Lancet is an international peer reviewed journal originally started by an English surgeon Mr Thomas Wakley in 1823.The editorial offices for Lancet are based at London, New York and Beijing. It is currently owned by an international medical publishing company called Elsevier based in Amsterdam, Netherlands.
Lancet published an article “Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implication for human health: an environmental point prevalence study” in one of its specialty journals, Lancet infectious diseases, dated 7th April, 2011.
The chief author for this study is Prof Timothy Walsh, who lives in England but works as a Professor of medical microbiology and antibiotic resistance at Cardiff. The co-authors for this study include Janis weeks, David Livermore and Mark Toleman.
The newly published article is about the study conducted by Prof Walsh and his team members to measure the prevalence of the NDM-1 gene in drinking water and seepage samples in New Delhi.
This study involved collecting 170 seepage water samples and tap water samples from New Delhi and evaluating the samples for the presence of the so called NDM-1 gene namely blaNDM-1, by PCR and DNA probing. As a control group 70 water samples were collected from Cardiff Waste water treatment works.
These water samples from New Delhi were transported to the UK and tested for the presence of NDM-1 gene. The samples were collected in the time period between the 26th of September 2010 and the 10th of October 2010.
The current study appears to be a follow up to an earlier article titled “Emergence of a new antibiotic resistance mechanism in India, Pakistan and the UK: a molecular, biological and epidemiological study” also published in one of its specialty journals, Lancet infectious diseases.
The earlier study has come up with some findings suggestive of the presence of enteric bacteria that may have stable beta lactamase variant that could impart resistance to antibiotics in these bacteria
The blaNDM-1 in two of the 50 drinking water samples and 51 of 171 seepage water samples from New Delhi. The gene was not found in any of the samples from Cardiff. Bacteria with blaNDM-1 were grown from the 12 out of 171 seepage samples and two out of 50 water samples and included 11 species in which this particular beta lactamase enzyme has not been reported and these species included Shigella boydii and Vibrio cholerae.
The study also came up with the finding that carriage of the this so called NDM-1 beta lactamase by enterobacteria, aeromonas and Vibrio Cholerae was stable, generally transmissible and also associated with resistance patterns typical for the particular beta lactamase. On the other hand carriage by non- fermenters was unstable in many cases and also not associated with typical resistance.
20 strains of bacteria were found in the samples, 12 of which carried blaNDM-1 on plasmids, which ranged in size from 140 to 400 kb. The gene was also found on isolates of Aeromonas caviae and V. Cholera on their chromosomes.
Conjugate transfer was more common at 30 degrees C rather than at 25 degrees C and 37 degrees C.
The final conclusion as per the study was that NDM-1 beta lactamase was present in the environment samples in New Delhi and also stressed on the significance of its implications for the people living in the city who are reliant on public water and sanitation facilities.
The authors then went on to recommend that international surveillance of resistance, incorporating environmental sampling as well as examination of clinical isolates needs to be established as a priority.
The above study essentially looks like a follow up study to a controversial earlier study titled “emergence of a new antibiotic resistance mechanism in India, Pakistan and the UK: a molecular, biological and epidemiological study”, published in Lancet in September, 2010 edition.
The main author of this above mentioned study was Karthikeyan Kumarasamy a microbiology PhD student and he immediately distanced himself from the study suggesting that the results were manipulated at the time of publication.
Six months after the above study was published we now find that the main author Prof Tim Walsh and two authors, David Livermore and Mark Toleman involved in the current study were also authors in the above discredited study. Essentially all the three of them seem to be hell bent on tracing back the origin of this particular plasmid mediated beta lactamase enzyme, blaNDM-1 back to India.
One of the earlier studies published in Antimicrobial Agents and Chemotherapy, Dec 2009 edition raised the possibility of origin of plasmid mediated beta lactamase enzyme from India. The article’s title is “Characterisation of a new metallo- Beta lactamase gene blaNDM-1 and a novel erythromycin esterase gene carried upon a unique genetic structure in Klebsiella pneumonia sequence type 14 from India.
Mark toleman and Timothy Walsh were both authors in this international study. The study highlighted the presence of an isolate Klebsiella pneumonia with carbapenem resistance and shown to possess a metal-beta – lactamase(MBL) in a Swedish patient of Indian origin with known history of diabetes who travelled to India and acquired a urinary tract infection after having received antibiotic treatment in India for a infected gluteal abscess.
The study also found another plasmid conferring resistance to erythromycin in the faeces of the same patient inferring the possibility of in vivo conjugation which is essentially another form of plasmid mediated resistance. The study at that time concluded that India has poor control on antibiotic prescriptions and the rapid dissemination of such a plasmid conferring multiple antibiotic resistance to bacteria is alarming.
When we look at all studies related to the so called New Delhi Beta lactamase enzymes and its conferred antibiotic resistance there is lot of emphasis placed on the patients travel history and associated hospital treatment in Indian hospitals. To some extent they may have been right in raising the possibility of causation factor being indiscriminate usage of antibiotics in some of these patients. But to quickly conclude that plasmid mediated resistant enzymes and the related DNA has actually originated from India is tantamount to exaggeration.
What these authors seem to be selectively ignorant to is the fact was that NDM producing enterobacteriaceae has now been reported in many countries and regions including Australia, Austria, Canada, Belgium, France, Germany, Japan, the Netherlands, Norway, Oman, Sweden, Singapore, Taiwan, the UK and the USA.
These above studies simply keep resonating the finding in only some of these above cases of association between the resistant bacteria and patients travel to India. All the above three studies with the above mentioned authors were funded partly or entirely by European Union
Many of these patients belong to European nations which are now a part of European Union. What the authors again seems to have selectively ignored is the fact that most of these patients have also received treatment in their countries of residence and may not have travelled to India at all.
Indian Government’s statement
Indian government discredited the latest studies reports as non significant findings and unsupported by any clinical or epidemiological evidence. The study report does not highlight the unstable character of the isolates.
The Director -general of Health services in India Mr R K Srivastava strongly refuted the claims that the so called New Delhi metallo-Beta Lactamase -1(NDM-1) bacteria or superbug was a threat to the public health in India.
Mr Srivastava was confident that the chlorination carried out for making water safe for drinking inactivates sensitive and drug resistant bacteria alike.
He also said that the NDM-1 bacteria has been present in environment for a long time and the fact that patients respond well to medical and post surgical treatment antibiotics indicate that NDM-1 is not a significant problem in the country.
Dr Srivastava also pointed out that the publication itself mentions that NDM-1 is not a stable character in most of the isolates, indicating that any time it can revert back to sensitive state.
Carbapenem resistance develop mainly in patients who are receiving carbapenem therapy in the first place. This therapy is sparingly used under the supervision of doctor, Dr Katoch explained.
The above study conducted by Prof Timothy Walsh is a point prevalence study. A highly reputed peer review journal should be aware to the fact that point prevalence study is impractical and carries very little statistical significance. The above study has poor methodology and findings have minimal validity.
The samples were collected in New Delhi during the Common Wealth games when New Delhi was flooded by tourists and visitors from all over the word and especially from UK, Australia and Canada. The seepage samples could have contained the faecal contaminant from any of these nationals.
The worrying fact about the validity of this article is especially the fact that the above latest article about the so called superbugs was based on an independent research carried out by Tom Clarke, a science correspondent for channel-four.