Chasing India’s target of eliminating tuberculosis by 2025, scientists at the Indian Council of Medical Research have recruited about 12,000 participants for a phase III study of two potential vaccines.

The researchers want to see how effective the vaccines are in preventing the disease in adult household members of a person newly diagnosed with TB. The participants from across seven sites in India will be monitored for three years before the potential vaccines are approved for use commercially or under the national TB programme.

“Recruitment in the middle of a pandemic was a huge challenge for us because we had to motivate healthy people in a household where TB was detected to come to the DOTS centres for vaccination,” one of the scientists said on condition of anonymity. DOTS, or directly observed treatment, is the name given to the TB control strategy recommended by the World Health Organization.

“For Covid-19 vaccines and therapeutics, the initial results can start coming in within months,” the researhcer said. “But TB is a long-term illness, and we will have to observe the participants for a longer duration to arrive at any result.”

One of the vaccines being tested to prevent tuberculosis of the lungs is Immuvac, which was developed to prevent leprosy. Immuvac, also known as mycobacterium indicus pranii, displays antigens similar to both the leprosy bacterium and the TB bacterium.

The other vaccine candidate is VPM1002, a recombinant BCG that is the most widely used vaccine in the world. The new vaccine developed in Germany has the genetic code of the BCG edited in a way that leads to better availability of the TB antigens, thus training the immune system to better fight tuberculosis.

Another trial of the same candidate is underway to prevent recurrence of TB in adults. VPM1002 is also being tested to see whether it can offer protection against Covid-19.

The BCG vaccine currently in use is a live, weakened form of the bacteria to train the immune system. It is only for use in children. Although it offers protection against the most severe forms of tuberculosis such as TB in the brain, it is not very effective against getting an infection, reactivation of a latent infection, and against the most common form of TB in the lungs. Yet, in the 100 years since the vaccine was developed, there have been no alternatives.

Experts say the government’s push towards eliminating tuberculosis and the formation of a research consortium are the reasons for the focus on TB vaccines.

“Unlike Covid-19 that affected the rich and the poor countries alike, tuberculosis disproportionately affects those in poorer countries and from poorer neighbourhoods,” said Dr DJ Christopher, professor of pulmonary medicine at Christian Medical College in Vellore, and former chair of RePORT India, a consortium for Indo-US collaborative TB research. “There is not enough interest or funding for research of a TB vaccine.”

India’s strategy to eliminate TB hinges on funding 3-4 vaccine candidates for phase I or II trials and have at least one final product co-owned by the government by 2025.

“Studying TB is not very popular. The government’s focus on elimination has certainly helped,” said Dr Pradeep D’Costa, intensivist and head of ICU care at KEM hospital in Pune, where he is heads the trial of VPM1002. “Vaccines will be an important contribution to the programme, but there is still ways to go,”

Even though research into TB vaccines is a step in the right direction, for now the mainstay of the elimination programme is early detection of new cases, testing for drug resistance and treating the disease completely, experts say.

“We don’t yet have effective vaccines. The vaccines currently being developed are also for specific populations, such as those at high risk of TB. And even then they are likely to take years to reach the market,” said Dr Christopher.

Vaccines are unlikely to be an important tool in the fight against TB in the foreseeable future, he said. “What we need to focus on instead is point of care testing. Tests such as CBNAAT and TrueNat are more sensitive than microscopy. They can also detect whether the TB is drug resistant,” the professor of pulmonary medicine said. “We need to make these tests the first line of diagnosis across the country.”

India is unlikely to achieve its 2025 target, Dr Christopher said. “We would not have made the 2025 target even without the pandemic,” he said. “With the pandemic, the timeline has been pushed further by probably five years.”

There was a 25 percent decline in the number of TB cases reported in 2020, government data show. It was mainly due to the lockdown and fear of going to health care facilities due to pandemic, experts said.

In addition, there have been challenges such as several centres in India reporting a shortage or stock-outs of CBNAAT cartridges. “There were some issues with the procurement of the CBNAAT cartridges,” an official from one of the biggest TB centres in Delhi said on condition of anonymity. “Because of the shortage of the reagents, many of the centres under the TB programme could not perform the test.”

“With Covid-19, TB has definitely taken a back seat, but we are slowly moving in the right direction,” Dr D’Costa said. “Our national programme is fairly widespread and the MDR (multi-drug resistant) detection kits are now available even in rural centres. There is also a need to ramp up counselling of patients and their family members because the stigma is still high.”

“Focus group discussions with our own staff showed that there was still significant stigma about TB. Many doctors did not notify their cases to the government,” said Dr Dinesh Kumar, former professor of community medicine at Government Medical College in Jammu. “The stigma is the community is likely to be higher. We need to address this in order to detect cases early on.”

“In addition, we have seen when we carried out active case finding, we were able to detect several latent TB cases that otherwise would not have reached a health centre,” he said.