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Timing it right

Catching drug-resistant tuberculosis early and accurately is the objective of a startup with a diagnostic tool that could be a lifesaver

Tuberculosis (TB) patients, once diagnosed, are put on a first line of treatment that typically runs for four to six months. That’s straightforward enough. The problem occurs when the patient doesn’t respond to treatment because, more often than not, the TB bacteria may have developed a resistance to standard drugs. Left undetected, this could lead to organ failure, dangerously low immunity, even death.

Switching from first-line treatment of TB to the second involves a thorough investigation that can take months, precious time a patient may not have. Nagasuma Chandra, cofounder of the precision medicine and health systems startup HealSeq, understands this better than most.

For the last few years, Dr Chandra and her team have been working to devise a quick and accurate test that will do two critical things. First, diagnose the presence of TB in a patient in a few hours (a standard test takes between 12 and 24 hours). And second, figure out if the patient is not responding to first-line treatment and needs to be moved to the next. This second part, Dr Chandra expects, should take no more than two weeks, rather than the two-four months currently needed.

The TB testing tool fashioned by HealSeq, which is funded and supported by the India Health Fund, an associate of the Tata Trusts, will be a ‘host RNA biomarker-based investigation’. This means it will be able to read signatures of RNA — or ribonucleic acid, a nucleic acid similar to the DNA in living cells — in TB patients just two weeks after they have started treatment.

The expression of these signature genes will help doctors identify if a patient is responding well or poorly to the initial treatment. Slow responders, sometimes referred to as drug-resistant patients, can then be put on the second line of treatment.

A HealSeq researcher analysing a blood sample

Tackling TB

“A TB patient is typically given a cocktail of drugs,” explains Dr Chandra. “If the first line of treatment is not working, the drugs need to be modified. Picking the right cocktail, and quickly, is important because the drug-resistant bacteria may proliferate very fast.”

Sometimes the first detection and diagnosis itself comes late because people take their time to go to a doctor. “You think it’s a cough or fever that will pass,” adds Dr Chandra. “By the time you reach the doctor, tests are ordered and the condition is diagnosed, you have already wasted a lot of time.”

Drug resistance occurs for various reasons, the most common being prolonged exposure to certain antibiotics that makes the TB bacteria mutate and change their molecular structure. “Current drug resistance detection mechanisms cater only to the most frequently encountered mutations, even though various kinds of mutations are taking place,” says Dr Chandra.

The best way to test drug resistance is by culturing, which means putting the bacteria in an antibiotic culture to see if it dies or proliferates. But this takes at least two months. “There is also the danger of samples getting contaminated, there are high costs involved, and the treating doctor may not get accurate feedback,” says Dr Chandra. “Hence the delay in moving to the second line of treatment.”

Meanwhile, because patients are up and about many a time, there is a big risk of them transmitting the disease. India has 1.93 million reported cases of TB, which is approximately 17% of the global burden. Only 3-4% of these cases are multi-drug resistant (MDR), but about 10% within this bracket are prone to relapses that can be lethal.

“While MDR transmission is a concern, we also have extensively drug resistant [XDR] bacteria,” says Dr Chandra. “If that gets passed onto the community, it will be a big problem.” For example, if ever-evolving bacteria becomes resistant to all antibiotics, what can doctors prescribe?

This means that if the XDR strain starts spreading through community transmission, there may be large-scale fatalities. “That would be like going back to the pre-antibiotic days, where we didn’t have any medicine at all for TB and patients just died,” adds Dr Chandra.

The HealSeq test, besides yielding quick and accurate results, has the potential to benefit patients in a number of ways. The project team at the startup is trying to keep initial costs down to 1,000 or less. While still unaffordable for most people in India, this is less than the cost of a battery of tests needed for a conventional diagnosis.

Easy does it

Ease of use is another benefit. This is a blood sample-based test that a compounder at a rural healthcare centre can administer (all it requires is 2.5ml of blood). “The gold standard of detection is still a culture, but that takes time and must be carried out in a biosafe laboratory facility with trained staff,” says Dr Chandra. “Without proper facilities, testing and diagnosis is a major challenge.”

The HealSeq technology is now being considered for other kinds of ailments as well. In the pipeline, says Dr Chandra, are tests for a spectrum of TB ailments (extrapulmonary TB, for instance, which is hard to detect).

Nagasuma Chandra, the company’s cofounder
Nagasuma Chandra, the company’s cofounder

The ultimate beneficiary will, of course, be TB patients. Since the majority of them are treated at government-run centres, Dr Chandra hopes that once the HealSeq test has been rolled out, it will be included in the government treatment protocol and offered to a much larger group of patients.

“It has to be proven to be effective and must receive third-party validation from various institutions,” says Dr Chandra. “Once we manage to convince them of its efficacy and they see value in it, they will surely offer it to patients. That would be the best thing to happen for everybody.”

A member of the HealSeq team works on a blood test
A member of the HealSeq team works on a blood test