NDM-1: More Evidence It Started in India

So it looks like the researchers who named NDM-1 — New Delhi metallo-beta-lactamase, the “Indian super-enzyme” that renders common gut bacteria impervious to all but one or two antibiotics — were right all along.

According to a study just published in Antimicrobial Agents and Chemotherapy, the problematic gene that produces it has been circulating in Indian hospitals since at least 2006.

Kinda undermines the claims by Indian politicians and the country’s health ministry that the resistance factor did not originate in India, but was given its name in an act of “malicious propaganda” aimed at undermining the subcontinent’s multimillion-dollar medical-tourism industry.

A brief recap:

Back in 2008, clinicians in Sweden and collaborators at the University of Cardiff identified a novel resistance factor in an isolate of Klebsiella pneumoniae from the urine of a Swedish resident of Indian origin who had returned to New Delhi for a visit and was hospitalized there, and subsequently hospitalized again at home. In accordance with convention, they named the enzyme and the gene that directs its production for its apparent source, making it the latest on an internationally recognized list of resistance factors named for cities in Italy, Germany, Brazil and so on.

That initial finding didn’t get much notice, even though Britain’s Health Protection Agency published a worried alert in 2009 about the resistance factor’s spread there. Ditto for a bulletin from the U.S. Centers for Disease Control and Prevention last summer. Both the British cases and the three in the United States had connections — personal travel or medical treatment — tying them to South Asia.

Then last August, the original team plus collaborators from six Indian institutions published a substantial update in which they found 180 instances of bacteria manufacturing the enzyme in Britain, India and Pakistan; clear epidemiologic links from South Asia into the West; and further spread of bacteria carrying NDM-1 to other patients with no ties to India.

The mud flew. The British researchers at the head of the team were denounced as “unscientific,” “irrational” and the perpetrators of a “sinister design of multinational companies” — claims that conveniently ignored three alarmed reports of NDM-1 that were published in Indian medical journals by Indian scientists earlier in 2010.

But now: In this new paper, another multinational team — Iowa, Massachusetts, Australia, India — delves into bacterial samples that came from 14 Indian hospitals in 2006 and 2007 and were sent to SENTRY, an international surveillance network (run by Iowa’s JMI Laboratories). Out of 1,443 isolates of Enterobacteriaceae (the bacterial family that includes Klebsiella, in which NDM-1 was first identified), they found 15 carrying the key gene, blaNDM-1, one carrying blaVIM-5 — that produces the resistance factor named after Verona, Italy — and 10 carrying yet another new resistance gene, blaOXA-181. The isolates came from patients in hospitals in Mumbai, Pune … and New Delhi.

The authors emphasize that:

These are the earliest NDM-1-producing isolates reported to date, indicating that isolates producing this carbapenemase have been present in India earlier than previously appreciated.

As with the original Swedish isolate (which these predate by two years) and the U.S. and British ones, these Indian isolates were highly resistant to multiple families of drugs, including to the last-resort category called the carbapenems. They could be treated only by the new and imperfect drug tigecycline and the old and toxic drug polymyxin B. And as in the other NDM-1 reports, the genes were contained on mobile genetic elements, meaning they would be capable of moving easily between individual bacteria and entire bacterial species — something that other researchers have reported observing.

The value of this study isn’t only to show the need for national bacterial-surveillance systems. If India had one in 2006 — or even had one now — NDM-1 might have been identified years earlier than it was, and its spread to a dozen other countries and dissemination into everyday life might at least have been slowed down. And it isn’t to show that the original discoverers of NDM-1 were vilified unfairly — though that’s important, because they were.

Primarily it demonstrates the utter pointlessness of pretending that bacteria respect either borders or the pontifications of politicians who deny their existence.

That’s a lesson that China learned the hard way, when it denied and tried to conceal the start of SARS in late 2002 — an effort that worked for approximately six months, until a physician who had been infected in his own hospital fled to Hong Kong carrying the virus and sparked an epidemic that girdled the globe in a month and killed almost 800 people. It’s absurd that, seven years later, another country has to demonstrate the same lesson again.

Cite: Castanheira M et al. “Early Dissemination of NDM-1- and OXA-181-producing Enterobacteriaceae in 14 Indian Hospitals: Report from the SENTRY Antimicrobial Surveillance Program (2006-2007).” doi:10.1128/AAC.01497-10

Image via ORBIS US/Flickr/CC


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