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Clinical application of a rapid lung-orientated immunoassay in individuals with possible tuberculosis

¹ Department of Immunology, Royal Free and University College Medical School, London, UK
² Departments of Thoracic and HIV Medicine, Royal Free Hospital, London, UK
³ Department of Primary Care and Population Science, Royal Free and University College Medical School, London, UK
⁴ Centre for Medical Microbiology, Royal Free and University College Medical School, London, UK

Correspondence to:
Dr R A M Breen, Department of Thoracic and HIV Medicine, Royal Free Hospital, London NW3 2QG, UK; r.breen{at}doctors.org.uk

Background: 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 uses higher frequency antigen-specific responses than in blood.

Methods: A prospective evaluation was undertaken of a flow cytometric assay measuring the percentage of interferon- synthetic CD4+ lymphocytes following stimulation with purified protein derivative of Mycobacterium tuberculosis (PPD) in bronchoalveolar 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% (106/111) had a positive immunoassay (95% CI 89% to 98%). In 139 individuals deemed not to have active TB, 105 (76%) were immunoassay negative (95% CI 68% to 82%). Of the remaining 24% (34 cases) with a positive immunoassay, a substantial proportion had evidence of untreated TB; in two 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 PPD was more sensitive than nucleic acid amplification testing (94% vs 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 findings suggest that lung-orientated immunological investigation is a potentially powerful tool in diagnosing individuals with sputum smear-negative active TB, regardless of HIV serostatus.

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				G. H Bothamley New tests for tuberculosis: local immune responses have greater specificity Thorax, January 1, 2008; 63(1): 4 - 5. [Full Text] [PDF]