{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T14:47:16Z","timestamp":1784040436541,"version":"3.55.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Diagnosis of tuberculosis (TB) in children remains challenging due to unspecific clinical presentation and low bacillary load. In low TB incidence countries, most cases are diagnosed by a contact screening strategy after exposure to an index TB case. Due to the severity of TB in young children, the priority is to determine whether a child is infected or not, whereas differential diagnosis between active TB (aTB) and latent TB constitutes a second step. In Belgium, a low TB incidence country, we prospectively included 47 children with a defined <jats:italic>M. tuberculosis<\/jats:italic> infection status (12 children with aTB, 18 with latent TB, and 17 uninfected) (exploratory cohort), and determined the optimal combinations of cytokines secreted by their peripheral blood mononuclear cells in response to a 5-days <jats:italic>in vitro<\/jats:italic> stimulation with four different mycobacterial antigens, in an attempt to classify the children according to their infectious status. Correct identification of all infected children was obtained by several combinations of two purified protein derivative (PPD)-induced cytokines (IFN-\u03b3 and either GM-CSF, MIP-1\u03b1, sCD40L or TNF-\u03b1), or by combining PPD-induced IFN-\u03b3 with culture-filtrate protein-10 (CFP-10)-induced TNF-\u03b1. Alternatively, combining CFP-10-induced TNF-\u03b1 and IP-10 with heparin-binding haemagglutinin (HBHA)-induced-IFN-\u03b3 was more effective in testing recently BCG-vaccinated children or those suspected to be infected with non-tuberculous mycobacteria, providing a correct classification of 97% of the <jats:italic>M. tuberculosis-<\/jats:italic>infected children. This combination also correctly classified 98% of the children from a validation cohort comprising 40 <jats:italic>M. tuberculosis<\/jats:italic> infected children and 20 non-infected children. Further differentiation between aTB and children with latent TB was more difficult. Combining ESAT-6-induced MIP1-\u03b1 and IP-10, CFP-10-induced MIG, and HBHA-induced MIG provided a correct classification of 77% of the children from the exploratory cohort but only of 57.5% of those from the validation cohort. We conclude that combining the measurement of 2\u20134 cytokines induced by three different mycobacterial antigens allows an excellent identification of <jats:italic>M. tuberculosis-<\/jats:italic>infected children, whereas differentiating children with aTB from those with latent TB remains far from perfect.<\/jats:p>","DOI":"10.3389\/fimmu.2021.575519","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T04:41:42Z","timestamp":1615783302000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Specific Host Signatures for the Detection of Tuberculosis Infection in Children in a Low TB Incidence Country"],"prefix":"10.3389","volume":"12","author":[{"given":"Alexandra","family":"Dreesman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Corbi\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Libin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Racap\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Collart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahavir","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Locht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Mascart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violette","family":"Dirix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"B1","unstructured":"WHO Global Tuberculosis Report2019"},{"key":"B2","unstructured":"Roadmap Towards Ending TB in Children and Adolescents2018"},{"key":"B3","doi-asserted-by":"publisher","first-page":"S29","DOI":"10.1093\/infdis\/jiu821","article-title":"Defining the needs for next generation assays for tuberculosis","volume":"211","author":"Denkinger","year":"2015","journal-title":"J. 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