The right dose, the right chance: India's battle with drug-resistant TB

Every Monday Dr. Zarir Udwadia runs a free tuberculosis clinic at P.D. Hinduja hospital in Mumbai, the forefront of India’s drug-resistant epidemic.

It’s gone from almost no patients 25 years ago when drug-resistant TB was rare, to today where patients have travelled from all across the country to line up along the hospital’s corridors to see the renowned lung specialist.

The private, nonprofit facility caters to around 350,000 people per year and compared with many other hospitals across the country, it’s significantly more organized and clean, with the smell of disinfectant lingering in the air.

As a medical trainee in the United Kingdom, Udwadia worked in Sir John Crofton’s former TB unit in Edinburgh. To his medical students, Crofton was a “towering name” in the TB world; someone the students looked up to.

Years later when Dr. Udwadia returned to India, TB dominated the pulmonary landscape. It was then he saw Zubin Irani, a teenage hemophiliac and his first multiple drug-resistant TB patient. In a desperate attempt to cure him, Dr. Udwadia wrote to Peter Davies, a chest physician in the U.K., who was generous in his advice.

While Zubin died of the disease, a strong bond between Udwadia and Davies was formed and it was then the doctor decided to commit himself to fighting the disease and eventually set up a free TB clinic at a time when MDR-TB was rare.

“TB remains a disease of poverty and also impoverishes many of those it afflicts,” he told Devex in his clinic between patients. “Struggling along with one of my really impoverished MDR-TB patients from this clinic over the arduous two-year course and clasping their hand when they are finally cured gives me more satisfaction than anything could.”

While significant global progress has been made in the fight against TB, if deaths are going to be reduced by 95 percent and new cases cut by 90 percent by 2035 as per the End TB strategy, then there’s never been a more urgent time to combat drug-resistance.

Challenges to eliminating TB

Too few diagnostic laboratories, thousands of people living in crowded, unsanitary slum conditions and not enough adequately-trained health care workers have made India home to the world’s largest epidemic of drug-resistant TB.

Coupled with problematic biosocial factors including alcohol use, diabetes, smoking and pollution, this means that commitments to eliminate TB as a global epidemic by 2035 seem rather premature in India, where a patient dies every two minutes and where TB infects more than 2 million people each year.

According to the World Health Organization, more than 60,000 people in India have a type of TB that is resistant to at least four types of drugs. But what’s more worrisome is that as many as 15,000 people may have extensively drug-resistant TB, known as XDR-TB, meaning they are resistant to all first and second line drugs, making treatment almost impossible.

At the best TB facilities in the world, the rate of cure for MDR-TB is about 70 percent, and for XDR-TB, it hovers at around 5 percent, Udwadia said. And that’s in the world’s top facilities.

In the early 1990s India adopted DOTS — directly observed treatment, short-course — a WHO-developed program for ordinary TB infections. The program was designed specifically to ensure patients in the developing world had the opportunity to complete the six-monthlong, first-line treatment at an affordable cost.

Ironically, while India recorded high treatment success rates after managing to dispense free medicines to those who needed it the most, it was simultaneously brewing drug-resistant germs because so few high-risk patients were tested to see if they were susceptible to different TB drugs. The administration of improper treatment regimens along with a failure to ensure that patients completed the whole course of treatment meant India was creating another epidemic of a different magnitude.

“This one size fits all approach doesn’t work,” Udwadia said of the DOTS program. “It’s a recipe for disaster. Patients are labelled as having TB when they have drug-resistant TB. The government standardized regime will not work for this. Sadly, this is a question of logistics and many patients have just fallen through the gaps.”

On top of the fact India spends only 1 percent of its gross domestic product on health; has a severe doctor shortage; and a dearth of laboratories that can test for resistance to different TB drugs, Udwadia expects to see more and more patterns of resistance and even more patients lining up to see him.

It’s an arduous task for a doctor that on a daily basis sees the burden the disease places on families.

Look beyond the one-size-fits-all approach

In 2011, things got worse when the laboratory at Hinduja identified a fourth patient infected with TB that was resistant to all 12 of the first-line, second-line and last-resort drugs available at the hospital.

Concerned with the trend, Udwadia wrote to the Clinical Infectious Diseases journal declaring an outbreak of what he termed “totally drug-resistant TB.”

While the WHO questioned the term, saying that it was “not clearly defined” and that defining resistance beyond XDR-TB was not recommended, Udwadia’s concerns seemed to stir something within the government. In response, the government increased the budget for its national tuberculosis control program and dozens of rapid GeneXpert machines that can conduct highly sensitive molecular diagnostic testing of resistant strains were dispatched to some district hospitals.

While the machines are still in short supply, they do enable doctors to detect resistance to first-line drugs within two hours, rather than weeks.

Future goals: Rapid diagnosis and drug provision

But of course, machines alone will not fix India’s drug-resistant TB epidemic nor help the world reach the 2035 elimination target.  

“Talk of TB elimination by 2035 is optimistic but sadly it’s too entrenched in the developed world for this to happen,” Udwadia said.

To address drug-resistant TB in India and other countries such as Russia, China and South Africa, Dr. Udwadia said there were four major steps that needed to happen: “We need to diagnose TB more rapidly; treat it more scientifically, following standard protocols; accelerate the provision of new drugs to patients who do desperately need them; and we need more government commitment and funding.”

Aside from diagnosis and treatment, drug-resistant TB also raises important ethical questions for those working in the field.

A case in point is 24-year-old Tabassum Shalich who was diagnosed with XDR-TB in 2013. Fast-forward three years and she’s sickly, thin and unable to eat. Despite being on drugs for three years, she isn’t getting any better.

“She is therapeutically destitute,” Udwadia said as he looked at an X-ray of her left lung. “We don’t have the drugs available to treat her. In fact, she’s untreatable. The drugs don’t exist anywhere. What is more soul-destroying than being on treatment for three years and getting worse and worse?”

Udwadia faced the difficult decision to let her go back to her village and infect less people, or stay in Mumbai infecting more people.

“It sounds heartless but what can I do? Do we call it a day and let her go?,” he asked.

Asking Shalich to leave the room, Udwadia spoke with the young girl’s mother who, looking deflated, agreed to take her daughter back to their village.

While most experts who have done as much as Udwadia has would be making retirement plans, the doctor remains more committed than ever to shaking more and more patients hands; the sign that they’ve successfully overcome the disease.

“TB is very unforgiving, but every patient with drug-resistance needs a shot at getting better,” he said. “Given the right dose, they have a chance.”

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