Tuberculosis biomarkers discovery: developments, needs, and challenges

Lancet Infect Dis. 2013 Apr;13(4):362-72. doi: 10.1016/S1473-3099(13)70034-3. Epub 2013 Mar 24.

Abstract

Biomarkers are indispensable to the development of new tuberculosis therapeutics and vaccines. The most robust biomarkers measure factors that are essential to the underlying pathological process of the disease being treated, and thus can capture the full effects of many types of interventions on clinical outcomes in multiple prospective, randomised clinical trials. Many Mycobacterium tuberculosis and human biomarkers have been studied over the past decade. Present research focuses on three areas: biomarkers predicting treatment efficacy and cure of active tuberculosis, the reactivation of latent tuberculosis infection, and the induction of protective immune responses by vaccination. Many older, non-specific markers of inflammation, when considered in isolation, do not have sufficient predictive values for clinical use in tuberculosis. Although no new accurate, tuberculosis-specific biomarkers have yet been discovered, substantial progress has been made in some areas. However, the qualification of biomarkers as a surrogate for a clinical endpoint in tuberculosis is very challenging, and, for biomarkers that are non-culture-based, impossible to pursue without the availability of well characterised biobanks containing biospecimens from patients who have had adequate follow-up to establish long-term treatment outcome. We review progress in tuberculosis biomarker development and efforts being made to harness resources to meet future challenges.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, Bacterial / urine
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Biomarkers* / metabolism
  • DNA, Bacterial / isolation & purification
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Fluorodeoxyglucose F18
  • Gene Expression Regulation, Bacterial
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-18 / metabolism
  • Lipopolysaccharides / urine
  • Metabolome
  • MicroRNAs / isolation & purification
  • Multimodal Imaging
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / isolation & purification*
  • Polymerase Chain Reaction
  • Positron-Emission Tomography
  • Predictive Value of Tests
  • Recurrence
  • Reproducibility of Results
  • Tomography, X-Ray Computed
  • Tuberculosis / blood
  • Tuberculosis / diagnosis*
  • Tuberculosis / drug therapy
  • Tuberculosis / immunology
  • Tuberculosis / metabolism
  • Tuberculosis / prevention & control
  • Tuberculosis Vaccines / immunology*

Substances

  • Antigens, Bacterial
  • Antitubercular Agents
  • Biomarkers
  • DNA, Bacterial
  • Interleukin-18
  • Lipopolysaccharides
  • MicroRNAs
  • Tuberculosis Vaccines
  • lipoarabinomannan
  • Fluorodeoxyglucose F18
  • Interferon-gamma