Latent Tuberculosis Infection Testing in People with Compromised Immunity Prior to Biologic Therapy: A Review of Diagnostic Accuracy, Clinical Utility, and Guidelines

Tuberculosis (TB) is a chronic communicable disease that primarily affects the respiratory system. It is caused by infection with Mycobacterium tuberculosis, a species of bacteria in the Mycobacteriaceae family. As much as 25% of the global population is estimated to have TB infection, although only a small portion of infected individuals are ill as a result of the infection. The incidence of TB varies greatly by country. For example, the rate of active TB in Canada is approximately 4.9 per 100,000 population, although this rate is considerably higher in Canadian-born Indigenous populations (21.5 per 100,000 population). By comparison, the incidence of active TB in the Philippines, which is classified as a high-burden country, is estimated to be 554 per 100,000 population. There are two stages to TB: 1) latent TB infection, and 2) active TB infection. Latent TB typically occurs immediately following exposure to the bacteria. Although an individual who has latent TB infection will not exhibit any symptoms and they are not considered contagious, there are dormant bacteria residing in their lungs. If latent TB is left untreated it can progress to active infection. Those who have active infection are contagious and may show symptoms such as coughing, chest pain, unexpected weight loss, loss of appetite, night sweats, fever, fatigue, and chills. Without medical intervention (e.g., rifampin, isoniazid, pyrazinamide, ethambutol), TB can be fatal. Individuals with who have HIV, are transplant recipients, are on biologic therapies (e.g., TNF [tumour necrosis factor] inhibitors), and those who have impaired or compromised immune systems for other reasons are at an increased risk for latent TB reactivation. There is no established gold standard technique for diagnosing latent TB infection. The most commonly used screening methods are the tuberculin skin test (TST) and interferon gamma release assays (IGRAs); however, these diagnostic tools have limited sensitivity and specificity. The objective of the current report is to evaluate the evidence regarding the diagnostic accuracy and clinical utility of the TST for patients with compromised immunity prior to initiating biologic treatment. Additionally, evidence-based guidelines regarding testing for latent TB infection in patients with compromised immunity prior to initiating biologic therapy will be reviewed. This report expands upon a previously completed CADTH report (list of references). This report is a component of a larger CADTH Condition Level Review on TB. A condition level review is an assessment that incorporates all aspects of a condition, from prevention, detection, treatment, and management. For more information on CADTH’s Condition Level Review of TB, please visit the project page (https://www.cadth.ca/tuberculosis).