Saturday, March 31, 2012

India: Politics, Greed, and the Attack of the Superbugs

The emergence of antibiotic-resistant bacteria has become a growing problem. Sonia Shah has an article in Foreign Affairs that discusses what is perhaps the most dangerous of the identified bacteria as it has emerged in India: When Superbugs Attack: Antibiotic Resistant NDM—1 Is Undermining India’s Medical Sector.

Hospitals have traditionally been the most efficient locations for producing infections. The nature of the services provided and the population of sick people make the probability of infection significant. It is traditional to support most procedures with a regimen of antibiotics to avoid complications, but this has become a less than certain safeguard. An article in The Economist provides some needed background about these superbugs.

"The best-known is methicillin-resistant Staphylococcus aureus, known as MRSA. In America the Centres for Disease Control and Prevention says that around 94,000 people get serious MRSA infections each year and 19,000 of them die. Yet around one-third of people carry some form of S. aureus without coming to any harm."

"Most people who die from MRSA succumb to the toxic shock that sets in when their immune system goes into overdrive. This is triggered by superantigens, which are powerful toxins produced by the bacteria and which activate a large number of the human immune system’s T-cells in the bloodstream. Usually only a small number of these cells are released to hunt down and destroy an infection, with more called up as reinforcements if necessary."

The insidious characteristic of these bacteria is that not everyone who is infected will receive treatment, allowing the threat of further infections to continue.

The development of antibiotic resistance seems inevitable, but the timescale for development can be speeded up by overuse of antibiotics. Consider this chart from another article in The Economist.

The greater the use of antibiotics, the more prevalent are the drug-resistant bacteria.

Sonia Shah, in her article, tells us that the emergence of a superbug is already serious in a developed country. When it occurs in a country where quality health care is not available to large fractions of the population it can be a disaster.

"Taming the new drug-resistant pathogens requires ever more toxic, expensive, and time-consuming therapies, such as a class of last-resort antibiotics called carbapenems, which must be administered intravenously in hospitals. In the United States alone, fighting drug-resistant infections costs up to 8 million additional patient hospital days and up to $34 billion every year."

"Now, the emergence in India of a particularly nasty form of antibiotic-resistant bacteria, which renders even the last-resort drugs obsolete, could bring about an era of unstoppable infections."

What has developed in India is not just a single form of bacteria, but the emergence of a gene that confers drug resistance on any bacteria that it manages to invade.

"The gene that conferred this extreme drug-resistance was dubbed "New Delhi metallo-beta-lactamase 1" or NDM-1. Scientists found that, unlike other drug-resistant bacteria, NDM-1 bacteria are able to quickly and prolifically spread their genes to other bacteria, easily jumping the barriers of species and genus. The pandemic potential of such a microbe is enormous. Indeed, according to Tim Walsh, a University of Cardiff medical microbiologist who has been chasing the dangerous gene, NDM-1 infections already turned up in more than 35 countries last year -- often in the bodies of medical tourists, who had traveled to India or Pakistan for cheap surgeries and other procedures. And NDM-1 bacteria have also been found in drinking water and in puddles around New Delhi."

And what has been the effect of the emergence of this drug resistance?

"Then, in 2010, a study of a New Delhi-area hospital found that 24 percent of bacterial infections there could resist the last-resort carbapenem antibiotics. Thirteen percent not only resisted carbapenem drugs, but overcame 14 other antibiotics, making treatment options exceedingly limited."

India is fertile ground for evolving bacteria.

"In India, antibiotic use is virtually unregulated. Antibiotics are widely available without a prescription and, as in the United States, affluent people tend to consume the drugs whether medically necessary or not -- for everything from colds to diarrhea. Meanwhile, when ill, India's poor tend to scrape together a few rupees to buy a couple doses of antibiotic at a time, enough to quell their symptoms but not enough to clear their infections. Both patterns of consumption contribute to the development of drug-resistant bacteria. So, it is no wonder that, even before the new super-resistant strain was first documented, over 50 percent of the bacterial infections that occurred in Indian hospitals were resistant to commonly used antibiotics."

Part of the problem is a lack of investment in healthcare.

"....government spending on health hovers at around one percent of GDP a year, a proportion that critics condemn as far too low for a country with a prospering economy that is still heavily burdened by infectious disease. (Only Burundi, Cambodia, Myanmar, Pakistan, and Sudan spend proportionally less.) In India's finance-starved public hospitals, overcrowding is common and corruption rife. Nearly one-third of patients report having to resort to bribes just to get clean bed sheets."

Strangely, while public sector healthcare is starved, private sector care for the wealthy thrives.

"....the private health sector has boomed. Encouraged by government tax exemptions, corporate hospital chains such as Apollo and Fortis, which are owned by large pharmaceutical and technology companies, dot the landscape, islands of apparent sterility amid the grime. Now, 80 percent of total Indian health expenditure goes to private clinics and hospitals. Besides caring for India's affluent, many of these hospitals market their upscale services to ‘medical tourists,’ patients from the UK, the United States, the Middle East, and elsewhere, who fly to India for procedures that are cheaper and quicker there than they would be home. It is a growth industry that brings in hundreds of thousands of foreign patients...."

"It was in the bodies of medical tourists who had traveled to India and Pakistan that the new super-resistant gene was first discovered by British scientists in 2009."

The British were alarmed and announced that medical tourists might be at risk. How did India respond?

"Indian politicians, news media, and physicians cried foul, suggesting a conspiracy to undermine the medical tourism sector. India's National Centre for Disease Control spent days openly denying the public health relevance of NDM-1. Government authorities sent letters to Indian researchers who had collaborated with British scientists on the NDM-1 studies, demanding that they disavow their research. They also tried to prevent scientists from taking samples of NDM-1 out of India for research purposes."

It would be unfair to imply that India did not try at all to respond appropriately to the threat.

"As the controversy over NDM-1 swirled, in 2011 New Delhi convened an advisory committee on the issue of antibiotic resistance which floated a proposal to ban the sale of antibiotics without a physician's prescription, and restrict the use of last-resort IV antibiotics to highly specialized hospitals. But after pharmacists went on strike in August 2011, the proposal was withdrawn."

If India’s politicians are unwilling or unable to take appropriate steps, surely the pharmaceutical companies are hard at work countering the threats provided by these superbugs.

"According to the Infectious Diseases Society of America, the drug industry has actively avoided developing new antibiotics. This is a business decision: drugs that are prescribed for months and years, such as anti-arthritis or cholesterol-lowering drugs, and those for which patients and insurers will pay almost any sum, such as anti-cancer drugs, provide better return on investment. Antibiotics are costly to develop, only prescribed for a handful of days at a time, and, despite their curative powers, rarely fetch more than $100 per course. Further, all antibiotics eventually render themselves -- and the R&D investment behind them --obsolete, since their use inevitably creates new drug-resistant pathogens."

A chart from the article in The Economist provides the evidence.

Drug companies don’t seem concerned; politicians don’t seem concerned—what might the future hold?

"Nobody knows how many people may have already died from NDM-1 bacterial infections, nor how many more may sicken or die should the gene become more widespread. It may be that NDM-1 has to gain more notoriety and ‘get a lot more scary,’ as the Times of India put it last spring, before political will to do something about it coalesces. For now, experts such as Walsh estimate that NDM-1 bacteria silently lurk in the guts of up to 200 million people in India alone, evolving, exchanging genes with other bacteria, and being shed into the environment. In an interconnected world, they will not remain quarantined there for long."

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