Current tests for tuberculosis are not sensitive enough, resulting in many cases going unrecognized and untreated. However, the chances of survival and quality of life are greatly improved, and the risk of transmission decreases, if tuberculosis can be identified and treated early. Identifying a tuberculosis biomarker could address a significant global health problem.
Patients with pulmonary tuberculosis are the greatest source for transmission. Diagnosis typically relies on cultures from sputum. However, cultures are not usually helpful as a diagnostic because Mycobacterial tuberculosis is a slow-growing organism. It can take 2 to 3 months to become visible on culture medium. Additionally, pulmonary infiltrates are not specific indicators of tuberculosis, and many of those with tuberculosis have normal chest radiographs, making reliance on radiology futile.
Unfortunately, tuberculosis cases are growing worldwide, at a rate of 1% per annum, indicating a need for better diagnostics. Tuberculosis is most frequent in areas where HIV infection is common.1
In 2011, Shui et al.2 were able to show that it is possible to use mycobacterial lipids as a tuberculosis biomarker by using electrospray ionization tandem mass spectrometry. This approach allowed the investigators to find a subclass of mycolic acids, extracted directly from patients’ sputum and mouse lungs, which can be used as a tuberculosis biomarker. Most importantly, the results showed a distinct difference between active tuberculosis and nonactive or cured tuberculosis. Additionally, this method was rapid because it was not necessary to culture and showed high sensitivity and selectivity in sputum and lung tissue.
Casrouge et al.3 propose an alternate methodology for identifying a tuberculosis biomarker. The investigators used an already validated assay (Thermo Scientific) to find a tuberculosis biomarker, CXCL10. They presented new tools to discriminate between its active and NH2-terminus and cleaved forms. Immune responses to infection, stress, or tissue damage induce chemokine activity. It has already been reported to be present in many viral, bacterial, and parasitic infections. CXCL10 has also been reported as a prognostic or diagnostic marker with potential applications in patient management. Although the methodology employed by investigators used the hepatitis C virus, tuberculosis infection also exhibits a CXCL10 response. The assay described can be applied to other chronic inflammatory diseases, including as a tuberculosis biomarker for managing disease.
Although DOTS has provided a framework for tuberculosis control, it remains a major public health problem. This is, in part, fueled by co-infection with HIV in some African regions. Globally, tuberculosis is responsible for more years of life lost than any other infectious disease, except AIDS and malaria.4
Biomarkers could improve diagnosis and management of tuberculosis. In turn, the spread through the community may be curbed.
1. Harries, A.D. and Dye, C. (2006) ‘Tuberculosis’, Annals of Tropical Medicine and Parasitology, 100 (5), (pp. 415-431)
2. Shui, G., et al. (2011) ‘Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice‘, EMBO Molecular Medicine, 4 (1), (pp. 27-37)
3. Casrouge, A., et al. (2011) ‘Discrimination of agonist and antagonist forms of CXCL10 in biological samples’, Clinical and Experimental Immunology, 167 (1), (pp. 137-148)
4. Corbett, E.L., et al. (2003) ‘The growing burden of tuberculosis: Global trends and interactions with the HIV epidemic‘, Archives of Internal Medicine, 163 (9), (pp. 1009-1021)