# Neutrophil-to-lymphocyte ratios as easy-to-use biomarkers for the diagnosis of active tuberculosis in children and adolescents

## TL;DR

This study shows that the neutrophil-to-lymphocyte ratio (NLR) can be a simple and effective tool for diagnosing active tuberculosis in children and adolescents.

## Contribution

The study identifies a specific logNLR threshold and subgroup-specific associations for diagnosing active tuberculosis in pediatric populations.

## Key findings

- A logNLR threshold of 0.9232 was found to be critical for diagnosing active tuberculosis.
- LogNLR was significantly associated with ATB infection in specific subgroups like males and those with MTB exposure.
- Children with low CD4+ T cell counts and MTB exposure had a much higher risk of active tuberculosis.

## Abstract

The diagnosis of active tuberculosis (ATB) in children and adolescents is limited by non-specific symptoms, paucibacillary infection, and the low sensitivity of traditional tools. These limitations can lead to delayed treatment and increased complications.

This retrospective study recruited 1,080 participants. We performed receiver operating characteristic (ROC) curves to evaluate the diagnostic performance of logarithmic neutrophil-to-lymphocyte ratio (logNLR) for ATB infection. We employed logistic regression, restricted cubic spline (RCS), stratified, and interaction analyses to evaluate the association between logNLR and ATB infection.

The logNLR was significantly associated with ATB infection in the adjusted model (OR = 1.38, 95% CI: 1.01-1.88, P = 0.044). The RCS curve indicated a non-linear relationship between logNLR and ATB infection, with the critical threshold of 0.9232. The breakpoint analyses further confirmed that when logNLR<1.379, the indicator logNLR was positively correlated with ATB infection. Stratified analyses showed logNLR was a reliable predictor in males, 0–7 and 15–17 years old, those with Mycobacterium tuberculosis (MTB) exposure, and participants with CD4+ T cell counts>414 cells/μL or CD8+ T cell counts>238 cells/μL (all P<0.05). Interaction analyses revealed that children with both CD4+ T cell counts ≤414 cells/μL and MTB exposure had a substantially higher ATB risk (OR = 19.31). Similarly, synergies were observed in combinations of CD4+ T cell counts ≤414 cells/μL with 0–14 years old, and MTB exposure with 0–14 years old.

The logNLR is a simple, low-cost, and effective biomarker for diagnosis of ATB in children and adolescents. The critical threshold and breakpoint of logNLR enable precise risk stratification, providing valuable support for early ATB identification in this population.

Graphical abstract on the use of neutrophil-to-lymphocyte ratios (NLR) as biomarkers for diagnosing active tuberculosis in children and adolescents. It includes tables of odds ratios and p-values for different models, a forest plot of subgroup analyses, and histograms depicting the data. A diagram presents the relationship between CD4 count, exposure, and age. Text describes NLR as a simple, cost-effective diagnostic tool.