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Cytokine diagnosis of pleural TB: will it stand the test of time?
  1. Marc Tebruegge1,2,3,4,
  2. Paul T Elkington1
  1. 1NIHR Biomedical Research Centre, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK
  2. 2Department of Paediatric Infectious Diseases and Immunology, Evelina London Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
  3. 3Great Ormond Street Institute of Child Health, University College London, London, UK
  4. 4Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
  1. Correspondence to Prof Paul T Elkington, Clinical and Experimental Sciences, University of Southampton, Southampton SO16 1YD, UK; p.elkington{at}soton.ac.uk

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The need for better diagnostics for TB has been repeated so frequently that there is a danger of message fatigue. However, the unfortunate return of TB as the number 1 cause of death due to an infectious disease must surely serve as a further call to action for researchers, clinicians and funders to redouble our efforts.1 The fundamental issues with TB diagnosis deserve repeating: standard diagnosis of pulmonary TB relies primarily on sputum smear tests, which have limited sensitivity and specificity, and have not significantly changed for over 100 years.2 Recent data show that staining for acid-fast bacilli remains the most commonly used diagnostic method globally.3 The development of interferon-gamma release assays (IGRAs) and molecular amplification tests such as Xpert MTB/RIF assays has improved the landscape somewhat, but both are critically limited by cost and the need for extensive infrastructure. In addition, IGRAs do not distinguish latent from active TB, have limited robustness and perform worse in children than in adults.4–6 Recent data suggest that the roll-out and scale-up of the Xpert MTB/RIF assays in resource-limited settings have been far slower than anticipated.7 Importantly, molecular assays require relatively high numbers of bacilli to achieve adequate sensitivity. The diagnosis of extrapulmonary TB is often more challenging than pulmonary TB, frequently with low bacterial loads in difficult-to-access locations. Therefore, the majority of TB diagnoses …

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