Can India deliver affordable TB diagnostics?

[NEW DELHI] Believing that affordable diagnostics are key to controlling tuberculosis (TB), world experts are looking to India to come up with suitable kits.  

Faith in India’s ability to deliver comes primarily from its track record of producing cheap, generic anti-HIV drugs and hepatitis B vaccines that are now popular in many developing countries.

"India has a lot of capacity not only for development of technology but also delivery of technology," observed Peter Small, deputy director for TB, Bill and Melinda Gates Foundation, at a meeting on TB diagnostics in Bangalore, end-August 2011.

"Innovation — in research, product and healthcare delivery — is central to India’s TB control programme. It met its target of investing US$ 14 for 70 per cent of its TB patients by digging deeper into its own and donors’ pockets," Small said.   

Small sees growing private and non-government organisation involvement in TB control in India as another advantage. 

According to the management consultancy McInsey India there are opportunities for domestic industry in the country’s projected US$ 60 million dollar market for TB diagnostics, scalable to US$ 100 million through exports.

Other experts who attended the two-day meeting in Bangalore pointed out the many hurdles India faces, starting with a huge population and limited resources.

India has the world’s highest TB burden, accounting for a fifth of cases. "Each year India has 1.98 million new cases and 280,000 deaths, while an estimated 95,000 people are co-infected with HIV and TB," said Kuldeep Singh Sachdeva, head of the Revised National TB Control Programme (RNTCP).

"For all the potential, talent, booming economic growth and biotech industry, India has not innovated (in TB). It is a depressing landscape that we need to change," said Madhukar Pai, professor at McGill University and co-chairman of Stop TB Partnership’s new TB diagnostics working group.

But Chris Dye from the WHO said what happens in India is crucially important for the world. "The bedrock of the epidemic is South-East Asia, which includes India."

Diagnostic kits are the key

The recognition that no new anti-TB vaccine is expected before 2015 has prompted experts to pin their hopes on improving diagnosis. 

Medical researchers have long battled the scourge of TB, caused by Mycobacterium tuberculosis, that commonly infects the lungs, but can also attack the brain, kidneys, and spine.

Often, people harbour TB bacteria but show no symptoms. When their immunity is weakened the bacteria multiply, resulting in bouts of coughing with telltale blood in the sputum, chills, fever, weight loss and fatigue. Untreated infections can be fatal.

TB tests come in a range. Latent infections can show up as a reaction when the protein, tuberculin, is injected under the skin. Blood tests may reveal immune molecules (gamma interferon) produced by the body to protect against the bacterium.

A surer test is the chest X-ray where white spots indicate infection. Microscopic examination offers further confirmation, though this method picks up less than 70 per cent of infections, dipping as low as 35 per cent in some settings and in patients co-infected with HIV.

TB is reliably confirmed when sputum samples are cultured in a laboratory with nutrients, but this technique takes two to four weeks, is costly and calls for technical training.

Last year, WHO endorsed an accurate two-hour test using DNA technology, but this is yet unaffordable in developing countries where the bulk of cases occur.   

Experts at the Bangalore TB conference admitted to having hit a wall in finding a test that is quick, cheap, effective and suitable for use in developing countries.

"The root cause (of problematic TB control) is undiagnosed and mistreated TB patients," said Small.  "Our detection progress is insufficient in the struggle against TB. Infected persons need to be diagnosed before they can pass on the infection."

India’s TB struggles

India has hiked up TB control funding from US$ 350 million in 2007-2012 to US$ 1,300 for 2012—2017. Its case finding efforts have risen from 140 per 100,000 suspects examined for TB in 2006 to 160 in 2010; and 1,522,147 patients were put on DOTS treatment in 2010, RNTCP’s Sachdeva said.

"We are aiming at nationwide coverage of drug-resistant TB cases by the yearend and complete geographic coverage by 2012 end," Sachdeva told SciDev.Net. 

Sachdeva conceded, however, that scaling up new diagnostics in India has been slow.

The country spends an average US$ 55 per person on healthcare, of which government expenditure is US$ 11, compared to US$ 5,000 in developed countries, and US$ 150 in China and Thailand, noted Nachiket Mor of the Hyderabad-based non-profit, IKP Centre for Technologies in Public Health.

Mor, a member of the Indian government’s high-level expert committee on universal healthcare, believed that kits costing around 15 cents each hold the answer. 

But, developing newer, cheaper and quicker test kits is not easy. For one thing, there is little consensus on benchmarks. Observed WHO’s Puneet Dewan: "The tools on the table are all compromises between accuracy, simplicity, cost and time."

McInsey India’s benchmarks include  90 per cent sensitivity and specificity; results within 24 hours; use of urine or blood samples rather than sputum; instruments that are compatible with tropical environments, portability and ruggedness.

A key criterion on the list is that the cost to the patient should be under US$ 1.2 per test.

Such a test kit will need to be validated by experts before it can be widely used.

Unlike malaria and HIV tests that are validated by public-funded laboratories there is no system in place for TB tests, said Varindar Chauhan, director of the International Centre for Genetic Engineering and Research, New Delhi.

Despite such hurdles, Small is optimistic that India “is poised for innovative, high-quality, affordable healthcare in TB.”

Bleak global picture

Globally, the TB picture looks bleak with poor funding and outdated tools.

"Diagnostic kits more than 100 years old. Drugs? The last new one is 40 years old. And a vaccine that is nearly 90 years old. These are the fantastic tools that we have to control TB with," observed Lucica Ditiu, executive secretary, Stop TB Partnership.

Despite progress in TB control — 35 per cent reduction in deaths since 1990; 41 million patients detected and treated, and six million lives saved from 1995 to 2009 — two million TB patients die each year, said Ditiu.

Some four million cases are estimated to go undetected worldwide. Only five per cent of HIV-infected persons are tested for TB; and only one per cent of those co-infected with HIV and TB receives TB treatment.

Small observed that the global plan to control TB needs US$ 46.7 billion in 2011-15. Of this, US$ 9.8 billion are needed for research and development; and US$ 2 billion for new diagnostics and vaccines.

Against those figures, in 2009, only US$ 614 million were available for TB research.

Ditiu estimates a US$ 4 billion funding gap by 2015, including research on new diagnostics, drugs and vaccines. What is needed, she said, is a “dramatic pushup.” 

Causes for worry in India

One cause for worry in India is a plateau in the number of new cases being detected at 87 per cent of actual infections, over the past five years.

"The plateau shows we have reached those who are easy to reach. The problem is those who are hard to reach — the tribals, people with poor access to healthcare, women and children," said Soumya Swaminathan, National Institute for TB Research, Chennai.

A key challenge is the "large, unregulated private sector characterised by market-driven diagnostics usage," said Sachdeva. An estimated 45 per cent of TB patients are treated outside the RNTCP.

An analysis shows that while government-funded laboratories use the more reliable sputum microscopy for diagnosis, private testing centres use a WHO black-listed enzyme test that costs about US$ 10.

The slow rate of decline of the disease in India is another concern, said Dye. TB rates are falling slowly, at two to three per cent each year, in patients under treatment, compared to the benchmark ten per cent seen in Europe and North America when drugs became available. 

Most recent TB infections in India are of young adults with a fifth being cases of ‘re-infections’. "This should not be the case if they are being treated properly in the first place," Dye noted.

Despite the drawbacks, global experts at the conference were optimistic that Indian diagnostic companies would soon form a world hub for high-quality generic diagnostics.

India’s national targets for 2015 exceed the UN Millennium Development goals of detecting at least 70 per cent of new cases and curing at least 85 per cent. 

"We need this type of boldness," said Ditiu. "I look to India to help us help others globally."