Prognostic value of interferon gamma release assays in predicting active tuberculosis among individuals with, or at risk of, latent tuberculosis infection

This study aims to determine which of the currently available tests for 'latent' tuberculosis (TB) infection best predicts the likelihood of subsequent development of active TB disease in groups of people at high risk of having been exposed to TB. Although individuals may become infected with TB following exposure to an infectious case, only about 10% go on to develop active TB disease. The risk of progressing to active disease is highest in the first two years after infection, although this may occur years after the infection. The tuberculin skin test, developed more than 100 years ago, does not reliably distinguish between those who will, and will not, go on to develop active TB disease and can be falsely positive or falsely negative due to a variety of complicating factors. New tests, known as IGRA tests, based on a different technology and requiring a blood specimen, have been developed in recent years but there remains uncertainty about their ability to predict the subsequent development of TB in people who may have been exposed and whether they predict any better than traditional tuberculin skin tests. This study is designed to determine the predictive value of the new tests, in comparison to tuberculin skin tests, and determine how cost effective it would be to employ the new tests in one of a number of testing strategy options. The study will be carried out in 10,000 participants, aged at least 16 years, at increased risk of TB identified in chest medicine clinics and GP surgeries in London (see full application for details). Close contacts of active cases of TB, and new entrants from high TB incidence countries, will be screened (as is current standard practice) but will be invited to undergo testing using both traditional tuberculin skin testing and IGRA testing based on collection of a blood sample. Some blood will be kept to allow repeat testing if the result of the first test is unclear and for future research as further new methods for diagnosing TB emerge. We will collect information on factors that have been shown to be associated with increased risk of TB including place of birth, ethnic group, time since entry to UK etc. Individuals with a positive test result will be assessed to make sure they are not currently suffering from TB. Those with a positive skin and blood test but without active disease (i.e TB infected) who are 35 years or younger, will be offered treatment to prevent the development of active TB, after having the advantages and disadvantages explained to them. Following national guidance, those older than 35 years will not be offered treatment as they have a greater likelihood of side-effects from the drugs used. We will actively monitor for TB in all participants for an average period of 24 months using a number of approaches. We will use the results from the study in an economic model to determine the screening approach that is likely to provide the best value for money.