title: A novel assay detecting recall response to Mycobacterium tuberculosis: Comparison with existing assays.
abstract: A strategy to reduce the burden of active TB is isoniazid preventive therapy for latent TB infection (LTBI). However, current assays used to diagnose LTBI all have limitations. In these proof of concept studies, we compared the agreement of a novel flow cytometry assay detecting CD25/CD134 co-expression with QuantiFERON-TB Gold In-Tube (QFN-GIT) and Tuberculin skin test (TST) in the detection of recall immune response to TB. The CD25/CD134 assay, QFN-GIT and TST were performed on 74 participants referred for TB screening in Sydney and on 50 participants with advanced HIV infection (CD4 ≤ 350 × 10(6) cells/L) in Bangkok. The agreement between CD25/CD134 assay and QFN-GIT was 93.2% (Kappa 0.631 95% CI 0.336-0.926) in Sydney and 90% (Kappa 0.747 95% CI 0.541-0.954) in Bangkok. Discordant results occurred around the cut off of both tests. The agreement between CD25/CD134 assay and TST was 73.6% (Kappa 0.206 95% CI 0.004-0.409) in Sydney and 84% (Kappa 0.551 95% CI 0.296-0.806) in Bangkok. The CD25/CD134 assay showed good agreement with QFN-GIT in detecting recall response to TB both in well and less resourced setting as well as in persons with advanced HIV infection. Further study into the performance of this assay is thus warranted.
authors.affiliation: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, NSW, Australia. d.hsu@amr.org.au
authors.forename: Denise C
authors.initials: DC
authors.lastname: Hsu
authors.forename: John J
authors.initials: JJ
authors.lastname: Zaunders
authors.forename: Marshall
authors.initials: M
authors.lastname: Plit
authors.forename: Craig
authors.initials: C
authors.lastname: Leeman
authors.forename: Susanna
authors.initials: S
authors.lastname: Ip
authors.forename: Thatri
authors.initials: T
authors.lastname: Iampornsin
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Pett
authors.forename: Michelle
authors.initials: M
authors.lastname: Bailey
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: Sasiwimol
authors.initials: S
authors.lastname: Ubolyam
authors.forename: Anchalee
authors.initials: A
authors.lastname: Avihingsanon
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015658:HIV Infections / Q000150:complications / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D055985:Latent Tuberculosis / Q000150:complications / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D053262:Receptors, OX40 / Q000378:metabolism; D015203:Reproducibility of Results; D014374:Tuberculin Test; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D015415:Biomarkers; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human; D007371:Interferon-gamma