title: Assessment of the novel T-cell activation marker-tuberculosis assay for diagnosis of active tuberculosis in children: a prospective proof-of-concept study.
abstract: BACKGROUND
  The diagnosis of paediatric tuberculosis is complicated by non-specific symptoms, difficult specimen collection, and the paucibacillary nature of the disease. We assessed the accuracy of a novel immunodiagnostic T-cell activation marker-tuberculosis (TAM-TB) assay in a proof-of-concept study to identify children with active tuberculosis.
  
  
  METHODS
  Children with symptoms that suggested tuberculosis were prospectively recruited at the NIMR-Mbeya Medical Research Center in Mbeya, and the Ifakara Health Institute in Bagamoyo, Tanzania, between May 10, 2011, and Sept 4, 2012. Sputum and peripheral blood mononuclear cells were obtained for Mycobacterium tuberculosis culture and performance assessment of the TAM-TB assay. The children were assigned to standardised clinical case classifications based on microbiological and clinical findings.
  
  
  RESULTS
  Among 290 children screened, we selected a subgroup of 130 to ensure testing of at least 20 with culture-confirmed tuberculosis. 17 of 130 children were excluded because of inconclusive TAM-TB assay results. The TAM-TB assay enabled detection of 15 of 18 culture-confirmed cases (sensitivity 83·3%, 95% CI 58·6-96·4). 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. The median time to diagnosis was 19·5 days (IQR 14-45) for culture.
  
  
  CONCLUSIONS
  The sputum-independent TAM-TB assay is a rapid and accurate blood test that has the potential to improve the diagnosis of active tuberculosis in children.
  
  
  BACKGROUND
  European and Developing Countries Clinical Trials Partnership, German Federal Ministry of Education and Research, and Swiss National Science Foundation.
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Damien
authors.initials: D
authors.lastname: Portevin
authors.affiliation: NIMR-Mbeya Medical Research Center, Mbeya, Tanzania; Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich, Germany.
authors.forename: Felicien
authors.initials: F
authors.lastname: Moukambi
authors.affiliation: NIMR-Mbeya Medical Research Center, Mbeya, Tanzania; Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Clowes
authors.affiliation: NIMR-Mbeya Medical Research Center, Mbeya, Tanzania; Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich, Germany.
authors.forename: Asli
authors.initials: A
authors.lastname: Bauer
authors.affiliation: NIMR-Mbeya Medical Research Center, Mbeya, Tanzania.
authors.forename: Mkunde
authors.initials: M
authors.lastname: Chachage
authors.affiliation: NIMR-Mbeya Medical Research Center, Mbeya, Tanzania.
authors.forename: Nyanda E
authors.initials: NE
authors.lastname: Ntinginya
authors.affiliation: Ifakara Health Institute, Bagamoyo, Tanzania.
authors.forename: Elirehema
authors.initials: E
authors.lastname: Mfinanga
authors.affiliation: Ifakara Health Institute, Bagamoyo, Tanzania.
authors.forename: Khadija
authors.initials: K
authors.lastname: Said
authors.affiliation: Ifakara Health Institute, Bagamoyo, Tanzania.
authors.forename: Frederick
authors.initials: F
authors.lastname: Haraka
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich, Germany; German Centre for Infection Research, Partner Site Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rachow
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich, Germany; German Centre for Infection Research, Partner Site Munich, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Saathoff
authors.affiliation: Ifakara Health Institute, Bagamoyo, Tanzania.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Mpina
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; Ifakara Health Institute, Bagamoyo, Tanzania.
authors.forename: Levan
authors.initials: L
authors.lastname: Jugheli
authors.affiliation: Ifakara Health Institute, Bagamoyo, Tanzania.
authors.forename: Fred
authors.initials: F
authors.lastname: Lwilla
authors.affiliation: Children's Hospital at Westmead, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Marais
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich, Germany; German Centre for Infection Research, Partner Site Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoelscher
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Daubenberger
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; Ifakara Health Institute, Bagamoyo, Tanzania. Electronic address: klaus.reither@unibas.ch.
authors.forename: Klaus
authors.initials: K
authors.lastname: Reither
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich, Germany; German Centre for Infection Research, Partner Site Munich, Germany. Electronic address: geldmacher@lrz.uni-muenchen.de.
authors.forename: Christof
authors.initials: C
authors.lastname: Geldmacher
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007159:Immunologic Tests / Q000379:methods*; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000382:microbiology*; D008213:Lymphocyte Activation; D008297:Male; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D011446:Prospective Studies; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D013636:Tanzania; D013997:Time Factors; D014376:Tuberculosis / Q000145:classification / Q000175:diagnosis* / Q000276:immunology
chemical_list: D015415:Biomarkers