Mumbai researchers use blood samples to diagnose pulmonary TB, MDR-TB

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Dr. Deepak Modi and other researchers have found two microRNAs at abnormal amounts in people with drug-sensitive TB and MDR-TB.

Mumbai-based researchers have identified two microRNA biomarkers present in serum samples that could potentially be used for TB diagnosis and TB disease prognosis. It could be used both for drug-sensitive pulmonary TB and MDR-TB diagnosis. The results were published in the journal Tuberculosis.

Compared with controls, the microRNA miR-16 level in 30 newly diagnosed drug-sensitive pulmonary TB patients was 5-6 times higher and the miR-155 level was about two times lower.

Of the 30 patients studied, serum samples collected from 10 patients were tested for the two microRNAs at the time of diagnosis and after the completion of treatment. “The levels of miR-16 and miR-155 returned to normal level once the patients completed the treatment,” says Dr. Deepak Modi from the National Institute for Research in Reproductive Health, Mumbai and one of the authors of the paper.

The changes in the levels of the two microRNAs during the course of treatment are, however, not known as samples were not collected at different time points. “We plan to undertake a longitudinal study soon,” he says.

MDR-TB diagnosis

The levels of these two microRNAs are very different in people with MDR-TB compared with drug-sensitive pulmonary TB and healthy individuals. Serum samples from 19 MDR-TB patients were studied by the researchers.

The miR-16 shows better predictive value than miR-155 in both drug-sensitive pulmonary TB and MDR-TB cases.If the miR-16 is elevated 5-6 times in people with drug-sensitive TB, it is two times lower than the normal level in people with MDR-TB. In the case of miR-155 the reduction is only slightly less compared with drug-sensitive TB (it is intermediate between drug-sensitive TB patients and normal level). “We don’t know why the two microRNAs behave differently in MDR-TB patients compared with drug-sensitive TB,” Dr. Modi says.

The use of these biomarkers may expedite the diagnosis of MDR-TB. In India, patients are usually first treated with drug-sensitive TB drugs. It is only when they do not show any improvement even after a couple of months of medication is MDR-TB suspected. “In patients undergoing TB treatment if the miR-16 level is lower or if the miR-155 level is not increasing then MDR-TB should be suspected,” says Dr. Modi.

“The miR-16 shows better predictive value than miR-155 in both drug-sensitive pulmonary TB and MDR-TB cases,” says Vishal Wagh from the National Institute for Research in Reproductive Health, Mumbai and the first author of the paper.

Advantage blood test

“The blood-based TB diagnosis using these biomarkers has great advantages. Even in adults a good number of them are unable to give sputum samples. Children, especially younger children, do not produce sputum samples. So diagnosis of pulmonary TB in these cases is difficult when we rely on sputum samples,” says Dr. Chander Puri, Pro-Vice Chancellor of MGM Institute of Health Science, Mumbai and who was not involved in the study.

The researchers are expanding the study to cover a larger population of drug-sensitive, MDR-TB and extra pulmonary TB patients. “There is no reason why the biomarkers should not be present in the blood even when TB is extra-pulmonary,” says Dr. Puri.

The difference 

The serum test developed by the NIRRH researchers is different from the serological test for TB, which is banned both by the World Health Oraginsation and India’s RNTCP. While the banned serological test is based on antibody response for diagnosing active tuberculosis (both pulmonary and extra-pulmonary), the one now being tested relies on microRNAs.

Published in The Hindu on November 6, 2016

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