Overcome low levels of detection limit and choice of antibody affects detection of lipoarabinomannan in pediatric tuberculosis

PLoS One. 2022 Oct 11;17(10):e0275838. doi: 10.1371/journal.pone.0275838. eCollection 2022.

Abstract

The World Health Organization (WHO) emphasizes that tuberculosis (TB) in children and adolescents is often overlooked by healthcare providers and difficult to diagnose. As childhood TB cases rise, finding a diagnostic high in sensitivity and specificity is critical. In this study 91 urine samples from children aged 1-10 years were analyzed for tuberculostearic acid (TBSA) by gas chromatography/mass spectrometry (GC/MS) and capture ELISA (C-ELISA). In C-ELISA the CS35/A194-01 antibody performed very poorly with both curve-based and model-based cutoffs. The area under the ROC curve (AUC) of the CS35 OD450 values was only 0.60. Replacing the capture antibody with BJ76 gave a better performance in both sensitivity and specificity (AUC = 0.95). When these samples were analyzed by GC/MS, 41 classified as 'probable/possible' for TB were distinctly TBSA positive with ten samples having <3 ng/mL LAM. However, from the 50 samples with 'unlikely' TB classification, 36 were negative but 7 had >3 ng/mL and were designated as LAM positive. This experimental assay assessment study signifies that i) the antibody pair CS35/A194-01 that has been successful for adult active TB diagnosis is not adequate when LAM level is low as in pediatric TB; ii) no one mAb appears to recognize all TB-specific LAM epitopes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies
  • Child
  • Epitopes
  • HIV Infections*
  • Humans
  • Limit of Detection
  • Lipopolysaccharides
  • Mycobacterium tuberculosis*
  • Sensitivity and Specificity
  • Tuberculosis* / diagnosis

Substances

  • Antibodies
  • Epitopes
  • Lipopolysaccharides
  • lipoarabinomannan