Indian researchers use a novel approach to kill TB bacteria

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The compound isolated from Shayla tree does not directly target the TB bacteria but modulates the immune system to kill the bacteria.

A team of Indian researchers has been able to achieve 100-fold reduction in TB bacterial load in lungs of mice after 60 days of treatment using bergenin — a phytochemical isolated from tender leaves of sakhua or shala tree (Shorea robusta). Unlike the regularly used antibiotic drugs that target the TB bacteria, the bergenin compound modulates the immune system to kill the bacteria found inside the macrophages (a type of white blood cells). The results were published in the journal Frontiers in Cellular and Infection Microbiology.

“Our studies show that the bergenin compound can be used to clear the bacteria, and when used in combination with other TB drugs can produce good results,” says Gobardhan Das from the Special Centre for Molecular Medicine at Jawaharlal Nehru University (JNU), a corresponding author of the paper. “Since the compound does not target the bacteria directly but modulates the immune system to kill the bacteria, it can be used against drug-resistant TB too.”

The researchers undertook several studies to understand the mode of action of the compound. The compound was unable to directly kill TB bacteria when treated with the compound. However, in the case of in vitro studies, the compound was able to kill the bacteria found inside infected cells. In mice infected with TB and treated with the compound, there was significant reduction in the bacterial load in the lungs. Unlike in the case of in vitro studies, in mice the compound was found to activate not only the macrophages but also other cell types (T cells) that led to effective killing of the bacteria. A significant reduction in the number of granulomatic lesions was seen in animals treated with the compound. Also, the bacterial load was 100-fold lower in mice treated with the compound compared with controls (animals that were not treated with bergenin). “These findings strongly suggest that the immune response enhanced by the compound is able to increase the capacity to clear the TB bacteria,” Prof. Das says.

The levels of nitric oxide and a cytokine (TNF-alpha) were found to be enhanced. “We found the bergenin compound was selectively enhancing the frequency of interferon-gamma and interleukin-17-producing T cells in the TB infected animals,” says Dhiraj K. Singh from ICGEB and a co-author of the paper. Interferon-gamma promotes bacteria-killing nitric oxide inside macrophages thus promoting the generation of protective immune responses against TB bacteria.

Previous studies have shown that T helper 1 (Th1) cells play a key role in protecting the host against TB bacteria, while Th2 cells oppose the protection offered by Th1 cells. “There is a dynamic balance between the Th1 and Th2,” says Ved P. Dwivedi from ICGEB and the first author of the paper. “While TB bacteria prevents Th1 response and facilitates Th2 response, the bergenin compound promotes the expression of Th1 and Th17 responses.”

Beats conventional drugs

The compound has been shown to heal wounds faster than conventional drugs. Dr. Debprasad Chattopadhyay, Director of the ICMR-National Institute of Traditional Medicine (ICMR-NITM) in Belgaum, Karanataka, and the other corresponding author of the paper, had isolated the compound. He had seen tribals using the leaves of shala tree for wound-healing.

“The stage is now set to test many more Ayurvedic and plant-derived natural products for their potency against pathogenic diseases,” says Dr. Anand Ranganathan from the Special Centre for Molecular Medicine at JNU and one of the authors of the paper.

Prof. Das with the help of ICMR-NITM plans to carry out further tests in larger animals. If used in combination with other TB drugs the compound can shorten the duration of treatment and prevent the emergence of drug-resistance, the authors write.

Published in The Hindu on May 19, 2017

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

IISc team unravels how vitamin C helps kill bacteria

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Prof. Dipankar Chatterji and Kirtimaan Syal found vitamin C was inhibiting (p)ppGpp synthesis.

That vitamin C, an anti-oxidant agent, boosts and strengthens immunity is well known. Its ability to speed-up recovery from tuberculosis and impede the TB causing bacteria from causing disease, and even kill the bacteria in culture at high concentration are also known. Now, a study by a team of researcher at the Indian Institute of Science (IISc), Bengaluru has found the molecular mechanism by which vitamin C impedes and even kills Mycobacterium smegmatis, non-pathogenic bacteria that belongs to the same genus as the TB causing mycobacteria. The results were published in the journal FEMS Microbiology Letters.

During times of stress or hostile conditions, such as increased temperature and presence of antibiotics, bacteria tend to come together and form a biofilm to protect themselves. The stress response pathway is crucial for bacteria to survive during hostile conditions. So blocking this pathway is a sure way of killing the bacteria.

In mycobacterium, the (p)ppGpp (Guanosine pentaphospahte or Guanosine tetraphosphate) is a key molecule in the stress response pathway. The (p)ppGpp is synthesised by Rel protein, which in turn is made by the Rel gene.

The team led by Prof. Dipankar Chatterji from the Molecular Biophysics Unit at IISc looked at the effects of vitamin C on the stress response pathway. “We chose vitamin C because its structure is similar to (p)ppGpp,” says Prof. Chatterji. “So we hypothesised that vitamin C should be competing to bind to the Rel enzyme and inhibiting (p)ppGpp synthesis.”

To test their hypothesis, the researchers conducted experiments using M. smegmatis; M. smegmatis is used as a model organism for TB causing Mycobacterium tuberculosis.

In vitro studies showed “significant” inhibition of (p)ppGpp synthesis in the presence of vitamin C. The inhibition level was seen to be increasing as the vitamin C concentration increased. More the vitamin C concentration the greater the possibility of vitamin C binding to the Rel enzyme, thus inhibiting (p)ppGpp synthesis. At about 10 mM concentration, the synthesis of (p)ppGpp was completely inhibited.

The binding of vitamin C to the Rel enzyme is weak and this explains why high concentration of vitamin C is needed to inhibit (p)ppGpp synthesis.

“Using Mycobacterial cells we found that 1 mM of vitamin C produced 50% inhibition in (p)ppGpp synthesis. Vitamin C is able to get inside cells and inhibit (p)ppGpp synthesis,” says Kirtimaan Syal from IISc and the first author of the paper.

When 2 mM of vitamin C was added, “significant” defect in biofilm formation was seen. There was more than 50% reduction in viability of cells in a matter of four days when M. smegmatis was treated with 2mM of vitamin C. The viability of cells reduced even further with time, raising the possibility of therapeutic implications.

“This suggests that vitamin C can act as a precursor for more potential inhibitors; it can be chemically modified into more potential derivatives,” they write. “Vitamin C is natural, and it can form one of the nutrient-based treatments of the disease. Vitamin C is water soluble and has no toxic effect,” says Dr. Syal.

“We are trying to synthesise derivatives of vitamin C to enhance inhibition of (p)ppGpp synthesis even at lower concentration,” Dr. Syal says.

Published in The Hindu on April 22, 2017

IISc’s potent molecules show promise for TB therapy

SEM photo of Mycobacterium tuberculosis bacteria. - Photo NIAD-Optimized

The two molecules were able to prevent biofilm formation and even disrupt biofilms that had formed.

Scientists at the Indian Institute of Science (IISc) Bengaluru have developed two new, potent molecules that can severely impact the survival of mycobacteria, including Mycobacterium tuberculosis that causes TB. The results were published in the journal Antimicrobial Agents and Chemotherapy.

Unlike most antibiotics that target the bacterial metabolism by aiming at the cellular components, the novel molecules inhibit the stress response pathway of mycobacteria. The stress response pathway is crucial for bacteria to survive during hostile conditions such as lack of nutrients and the presence of antibiotics, to name a few. So any inhibition of this pathway will lead to its death.

The master regulator of stress pathway in the case of mycobacteria is (p)ppGpp (Guanosine pentaphospahte or Guanosine tetraphosphate). Though a molecule that inhibits the (p)ppGpp formation has already been synthesised, the efficacy is not much. “Very high concentration of Relacin molecule is needed to inhibit the pathway and, therefore, the efficacy is low. So we synthesised two new molecules — acetylated compound (AC compound) and acetylated benzoylated compound (AB compound) — by bringing about a modification in the base of the Relacin molecule,” says Prof. Dipankar Chatterji from the Division of Biological Sciences at IISc and the corresponding author of the paper.

“We found both the molecules to be very good inhibitors of stress response. The two compounds affected the rate of synthesis of (p)ppGpp and also reduced the cell survival,” he says. Laboratory studies showed that the two molecules were not toxic to human cells and were able to penetrate the human lung epithelial cells.

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Inhibiting (p)ppGpp synthesis would target the survival of the bacteria, says Dr. Kirtimaan Syal.

“We found our compounds were targeting the Rel gene. The Rel gene makes Rel protein, which in turn synthesises (p)ppGpp. When the Rel gene is knocked out, the long-term survival of Mycobacterium smegmatis decreases,” says Prof. Chatterji.

“The Alarmone molecule “(p)ppgpp”, a modified nucleotide, is ubiquitous in bacteria and absent in humans. Inhibiting (p)ppgpp synthesis would specifically target the survival of bacteria without having any effects on humans,” says Dr. Kirtimaan Syal from the Division of Biological Sciences, IISc and the first author of the paper.

Earlier studies have shown that when the rel gene is deleted, the long-term survival ability under stress was lost; the M. tuberculosis bacteria was unable to persist in mice and unable to form tubercle lesions in guinea pigs.

“The major reason for prolonged treatment of TB is the bacterium’s ability to persist in dormant form, which is tolerant to most antibiotics used in the treatment regimen. So inhibition of (p)ppGpp-mediated persistence could help in shortening the treatment regime, dealing with the emergence of multiple drug resistance and treatment of chronic infections, Dr. Syal says.

Inhibiting biofilm

Under hostile conditions, bacteria tend to form biofilms, which protect the bacteria from stress and induce tolerance to antibiotics. Recent studies have shown that tuberculosis bacteria that cannot form a biofilm cannot survive inside the host. Evidences have shown that at the time of infection, the M. tuberculosis display a biofilm-like phenotype and this helps the bacteria to survive inside the host.

Studies carried out by the researchers showed that both the molecules were able to inhibit biofilm formation by M. tuberculosis and M. smegmatis and also disrupt the already formed biofilm. “The biofilm formed by TB bacteria is very dangerous. The ability of the molecules to destroy the biofilm and even prevent its formation is a very important achievement,” says Prof. Chatterji.

Since there are very few antibiotics that target the stress response pathway of the bacteria, the two molecules offer great promise. “The next step is to test the molecules on animals. We have not thought about it. It will also be interesting to see if the bacteria develop resistance against these molecules,” Prof. Chatterji says.

Published in The Hindu on April 15, 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

Why is TB bacteria not on WHO’s deadly superbug list?

Pharmacy - Photo R. PrasadOf the estimated 10.4 million new tuberculosis cases globally in 2015, nearly 0.5 million estimated cases were multidrug-resistant (MDR) TB cases. Another nearly one million were resistant to rifampicin drug alone. India accounted for 2.84 million new cases in 2015, of which 79,000 had MDR-TB. There were 1.4 million TB deaths worldwide in 2015.

For the first time in nearly 50 years, two new drugs, bedaquiline and delamanid, were approved by the US Food and Drug Administration for use in MDR-TB cases. The accelerated approval of bedaquiline by the FDA was based on interim Phase IIa data. The lack of large-scale safety data and the paucity of effective TB drugs, especially for MDR-TB, are the reasons why the World Health Organisation insists that the drug be used only when all “options to treat TB using existing drugs have been exhausted”. The WHO also makes it abundantly clear that all efforts should be taken to avoid TB bacteria from developing drug resistance to bedaquiline as a result of misuse.

Despite the gravity of the situation and a near-empty drug chest to fight TB in India, a WHO list, released on February 27 of drug-resistant bacteria that pose the “greatest threat to human health” and for which new drugs are desperately needed, has no mention of Mycobacterium tuberculosis, the bacteria which causes TB.

Not a priority pathogen?
This is the first time that the WHO has released such a list and the prime objective of listing the “priority pathogens”, in its own words, is to “guide and promote research and development of new antibiotics… and to address the growing global resistance to antimicrobial medicines”.

The list is divided into three categories — critical, high and medium —based on the urgency of need for new drugs. While the WHO reasons that malaria and HIV have not been included in the list as they are not bacterial infections, it cites a completely different reason for not including TB bacteria. According to the WHO, TB bacterium was not included in the list as it is already targeted by other “dedicated programmes”.

In a strongly worded open letter to WHO’s Director-General Dr Margaret Chan, The International Union Against Tuberculosis and Lung Diseases, or simply The Union, says it is “outrageous” that Mycobacterium tuberculosis was not considered for inclusion as it is “already a globally established priority for which innovative new treatments are urgently needed”.

“This explanation defies reason [and] contradicts the stated intent of the global priority pathogens list’s methodology to define the list,” the letter reads. “TB’s exclusion sends the false and counterproductive message that drug-resistant TB is not an urgent public health threat,” the letter says. It also send a strong message to policymakers to “deprioritise TB research”, it adds.

Meets criteria for inclusion
The reason why The Union has reacted so strongly is because the TB bacteria meets each of the 10 criteria used for inclusion in the list — how deadly the infections are, the number of infected people in a community, prevalence of resistance, how easily the bacterium spreads from one person to another, options to prevent the infection in hospital and community, treatment options and whether new drugs are already in the R&D pipeline.

The WHO states that new antibiotics most urgently needed will never be developed in time if it is left to market forces alone. This is best demonstrated in the case of TB. It took nearly 50 years for new TB drugs to be approved for MDR-TB and not a single antibiotic has been developed for drug-sensitive TB in half a century.

Since the WHO has stated that the list has been developed to allow periodic revisions and inclusions of other pathogens, including viruses and parasites, The Union wants the TB bacteria to be included in the list before the WHO publishes the full protocol and results by the end of May 2017.

Published in The Hindu on March 5, 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