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HEALTH

The challenges of treating drug-resistant TB in India
18 JULY 2017
'Be prepared to take medicines for a long, long time.' Once considered a 'disease of the past', TB has had a resurgence.

Lokhande before, during and after she underwent treatment for TB [Photo courtesy: Debshree Lokhande]
by
Mir Ubaid
Mumbai, India - There was so much Debshree Lokhande was looking forward to when she began her first job in the western Indian city of Ahmedabad. Starting a career in architecture, exploring a bustling new city, and at 23, finally living independently.

But within the first month of her move, she developed a persistent fever followed by bouts of heavy coughing and rapid weight loss. When over the counter medicines didn't help she went to a doctor who advised getting a chest x-ray.

She was diagnosed with tuberculosis (TB) - an infectious disease caused by bacteria that primarily affects the lungs. It can also affect other parts of the body, including the brain, the spine and the kidneys.

TB can spread from person to person through coughing, sneezing, even speaking - anything that can release microscopic droplets into the air. In most cases, tuberculosis is curable, but it can prove fatal without proper treatment.

The doctor prescribed Lokhande the standard first-line TB regimen - two drugs she had to take as she waited for additional recommendations based on the x-ray.

"Be prepared to take medicines for a long, long time," Lokhande recalls the doctor telling her in 2011 when she first received her diagnosis.

Her condition worsened: she experienced high fevers and would vomit blood - common side-effects, the doctor told her.

Why was my TB being shunned, not spoken about like cancer or diabetes? Why is it associated to only being a poor man's disease? Was it my fault that I got DRTB?

Debshree Lokhande, TB survivor
A month after her first x-ray, Lokhande found out that what she had was not ordinary tuberculosis, but a deadlier version of it called Multi-Drug-Resistant Tuberculosis (MDRTB).

Drug-resistant strains of TB arise when an antibiotic fails to kill all of the bacteria that it targets. The surviving bacteria become resistant to that particular drug and often to other antibiotics as well. MDRTB occurs when the patient is resistant to the two most potent TB drugs - isoniazid and rifampin.

Resurgence of TB
Often considered a 'disease of the past', TB has had a resurgence in some parts of the world in recent years. The World Health Organization (WHO) estimates that there are now 10.4 million new TB cases in the world.

In 2016, it reported that the epidemic was larger than previously estimated, owing to new data from India, and increased its India figures from 2.2 million in 2014 to 2.8 million in 2015. Six countries account for 60 percent of the total number of TB cases, with India leading the list, followed by Indonesia, China, Nigeria, Pakistan and South Africa.

The recent spread of Drug-Resistant TB (DRTB) is particularly difficult to treat using currently available medicines. For one, because it takes on different forms - Multi-Drug-Resistant TB and Extensively-Drug-Resistant TB - the infected person is resistant to at least four of the core anti-TB drugs.

Additionally, the two most effective drugs for TB, isoniazid and rifampicin, are not only largely ineffective but become toxic, so doctors are left prescribing less effective drugs which have to be taken for longer periods.

For both forms, patients have to take a large number of pills and be given painful daily injections for up to two years. "But even with this process, cure rates are around 60 percent, even at the best centres," explains Dr Zarir Udwadia, a pulmonologist based in the city of Mumbai.

"I had no energy to even open my eyes," Lokhande recalls. "My family was trying to keep me positive while they paid thousands in search of the proper treatment."

WATCH: TB ranks alongside HIV as the world's most deadly infection (1:36)
While the standard course of TB drugs - between four to six different medicines - can cost as little as $15, in the case of MDRTB, treatment can cost almost $2,000 for one year, which is the minimum duration of treatment. Additionally, patients have to get sputum cultures regularly during the course of their treatment, which can add another $800 to the bill annually. satin fabric sheer items for bridesmaid

The Indian government does offer treatment programmes for TB. In 1997, it rolled out a TB control programme, recommended by the WHO. Known as DOTS, the strategy is aimed at providing a global, standardised short course drug treatment to all TB patients.

By 2006, this programme reached over 600 districts across India. But it wasn't foolproof. Delays in diagnosing patients and prescribing medications perpetuated the cycle of disease transmission, as did the inconsistency in ensuring patients adhered to their regimens.

"Giving this one size fits all regimen to patients only amplified that drug resistance," says Udwadia, who is vocal about increasing access to medicines for TB.

READ MORE: Why is the world suffering from a penicillin shortage?

"There's a high incidence of TB and DRTB in India because of years of policy failure. The government initially ignored the drug-resistant TB patients, pretending they didn't exist, allowing the numbers to proliferate."

"Until recently Indian public health officials remained reluctant to admit there's a problem," adds Nerges Mistry, the director of the India-based Foundation for Medical Research. "They were always trying to deny it existed."

Indian government officials declined to comment on the matter.

The DOTS programme was reassessed and a revised version - DOTS Plus - was rolled out in 2000 taking into account DRTB. But implementing this has had its own set of challenges. The drugs needed are often very expensive and difficult to obtain.

An MSF nurse draws a blood sample from an Extensively-Drug-Resistant Tuberculosis patient [Photo courtesy: MSF]
Diagnostic errors
Over the next several months, Lokhande was on a carousel ride of different regimens.

"The doctor would prescribe one set of medicines to me for six months. When reports would show that didn't work, he would prescribe another set, changing up the 10-12 tablets I had to take daily," she says.

"My family and I trusted him, hoping that with each change my body would stop destroying itself."

But Lokhande's erratic treatment programme moved her further from being cured, and closer to being diagnosed with Extensively-Drug-Resistant TB or XDRTB.

She had already moved back in with her parents in Pune after her first diagnosis, and now she has an at home nurse to help her take her medication and deal with the intensified side-effects - the most significant being hearing loss.

"My doctor in Pune gave up on me. He declared he can't treat me any more," she recalls. "I had lost 20 kgs, one of my lungs was severely damaged, I was extremely depressed and had gone completely deaf."

Treatment for different forms of DRTB can also lead to blindness, liver and kidney toxicity, rashes and psychosis.

Keeping up with the regimen can get exhausting in itself, but it can only be effective if it is followed with utmost precision. When patients don't adhere to it, it promotes resistance.

For Lokhande, there was also the social stigma to deal with. The most recent study on TB related stigma, published in 2008 in the International Journal of Tuberculosis and Lung Disease found that stigma associated with TB is the highest in India, with women experiencing it most profoundly.

"We had an almost upper-middle class lifestyle, but the onset of TB shocked those we knew," she says. "Almost everyone made insensitive remarks, made fun of me, criticised my parents, avoided me, stopped calling, stopped visiting. We were ostracised."

"Why was my TB being shunned, not spoken about like cancer or diabetes? Why is it associated to only being a poor man's disease? Was it my fault that I got DRTB?" she asks.

The stigma stems primarily from a fear of infection.

"Most people know TB is infectious, but their knowledge is limited when it comes to infection control, and that leads to deeper socioeconomic consequences, especially for women in India," explains Dr Parag Pevekar, a psychosocial counsellor who often sees TB patients.

"TB is also often associated with factors that can themselves create stigma: HIV, poverty, drug and alcohol misuse and homelessness. Women are often blamed as the source of TB, and those affected by the illness may be divorced or considered unworthy of marriage."

With no improvement three and a half years into her treatment, Lokhande's family took her to see Dr Udwadia at Hinduja Hospital in Mumbai.

"I was appalled," he recalls. "Debshree [Lokhande] was being pushed around in a wheelchair and was extremely frail. She needed Bedaquiline," he says, referring to a new generation of antibiotics which are less toxic.

"Debshree had run out of all drug options and was in a sense 'therapeutically destitute'. This was the only new drug available at the time and she needed it."

Access to 'promising drug'
After 40 years of dormancy in the field of tuberculosis research, two powerful, less toxic medicines were released in 2012 - Bedaquiline and Delaminid.

"Amongst antibiotics in general, Bedaquiline is a first in its class," explains Dr Isaac Chikwanha, an advisor for the Doctors Without Borders (MSF) Access Campaign based in the Swiss city of Geneva.

"In comparison to other anti-TB medications, Bedaquiline has a completely different mode of action. It blocks the mechanisms that TB bacteria use to produce energy, thereby killing the bacteria," he adds.

Udwadia says tens of thousands of Indian patients are in dire need of these medicines.

But despite the Indian government announcing in 2016 that Bedaquiline would be made available in the country, most patients are still denied access to it.

Authorities in India say Bedaquiline is technically still in a trial phase and that its use, therefore, needs to be monitored carefully. It is also expensive, they add; in some high-income countries, patients have to pay more than $30,000 for a six-month course of the drug.

WATCH: Tackling Drug-Resistant TB (10:26)
"There are strict regulations on access to Bedaquiline in India," explains Niklas Bergstrand, advocacy and communications manager for MSF in New Delhi.

"It's important these promising drugs are made affordable in all countries where they are needed."

MSF provides rapid diagnostic testing, treatment and psychological support for TB patients in India and across the world, free of cost.

In India, the organisation has four projects that focus on reducing morbidity and mortality of TB and HIV through access to free quality medical services.

"At MSF we believe it is important to scale up DRTB treatment," Bergstrand says. "For these patients, access to these vital drugs is a matter of life and death."

In India, Bedaquiline is only administered at six government hospitals across the country (in New Delhi, Mumbai, Ahmedabad, Chennai and Guwahati), and simply having a form of DRTB does not guarantee access to the drug.

Strict government regulations mean one has to be a resident of the state where the drug is being administered - which excludes the majority of India's DRTB patients.

And access isn't necessarily easier elsewhere. According to MSF, fewer than five percent of the people in need around the world are treated with the new TB drugs.

"It is downright disheartening that, with hundreds of thousands of people living with deadly Drug-Resistant Tuberculosis [across the globe], only 4,800 people last year received the two new drugs that could dramatically increase the number of lives saved," says Dr Chikwanha from MSF.

WATCH: The rise of India's superbugs

Path to improvement
Despite the regulatory hurdles, Dr Udwadia was able to procure Bedaquiline for Lokhande.

Within six months of that treatment, Lokhande gained almost 10kgs and progressed to a milder form of TB.

The recent spread of Drug-Resistant TB is particularly difficult to treat [Photo courtesy: Siddhesh Gunandekar/MSF]
She regained her hearing after ear surgery in 2015 and can now hear between 80 and 90 percent of sounds.

"Hearing music completely will come with time," she says with a smile.

Six years after her first diagnosis, Lokhande finally received a negative TB report earlier this year. The emotional and physical healing, however, will still take time. She has surgery scheduled to remove part of her lung - damaged from the years of XDRTB and the wrong treatment.

"It is a supra major operation. I'm not sure she will survive it, but it offers her the best, and perhaps only chance of a cure," says Udwadia. In medical terms, a supra major surgery involves operating on vital organs which could endanger the life of the patient.

"I see this as the last hurdle towards eliminating TB from my life. I can't wait to cross that final obstacle, and get back to working full time," Lokhande says.

Over the past six years, she has mostly been at home. She is currently working on small, independent projects.

"I'm left with thin arms, injection scars, skin discolouration, skin dryness and soon after the surgery, I will have a scar like those after open heart surgeries.

"But TB has changed my life. It has taught me some great lessons, about what matters in life, about how lucky I am to have those who love me by my side through all of this," she says. "And as I approach this final obstacle, I will proudly wear my scars as signs of my strength."

WATCH: Why you should be afraid of an antibiotic apocalypse

The Cure - Antibiotic resistance: The end of modern medicine? (25:00)
Source: Al Jazeera News

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