Identification of Mycobacterium tuberculosis Infection in Infants and Children With Partial Discrimination Between Active Disease and Asymptomatic Infection

Frontiers in Pediatrics

article

Alexandra Dreesman¹  Mahavir Singh³  Camille Locht⁴  Françoise Mouchet²  Françoise Mascart¹  Violette Dirix¹  Kaat Smits¹  Véronique Corbière¹  Anne Van Praet¹  Sara Debulpaep²  Iris De Schutter⁹  Mariet-Karlijn Felderhof⁹  Anne Malfroot⁹ 

[1] Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles;Pediatric Department;Lionex Diagnostics and Therapeutics;INSERM;CNRS;Université de Lille;Centre d'Infection et d'Immunité de Lille, Institut Pasteur de Lille;Immunobiology Clinic, Hôpital Erasme;Department of Pediatric Pulmonology, Cystic Fibrosis Clinic and Pediatric Infectious Diseases, Universitair Ziekenhuis Brussel

关键词: Mycobacterium tuberculosis;    children;    diagnosis;    latent infection;    active tuberculosis;    lymphoblasts;    FASCIA;    dendritic cells;   

DOI  :  10.3389/fped.2019.00311

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background: Improved diagnostic tests are needed for the early identification of Mycobacterium tuberculosis- infected young children exposed to an active TB (aTB) index case. We aimed to compare the diagnostic accuracy of new blood-based tests to that of the tuberculin skin test (TST) for the identification of all infected children and for a potential differentiation between aTB and latent TB infection (LTBI). Methods: 144 children exposed to a patient with aTB were included, and those who met all inclusion criteria (130/144) were classified in three groups based on results from classical investigations: non-infected (NI: n = 69, 53%, median age 10 months), LTBI ( n = 28, 22%, median age 96 months), aTB disease ( n = 33, 25%, median age 24 months). The first whole blood assay consisted of a 7-days in vitro stimulation of blood with four different mycobacterial antigens (40 μl/condition), followed by flow cytometric measurement of the proportions of blast cells appearing among lymphocytes as a result of their specific activation. Thresholds of positivity were determined by Receiver Operating Characteristic (ROC) curve analysis (results of NI children vs. children with LTBI/aTB) in order to identify infected children in a first stage. Other cut-offs were determined to discriminate subgroups of infected children in a second step (results from children with aTB/LTBI). Analysis of blood monocytes and dendritic cell subsets was performed on 100 μl of blood for 25 of these children as a second test in a pilot study. Results: Combining the results of the blast-induced CD3 + T lymphocytes by Heparin-Binding Haemagglutinin and by Culture Filtrate Protein-10 identified all but one infected children (sensitivity 98.2% and specificity 86.9%, compared to 93.4 and 100% for the TST). Further identification among infected children of those with aTB was best achieved by the results of blast-induced CD8 + T lymphocytes by purified protein derivative (sensitivity for localized aTB: 61.9%, specificity 96.3%), whereas high proportions of blood type 2 myeloid dendritic cells (mDC) were a hallmark of LTBI. Conclusions: New blood-based tests requiring a very small volume allow the accurate identification of M. tuberculosis -infected young children among exposed children and are promising to guide the clinical classification of children with aTB or LTBI.

【 授权许可】

CC BY