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Assessment of the novel T-cell activation marker-tuberculosis assay for diagnosis of activetuberculosis in children: a prospective proof-of-concept study.

 

Portevin D1, Moukambi F2, Clowes P2, Bauer A2, Chachage M3, Ntinginya NE3, Mfinanga E4, Said K4, Haraka F4, Rachow A5, Saathoff E5, Mpina M4, Jugheli L6, Lwilla F4, Marais BJ7, Hoelscher M5, Daubenberger C1, Reither K8, Geldmacher C9.

Lancet Infect Dis. 2014 Aug 29. pii: S1473-3099(14)70884-9.

1Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.

2NIMR-Mbeya Medical Research Center, Mbeya, Tanzania; Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich, Germany.

3NIMR-Mbeya Medical Research Center, Mbeya, Tanzania.

4Ifakara Health Institute, Bagamoyo, Tanzania.

5Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich, Germany; German Centre for Infection Research, Partner Site Munich, Germany.

6Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; Ifakara Health Institute, Bagamoyo, Tanzania.

7Children’s Hospital at Westmead, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

8Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; Ifakara Health Institute, Bagamoyo, Tanzania. Electronic address: [email protected]

9Division 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: [email protected]

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-cellactivation 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 tuberculosisculture and performance assessment of the TAM-TB assay. The children were assigned to standardised clinical case classifications based on microbiological and clinical findings.

FINDINGS:

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.

INTERPRETATION:

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.

FUNDING:

European and Developing Countries Clinical Trials Partnership, German Federal Ministry of Education and Research, and Swiss National Science Foundation.

Copyright © 2014 Elsevier Ltd. All rights reserved.

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