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Published ahead of print on May 6, 2004, doi:10.1164/rccm.200403-307OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 3, August 2004, 288-295

A more recent version of this article appeared on August 1, 2004
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Submitted on March 12, 2004
Accepted on April 30, 2004

T Cell-based Tracking of Multidrug Resistant Tuberculosis Infection following Brief Exposure

Luca Richeldi1, Katie Ewer2, Monica Losi1, Barbara M Bergamini3, Pietro Roversi1, Jonathan Deeks4, Leonardo M Fabbri1, and Ajit Lalvani2*

1 Respiratory Disease Clinic, University of Modena and Reggio Emilia and Azienda Ospedaliera Policlinico di Modena, Modena, Italy, 2 Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom, 3 Paediatric Clinic, University of Modena and Reggio Emilia and Azienda Ospedaliera Policlinico di Modena, Modena, Italy, 4 Centre for Statistics in Medicine, Institute of Health Sciences, Oxford, United Kingdom

* To whom correspondence should be addressed. E-mail: ajit.lalvani{at}ndm.ox.ac.uk.

Molecular epidemiology indicates significant transmission of M. tuberculosis following casual contact with infectious tuberculosis cases. We investigated M. tuberculosis transmission following brief exposure using a T cell-based assay, the enzyme-linked-immunospot (ELISPOT) for interferon-gamma. After childbirth, a mother was diagnosed with sputum smear-positive multidrug-resistant tuberculosis. Forty-one neonates and 47 adults were present during her admission on the maternity unit; eleven weeks later, all underwent tuberculin skin testing (TST) and ELISPOT. We correlated test results with markers of exposure to the index case. The participants, who were asymptomatic and predominantly had no prior tuberculosis exposure, had 6.05 hours mean exposure (range: 0-65 hours) to the index case. Seventeen individuals, including two newborns, were ELISPOT-positive and ELISPOT results correlated significantly with three of four predefined measures of tuberculosis exposure. For each hour sharing room air with the index case, the odds of a positive ELISPOT result increased by 1.05 (95% CI: 1.02-1.09, p=0.003). Only 4 adults were TST-positive and TST results did not correlate with exposure. Thus, ELISPOT, but not TST, suggested quite extensive nosocomial transmission of multidrug-resistant M. tuberculosis following brief exposure. These results help to explain the apparent importance of casual contact for tuberculosis transmission, and may have implications for prevention.
Key words: Tuberculosis, T cell, Tuberculin Skin Test, Contact tracing Nosocomial




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