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The Clinical Application of a Rapid Lung-Orientated TB Immunoassay in Individuals with Possible Tuberculosis
  1. Ronan AM Breen (rambreen{at}doctors.org.uk)
  1. Royal Free Hospital, United Kingdom
    1. Simon M Barry
    1. Royal Free hospital, United Kingdom
      1. Colette J Smith
      1. Royal free and University College Medical School, United Kingdom
        1. Robert J Shorten
        1. Royal Free and University College Medical School, United Kingdom
          1. J Paul Dilworth
          1. Royal Free Hospital, United Kingdom
            1. Ian Cropley
            1. Royal Free Hospital, United Kingdom
              1. Tim D McHugh
              1. Royal Free and University College Medical School university college medical school, United Kingdom
                1. Stephen H Gillespie
                1. Royal Free and University College Medical School, United Kingdom
                  1. George Janossy
                  1. Royal Free and University College Medical School, United Kingdom
                    1. Marc CI Lipman
                    1. Royal Free Hospital, United Kingdom

                      Abstract

                      Rationale: Immunological ex-vivo assays to diagnose tuberculosis (TB) have great potential, but have largely been blood-based and poorly evaluated in active TB. Lung sampling enables combined microbiological and immunological testing and utilises higher frequency antigen-specific responses than in blood.

                      Objective and Methods: Prospective evaluation of a flow-cytometric assay measuring the percentage of interferon-gamma synthetic CD4+ lymphocytes following stimulation with purified protein derivate of M. tuberculosis (PPD) in broncho-alveolar lavage fluid from 250 sputum smear negative individuals with possible TB. A positive assay was defined as >1.5%.

                      Results: Of those who underwent lavage and were diagnosed with active TB 95% (106 of 111) had a positive immunoassay (95% confidence intervals 89%, 98%). In 139 individuals deemed not to have active TB, 76% (105 of 139) were immunoassay negative (95% confidence intervals 68%, 82%). Among the remaining 24% (34 cases) with a positive immunoassay a substantial proportion had evidence of untreated TB - in 2 of these active TB was subsequently diagnosed. Assay performance was unaffected by HIV status, disease site or BCG vaccination. In culture-positive pulmonary cases, response to purified protein derivative was more sensitive than nucleic acid amplification testing (94% versus 73%). The use of early secretory antigen target-6 (ESAT-6) responses in 71 subjects was no better than PPD; and 19% of those with culture-confirmed TB and a positive PPD-immunoassay had no detectable response to ESAT-6.

                      Conclusions: These data suggest lung-orientated immunological investigation is a potentially powerful tool in diagnosing individuals with sputum-smear negative active TB regardless of HIV sero-status.

                      • co-infection
                      • immune response
                      • interferon-gamma
                      • lymphocytes
                      • tuberculosis

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