title: T cell-based tracking of multidrug resistant tuberculosis infection after brief exposure.
abstract: Molecular epidemiology indicates significant transmission of Mycobacterium tuberculosis after casual contact with infectious tuberculosis cases. We investigated M. tuberculosis transmission after brief exposure using a T cell-based assay, the enzyme-linked-immunospot (ELISPOT) for IFN-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; 11 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 four 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 after brief exposure. These results help to explain the apparent importance of casual contact for tuberculosis transmission, and may have implications for prevention.
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom.
authors.forename: Luca
authors.initials: L
authors.lastname: Richeldi
authors.forename: Katie
authors.initials: K
authors.lastname: Ewer
authors.forename: Monica
authors.initials: M
authors.lastname: Losi
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Bergamini
authors.forename: Pietro
authors.initials: P
authors.lastname: Roversi
authors.forename: Jonathan
authors.initials: J
authors.lastname: Deeks
authors.forename: Leonardo M
authors.initials: LM
authors.lastname: Fabbri
authors.forename: Ajit
authors.initials: A
authors.lastname: Lalvani
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000627:therapeutic use; D003428:Cross Infection / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000635:transmission*; D018562:Disease Transmission, Infectious / Q000145:classification*; D018432:Drug Resistance, Multiple / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000150:complications / Q000276:immunology; D007231:Infant, Newborn; D007371:Interferon-gamma; D008297:Male; D009169:Mycobacterium tuberculosis; D016017:Odds Ratio; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014374:Tuberculin Test; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000635:transmission*
chemical_list: D001500:BCG Vaccine; D007371:Interferon-gamma