Rapid detection of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells.
There is no reliable means of detecting latent M. tuberculosis infection, and even in patients with active tuberculosis, infection is often unconfirmed. We hypothesized that M. tuberculosis antigen-specific T cells might reliably indicate infection. We enumerated peripheral blood-derived interferon gamma (IFN-gamma)-secreting T cells responding to epitopes from ESAT-6, an antigen that is highly specific for M. tuberculosis complex but absent from BCG, in four groups of individuals. Forty-five of 47 patients with bacteriologically confirmed tuberculosis had ESAT-6-specific IFN-gamma-secreting T cells, compared with four of 47 patients with nontuberculous illnesses, indicating that these T cells are an accurate marker of M. tuberculosis infection. This assay thus has a sensitivity of 96% (95% confidence interval [CI] 92-100) for detecting M. tuberculosis infection in this patient population. By comparison, of the 26 patients with tuberculosis who had a diagnostic tuberculin skin test (TST), only 18 (69%) were positive (p = 0.003). In addition, 22 of 26 (85%) TST-positive exposed household contacts had ESAT-6-specific T cells, whereas zero of 26 unexposed BCG-vaccinated subjects responded. This approach enables rapid detection of M. tuberculosis infection in patients with active tuberculosis and in exposed asymptomatic individuals at high risk of latent infection; it also successfully distinguishes between M. tuberculosis infection and BCG vaccination. This capability may facilitate tuberculosis control in nonendemic regions.
Lalvani
A
A
Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. ajit.lalvani@ndm.ox.ac.uk
Pathan
A A
AA
McShane
H
H
Wilkinson
R J
RJ
Latif
M
M
Conlon
C P
CP
Pasvol
G
G
Hill
A V
AV
D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000032:analysis*; D015704:CD4 Antigens / Q000032:analysis*; D018791:CD4 Lymphocyte Count; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D011446:Prospective Studies; D012016:Reference Values; D012680:Sensitivity and Specificity; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology
D000942:Antigens, Bacterial; D015704:CD4 Antigens; D018984:Epitopes, T-Lymphocyte