Combination of serological and cytokine release assays for improved diagnosis of childhood tuberculosis in Zambia (PROMISE-TB)

•Diagnostic gaps for childhood tuberculosis are significant in low-resource countries.•Statistical analysis selected antigen 85B antibodies, interleukin-2/interferon-γ ratio, and monokine induced by interferon-γ for the scoring system.•Combination of serological and T-cell markers could enhance chil...

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Published in:	International journal of infectious diseases Vol. 148; p. 107248
Main Authors:	Tuaillon, Edouard, Mwyia, Mwiya, Bollore, Karine, Pisoni, Amandine, Rubbo, Pierre-Alain, Richard, Matthias, Kremer, Laurent, Tonga, Maria M.W., Chanda, Duncan, Peries, Marianne, Vallo, Roselyne, Eymard-Duvernay, Sabrina, D'Ottavi, Morgana, Kankasa, Chipepo, de Perre, Philippe Van, Moles, Jean-Pierre, Nagot, Nicolas
Format:	Journal Article
Language:	English
Published:	Canada Elsevier Ltd 01-11-2024 Elsevier
Subjects:	Africa Children HIV Human health and pathology IFN-gamma release assay (IGRA) Immunology Infectious diseases Life Sciences Tuberculosis Tuberculosis Children HIV IFN-gamma release assay (IGRA) Africa Human Immunodeficiency Virus (HIV)
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Summary:	•Diagnostic gaps for childhood tuberculosis are significant in low-resource countries.•Statistical analysis selected antigen 85B antibodies, interleukin-2/interferon-γ ratio, and monokine induced by interferon-γ for the scoring system.•Combination of serological and T-cell markers could enhance childhood tuberculosis screening. The diagnostic gaps for childhood tuberculosis (TB) remain considerable in settings with high TB incidence and resource constraints. We established and evaluated the performance of a scoring system based on a combination of serological tests and T-cell cytokine release assays, chosen for their ability to detect immune responses indicative of TB, in a context of high prevalence of pediatric HIV infection. We enrolled 628 consecutive children aged ≤15 years, admitted for TB suspicion. Multiple cytokine levels in QuantiFERON Gold In-Tube supernatants and antigen 85B (Ag85B) antibodies were assessed in children who tested positive with either Xpert TB or mycobacterial culture. The results were compared with those of control children. Among the biomarkers most strongly associated with TB, random forest classification analysis selected Ag85B antibodies, interleukin-2/interferon-γ ratio, and monokine induced by interferon-γ for the scoring system. The receiver operating characteristic curve derived from our scoring system showed an area under the curve of 0.95 (0.91-0.99), yielding 91% sensitivity and 88% specificity. The internal bootstrap validation gave the following 95% confidence intervals for the score performance: sensitivity 71%-97% and specificity 79%-99%. This study suggests that supplementing the QuantiFERON assay with a combination of serological and T-cell markers could enhance childhood TB screening regardless of HIV status and age. Further validation among the target population is necessary to confirm the performance of this scoring system. [Display omitted]
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1201-9712 1878-3511 1878-3511
DOI:	10.1016/j.ijid.2024.107248