NDM-1 Superbug: Some thoughts

There has been considerable outrage over the recent Lancet Infectious Diseases article [1] in the Indian media during the past 48 hours.

“Such infections can flow in from any part of the world. It’s unfair to say it originated from India,” said ICMR director Dr VM Katoch. [Link]

“This is not supported by any scientific data. This occurs in nature and in the intestines of animals and humans universally. Similar strains found in the US and UK,” said National Centre for Disease Control Director RL Ichhpujani. [Link]

Nobody ever used the term Mexican swine flu though the disease originated there,” said Dr Shalini Duggal, consultant Microbiologist, Dr BL Kapoor Memorial Hospital. [Link]

“India strongly refutes the naming of this enzyme as New Delhi metallo beta lactamase (NDM-1) and also refutes that hospitals in India are not safe for treatment, including medical tourism. [Link]

“Intellectual scientific freedom is all very good but there is a conflict of interest in this research. Researches like these are examined separately according to the code of ethics,” added Srivastav. [Link]

Few comments on these statements:

1. The gene was named New Delhi metallo-beta-lactamase 1 (NDM-1) after it was isolated from a Swedish patient of South Asian origin who was operated in New Delhi in December of 2007. The patient acquired an urinary tract infection in January 2008 caused by a carbapenem-resistant Klebsiella pneumoniae strain. This K. pneumoniae strain (and later isolated E. coli) carried a novel metallo-beta-lactamase (MBL) gene. [2]

Considering the infection was likely to be nosocomial and picked up during the operation in New Delhi, the authors named the novel gene after the place where it might have come from. No malicious intent, just simple naming protocol. This is not out of the ordinary – consider for example Ebola virus is named after the river where it was first isolated. There are other variants of the lactamase gene named after Verona(Italy), Adelaide(Australia) and Paulo (Brazil).

2. The second is the more insidious charge against the authors that since they have ties to the pharmaceutical industry, they are lying (similar charge was bought up during the H1N1 is a WHO conspiracy hoax). All authors have to declare conflict of interest when publishing in biomedical journals(*). To not do so is unethical (Wakefield study that was published in Lancet is a good example). Having a conflict of interest does not by itself imply wrong doing.

3. The main point, in my opinion, is that people are presuming this as an attack on Indian Healthcare.  The reason being the comments made by the authors in the the discussion section of the paper:

Several of the UK source patients had undergone elective, including cosmetic, surgery while visiting India or Pakistan. India also provides cosmetic surgery for other Europeans and Americans, and blaNDM-1 will likely spread worldwide. It is disturbing, in context, to read calls in the popular press for UK patients to opt for corrective surgery in India with the aim of saving the NHS money. As our data show, such a proposal might ultimately cost the NHS substantially more than the short-term saving and we would strongly advise against such proposals. The potential for wider international spread of producers and for NDM-1-encoding plasmids to become endemic worldwide, are clear and frightening. [1]

Is this an over reaching statement made by the authors? Lets see the basis on which they make this claim.

The study found NDM-1 isolates in Chennai (44), Haryana (26), UK (37) and various cities in India, Pakistan and Bangladesh (73).  The cases are  found not only in patients in a hospital but in outside community (in people with UTIs {Urinary Tract Infections}). This is what concerned the authors.  This fear is validated by a study carried out by Deshpande et al at the Hinduja hospital who found 22 (out of 24) NDM-1 positive strains in a three month study [Link]. The ease of horizontal transfer of a plasmid borne gene coupled with human globe trotting, does indeed cast a somber view on the cost effectiveness of medical tourism. As I type this post, NDM-1 has claimed it’s first fatality and so it is safe to assume that the case for concern is not overstated.

It is not just the British doctors asking for caution. The call for alarms have been raised in India for years, only to be completely ignored. Since antibiotics are wrongly prescribed, over used and unregulated in India, it is easy to generate resistant strains. Several papers have been published documenting the rise of  antibiotics resistance in the sub-continent and the need for proper usage of antibiotics [Link].

It is important to see the rising resistance of pathogens in context of drug discovery.  While novel antibiotics discovery flourished in the 1940-80, we have in the past two decades put out one new antibiotic (oxazolidones)! (The rest have been modifications of existing classes).

Also, the absence of a Central Monitoring Agency (like in UK or US) to track antimicrobial resistance in India makes it hard to track how many resistant pathogens are out there.  Many countries have a multi-pronged approach in place to deal with the growing crisis of resistant drugs [3] but India has no such strategy. As Ghafur puts it:

“The easiest way of tackling the superbug problem is to use the notorious ostrich strategy which denies the existence of the problem: stop looking for these bugs, stop looking for the hidden resistance mechanisms and closing your eyes even if you find them.” [Link]

There is nothing to be outraged about with the details in the Lancet paper but much to be concerned about. An effective way to deal with the concerns raised in the Lancet paper would be to establish a central monitoring agency and to regulate antibiotics use in India. This would not only reassure the global medical community that India too is concerned with superbugs but also bring about much needed reforms in Indian medicine.

[1] “Emergence of a new antibiotic resistance in India, Pakistan, and the UK: a molecular, biological, and epidemiological study” by Kumarasamy et. al., The Lancet Infectious Diseases, DOI: 10.1016/S1473-3099(10)70143-2

[2] “Characterization of a New Metallo-?-Lactamase Gene, blaNDM-1, and a Novel Erythromycin Esterase Gene Carried on a Unique Genetic Structure in Klebsiella pneumoniae Sequence Type 14 from India” by Yong et.al., Antimicrob Agents Chemother. 2009 December; 53(12): 5046–5054.

[3]”Moving from recommendation to implementation and audit: Part 1, Current recommendations and programs: a critical commentary” by Carbon et; al, Clin. Microbiol. Infect. (Suppl. 2); 8:92-106

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