Immunodiagnosis of tuberculosis: state of the art.

Undiagnosed and mismanaged tuberculosis (TB) continues to fuel the global TB epidemic. Rapid, accurate and early diagnosis of TB is therefore a priority to improve TB case detection and interrupt transmission. Although considerable improvements have been made in TB diagnostics, there are two major gaps in the existing diagnostics pipeline: (1) lack of a simple accurate point-of-care test that can be used for rapid diagnosis at the primary care level; (2) lack of a biomarker (or combination of biomarkers) that can be used to identify latently infected individuals who will benefit most from preventive therapy. Currently available commercial serological (antibody detection) tests are inaccurate and do not improve patient outcomes. Despite this evidence, dozens of serological tests are sold and used in countries (e.g. India) with weak regulatory systems, especially in the private sector. Recognizing the threat posed by these suboptimal tests, a World Health Organization (WHO) Expert Group has strongly recommended against the use of serological tests for the diagnosis of pulmonary and extra-pulmonary TB. Another WHO Expert Group has discouraged the use of interferon-γ release assays for active pulmonary TB diagnosis in low- and middle-income countries. All existing tests for latent TB infection appear to have only modest predictive value and further research is needed to identify highly predictive biomarkers.