Interferon release assay best for diagnosing TB in low-prevalence populations

This prospective study found that an interferon γ release assay - the T-SPOT.TB - is more specific but less sensitive than the tuberculin skin test for diagnosing tuberculosis (TB)-associated uveitis and should be used in preference to the skin test in low-TB-prevalence populations. However, the authors found that the likelihood of TB-associated uveitis is greatest if both the T-SPOT.TB and the skin test are both positive.

The diagnosis of ocular TB is challenging. Most patients have no evidence of Mycobacterium tuberculosis (MTB) in ocular biopsies, and culture of MTB, detecting acid-fast bacilli in smears or detecting MTB DNA in ocular samples, often has a low yield. A presumptive diagnosis of TB-associated uveitis often is made in patients with uveitis and a positive skin test, a positive interferon release assay, lesions suggestive of pulmonary TB on chest X-ray and/or evidence of associated systemic TB infections. The traditional skin test or Mantoux test has a low specificity due to false positives in patients infected with nontuberculous mycobacterium or who have been previously vaccinated with bacillus Calmette-Guerin.

The authors conducted a prospective one-year study in 191 consecutive patients in Singapore with a new diagnosis of uveitis presenting with ocular signs suggestive of TB-associated uveitis. All patients underwent both tests.

Using Bayesian analysis to estimate the results, the authors found that the skin test was more sensitive compared to the T-SPOT.TB but the T-SPOT.TB was more specific than the skin test.

The T-SPOT.TB had a higher positive predictive value than the skin test but a lower negative predictive value. These results indicate that a positive T-SPOT.TB strongly suggests a tubercular cause in patients with uveitis and clinical ocular signs consistent with TB-associated uveitis, whereas a negative T-SPOT.TB in such patients should be interpreted with caution.

They found that patients who are skin test- and T-SPOT.TB- positive had a 95.1 percent likelihood of having TB-associated uveitis. Based on statistical decision theory, they conclude that in populations where the prevalence of TB-associated uveitis is high, the skin test should be the first choice, and in populations in which the prevalence of TB is low, the T-SPOT.TB should be performed. The results suggest that performing both tests increases the accuracy of diagnosing TB-associated uveitis, although discordant or negative results are less useful.

They caution that no single test establishes or refutes a diagnosis of TB-associated uveitis and clinicians must carefully evaluate all diagnostic information in establishing a diagnosis and making treatment recommendations.