<i>MYCOBACTERIUM TUBERCULOSIS</i>‐SPECIFIC CYTOKINE BIOMARKERS FOR THE DIAGNOSIS OF CHILDHOOD <scp>TB</scp> IN A <scp>TB</scp>‐ENDEMIC SETTING
Tuberculosis (TB) is responsible for the greatest number of deaths from a single infectious disease worldwide. The proportion of children infected with latent TB infection (LTBI) who progress to active disease is significantly greater than in adults, . Diagnosis of LTBI remains a significant challenge, especially in children, . It currently relies on a positive immunodiagnostic test result, namely a tuberculin skin test (TST) and/or interferon (IFN)-γ release assay (IGRA). However, these tests have limitations in diagnosing TB, particularly in children, . The World Health Organization (WHO) has called for the development of new diagnostic tests to address these shortcomings and allow more accurate diagnosis of TB in children. Biomarkers other than IFN-γ have shown promise for the diagnosis of both LTBI and active TB, et al. (10 authors)
Journal of Paediatrics and Child Health · 2020-05
Abstract
The tuberculin skin test and interferon-gamma release assays have limitations in diagnosing tuberculosis (TB), particularly in children.This study investigated the performance of candidate M. tuberculosis-specific cytokine biomarkers for TB in children in a TB-endemic setting.A total of 237 children with a household contact with smear-positive pulmonary TB were recruited.Importantly, a group of children with illnesses other than TB (sick controls) was included to assess specificity.Median IFN-ɣ, IL-1ra, IL-2, IL-13, IP-10, MIP-1β and TNF-α responses were significantly higher in children with active TB and latent TB infection (LTBI) than in both healthy and sick control children.Three of these cytokines -IL-2, IL-13 and IP-10 -showed better performance characteristics than IFN-ɣ, with IL-2 achieving positive and negative predictive values of 97.7% and 90.7%, respectively.Furthermore, IL-1ra and TNF-α responses differed significantly between active TB and LTBI cases, suggesting that they may be stage-specific biomarkers.Our data indicate that incorporating these biomarkers into future blood-based TB assays could result in substantial performance gains.
MeSH terms
- Medicine
- Mycobacterium tuberculosis
- Tuberculosis
- Immunology
- Cytokine