Current tuberculosis diagnostic tools & role of urease breath test

Abstract

Tuberculosis (TB) remains a significant public health issue worldwide especially in developing countries, where the disease is endemic, and effective TB diagnostic as well as treatment-monitoring tools are serious barriers to defeating the disease. Detection of pathogen-specific metabolic pathways offers a potential alternative to current methods, which focus on bacterial growth, bacterial nucleic acid amplification, or detection of host immune response to the pathogen. Metabolic pathway detection may provide rapid and effective new tools for TB that can improve TB diagnostics for children and HIV infected patients. Metabolic breath tests are attractive because these are safe, and provide an opportunity for rapid point of care diagnostics and tool for drug efficacy evaluation during clinical trials. Our group has developed a rabbit urease breath test model to evaluate the sensitivity and the specificity of urease based detection of Mycobacterium tuberculosis. TB infected rabbits were given stable isotopically labelled urea as the substrate. The urea tracer was metabolized to 13 C-CO 2 and detected in exhaled breaths using portable infrared spectrometers. The signal correlated with bacterial load both for primary diagnostics and treatment monitoring. Clinical trials are currently ongoing to evaluate the value of the test in clinical management settings. Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and treatment response.

Fig. 1

The 22 high burden TB countries in the word (Source: Kaiser Family Foundation, www.GlobalHealthFacts.org, based on WHO, Global tuberculosis control 2010, Slide Date: March 04, 2011; reprinted with permission from the Henry J. Kaiser Family Foundation, California, USA).

Fig. 2

Labelled urea is degraded by H. pylori in the stomach whereby the labelled CO₂ produced is then exhaled and detected in the lungs. The detection of the labelled CO₂ implies infection with H. pylori.

Fig. 3

UBT signal increased in rabbits infected by M. tuberculosis and declined significantly in response to partial TB therapy. Source: Ref 29 (Reprinted with permission).

Fig. 4

Materials to get exhaled air breath from anaesthetized rabbits and transfer into Breathek™ air bag.