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Professor Brahmachari, dir. CSIR and OSDD.
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Ward at LRS Institute of TB and Respiratory Diseases i New Delhi.
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18-year Mdich Momachan, with MDR TB gets his medicine.
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Dr. D. Behera dir. of LRS Institute of TB and Respiratory Diseases.
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Bala Subramanian and Manos Perros at Astrazeneca in Bangalore.
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Picture of Dr. D. Behera when he met the philantrope and IT-billionaire Bill Gates. Photo: LRS
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Spottprover på LRS Institute of TB and Respiratory Diseases i New Delhi. Foto: Johan Bergendorff
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Diagnoslabb på LRS Institute of TB and Respiratory Diseases i New Delhi. Foto: Johan Bergendorff
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Väntrum för tbc-patienter LRS Institute of TB and Respiratory Diseases i New Delhi. Foto: Johan Bergendorff

"India wants to save the world from TB" translated to english.

Vetandets värld 20120529
19 min

According to WHO, every third person on earth is infected with TB bacteria. No new drugs has been produced in more than 40 years and more cases of multidrug-resistant TB occur every year. New types of antibiotics that can fight the TB bacterium is desperately needed, and a lot is done in India to change the situation.

It is an extremely tricky and resistant bacteria that can survive an entire human life in hibernation inside the body and breaks out only when our immune system is weakened (as of a child or elder person) or by other diseases or malnutrition. Every year nine million people globally develops tuberculosis and about one and a half million die. TB is one of the infectious diseases globally to take most lives, and the country in the world where most people die of TB is India.

The waiting room corridor at L.R.S. Institute of Tuberculosis and Lung Diseases in New Delhi is crowded by young and old, women in colorful saris and Sikh men with turbans. Most wear pieces of cloth wrapped over their mouths and I can´t help thinking, I hope I do not get infected with multidrug-resistant TB. The doctors have assured that as long as patients do not cough right at me and have their mouths covered the risk is much greater of getting infected anywhere outside the hospital by someone who still does not take medicine.

I try to convince myself that since I am old enough to be TB-vaccinated at school in the 1980s I am safe, but I have unfortunately read that the protection of the TB-vaccine is weak for an adult.

TB bacteria usually affects the lungs and after several years of untreated infection the will stop working, but it can also infect the brain, lymph nodes, joints, bones, intestines, or the entire bloodstream in worst case.

Dr. Nita Singla is a TB researchers with a black dot painted between the eyebrows and draped in a sober blue sari. She takes me to the office where Mdich Momachan, a 18-year-old boy in blue jeans and a stylish black shirt with the label "dude" embroidered in white on the chest, just is to get his medicine. He has multidrug-resistant TB, so instead of a treatment with the usual 3-4 different kinds of pills for 6 months, he now take drugs with more side effects for two years.

- I thought I was going to die, says Mdich behind the white mask and looks at me with dark serious eyes. For two years he had such a strong cough and fever that he could not manage anything but lie in bed, he was so breathless that he could not even talk.

Mdich comes from a small village in the impoverished state of Bihar in northeastern India, and when he first began to cough, he took the bus two hours to the nearest town and visited a doctor who said he had TB and gave him pills. But when he returned to the village he was persuaded by neighbors to stop taking this medication because they said he did not have tuberculosis. Instead, he received a brown powder which was suspended in water and which Dr. Nita translates as medicine of witchcraft.

Eventually, he let himself be persuaded by a village doctor that he must do the 800 km trip to New Delhi for help, and now he lives with an uncle in this city. Mdich have been taking medication for three months and is now able now to walk and feel much better, even if he sometimes still feels short of breath.

This is India's main TB hospital with 500 beds and the only one in the country that has two sections with a ward with negative air pressure for patients with multidrug-resistant TB. Dr. Singla shows the lavish facility that prevents the TB bacteria coughed into the air to escape from the rooms. Patients lay in small single rooms almost cell-like behind thick doors. The ordinary hospitals in India however, it is often extremely overcrowded and patients with all kinds of diseases are mixed, which of course increases the risk spreading the infection.

This university hospital conducts a lot of research, including how diagnostics can be accelerated. Normally, it takes months to grow a sputum sample because TB bacteria multiply so slowly. The hospital lab is quality audited and internationally certified.

It is not easy to determine precisely which of the handful of medications that are available that this particular patient's TB infection is resistant to. Last winter Indian newspapers also wrote that the country is now experiencing total-resistant TB, where the ordinary medications don´t help, something that also been documented in Italy and Iran. But when I meet the hospital director, Dr. Behera inside his office over a cup of tea, he disagree with that claim.

- It may well be that there are strains of the total resistant TB in India, given the poor treatment by some doctors in private practice who do not prescript the right medicine at the right doses, and because many patients stop their treatment in advance once they feel better, says Dr. Behera. But the Indian laboratories who said in media that they had discovered total drug resistant cases of TB are not accredited and can´t test against all currently known TB drugs, according to Dr. Behera.

With today's medications this hospital can only cure 60-70 percent of patients, even if they do not have resistant TB. Many are already too weak of other diseases such as HIV, diabetes or liver- and kidney failure. It has not been any new drugs since the 60's because pharma companies have focused on diseases of the rich world's population that they can earn far more money on, according to Dr. Behera.

Dr. Behera wants new, modern and more effective drugs as soon as possible, with less side effects and where treatment can be shortened. It's really a rush to launch studies so that we can save more patients. He glances up at a photo of the wall where he and some of the doctors at the hospital are smiling at the camera together with the IT billionaire Bill Gates, who visited last year. Bill Gates has given out millions of dollars to ensure that something finally happens on new TB drugs.

In the mid 90's, the World Health Organization warned of a global TB epidemic. In the year 2000 foreign aid organizations, researchers and industry together formed the "TB Alliance". The Alliance has billions of Swedish crowns to distribute to tuberculosis research at universities and pharmaceutical companies. Currently there are dozens of potential TB-drug molecules tested in the labs and even in patients.

One of the new hopes is called AZD5847 and was developed by AstraZeneca, with a large research facility in Bangalore focused on tropical diseases. Nine o'clock in the morning hundreds of scientists are on the way to work through the entrance gates. Many of them have worked hard for many years to better understand the tuberculosis bacterium's weaknesses. Also some of the drug giant's American, Swedish and British staff have had a hand in producing the pill that is now being tested in smaller trials on TB patients.

If this study is crowned with success, that the drug really is better than the placebo effect and not toxic in any way, next step is larger trials in several countries and in combination with other pharmaceutical companies' drug candidates.
- The TB bacteria can only be fought with an arsenal of different weapons, says Bala Subramanian who is Director of Bioscience, at AstraZeneca in India.

The tuberculosis bacterium has a tough armor, like a wax ball, which is very difficult to penetrate, and it also has several stages and can hide in most tissues of the body. AstraZeneca AZD5847 prevent the tuberculosis bacterium to proliferate. Drug molecules that are tested by other pharma companies targets other mechanisms in the bacterium.

Already in the 80's the Swedish pharmaceutical company Astra established a lab in India.
- The strength for us here is that we have a very good supply of skilled labor and, in addition our researchers do not only understand the tuberculosis bacterium, they are living with TB in the society, says Bala Subramanian. 40 percent of India's population is infected, many of our scientists as well, I'm one of them says Bala.

But why have Astrazeneca had engaged in tuberculosis research, as after all, is a disease that affects the poor who will not be able to afford expensive medications and where the company also will have to share revenue with competitors whose medications are also part of a new future cocktail ? It costs after all, hundreds of millions of dollars today to get a drug from the lab to the pharmacy.

Manos Perros, a tall Spaniard who is the drug giant's global head of infectious disease research answers:
- I can say with some certainty that Astrazeneca is not doing this for revenue. Sometimes you simply have to do the right thing, says Manos Perros.
- But you have shareholders with profit. Do you get any of the "TB Alliance" millions of dollars to do this job, I wonder, though that is not something Manos Perros may reveal. He'd rather talk about all the good forces now in joining hands, and that without the drug companies there would be no new drugs for TB at all.

-It really is doing something for society. To operate in India and other countries where TB is a mayor healthcare challenge. We are the only companies that really can do this. Academic research can lead to a better understanding of a disease but medicines are overwhelmingly discovered and developed by pharma. We have to do this, if we don´t who will, asks Manos Perros?

Back in New Delhi, I meet a person who has one possible answer to that question.
Professor Samir Kumar Brahmachari is an energetic and jovial man with thin mustache and thin hair. He is the head of one of India's largest research councils CSIR "Council for Scientific and Industrial Research" and launched four years ago an open research project called "Open Source Drug Discovery". Anyone can join through a web portal and solve different sub problems about TB and share knowledge. So far, 5500 students, researchers and companies from more than 100 countries have joined the project, even though the majority are from India.

Each researcher posts and contributions will be logged to clearly show who did what, because if it ever becomes necessary to go to Stockholm to receive the Nobel Prize, it's important to know who was first, chuckles Professor Brahmachari.

He is mighty proud of his creation. It took only a few months for 800 university students to go through the 4,000 genes in the tuberculosis bacterium's genome and in a standardized protocol write down the function of each bit of the genome. So far, the open Web project have developed two drug molecules that are now undergoing animal testing. It has also teamed up with "TB Alliance" for future trials in patients and also attracted one of AstraZeneca's top research directors to lead this effort.

The IT revolution was started by people under 25, says Prof. Brahmachari. But they are not allowed into the drug development process, no wonder that only one of 100 ideas, eventually, become a medicine. Brahmachari has created a social network for all young hungry and smart researchers who likes to solve real world problems together, he says, and expects that this initiative can accelerate the process and bring down the cost of drug development.

Brahmachari also reminds us that India is the world leader in manufacturing pills super cheap if they are not protected by patents and that the country has an obligation to address the tuberculosis threat without too much focus on profit.

Back to 18 year old Mdish with MDR TB who expect an improvement after 3 months of treatment but where more than a year and a half remains. He hopes he can return to his village in Bihar province, with the help of the doctors and of Allah and that he will be able to finish his ninth grade. Perhaps he can also go high school so he can get a job that gives the family enough money for his three dowry.

But how long will it be before there are new medicines that really cure all patients with TB and not requires incredibly long treatment?
- The global anticipation with all our partners together is that by mid 2020s we would certainly have an entirely new cocktail of TB-drugs, says Bala Subramanian on Astrazeneca.
- But if you fail to develop new medications that work and if the resistance continues to increase, what will happen, I wonder anxiously?
- Sad to say, back to the pre-antibiotic era of how TB.patients where managed. Good care, well ventilated rooms in sanatoriums.

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