Diagnosis and treatment of latent infection with Mycobacterium tuberculosis


  • The Authors: Cynthia B.-E. Chee, MBBS, FRCP, is senior consultant respiratory physician at the Tuberculosis Control Unit and Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore. Her research interests are clinical and public health aspects of TB. Martina Sester, PhD, is a Professor of Transplant and Infection Immunology at Saarland University, Germany, and her research interests focus on the characterization of cellular immune responses for the control of clinically relevant pathogens. Wenhong Zhang, MD, PhD, is a Professor of Medicine at Fudan University, China. He is the director of the Department of Infectious Diseases. His research interests include diagnosis and treatment of infectious diseases, especially TB. Christoph Lange, Dr. med. Dipl.-Biol, FIDSA, is a Professor of Medicine at the University of Lübeck, Germany. At the Research Center Borstel, Germany, he is the principal attending physician of the Medical Clinic and the Head of the Division of Clinical Infectious Diseases. His research interests include topics of the prevention, diagnosis and treatment of TB.
  • Conflict of Interest Statement: MS and CL have received kits free of charge from Cellestis and Oxford Immunotec to study the performance of interferon-γ release assay responses in immune-compromised patients. CL has conducted investigator-initiated clinical trials, where QuantiFERON-TB Gold In-Tube and T-SPOT.TB test kits were provided by the manufacturers free of charge. MS has a patent application entitled ‘In vitro process for the quick determination of a patient's status relating to infection with Mycobacterium tuberculosis’ (international patent number WO2011113953/A1).

Correspondence: Christoph Lange, Clinical Infectious Diseases, Research Center Borstel, 23845 Borstel, Germany. Email: clange@fz-borstel.de


In clinical practice, latent infection with Mycobacterium tuberculosis is defined by the presence of an M. tuberculosis-specific immune response in the absence of active tuberculosis. Targeted testing of individuals from risk groups with the tuberculin skin test or an interferon-γ release assay is currently the best method to identify those with the highest risk for progression to tuberculosis. Positive predictive values of the immunodiagnostic tests are substantially influenced by the type of test, the age of the person who is tested, the prevalence of tuberculosis in the society and the risk group to which the person belongs. As a general rule, testing should only be offered when preventive chemotherapy will be accepted in the case of a positive test result. Preventive chemotherapy can effectively protect individuals at risk from the development of tuberculosis, although at least 3 months of combination therapy or up to 9 months of monotherapy are required, and overall acceptance rate is low. Improvements of the current generation of immunodiagnostic tests could substantially lower the number of individuals that need to be treated to prevent a case of tuberculosis. If shorter treatment regimens were equally effective than those currently recommended, acceptance of preventive chemotherapy could be much improved.