NDM-1 in India: Drug Resistance, Political Resistance

It’s been more than a year since the “Indian superbug” NDM-1 — not actually a bacterium, but a gene that directs production of an enzyme — hit the news. The enzyme, whose acronym is short for New Delhi metallo-beta-lactamase-1, disables almost all antibiotics directed against it, leaving the bacteria in which the gene appears vulnerable to only two imperfect and sometimes toxic drugs.

The enzyme and its gene, blaNDM-1, were first identified in 2008 in people who had traveled in India or sought medical care in South Asia. Hence its name: Many beta-lactamases, enzymes that denature the very large class of everyday antibiotics known as beta-lactams, are named for countries and cities where they were first identified. Since its identification, NDM-1 has been discovered in patients in more than a dozen countries and has also been found to be widely harboured outside hospitals in India, and in surface waters and sewage there.

The unveiling of NDM-1 clearly caused embarrassment for India, and media and lawmakers there struck back, throwing around intemperate language and claiming the naming of the enzyme was a plot to derail the subcontinent’s medical-tourism industry — even though the Indian doctors had attempted to raise the alarm earlier and had been ignored.

So it seemed like a promising signal of openness when an international conference on antibiotic resistance opened in New Delhi a week ago. But in its wake, just what is going on in India — and whether its government is willing to face up to what might be an international crisis — is less clear than ever.

In the run-up to the conference, health authorities and researchers were clearly hoping that India would back off from its defensive posture and allow collaborations with European scientists in the West who have gotten further in researching the bug. That doesn’t seem to have happened. But the chorus of competing voices coming out of New Delhi in the wake of the meeting seems to indicate that opinion regarding NDM-1 is not monolithic, and maybe that at least is a hopeful signal.

A little background: The gene for NDM-1 travels on a plasmid, an extrachomosomal loop of DNA that can be traded freely among bacteria. It has been found so far in a variety of bacterial species, but particularly in the gut bacteria that can cause serious infections in vulnerable hospital patients. In hospitals, bacteria carrying NDM-1 move from person to person when patients who have received many antibiotics and other drugs develop diarrhea and traces of feces contaminate surfaces, equipment and healthcare workers’ hands. Out in the community, the bacteria carrying the enzyme passes from person to person when traces of feces contaminate municipal water supplies — and with a large percentage of the population lacking any access to sanitation, India has significant water-quality problems.

The best news out of the conference seems to have been the activism of the Times of India, which on Oct. 5 showcased the results of a study done at private Sir Ganga Ram Hospital. The study found NDM-1 in 8 percent of E. coli samples and 38 percent of Klebsiella pneumoniae. (The Times said the total number of isolates in the study, from hospital wards and the intensive care unit, was 10,889, but didn’t break that number down by species.) The newspaper quoted Dr. S. P. Byotra, the hospital’s chair of medicine:

The idea behind this study is to stop denying the crisis NDM-1 poses and work out strategies to check its spread. Antibiotic usage needs to be monitored strictly and good infection-control methods should be put in place at hospitals.

On the same day, the website CGpage quoted the chairman of Indian’s Immunology Foundation saying that hospital waste was carrying NDM-1 into municipal water supplies. The news network IBNlive announced that four infants in the pediatric ICU of a hospital in West Bengal had died within 72 hours as a result of bacteria made untreatable by NDM-1, and that the Public Health Foundation of India believes that 60,000 infants per year are dying of drug-resistant infections.

But if those stories were an attempt by prominent Indian researchers to guide the public conversation, they did not work. Three days later, the health minister of Delhi, A.K. Walia, said that a competing government-funded study had also found bacteria carrying NDM-1 in the ICUs of four hospitals including Ganga Ram — but at much lower rates than the hospital’s own study. “The prevalence rate of NDM-1 is in the range of 0.04 percent to 0.08 percent, which cannot be stated as alarming.” he said.The superbug has not been found in water and sewer lines in Delhi.

At the same time, the government backed off a previous promise to rein in the unlimited over-the-counter sales of antibiotics that are widely believed to contribute to the spread of resistant organisms. Officials who said the ban needed to be delayed cast it as an action on behalf of rural residents. Dr. V.M. Katoch, director general of the Indian Council of Medical Research, said: “Several parts of rural India do not even have doctors to prescribe an antibiotic. At present, people go to shops and purchase the antibiotics needed to cure their illnesses. Bringing in this schedule would mean that shops wouldn’t have the drugs.”

And simultaneously, the government announced strict new curbs on taking biological samples out of India without abundant paperwork — an action that certainly seemed aimed at the British and Scandinavian researchers who exposed the wide distribution of NDM-1 in South Asia by analyzing samples smuggled out  with the help of a TV crew.

Despite what seems to be an obdurate refusal to face the risks its own citizens are exposed to — and which India is inadvertently exporting, in what seems to be contravention of the World Health Organization’s International Health Regulations — there was a glimmer of hope. The Times of India reported:

The state health department has been jolted into action. It has called an emergency meeting of all stakeholders to analyse the report and find a solution to the danger. Delhi Health Minister A.K. Walia said the meeting will be held on Friday and representatives from Ganga Ram hospital… Indian Council of Medical Research (ICMR), National Centre for Disease Control (NCDC) and pathologists from Lok Nayak hospital among others are expected to attend.
“It is a serious issue… I have called a meeting of all stakeholders to discuss the matter,” said Walia.

If India is moving to contain NDM-1, it is doing so barely in time. Dr. Timothy Walsh, who first isolated the gene and enzyme in a resident of Sweden who had been hospitalized in India, told the Times of India:

We estimate that the carriage rate of NDM-1 in India is between 100 and 200 million, which means that NDM-1 has become a very serious public health issue… With globalization, NDM-1 will continue to spread unchecked around the world and once established in higher enough numbers in a particular country, will further disseminate.

We are desperate to help in any way we can to initiate studies to realize the full impact of NDM-1 on Indian society… I cannot say whether the Indian government is finally taking the issue seriously — only they can answer that charge. However, what is clear is that we have lost a year fighting amongst ourselves when our energies and resources should have been focused elsewhere — on NDM-1.

See Also:

Klebsiella, Public Health Image Library, CDC


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