Diagnosis of Tuberculosis in Swiss Children

Официальное название

Evaluation and Validation of Novel Immunodiagnostic Tests for Childhood Tuberculosis Infection and Disease in Switzerland. The CITRUS (ChIldhood TubeRcUlosis in Switzerland) Study.

Обзор

1. The primary objective is to improve the sensitivity of novel immunodiagnostic tests for detection of TB disease in children. 2. The secondary objective is to determine biomarkers that discriminate children with TB infection and disease.

Подробное описание

1. This will be done by measuring a variety of parameters in the blood samples and compare them with the current diagnostic gold standard for TB or for culture/NAAT non-confirmed TB cases a consensus case definition is used.

Currently available immunodiagnostic tests (IGRA/TST) will be compared to novel immunodiagnostic tests which will include: * several novel, additional M. tuberculosis-specific Antigens * cytokines that are highly expressed 2. Since there is no diagnostic gold standard for TB infection we will rely on a clinical composite reference standard for diagnosing TB infection. Biomarkers will be determined by:

* including M. tuberculosis-specific antigens that are specifically expressed in either TB infection or disease, * measuring phenotypes and cytokine production of M. tuberculosis-specific cells. * performing NMR Analysis with biofluids in order to identify metabolomic signatures in patients with TB disease and TB infection

Вмешательства

• Диагностический тест Secreted cytokine assay
  Blood collected in a sodium-heparin tube will be used for the assay using novel TB-specific antigens. After incubation the supernatant will be harvested and cryopreserved at -80 °C for further testing of cytokines. Cytokines will be measured using a bead-based multiplex assay reader (MAGPIX, Luminex Crop., Austin, USA).
• Диагностический тест Intracellular cytokine assay
  Blood will be stimulated with recombinant MTB-specific antigens, ESAT-6, CFP-10, positive control or left unstimulated. Following an initial duration of stimulation, Brefeldin-A will be added and the blood incubated for a further 5 hours. White cells will be fixed and cryopreserved at - 80°. Batched analysis within 6 months of cryopreservation will be done using multi-colour flow cytometry.

Первичные конечные точки

• Improvement of immunodiagnostic tests for TB in children. [Срок оценки: 27 months]

Вторичные конечные точки (1)

• Indicative markers identification for TB infection and disease distinction [Срок оценки: 27 months]

Критерии участия

Критерии включения

• all children / adolescents < 18 years of age undergoing evaluation for TB exposure, infection or disease.

Критерии исключения

• children / adolescents with TB infection or disease who have already been started on anti-mycobacterial treatment, children who have been treated for TB previously.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Швейцария · 8 центров

• Kantonspital Aarau — Aarau
• Nina Vaezipour — Basel
• Ospedale Regionale di Bellinzona — Bellinzona
• Inselspital Bern — Bern
• Hôpital des enfants - HUG — Geneva
• Kinserspital Luzern — Lucerne
• Kinderspital St Gallen — Sankt Gallen
• Kinderklinik Zürich — Zurich

Публикации

• Neudecker D, Fritschi N, Sutter T, Lu LL, Lu P, Tebruegge M, Santiago-Garcia B, Ritz N. Evaluation of serological assays for the diagnosis of childhood tuberculosis disease: a study protocol. BMC Infect Dis. 2024 May 10;24(1):481. doi: 10.1186/s12879-024-09359-0. PMID 38730343

Идентификаторы

NCT: NCT03044509 · CITRUS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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