Distinguishing Between Active And Latent TB

A panel of cytokines and chemokines could act as a marker that accurately distinguishes active from latent TB infections.

AsianScientist (Jan. 14, 2015) – Doctors treating tuberculosis (TB) now have another tool in their arsenal against the disease: a test that is able to distinguish between patients with an active infection and those with latent TB infections (LTBI). The study describing the new test has been published in the Journal of Molecular Diagnostics.

“The World Health Organization reports that one third of the world’s population is latently infected with Mycobacterium tuberculosis (MTB). It has been estimated that in 5 to 10 percent of LTBI individuals, the infection progresses to an active disease state, and the conversion rate is greater in immunosuppressed individuals such as those with HIV,” explains Dr. Lee Hyeyoung, of the Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University.

“Therefore, rapid diagnostic tests and effective treatment of LTBI are important to reduce and control the TB burden.”

At present, neither the tuberculin skin test (TST) nor interferon-gamma release assays (IGRAs) are capable of distinguishing active from latent infection or predicting the chance of reactivation.

In previous work, the researchers quantified interferon-γ (IFN-γ) mRNA expression levels using real-time PCR (RT-PCR) as an indicator of IFN-γ levels in an IGRA test. However, the results of IFN-γ RT-PCR showed poor specificity and sensitivity, and the test could not be used to distinguish between active and latent TB.

With these results in mind, the investigators developed a multiple-target RT-PCR TaqMan assay that could target eight human immune markers, including Th1-type factors, Th2-type cytokines, and IFN-γ-induced chemokines. MTB-specific, antigen-dependent mRNA expression levels were then measured in blood samples from 28 patients with active pulmonary TB, 22 with LTBI and 29 non-TB controls.

When five of the human immune markers were evaluated individually, three were found to be suitable for detecting active pulmonary TB: TNF-α, IL-2R, and CXCL10, with sensitivities ranging from 96.43 to 100 percent. Two individual markers, IL-2R and CXCL10, were able to detect LTBI, with sensitivities of 86.36 and 81.82 percent, respectively.

To optimize sensitivity, Lee and her colleagues used the assay to simultaneously detect multiple targets. They found that the combination of TNF-α, IL-2R, CSCL9, and CSCL10 could differentiate active pulmonary TB from healthy controls (P <0.001) and LTBI from healthy controls (P <0.01). More importantly, the combination could differentiate those with active pulmonary TB from those with latent infection (P <0.01). The combination had a sensitivity of 100 percent for active disease and 81.82 percent for LTBI.

“These results imply that a combination of suitable single markers is very useful for the efficient diagnosis and differentiation of MTB infection,” says Lee.

The article can be found at: Kim et al. (2015) Diagnostic Performance of a Cytokine and IFN-γ–Induced Chemokine mRNA Assay after Mycobacterium tuberculosis–Specific Antigen Stimulation in Whole Blood from Infected Individuals.

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Source: Elsevier Health Sciences; Photo: Shutterstock.
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