What are the diagnostic criteria for active Tuberculosis (TB) disease?

From the Guidelines

Determining active TB disease requires a comprehensive approach that prioritizes clinical evaluation, imaging, and laboratory testing, with the most definitive method being the isolation of Mycobacterium tuberculosis through culture, as stated in the study by 1. The initial assessment should include a chest X-ray to identify characteristic lung abnormalities, followed by the collection of appropriate specimens for acid-fast bacilli (AFB) smear microscopy, culture, and nucleic acid amplification tests (NAATs) like GeneXpert MTB/RIF. Some key points to consider in the diagnosis of active TB disease include:

• Chest radiography has high sensitivity for detecting manifestations of active TB, but relatively poor specificity due to the overlap of findings with nontuberculous pulmonary infection, as noted in the study by 1.
• A positive AFB smear provides strong evidence for the diagnosis of tuberculosis, as mentioned in the studies by 1 and 1.
• A purified protein derivative (PPD)-tuberculin skin test may be performed at the time of the initial evaluation, but a negative test does not exclude the diagnosis of active tuberculosis, while a positive test supports the diagnosis of culture-negative pulmonary tuberculosis or latent tuberculosis infection, as stated in the studies by 1 and 1.
• The decision to initiate combination antituberculosis chemotherapy should be based on clinical, pathologic, and radiographic features of the patient, as well as epidemiologic information and the results of initial series of acid-fast bacilli (AFB)-stained sputum smears and culture for mycobacteria, as recommended in the studies by 1 and 1.
• In patients with a high suspicion of tuberculosis or those who are seriously ill, treatment with a four-drug regimen should be initiated promptly, often before AFB smear results are known and usually before mycobacterial culture results have been obtained, as stated in the studies by 1 and 1. Some of the key diagnostic approaches and tests that can be used to determine active TB disease include:
• Chest X-ray to identify characteristic lung abnormalities
• Collection of appropriate specimens (sputum, bronchoalveolar lavage, or tissue) for acid-fast bacilli (AFB) smear microscopy, culture, and nucleic acid amplification tests (NAATs) like GeneXpert MTB/RIF
• Histopathological examination showing granulomatous inflammation with caseous necrosis in tissue samples
• Evaluation of extrapulmonary sites through appropriate sampling
• Tuberculin skin tests (TST) or interferon-gamma release assays (IGRAs), although these cannot distinguish between latent infection and active disease.

From the Research

Determining Active TB Disease

• The diagnosis of latent tuberculosis (TB) infection is crucial for TB prevention, and it requires a positive test for infection and negative evaluation for active disease 2.
• Current tests for latent TB infection include the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs), such as T-SPOT.TB and QuantiFERON 2, 3.
• IGRAs are preferred in bacille Calmette-Guérin-vaccinated populations, while TST is still used when cost or logistical advantages exist 2, 3.
• A study found that IGRAs have a better predictive ability than TST for the progression of latent infection to active TB disease, with a pooled risk ratio of 9.35 compared to 4.24 for TST 4.
• The positive predictive value (PPV) of IGRAs was 4.5% compared to 2.3% for TST, while the negative predictive value (NPV) was 99.7% for IGRAs and 99.3% for TST 4.

Comparison of TST and IGRA

• A meta-analysis found that T-SPOT.TB was significantly more sensitive than TST, with a sensitivity of 90% compared to 64% for TST 3.
• The specificity of T-SPOT.TB was higher than that of TST, but there was overlap between confidence intervals 3.
• Another study found that the agreement between IGRA and TST was low using a 10 mm cutoff, but intermediate using a 15 mm cutoff 5.
• The odds ratio for the development of active TB was higher for IGRA-positive patients and those with positive TST and IGRA results 5.

Use of Chest Radiograph

• A study found that the use of chest radiograph can improve the selection of migrants for treatment of latent TB infection, particularly when used in combination with TST and IGRA 6.
• The chest radiograph was found to predict subsequent reactivation of TB, and its use is recommended when interpreting a TST result of 5-9 mm 6.