The Use of Interferon Gamma Release Assays in the Diagnosis of Active Tuberculosis

Interferon gamma release assays (IGRAs) are in vitro immunologic diagnostic tests used to identify Mycobacterium tuberculosis infection. They cannot differentiate between latent and active infections. The cutoff suggested by the manufacturer is 0.35？IU/mL for latent tuberculosis. As IGRA tests were recently approved for the differential diagnosis of active tuberculosis, we assessed the diagnostic accuracy of the latest generation IGRA for detection of active tuberculosis in a low-incidence area in Germany. Our consecutive case series includes 61 HIV negative, Mycobacterium tuberculosis culture positive patients, as well as 234 control patients. The retrospective analysis was performed over a period of two years. In 11/61 patients with active tuberculosis (18.0%) the test result was <0.35？IU/mL, resulting in a sensitivity of 0.82. We recommend establishing a new cut-off value for the differential diagnosis of active tuberculosis assessed by prospective clinical studies and in various regions with high and low prevalence of tuberculosis. 1. Introduction Tuberculosis (TB) remains a major public health problem affecting one-third of the world’s population [1, 2]. Diagnosis of TB is usually based on a combination of anamnestic symptoms, clinical presentation, radiological and pathological changes, bacteriological findings of acid/alcohol-fast bacilli, and molecular tests [3]. Definitive TB diagnosis is based on the detection of Mycobacterium tuberculosis (MTB) in the culture, which usually takes four to six weeks. For decades, tuberculin skin test (TST) has been used as diagnostic tool to support the physician’s decision process. With the introduction of interferon gamma release assays (IGRAs), a more specific method became available. Although primarily developed for the diagnosis of latent TB, clinicians have also been searching for improved diagnostic tools and explored IGRAs for the immunodiagnosis of active TB. In 2010, the Centers for Disease Control and Prevention (CDC) updated their guidelines for testing for TB infection, concluding that IGRAs “may be used instead of a tuberculin skin test in all situations in which the CDC recommends the tuberculin skin test as an aid in diagnosing M. tuberculosis infection” [4, 5]. Nevertheless, with the cutoff for the diagnosis of latent TB as given by the producers, pooled sensitivity for the diagnosis of culture positive TB did not exceed 80% in the most recent meta-analyses [6, 7]. The present case series constitutes one of the largest reports of latest generation IGRA used in culturally proven HIV-negative TB