With India chasing the target of eliminating tuberculosis by 2025, five years ahead of the global sustainable development goal, Union Health Minister Mansukh Mandaviya recently announced a “Made in India” TB skin test to be used in the disease control mission.
The test, which will be manufactured and marketed as Cy-TB by the Serum Institute of India, is a slightly tweaked version of a century-old test where a protein extract of tuberculosis bacteria was injected under the skin to test for reaction to the infection .
Why is the test necessary? Because it can help detect latent tuberculosis infections. At present, the national TB program focuses solely on detecting and treating those with an active infection, meaning those who have already started showing symptoms. There are two methods of detecting an active infection – microscopy, where a lab technician literally checks the patient sample under the microscope, or the nucleic acid amplification test, where the genetic material of the pathogen is amplified and its segments are automatically matched by the machine to give a positive result (just like an RT-PCR test for COVID-19). These tests, however, use a patient’s sputum sample and cannot detect a latent infection.
It is estimated that almost one-fourth of the world’s population carries the TB bacteria in the latent form, but some of them may go on to develop an active infection, especially if their immune system gets compromised by other illnesses or medication. Although people with latent TB cannot spread the infection, they act as a reservoir for the pathogen to persist in humans.
“In India, anywhere between 30 and 40 per cent of the population has latent TB infection and five to 10 per cent will go on to develop active TB. Even a small percentage in India translates to crores of people. In order to achieve the elimination target, other than testing and treating those with an infection, we also have to prevent new infections,” says Dr Rajendra Joshi, deputy Director-General, National TB Elimination Programme.
For detecting the latent TB cases, either a blood test or a skin test can be performed. The problem with the hundred-year-old skin test, also known as Mantoux test, is that it also shows positive for those who have received the BCG vaccine for tuberculosis. BCG vaccine is a part of the routine immunization for children in India, making the test useless.
“Since most people in India have received the BCG vaccine, the 5mm cut-off for the wheal (skin bump) used by the world does not work in India. We have to keep the cut-off at 10 mm and this might be leading to us missing several cases. It also does not work very well with those who have HIV,” said Dr Joshi. With the c–TB test using a specific infection-causing part of the TB, the 5 mm cut-off for a test to be positive can be followed for all, including HIV patients.
The test will be used to detect latent tuberculosis in contacts of a patient with active TB and among those with conditions such as HIV and cancers who are at a higher risk of developing active TB.
Not only does the c-TB test produce more accurate results – as accurate as the lab-based blood test – it also does not need extracts from the actual bacteria making the manufacturing easier.
It is relatively cheaper than the blood tests for latent TB and does not require laboratory facilities. The skin test can be used to screen for TB in the community.
The new test, instead of using a protein extract of the entire bacterium, measures the body’s immune response to two of the antigens or infectious parts of tuberculosis — EAST-6 and CFP10.
To perform the test, the compound is injected just under the skin on the arm which forms a bump. This is then measured two to three days later to see whether the person has the infection. The bump grows larger if they are carriers of the pathogen.
The test was developed by the Statens Serum Institute, Denmark with which SII has a partnership. The skin test can be used to screen for TB in the community.
A clinical trial has found that it is as safe as the Mantoux test but has better sensitivity in the general population as well as household contacts of a TB patient and those at a high risk of contracting the disease. The test will be available for adults while the company will be conducting a trial in those below the age of 18 years, according to the subject expert committee under India’s apex drug regulator.