Ending TB in India key to global elimination goals

“We cannot eliminate TB (tuberculosis) unless we end it in India.” That was the telling remark with which Jamhoih Tonsing, director of the South East Asia office of the International Union Against Tuberculosis and Lung Disease launched the network’s 50^th global conference in Hyderabad earlier this month (30 October to 2 November 2019).

India has the highest TB burden in the world, housing a quarter of the global TB cases.

In 2018, India had 2.69 million TB infections. The country adds about 1.9 million new cases every year¹. Of these only 2.15 million were reported till 2018 to the Indian government, which means more half a million patients remain unreported or undiagnosed.

About 40 per cent Indians, therefore, harbour a possible silent or ‘latent’ infection without symptoms.

India also has the highest incidence of multi drug resistance tuberculosis (MDR TB) -- when strains of TB-causing Mycobacterium tuberculosis become resistant to the two most powerful anti-TB medicines rifampicin and isoniazid.

While the number of infections is going down, experts at the conference felt “TB is not falling fast enough in India, progress is still too slow” to meet the government’s target of eliminating TB.

India initiatives

Amidst these grim statistics, the National Institute for Research in Tuberculosis (NIRT), Chennai, has initiated multi-centric trials this year on the effectiveness of two new preventive vaccines, as well as two new anti-TB drugs approved for use in India.

In 2013, the World Health Organization also gave hope by approving bedaquiline developed by Johnson and Johnson to treat MDR-TB. It gave conditional approval to delamanid, developed by Japan’s Otsuka Pharmaceuticals, in 2014. A third new drug, pretomanid was approved for use by the US Food and Drug Administration (FDA) in August 2019 to treat extensively drug-resistant or XDR-TB, a type of MDR TB that is resistant to, isoniazid and rifampicin, any fluoroquinolone and at least one of three injectable second-line drugs (i.e. amikacin, kanamycin, or capreomycin).

The NIRT trials will test the efficacy of a new combination treatment of bedaquiline, delamanid, linezolid, and clofazimine for six to nine months in patients with pre-XDR or XDR lung TB. India introduced regimens containing delamanid in seven states in 2018², and rolled out a WHO-approved shorter drug treatment plan that includes bedaquiline in all 28 states in 2016³.

NIRT has also initiated phase III trials on two preventive vaccines -- Immuvac, a vaccine originally developed to fight leprosy by the Ahmedabad-based Cadila Pharmaceuticals; and VPM1002, a genetically engineered BCG (Bacille Calmette Guerin) vaccine developed by Pune-based Serum Institute of India. The studies in 12,000 healthy household contacts of persons newly diagnosed with the infection in six states will additionally look at latent infection and incidence of serious adverse events.

NIRT is part of a multinational multi-centric clinical trial (STREAM or Standard Treatment Regimen of Anti-tuberculosis Drugs for MDR-TB patients) involving 13 sites in 7 countries, comparing three regimens – one which is similar to the 9 month regimen used in the National TB programme, and two that use bedaquiline. One of the bedaquiline containing trials is a fully oral 9 months regimen.

The NITR trials come even as scientists worldwide are beginning to caution against the natural resistance to bedaquiline and delamanid in patients who have never received these drugs. There are some preliminary observations in India too. “We have started to see resistance, but it is not on a scary scale,” says Zarir Udwadia from Hinduja Hospital in Mumbai.

The Foundation for Innovative New Diagnostics (FIND) announced at the conference a new initiative, supported by Johnson and Johnson, which will help build and strengthen at least seven facilities for TB culture and drug susceptibility testing (C & DST). This is in line with India’s revised national TB control programme (RNTCP), which emphasizes the need for expanding C&DST laboratories.

If each laboratory can test about 9,000 samples every year, it will increase India’s testing capacity by at least six times that number when the project ends, RNTCP deputy director general Kuldeep Sachdeva says.

The US National Institutes of Health (NIH) also announced at the conference that India is in the shortlist of 12 countries for clinical trials of delamanid to prevent onset of drug resistant tuberculosis infection among close family contacts of already infected patients. The trials will likely be conducted in Chennai and Pune.

Research initiatives notwithstanding, access to affordable new drugs remains critical for developing countries mostly burdened by the disease. Pretomanid has raised hopes for the treatment of XDR TB and is available in India through a partnership between the non-profit TB Alliance and Mumbai-based Macleods Pharmaceuticals. However, at a global access price of $364 for a six-month treatment, it is out of reach for poor patients.

The fight against TB is still uphill.

References

1. Global Tuberculosis Report, World Health Organization (2019) PDF

2. Guidelines for use of Delamanid (Dlm) in the treatment of drug-resistant TB (DR-TB) in India (2018) PDF

3. Guidelines for Use of Bedaquiline in RNTCP PMDT in India (2016) PDF