Breaking the drug-resistant TB transmission cycle important

GeneXpert

Nearly two months after the Health Ministry set a highly ambitious target of working towards elimination of tuberculosis by 2025, a study published in The Lancet Infectious Diseases indicates that India’s TB crisis is all set to snowball by 2040 when one in 10 cases could be drug-resistant. What is even more alarming is that the increased number of drug-resistant cases — both multidrug-resistant TB (resistant to more than one of the first-line drugs) and extensively drug-resistant TB (additionally resistant to fluoroquinolones and at least one of the second-line injectable drugs) — will come from direct transmission from infected people to others rather than by strains acquiring resistance to TB drugs during treatment due to inappropriate treatment or discontinuation of treatment midway. The study found that “most incident” MDR cases are “not caused” by acquired drug resistance, and that acquired drug resistance will become a “decreasing cause” of drug-resistant TB. The increased availability of drugs to fight drug-sensitive TB has led to the emergence of MDR-TB strains. With increasing number of MDR-TB cases, there has been a shift in the way people get infected with drug-resistant TB — from strains acquiring drug resistance during treatment to direct transmission of MDR-TB strains from an infected person. The same trend is seen in the case of XDR-TB too. As a result, in high MDR-TB burden countries such as India, improved treatment outcomes in people might only reduce and not eliminate drug-resistant TB. Till 2015, only about 93,000 people with MDR-TB have been diagnosed and put on treatment.

The study, based on a mathematical model to forecast how TB is likely to progress in the four most-affected countries (Russia, the Philippines and South Africa, India), suggests that the number of new MDR-TB cases in a year in India will touch 12.4% by 2040, up from 7.9% in 2000. In the case of XDR-TB, the incident cases will rise to 8.9%, up from 0.9% in 2000. In 2015, the four countries accounted for about 40% (more than 230,000) of all drug-resistant TB cases in the world. Besides increasing the number of people who are diagnosed early and successfully treated, India’s TB control programme has come up with enhanced interventions to break the transmission cycle of the bacteria in the community. One of the ways this can be achieved is by carrying out immediate screening of all family members of a patient who has been diagnosed with the disease. Contact screening of family members and preventive treatment of all children below the age of five years who have not developed TB disease are already a part of the Revised National Tuberculosis Control Program (RNTCP) but is rarely done. Another important strategy that has to be adopted is making drug susceptibility testing universal and mandatory. Developing more accurate, cheaper and effective diagnostic tests and improved treatment regimens that are less expensive and of shorter duration will also go a long way in winning the war against the disease.

Published in The Hindu on May 12, 2017

Without a magic wand, India cannot eliminate TB by 2025

GeneXpert

Only 93,000 MDR-TB cases have been diagnosed till 2015 in India.

At the end of 50 years of tuberculosis control activities, the disease remains a major health challenge in India. As per new estimates, the number of new cases every year has risen to 2.8 million and mortality is put at 4,80,000 each year. These figures may go up when the national TB prevalence survey is undertaken in 2017-18. Against this backdrop, the Ministry of Health and Family Welfare, in its national strategic plan for tuberculosis elimination (2017-2025), has set a highly ambitious goal of “achieving a rapid decline in burden of TB, morbidity and mortality while working towards elimination of TB by 2025.”

Though the Revised National Tuberculosis Control Programme (RNTCP) has treated 10 million patients, the rate of decline has been slow. Providing universal access to early diagnosis and treatment and improving case detection were the main goals of the national strategic plan 2012-17. But the RNTCP failed on both counts, as the Joint Monitoring Mission report of 2015 pointed out. Going by the current rate of decline, India is far from reaching the 2030 Sustainable Development Goals — reducing the number of deaths by 90% and TB incidence by 80% compared with 2015. Yet, the latest report for TB elimination calls for reducing TB incidence from 217 per 1,00,000 in 2015 to 142 by 2020 and 44 by 2025 and reduce mortality from 32 to 15 by 2020 and 3 per 1,00,000 by 2025.

Incidentally, nearly 50% of people in India are latently infected with TB. According to CDC, 5-10% of infected people will develop TB disease at some time in their lives. “About half of those people who develop TB will do so within the first two years of infection,” the CDC says. With the latently infected people acting as a reservoir, it will be nearly impossible to eliminate TB in India by 2025.

Radical approaches are needed to come anywhere close to reaching these ambitious targets. Most importantly, the TB control programme plans to do away with the strategy of waiting for patients to walk in to get tested and instead engage in detecting more cases, both drug-sensitive and drug-resistant. The emphasis will be on using highly sensitive diagnostic tests, undertaking universal testing for drug-resistant TB, reaching out to TB patients seeking care from private doctors and targeting people belonging to high-risk populations.

The other priority is to provide anti-TB treatment — irrespective of where patients seek care from, public or private — and ensure that they complete the treatment. For the first time, the TB control programme talks of having in place patient-friendly systems to provide treatment and social support. It seeks to make the daily regimen universal; currently, the thrice weekly regimen is followed by RNTCP, and the daily regimen has been introduced only in five States. There will be a rapid scale-up of short-course regimens for drug-resistant TB and drug sensitivity testing-guided treatment. In 2013, India “achieved complete geographical coverage” for MDR-TB (multi-drug-resistant tuberculosis) diagnosis and treatment.  Yet, only 93,000 people with MDR-TB had been diagnosed and put on treatment till 2015; several MDR-TB cases are simply not diagnosed.

What next?

Though Bedaquiline, the drug for people who do not respond to any anti-TB medicine, is provided in six sites in the country, the number of beneficiaries is very small. It has been a battle to get the drug for treatment, as in the case of an 18-year-old who had to approach the Supreme Court for help. Yet, the report envisages a countrywide scale-up of Bedaquiline and Delamanid.

In a marked departure, the report underscores the need to prevent the emergence of TB in susceptible populations. One such segment is those in contact with a recently diagnosed pulmonary TB. Incidentally, active-case finding is already a part of the RNTCP programme but rarely implemented. It wants to increase active case finding to 100% by 2020. Since RNTCP expenditure has increased by 27% since 2012 and is inadequately funded, the Ministry proposes to increase funding to ₹16,500 crore.

Acknowledging that the business-as-usual approach will not get the Health Ministry anywhere close to the goals, it has earmarked critical components that will be addressed on priority. These include sending customised SMSes to improve drug compliance, incentivising private doctors to notify cases and providing free medicines to patients approaching the private sector, facilitating nutritional support to TB patients, including financial support, rewarding States performing well in controlling TB, and using management information systems to monitor all aspects of TB control. “The ultimate impact of this national strategic plan will be transformational improvements in the end TB efforts of India,” the report says. It plans to take a “detect-treat-prevent-build approach” in its war against TB.

Published in The Hindu on March 19, 2017

Nandita: Deaf but not out

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Nandita Venkatesan lost her hearing in the blink of an eye due to TB injection. – Photo: R. Prasad

When she woke up after a short afternoon nap on November 22, 2013, two days after her 24th birthday, Nandita Venkatesan could see her mother and brother talking to her but could understand nothing; she could hear sounds but could not comprehend them. The noisy world around her almost fell silent. Her hearing loss was 80 per cent in the left ear and 50-60 per cent in the right ear. It has since deteriorated to over 90 per cent in both ears. The villain was the second-line anti-tuberculosis injection kanamycin that she had had for about three months.

Venkatesan’s first tryst with tuberculosis (TB) was in August 2007 when she was diagnosed with intestinal tuberculosis just a month after starting college in Mumbai. Popping 10-15 pills a day for 15 months and battling with the side effects of medication left her with little time to enjoy the pleasures of college life.

As if once was not enough, TB came to haunt her again; she suffered a severe reinfection in 2013. “The memories of the first bout came back to haunt me,” she says in an email. But what she did not realise was that the bacteria were intent on striking a body blow.

The TB infection was severe and medicines alone were ineffective the second time around. “The gnawing abdominal pain was far more severe than the first time and continued despite the medication. I convulsed with acute pain and it started hampering my day-to-day activities. Anything I ate immediately hurt my stomach and passed out undigested,” Venkatesan recalls. The only option left was to undergo a surgery to remove the infected portion of her intestine.

As she was wheeled in to the operation theatre, she reassured herself that things couldn’t get out of hand and she would be on the road to recovery very soon. But that was not to be. Normal life after surgery was short-lived; in a week, she was back in a bigger hospital as her condition had turned critical. Days stretched to months and one surgery turned to four as the infection spread. She underwent three major operations back to back and began second-line drugs after the second surgery when doctors found TB had spread beyond the intestine and she was not responding to first-line drugs. But the culture test result revealed that she was not infected with drug-resistant TB.

Walking skeleton

Solid food was ruled out and only small sips of water every hour were allowed. Nutrition plays a crucial role in recovering from TB but she had to subsist on IV fluids alone and this took a huge toll on her body. She became a walking skeleton after losing 23 kg. Her hair started to fall out. “I vividly remember going for a small walk in the hospital and seeing a reflection of myself in a glass window — with bald patches. I couldn’t recognise myself,” Venkatesan says.

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Nandita at the hospital.

“I was in hospital for two months. Since TB had started to spread to other parts of my body, it led to serious complications. Honestly, I didn’t know if I would survive, all I knew was that I was not going to give up,” she says.

After the surgeries, Venkatesan thought she was done with her quota of pain. Little did she realise that the worst was yet to come: her ordeal had just begun with permanent hearing loss. Soon she was hurtling from one problem to another — low BP, low sugar leading to memory loss on five occasions, and elevated creatinine levels.

“It felt like I would never be able to laugh again in my life,” she says. “But I soon realised I had to make the best of the worst situation. I could not sit and feel sorry for myself. In concentrating too much on the closed doors, I forgot to pay attention to the small windows of opportunity and hope. The way out, I felt, was to accept the situation and learn from it. Acceptance helps you move on and find solutions rather than wallowing in self-pity.”

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Despite being profoundly deaf, she still dances.

Surviving two bouts of TB infection has taught her to be a fighter and never give up even when pushed to the edge. The inner strength that once turned her into a warrior while in hospital emerged once again. She went back to dancing, her first love, but this time without the luxury of hearing the music. “I took to dance as a way to emerge from my closet and as a means to regain my shattered confidence. I saw it as a means to channel my pent-up energy and exasperation,” Venkatesan says. When she learnt that her dance school was organising a programme, she embraced the opportunity.

Determination, perseverance and imagination have been her strengths. Though profoundly deaf (she can only hear sounds as loud as the bursting of crackers), she slowly learnt to grasp dance steps and co-ordinate with her partners. The dancer in front of her acted as a cue and she memorised the beats, lyrics and steps. She could also feel the vibrations of the rhythm with the help of a hearing aid. “I also use number counts to grasp the beats. For example, if the beats are: Tai…Ta Ka Ki Ta, I convert them to numbers 1…1-2-3-4,” Venkatesan says. “Dance has proved to be incredibly cathartic. It has helped me embrace this ‘rebirth’ and the next stage of my life with more conviction. I guess, ultimately, the desire to dance won against the instinct to flee!”

Battle ready

It may not be an exaggeration to say that Venkatesan has mastered the art of adaptability. Having learnt to lip-read quite well, she has now started learning sign language. She has also learnt to handle everyday challenges like crossing the road by following a person. Venkatesan has been working in a financial newspaper in Mumbai since April this year. “I took a big step towards conquering my disability and kicking TB out of my life,” she says about her decision to work.

Besides actively participating in several programmes to raise awareness about TB as a survivor, Venkatesan is thinking big. She will be participating in the international group action.org’s TB R&D media and public speaking programme to be held in Berlin in January 2017. She also intends to pursue a doctorate in a few years.

“I am far more comfortable in my skin than before. The deafness does bother me sometimes but I have understood what I am capable of,” she says. As a message to other TB survivors, Venkatesan says: “The key is this: be brave; be determined. Take it as a second chance at life. Besides, when life pushes you over, you ought to push back harder!”

Published in The Hindu on December 10, 2016

About 0.5 million TB patients approaching RNTCP centres are not treated

GeneXpert

In 2013, only 39 per cent of 2.7 million TB patients in India had one year of recurrence-free survival.

In 2013, India had about 2.7 million people with TB, which is 23 per cent of the global burden of TB. India also accounted for 27 per cent (760,000) of the world’s “missing” patients — those may not have received effective TB care or may have received potentially suboptimal TB care in India’s private sector.

According to estimates by a team of researchers, of 2.7 million patients, only 72 per cent were evaluated at RNTCP facilities, about 60 per cent successfully diagnosed, 53 per cent registered for treatment, and 45 per cent completed treatment.  In all, only 39 per cent of 2.7 million patients achieved optimal outcome of one-year recurrence-free survival. The results of study that looked at TB cascade of care at RNTCP were published on October 25 in the journal PLOS Medicine.

“Though most of 27 per cent of “missing” patients are being treated in the private sector; a smaller percentage may not have received any care for TB, though it is hard to know how large this untreated population is. The WHO’s revision of India’s TB burden, released last week, would suggest that this percentage of patients who don’t come into contact with RNTCP TB services is larger than we have estimated,” says Dr. Ramnath Subbaraman from the Division of Infectious Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, U.S and the first author of the paper.

The bottom line is that about 500,000 patients (one-fifth of all TB patients) who interfaced with government TB clinics are either not successfully diagnosed or are diagnosed with TB but lost to follow-up before starting treatment.

If only 1.3 per cent of TB smear-positive patients who reached RNTCP diagnostic centres were not correctly diagnosed, 38 per cent of new smear negative patients and 27 per cent of retreatment smear negative patients were not diagnosed. So of all TB patients seeking care at government TB facilities, 16 per cent are not successfully diagnosed.

Soumya Swaminathan. - Photo R. Prasad

We need to know more about how anand where patients seek care, says Dr. Soumya Swaminathan.

“To reach all TB patients and avoid delays in diagnosis, TB services must be available where patients seek care. We need to know more about how and where patients seek care,” says Dr. Soumya Swaminathan, Director-General of ICMR and one of the authors of the paper. “Active case finding in vulnerable populations, use of molecular diagnostics and more suspicion of extrapulmonary TB by doctors are needed to improve TB diagnosis. Attention has to be paid to all steps of cascade.”

Currently, smear-negative TB patients are diagnosed using a multi-step diagnostic workup. As a result, at least 60-80 per cent of patients with negative sputum smear never complete the workup. “While the RNTCP is trying to implement a new diagnostic algorithm for smear-negative TB, the best solution for diagnosing more smear-negative patients would probably be use of new but more expensive diagnostic tests such as Xpert MTB/Rif, which diagnoses a substantially greater percentage of patients with smear-negative TB,” Dr. Subbaraman says.

Ironically, 13 per cent (over 200,000) patients who were diagnosed were lost before the start of treatment — about 16 per cent of smear-positive TB patients and about 10.5 per cent of smear-negative patients.

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Only 11 per cent of MDR-TB patients survived for one year after treatment, says Prof. Madhukar Pai

“There are many reasons why diagnosed TB patients don’t start treatment. But the bottom line is that better record keeping and aggressive tracking of newly diagnosed patients might help to reduce the number of patients who are diagnosed but not enrolled in TB treatment,” says Dr. Subbaraman.

“For patients with MDR-TB, out of the 61,000 who reached government TB clinics, only about 11 per cent completed appropriate treatment and survived for one year after treatment without experiencing disease relapse, ” says Prof. Madhukar Pai, a TB expert from McGill University, Montreal, Canada and one of the authors of the paper.

“The major problem we highlight is not that MDR-TB patients are not seeking care. Rather, a very large percentage of them (59 per cent) were not successfully diagnosed in 2013. I should note that, since 2013, the number of MDR-TB patients diagnosed in the RNTCP has increased a bit in 2014 and 2015, but the percentage of MDR-TB patients successfully diagnosed is still probably abysmally low,” Dr. Subbaraman says.

“There is expansion of Xpert for diagnosing MDR-TB cases. But we need more decentralised rapid MDR diagnostics,” says Dr. Swaminathan.

Published in The Hindu on October 26, 2016

Did WHO’s TB care advice cause more MDR-TB cases?

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A scanning electron microcope picture of Mycobacterium tuberculosis bacteria. – Photo: NIAD

Between 1993 and 2002, the World Health Organisation violated sound medical care by urging low- and middle-income countries to follow less expensive, largely untested and ineffective treatment protocols to treat people with multidrug resistant TB (MDR-TB), says a paper published on June 21, 2016 in the Health and Human Rights Journal.

Cost factor was the main consideration for the WHO to not recommend the available standard of care used successfully to treat MDR-TB cases in rich countries. The paper, by Thomas Nicholson from the Sanford School of Public Policy, Duke University, Durham and others, accuses the WHO of practising double standard for TB care in low- and middle-income countries by virtue of being the advisor to donor agencies and governments.

For instance,  rifampin, a potent TB drug cured TB in 6-9 months. While it became the bedrock of TB treatment in rich countries, due to cost considerations, low- and middle-income countries did not have access to the medicine till such time the patent expired in 1987. “Before then, many public health experts advocated more toxic, less effective drugs for use in poor countries,” the authors note.

For most of the 1990s, donors and governments were told “not to treat MDR-TB patients” but instead focus on preventing the emergence of such cases. “Weak health systems in poor countries, lack of capacity to implement complex health interventions, and even scientifically disproven ideas that drug-resistant strains would not be as transmissible” were the rationalizations forwarded by the WHO for this policy, says the paper. “However, the driving force was a concern over cost.”

In the late 1980s, outbreaks of MDR-TB were reported all over the U.S, most notably in New York City. In the early 1990s, New York City successfully prevented transmission of MDR-TB by treating patients with recently acquired disease promptly, appropriately, and completely —ideally, with directly observed therapy (DOT).

In 1995 MDR-TB outbreak was reported in a slum area in Lima, Peru. Even as the guidelines for treating drug-resistant TB were drawn up by the WHO, the global health body advised the Peru government to use an “untested standardised therapy”. And unlike in the case of New York City, no drug sensitivity testing was involved. So patients received drugs to which they were already resistant to. “Unsurprisingly, only 48 per cent achieved cure and a significant number died. Many acquired further drug resistance,” says the paper.

However, an NGO Partners in Health (PIH) in Peru rejected the WHO’s treatment regimen and adopted the same approach as in New York City after tailoring to the local needs and demonstrated that a higher cure rates — 66 per cent validated cure for all enrolled MDR patients— could be achieved.

“For many countries, the MDR-TB epidemic worsened from 1995 to 2005,” the paper says. Belarus adopted the WHO treatment protocols that was rejected by PIH and U.S. CDC and six years later nearly half of diagnosed TB patients had MDR-TB or XDR-TB. “The WHO’s persistence in choosing to recommend sub-standard treatment regimens due to cost for treatment of DR-TB in these countries clearly had deadly stakes,” the paper notes.

“While championing the cost-sensitivity of its standard protocol for low-resource settings, it was insufficiently sensitive to the protocol’s fundamental biomedical adequacy for large groups of patients. Far from an ambitious program to stop TB using the drugs known to combat the disease and improve patient health, the protocol arguably set up millions to miss the boat of effective treatment,” the paper highlights.

A press release from Duke University says that despite second-line drugs becoming available in 2002 for treating MDR-TB patients in low- and middle-income countries, the WHO guidelines on treatment of MDR-TB patients were not rewritten till 2006. Salmaan Keshavjee, a co-author from the Department of Global Health and Social Medicine, Harvard Medical School, Boston, served on the committee that rewrote the guidelines.

According to WHO, globally, 190,000 people died of MDR-TB and an estimated 480,000 cases occurred in 2014 alone. Of these, only 123,000 were detected and reported, even fewer received appropriate treatment, and only half of those treated were cured. Between 2000 and 2009, an estimated 5 million people were infected with MDR-TB.

With TB being an airborne disease, advocating different standards of treatment for rich and poor countries runs counter to good public health policy.

Published in The Hindu on June 26, 2016

 

A step closer to a safer, more efficacious TB vaccine

Prof. Kaufmann (left) and Dr. Grode. - Photo R. Prasad-Optimized

The TB vaccine is intended to protect children and possibly adults against drug-sensitive and drug-resistant TB, says Stefan Kaufmann (left), who led a team that designed the vaccine – Photo: R. Prasad

A potent vaccine against tuberculosis is getting readied at the Pune-based Serum Institute of India Limited. The institute started a ‘Phase 2b’ clinical trial in neonates in South Africa late last year using a novel, recombinant BCG (bacillus Calmette-Guérin) vaccine. The new TB vaccine (VPM1002) is based on the BCG vaccine in use today, but what makes it more powerful is that it contains a gene which makes it easier for the vaccine to be better recognised by cells of the immune system.

The ‘Phase 2b’ trial will be studying 416 babies (newborns) whose mothers are HIV-positive and negative. A single dose will be administered to babies immediately after birth and will be followed up for a year. The trial, to be completed by mid-2017, will study safety and the level of cellular immune response (which does not involve antibodies) produced by the vaccine.

India-based trials

A ‘Phase III’ trial involving newborns will begin in India once ‘Phase 2b’ ends. By the end of this year, the institute also plans an independent ‘Phase III’ trial, again in India, involving nearly 2,500 adult TB patients who have been successfully treated.

The rationale for targeting this high-risk subset of the adult population is because each year in India, TB recurrence (reinfection and relapse) is seen in at least 2,00,000-2,50,000 people who have been successfully treated. According to the medical director at the institute, Dr. Prasad S. Kulkarni, it will be easy to clinically prove the vaccine’s efficacy as the study will be restricted to a relatively fewer number of people.

The recombinant vaccine, which was developed by a group headed by the founding director of the Max Planck Institute for Infection Biology, Berlin, Stefan H.E. Kaufmann, has already shown promise in animal and small-scale human trials. Prof. Kaufmann said the amount of bacteria reduced 100-fold in all animals studied when the recombinant vaccine was administered. Studies in two separate ‘Phase I’ human clinical trials in 80 adults in Germany (2009) and 24 adults in South Africa (2010) and one ‘Phase 2a’ trial in 50 newborn infants in South Africa in 2012 have confirmed safety and sufficient strengthening of the immune system against TB, thus raising hopes for a higher efficacy vaccine.

The trials in Germany and South Africa were carried out by Vakzine Projekt Management GmbH (VPM), Hanover, Germany. The Max Planck Institute holds the patent and has licensed the vaccine to VPM; VPM, in turn, has out licensed it to the Serum Institute.

The recombinant BCG vaccine is intended to protect children and possibly adults against drug-sensitive and drug-resistant TB. The hope is that the vaccine will be able to protect against pulmonary and extra-pulmonary TB. In comparison, the classical BCG vaccine can only protect against severe forms of the disease in children but cannot prevent pulmonary TB in all age groups, including children.

VPM 1002 TB vaccine

Candidate TB vaccine.

More efficacious, safer

Besides better efficacy, the recombinant BCG vaccine has been found to be superior safety-wise. Unlike the currently used vaccine that causes BCG-related disease in HIV-positive babies (as they have reduced immunity), the recombinant vaccine is expected to be safe in this population. Better safety of the new vaccine was demonstrated even during animal trials — immuno-compromised mice died when the existing BCG vaccine was administered but not when the recombinant vaccine was used. Prof. Kaufmann and others strongly believe that a difficult pathogen like Mycobacterium tuberculosis, which expresses some 3,000 different antigens, cannot be dealt with by a vaccine containing one or a few antigens. “Since BCG shares almost all antigens with tuberculosis, we decided to improve BCG with respect to its ability to provoke an immune response,” he said. “Indeed, our strategy has been termed by others as [a] rational vaccine design”.

The hypothesis was that the vaccine would induce broader cellular immunity (that does not involve antibodies) but something unexpected happened. “Antibody response was also seen in animals. This was unexpected and is good,” he said.

“The vaccine being tested is intended to replace the current BCG vaccine and will be administered to young children to protect them against tuberculosis. Adults may also be able to benefit from it later,” Prof. Kaufmann added.

Since its use in 1921, BCG has become the “most widely administered vaccine in history with approximately 4 billion doses administered worldwide”.

“Besides assured supply, [the] Serum [Institute] manufacturing the vaccine will mean that [the] cost will be reasonable,” said the Director-General of the Indian Council for Medical Research, New Delhi, Dr. Soumya Swaminathan.

With a capacity of 100 million doses, the Pune institute meets the global demand for BCG vaccine and is well equipped to supply the new vaccine when the trials are completed. This will mark the end of a long journey that began when the recombinant vaccine was constructed in the late 1990s and tested in different animal models to determine its safety and protective effect.

Published in The Hindu on February 21, 2016

Pilot testing of bedaquiline drug on TB patients to start soon

BedA pilot programme to test the toxicity, particularly cardio-toxicity, of bedaquiline drug (used for combating multidrug-drug resistant TB) in the Indian population, assess its ability to achieve culture conversion and check the operational feasibility of using the drug to treat MDR-TB patients would start in India by the end of this month or on World TB day.

Six hundred MDR-TB patients would be enrolled in six institutions — two in Delhi, and one each in Mumbai, Ahmedabad, Guwahati, and Chennai — to study the suitability of the drug for the Indian population. Only those patients who are resistant to both rifampicin and isoniazid, the first-line TB drugs, will be enrolled in the programme.

In its interim guidance, the World Health Organisation (WHO) had laid special emphasis on closely monitoring the response to treatment and informing the patients of the benefits and possible harms of the drug.

The pilot programme would last for six months. As per the WHO’s recommendation, bedaquiline will be given to the patients in addition to the regular multidrug treatment regimen.

Unlike clinical trials, the six institutions will not enrol a certain number of patients each.  Instead, patients willing to participate in the programme will be enrolled in any of the institutions on a first come first served basis.

The pilot implementation was supposed to have been launched on January 29 and then later pushed to February 4.  Enrolment of 600 MDR-TB patients is expected to take time as second-line drug susceptibility testing has to be first carried out in those willing to participate and their informed consent has to be taken. The toxicity of the drug may delay the enrolment, a senior official told The Hindu.

Phase III trials using this drug have not been completed yet and based on Phase IIb trials done outside India, the drug was found to disturb the functioning of the heart (cause abnormal and potentially fatal heart rhythm) and cause adverse drug reactions in the liver. Most importantly, unexplained increase in mortality was reported during the trials.

Published in The Hindu on February 19, 2016