A research paper entitled “Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study” published by Karthikeyan K Kumarasamy et al in Lancet Infectious Diseases has generated an enormous amount of controversy over the last 48 hours. The article has resulted in an staggering media uproar in India primarily based on certain recommendations presented in the conclusions section. The authorities have also issued a Clarification on this matter, something I’m at least not aware of any government ever doing in the aftermath of a single peer-reviewed biomedical publication. (Incidentally, it is a minor point, but the Clarification misstates the name of the journal as Lancet when it was published in Lancet Infectious Diseases, a sister publication).
The summary of the manuscript is here and has been discussed in accessible terms by Maryn McKenna. A number of concerns have been voiced in various outlets and I’m discussing some here.
1) The first concern is that the naming of the plasmid enzyme as New Delhi metallo-β lactamase and the gene as blaNMD-1 are malicious. However, this type of strain designation is not uncommon in microbiology. In fact, the location where the strain is most likely to have originated is quite often used. For example, the most common metallo-β-lactamase enzyme (which confers resistance to antibiotics) in clinical isolates is the VIM-2 β-lactamase named after Verona in Italy where it was first isolated. Incidentally, Italy did not lodge a formal complaint anywhere (as far as I know) after it was discovered. I’ll discuss why India chose to do so when I get to the third concern.
Additionally, there are other diseases and pathogens named after locations as diverse as Marburg, Germany; Ebola, Congo; and even the Rocky Mountains in the US. No one ever blinked as far as I know.
Now, some information on the history of the NMD-1 strain is warranted. The first case using this designation was discovered in the middle of 2009 in an article published later in December. In other words, the strain was named a year to six months before the Lancet Infectious Diseases paper at the center of the current storm came out.
In the earlier article, the case history of the first patient harboring a bacterial strain with NMD-1 was provided.
In November 2007, [the patient] traveled to India and on 5 December was hospitalized in Ludhiana, Punjab, with a large gluteal abscess. In December 2007, he was admitted to a hospital in New Delhi, where he was again operated on and where he developed a decubital ulcer. On 8 January 2008 he was referred to Örebro, Sweden. During his stay in New Delhi he received amoxicillin (amoxicilline)-clavulanic acid, metronidazole, amikacin, and gatifloxacin (all of them parenterally). Clinical isolate K. pneumoniae 05-506 was derived from a urinary culture on 9 January 2008.
It is this clinical isolate that bore the plasmid with the infamous NMD-1 strain. While it is formally possible that the patient picked up the infection during his flight back to Sweden, knowing what we know about the bacteria that harbor it and how it spreads nosocomially in susceptible patients during operative stages, it is very likely that it was picked up during the patient’s operation and hospital stay in December 2007 in New Delhi because the patient simply had not had an operation after that date in any other location. In light of this information the hue-and-cry over the naming is overblown.
2) The second concern is about a potential conflict-of-interest. This has been treated as a revelation by sections of the media. The lead author received a travel grant from Wyeth. Another author holds shares of some major pharmaceutical companies. This was not not unearthered through any investigative reporting; in the interest of full disclosure, this information was mentioned in the actual research paper itself (as is customary practice for all biomedical journals):
KK has received a travel grant from Wyeth. DML has received conference support from numerous pharmaceutical companies, and also holds shares in AstraZeneca, Merck, Pfizer, Dechra, and GlaxoSmithKline, and, as Enduring Attorney, manages further holdings in GlaxoSmithKline and Eco Animal Health. All other authors declare that they have no conflicts of interest… Our work was funded by EU grant LSHM-CT-2005-018705 and WellcomeTrust grant 084627/Z/08.
Obtaining travel money or external seed money does NOT preclude an author from publishing work. All papers at major scientific journals go through a rigorous peer-review process regardless of funding source. What this means is that two or more anonymous, independent scientific experts review the manuscript prior to consideration for publication. I’ll be the first to admit that this process isn’t perfect. But over 130 years, it is the process that scientists have stuck with. The due peer-review process happened for the Lancet Infectious Diseases article too.
What those screaming about “conflict-of-interest” are really implying is there is an occurrence of a gross ethical violation that may be tantamount to the falsification of data. This is a serious unsubstantiated allegation and were those harping loudly to say this directly, they would probably face libel charges in a court of law. An easier way to get around that is to dispute the conclusions which is what the government has done by putting out the release.
What you may not know is the fact is that often the most successful scientists in medicine and biomedical research are those with stakes in companies and startups or those who receive grant-money from pharmaceutical companies. What about those that work for pharmaceutical companies? Should they be banned from ever publishing? Many of us would be out of jobs if that ever came to pass.
As an anecdote I’ll mention that at any cancer meeting, almost all the presenters mention funding sources and startups they are associated with for the sake of full disclosure. Those outside of science may be uncomfortable with this approach, but it is not sufficient to single out a particular paper in a field where it is a common occurrence.
3) The third concern is that the conclusions will harm India’s economy. The most vehement arguments are against the final conclusion of the paper which is stated below:
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.
This is what it is all about, folks! This is the center of the acrimonious debate and is stated directly in the accompanying news-feature too. This is the line that UK media outlets are seizing to call for a moratorium on medical tourism and that their counterparts in India are quashing as biased. The underlying concern is that were medical tourism to get reduced then the Indian economy would get impacted. This is a valid economic concern, but irrelevant to the scientific argument regarding the concern that surgical practices might be unsafe.
With respect to this concern I agree, at least in part, with the government clarification and the viewpoint in the Indian media. The size and scale of testing (44 isolates in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan) does not warrant avoidance of all surgical treatments in India – a country of over one billion people. And the fact that some major media outlets are portraying surgery in India as unsafe is disconcerting.
However,why is a single interpretation in the discussion section being used to question the credibility of the results of the entire study? In my opinion, the proper procedure for damage control in the light of the warning sign that the paper presents is to exert caution and to heighten surveillance. Make sure the doomsday scenario doesn’t happen. So often we’ve seen wounded nationalist pride and blame-shifting, and the potential it has to turn ugly . When SARS first erupted, in order to save its economy, China hid reports so that it could deny the severity of the outbreak – an action that ended up endangering countless lives and devastating the economies of a number of East Asian countries.
By drawing the analogy I am not implying that this is what is going to happen with the NDM-1 strain. What I am saying is that I, you, or anyone else cannot claim to know the severity of a possible outbreak should it happen. Before accepting or denying the threat possibilities shouldn’t we first try to do a proper risk assessment?
For exceptional commentary on additional points related to the unnecessary outrage, I highly recommend reading Sakshi’s and Bongopondit’s responses to some of the other relevant concerns.
Disclaimer: These are my personal views and do not necessarily represent the position of my current or former employers. I am not a physician and do not profess to offer any medical advice here. If you feel you are suffering from an infectious disease ,seek immediate medical attention.