A Model Based on the Combination of IFN-γ, IP-10, Ferritin and 25-Hydroxyvitamin D for Discriminating Latent From Active Tuberculosis in Children.

Patricia Comella-Del-Barrio,Tomas M Perez-Porcuna,Jose Dominguez,Raquel Villar-Hernández,Beatriz Sallés Mingels,Carlos Ascaso,Lydia Canales Aliaga,Mariette Doresca Jean Coute,Irene Latorre,Margareth Narcisse,Jacqueline Gautier,Rosa Abellana

doi:10.3389/fmicb.2019.01855

Abstract

In recent years, pediatric research on tuberculosis (TB) has focused on addressing new biomarkers with the potential to be used as immunological non-sputum-based methods for the diagnosis of TB in children. The aim of this study was to characterize a set of cytokines and a series of individual factors (ferritin, 25-hydroxyvitamin D [25(OH)D], parasite infections, and nutritional status) to assess different patterns for discriminating between active TB and latent TB infection (LTBI) in children. The levels of 13 cytokines in QuantiFERON-TB Gold In-Tube (QFT-GIT) supernatants were analyzed in 166 children: 74 with active TB, 37 with LTBI, and 55 uninfected controls. All cytokines were quantified using Luminex or ELISA. Ferritin and 25(OH)D were also evaluated using CLIA, and Toxocara canis Ig-G antibodies were detected with a commercial ELISA kit. The combination of IP-10, IFN-γ, ferritin, and 25(OH)D achieved the best diagnostic performance to discriminate between active TB and LTBI cases in children in relation to the area under receiver operating characteristic (ROC) curve 0.955 (confidence interval 95%: 0.91–1.00), achieving optimal sensitivity and specificity for the development of a new test (93.2 and 90.0%, respectively). Children with TB showed higher ferritin levels and an inverse correlation between 25(OH)D and IFN-γ levels. The model proposed includes a combination of biomarkers for discriminating between active TB and LTBI in children to improve the accuracy of TB diagnosis in children. This combination of biomarkers might have potential for identifying the onset of primary TB in children.

Highlights

At least one-quarter of the world’s population is infected with Mycobacterium tuberculosis (World Health Organization [WHO], 2018a)
Infants and young children have a higher risk of progressing to TB following a primary M. tuberculosis infection, usually due to a child being exposed to an infectious adult with active TB (Augustynowicz-Kopecet al., 2012) and to the development of severe forms of the disease (Marais et al, 2004)
A total of 305 children suspected of having latent TB infection (LTBI) or TB were screened in the hospital, whereas a total of 96 uninfected children were screened in a school and a kindergarten

Summary

Introduction

At least one-quarter of the world’s population is infected with Mycobacterium tuberculosis (World Health Organization [WHO], 2018a). Childhood tuberculosis (TB) represents at least 10% of the burden of the disease worldwide, being one of the most significant causes of childhood morbidity and mortality (World Health Organization [WHO], 2018b). Estimations show that there are far more children with TB globally than previously thought, with the majority being undiagnosed and untreated (Dodd et al, 2017). Infants and young children have a higher risk of progressing to TB following a primary M. tuberculosis infection, usually due to a child being exposed to an infectious adult with active TB (Augustynowicz-Kopecet al., 2012) and to the development of severe forms of the disease (Marais et al, 2004). Household detection of index TB cases, together with early detection of the infection and TB disease, followed by a prompt treatment, are fundamental in preventing disease progression (Dodd et al, 2018)

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