TAM-TB: New sputum-independent diagnostic tool for tuberculosis in children

Today, The Lancet Infectious Diseases published the results of a sputum-independent assay developed in Tanzania that is able to diagnose active tuberculosis in children. The T cell activation (TAM)-TB) assay is the first immunodiagnostic tool which can detect active tuberculosis disease in children with sensitivity similar to culture and with excellent specificity in a tuberculosis-endemic setting.

The assay measures the CD27 phenotype of CD4+ T cells producing IFNg in response to Mycobacterium tuberculosis antigens using a standard intracellular cytokine staining procedure for flow cytometry.

The TAM-TB assay was tested in a proof-of concept study carried out between May 2011 and February 2013 in 290 children that presented symptoms of tuberculosis were recruited and followed-up at the National Institute for Medical Research (NIMR)-Mbeya Medical Research Center in Mbeya and the Ifakara Health Institute in Bagamoyo, Tanzania.

The assay enabled the detection of 15 of 18 culture-confirmed cases (sensitivity 83.3%, 95% CI, 58.6–96.3). Specificity was 96.8% (95% CI 89.0–99.6) in the cases that were classified as not tuberculosis (n=63), with little effect from latent tuberculosis infection. The TAM-TB assay identified five additional patients with highly probable or probable tuberculosis, in whom M. tuberculosis was not isolated.

TB CHILD

TB CHILD was conducted by research teams headed by Dr Fred Lwilla (Ifakara Health Research and Development Centre, Tanzania) and Dr Klaus Reither (Swiss Tropical and Public Health Institute, Switzerland). The TAM-TB assay was developed by Dr Christof Geldmacher (Ludwig-Maximilians University of Munich (LMU), Germany) and jointly evaluated by the Department for Infectious Diseases, Tropical Medicine, University of Munich, Germany; the Swiss Tropical and Public Health Institute, Switzerland; the NIMR-Mbeya Medical Research Center and the Ifakara Health Institute, Tanzania.

EDCTP was the main funder of this study which also received funding from Aispo-Nsambya Hospital (Uganda/Italy); Bundesministerium für Bildung und Forschung (BMBF, Germany); FIND (Switzerland); Fondazione Centro San Raffaele del Monte Tabor (Italy); Ministry of Foreign Affairs – Italian Directorate for Development Cooperation (Italy); LMU-Klinikum of the University of Munich (Germany); State Secretariat for Education and Research SER/Swiss National Science Foundation (Switzerland); and the Swiss Agency for Development and Cooperation (SDC, Switzerland)

Publication

The Lancet Infectious Diseases (Vol.14,10, October 2014): Assessment of the novel T-cell activation marker–tuberculosis assay for diagnosis of active tuberculosis in children: a prospective proof-of-concept study