulmonary sites

Infectiousness Assessment

Patients with active TB are considered infectious if they:

• Are coughing
• Are undergoing cough-inducing procedures
• Have positive AFB sputum smears
• Are not on chemotherapy, have just started chemotherapy, or have a poor clinical/bacteriologic response to therapy 1

Clinical Pearls and Pitfalls

• Important caveat: Some patients with active TB may be asymptomatic or have minimal symptoms, especially early in the disease course or in immunocompromised hosts.

• Common pitfall: Relying solely on tuberculin skin test (TST) or interferon-gamma release assay (IGRA) results to rule out active TB. These tests cannot distinguish between latent and active TB 1.

• Critical consideration: Patients with suspected active TB should be isolated until three consecutive negative sputum smears are obtained and clinical improvement is demonstrated 1.

• Monitoring recommendation: Patients on treatment for latent TB should be educated about symptoms of hepatotoxicity (anorexia, nausea, vomiting, abdominal discomfort, fatigue, dark urine, pale stools, jaundice) which could necessitate stopping treatment 1.

• Special populations: Patients on biologic disease-modifying antirheumatic drugs (especially anti-TNF agents) require careful monitoring as they have increased risk of TB reactivation 5.

By recognizing these signs and symptoms early, clinicians can promptly diagnose and treat active TB, reducing morbidity, mortality, and disease transmission.