Interview: Dr Rajesh Gokhale
India requires newer drugs and diagnostic tools to tackle extra-pulmonary TB: Dr Rajesh Gokhale
Gunjan Sharma|
Wednesday, February 14, 2018

Dr Rajesh Gokhale, former director, Institute of Genomics and Integrative Biology, is an eminent scientist. After a path-breaking research in leucoderma, he is now working to find an effective treatment for bone TB.

He talks to Gunjan Sharma about his research, the growing burden of extra-pulmonary tuberculosis and how India can eliminate tuberculosis by 2025.
 
India plans to eliminate tuberculosis by 2025. Do you think it is achievable?

As a scientist, I can never say 'never' because there is always a possibility of wonders happening. But I feel eliminating tuberculosis requires drastic measures: the Revised National Tuberculosis Control Programme is not enough. The government has started some advertisement campaign, which is fine, but what we need are well-defined goals.
Tuberculosis in this country is a multifaceted problem: it requires newer drugs as well as diagnostic tools. We need to address latent TB.

How big is the problem in India?

Mycobacterium Tuberculosis is one of the longest surviving bacteria in the world. It has an ability to adapt in different environments. We believe that latent TB is present in a large, around 70-90 percent, population of India and the disease manifests only in 8 to 10 percent. 
Initially, we blamed malnutrition for converting latent TB into infection but now we have begun to understand that it’s the body’s immunity which is responsible for the manifestation of the disease.

Besides, earlier, tuberculosis was considered a pulmonary infection but now we see a lot of cases of extra-pulmonary TB. Over 25 percent patients at CMC Vellore's OPD come with spine, brain, lymph nodes and even abdomen TB.

So, what do you think is the reason?

Talking about the host, that's us, our immunity has improved a lot in the last 60-70 years and it is evident from the fact that the life expectancy has increased from 46 to 67 years. At the same time, tuberculosis pathogen has also changed. I feel that TB bacteria are trying to adapt to different body tissues now.  If it is so, we have to be ready to manage it.

How do we treat extra-pulmonary tuberculosis?

Doctors give the same TB drugs for longer duration –from 12, to16, to18 months. In fact, WHO's recommendations are also the same.

But I strongly feel that we should not do this. PKPD (Phamaco Kinetics and Pharmaco Distribution) is an important aspect of the treatment. The current drugs have been optimised for the lung tissue, we do not know if the same drug reaches the sclerotic lesions of the bone and in what concentration.

The only study I could find was done in mice, which shows that less than 0.1 percent drug reaches the bone tissue. Bone tissue is very different from the oxygenated lung tissue.

Generally, we take different drugs for different set of organs. Take for example, doctors prescribe different antibiotics for urinary tract infection and throat infection.

Are there drugs for extra-pulmonary tuberculosis under development?

Ironically, though maximum number of researchers in India are working on tuberculosis, none is working on extra-pulmonary TB. Pulmonary TB is our existing problem, but extra-pulmonary TB could be a bigger problem in the next 5-10 years.

What challenge does it pose?

If we keep treating extra-pulmonary TB the way we do now, people with bone, gastric, and brain TB would become the biggest reservoirs of resistant tuberculosis.

The problem is we do not have diagnostic tools to confirm extra-pulmonary TB. We work on hit and trial method. To give you an example, Crohn’s disease or Inflammatory Bowel disease is an auto-immune disease whose symptoms are same as that of intestine tuberculosis. A patient needs to take immune-suppressants to treat Crohn’s but if it is TB, immune-suppressants can aggravate it. So, most doctors give anti-TB medicine when in doubt and if the patient doesn’t respond to it, they change the treatment. But in the process, they do a lot of harm to the patient.

There is no definite diagnoses for brain TB or spinal TB either.
 
And what do you think India needs to do to tackle the challenge of extra- pulmonary TB?

Since extra-pulmonary TB is not present in western countries, and so it is not their concern. We need to set up our own research units with a special focus on extra-pulmonary TB.
We need an animal model of extra-pulmonary tuberculosis so that we can develop drugs to treat it effectively.

Besides, we need to bring all the researchers working on tuberculosis together. We need to involve younger people in research who have at least 10-15 years of career ahead of them so that they can pursue a project to its completion. We need to change the way we promote scientists-- we cannot look at individual's achievement in research as research is a team effort.

What are you presently working on?

I am studying how different organs crosstalk when TB bacteria enters the body. I believe that diseases are not localised to one organ but are actually systemic in nature. For example, when TB infection begins, the lipid profile of the body, which is regulated by the liver, goes down. But we don't treat liver of a TB patient.

In Ayurveda also it is believed that liver has a critical role to play in every disease.

We have genome sequenced 56 strains of TB bacteria, all of them are found to be similar. That means it is the same bacteria that adapts to different tissues.

I wanted to know where TB bacteria live in the bone. The bone is made up of two types of cells—osteoclasts that destroy the bone cells and osteoblasts that generate new bone cells. Mycobacterium survives in osteoclasts and  makes them bigger and more active. As a result they eat up the bone faster than the osteoblasts can make it.

Eventually, I want to see if there are antibiotics that can kill the TB bacteria residing in osteoclasts effectively. The idea is to come up with a drug or drug regimen to treat bone TB more effectively.

A lot of doctors are now emphasising on the need to build the body’s innate immunity to deal with drug-resistant TB. What do you think?

Yes. It is an important aspect. We are also trying to study the host's immunity. There are studies that show that hepatic cells regulate the immunity. If we can establish it, we will be able to treat TB more effectively.

Do you believe in Ayurveda concepts?

Absolutely. Ayurveda's concept of looking at the body as a whole is right. We have to validate these principals scientifically to reap the benefits.
 
 

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