TB's deathly march along India, China growth

World TB Day

Over the millennia it has killed more humans than any other disease, decimating a billion people in the last century and 1.7 million people in 2009 (the most recent year for which statistics are available) or about 5,000 a day. But although the Mycobacterium tuberculosis, TB for short, is the world’s number one killer, it is completely curable.

In rich parts of the world, TB has a medieval resonance. In the 17th and 18th centuries it was the cause of a quarter of all deaths in Europe. Today, the microbe has shifted geographies and it is in Asia and Africa that it mainly wreaks its devastation.

Ironically the countries with the highest TB burden in the 21st century are the very two that are most often touted as the world’s new super-powers in waiting: China and India.

Despite a large scale, ongoing campaign undertaken by the Indian government to arrest the spread of TB since the late 1990s, the WHO (World Health Organisation) estimated 2 million new cases of the disease in India in 2009, of which 1.3 million were actually reported or notified. This makes India the country with the largest absolute number of TB patients in the world, second to China which had an estimated 1.3 million new cases in the same year.

Worldwide, 9.4 million new cases of the bacteria were estimated, with 5.8 million actually being notified. Despite the availability of a cocktail of drugs that if taken as prescribed can fully cure TB, the disease thus continues a deathly march across the poorer parts of the world.

The most worrying development is that over the last 15 years or so the microbe has been showing increasing resistance to antibiotics, spawning hundreds of thousands of cases of what is known as multidrug-resistant TB or MDR-TB.      

Dr Mario Raviglione, Director of the WHO’s Stop TB Department, explains that somewhat counter-intuitively, one reason for this development is in fact the increased access to TB drugs in poor countries.

The usual course of treatment for ‘normal’ TB is an arduous 6 months long process, involving a six-drug combination. But if patients stop taking the drugs before the course is complete, as if often the case once they begin to feel better, or alter the composition of their dosage, by stopping one or more of the 6-drugs involved, the resilient TB bacterium develops resistance to the treatment.

For the patient the result is MDR-TB a far more complicated disease to cure. MDR-TB is not only more difficult and expensive to diagnose, it takes up to 2 years of treatment to treat. While the cure rate for those with regular TB is at around 90 percent, only some 60% of those with MDR-TB recover.     

India had an estimated 100,000 cases of MDR-TB in 2009, while the global figure was 440,000. Officially notified cases of drug resistant TB are however very few, globally numbering some 30,000 cases.


MDR-TB is treated with a combination of a variety of second line drugs. But a decade ago these were both prohibitively expensive and largely unavailable in countries like India.

Dr Patrizia Carlevaro who heads the pharma giant Eli Lilly and Company’s international aid efforts explains that TB has not been a priority for western pharmaceutical research, because there are scant profits to be made in developing drugs for it.

The majority of those infected with TB live in developing countries with limited means to pay for expensive drugs. As a result, unlike HIV (the AIDS virus) which has received huge attention and funding over the last few decades, TB research has languished as something of a step sister.

She says that there has been a shift in recent years, with TB coming back into focus, partly as a result of the WHO’s efforts and partly because of the discovery of its synergistic mingling with HIV (a quarter of those with HIV die as a result of contracting TB). But even today, the market for TB drugs is small, worth a few hundred million dollars a year.
   
Eli Lilly is thus unusual in having made MDR-TB the main focus of its international aid, a decision the company took around 10 years ago, following discussions with the NGO Medcine Sans Frontières. Eli Lilly manufactured two of the main second line drugs used to treat MDR-TB. It decided towards the end of 2000, to offer the transfer of technology and expertise to manufacture these two antibiotics to appropriate partners in high-burden countries.

Dr Carlevaro recalls that at the outset there were few takers for their offer.  “We met with Indian companies but they were simply not interested because it was too small a market and they felt it would not be commercially viable.”

Eventually Eli-Lilly set up an MDR-TB partnership with 17 different entities, including NGOs, universities and drug manufacturers in 2003. In India they entered into a technology transfer agreement with Shasun Chemicals and drugs.

Currently Shasun in India and Eli’s partner company in China manufacture the API (active pharmaceutical ingredients) for the drugs which are then sent to South Africa and Russia where other members of the partnership develop the final formulations.

“It’s a great example of south-south cooperation,” says Dr Carlevaro.

But programmes like the Lilly MDR-TB partnership are a drop in the ocean. The WHO’s Dr Raviglione explains that one of the main challenges raised by MDR-TB is its diagnosis. Standard TB is tested via a smear test, whereas to identify MDR-TB a culture of the bacteria must be made. While a smear test takes 20 minutes, developing a culture can take weeks and is much more expensive.

In India there is one lab per 100,000 people capable of conducting a sputum smear test. But for cultures, the ratio of qualified facilities to the population stands at one to 50 million people. There is thus a high degree of probability that the vast majority of those with MDR-TB in India remain undiagnosed.

The TB situation in India is currently “stable” says Dr Raviglione, with the number of new cases per year holding flat. This is itself is an achievement that should not be downplayed he hastens to add. But the fact that a curable disease still costs a thousand lives a day in the country is a “scandal.”

Moreover, TB has always been associated with industrialization. The industrial revolution in Europe went hand in hand with the disease, known then as consumption. In countries like India millions of people are expected to migrate from villages to crowded cities and slums over the next few years, providing a fertile gestational ground for the spread of the bacteria.
 
TB thus remains one more powerful examples of the schizophrenic nature of India today. A global power that lacks the capacity, or some would argue the will, to protect its own citizens from a curable mass-killer.