17 August 2010

Emergence of a new antibiotic resistance in India

A study on Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study published online in The Lancet Infectious Diseases on 11 August 2010 has some substantive results, but unfortunately, has come into the news for wrong reasons. I will elaborate on the study later, but first a brief background. This study is co-authored by 31 persons who are spread across 13 institutions in five countries with the lead author Karthikeyan K Kumarasamy, a microbiologist, being based at Dr ALM PG IBMS (Dr Arcot Lakshmanaswami Mudaliar Post Graduate Institute of Basic Medical Sciences), University of Madras, Chennai; the corresponding author Timothy R Walsh being based at the School of Medicine, Cardiff University, UK (United Kingdom); and 15 authors (some of them with South Asian origin names) being based at the Health Protection Agency Centre for Infections, London, UK.

The Indian media 'picked up' an incidental observation indicating a potential danger for patients in UK if they opt for corrective medical surgery in India. In fact, the observation was rather in response to a media hype in the UK to save millions to the National Health Service by building a case in favour of 'medical tourism'. Further, raising a jingoistic diatribe coinciding with the run-off to independence day celebrations in India was uncalled for. This raises the suspicion that this is likely to be a 'paid news' that diverts attention from more substantive issues that the paper raises.

One of the most important issues, as the title of the paper clearly suggests, is the emergence of a new antibiotic resistance mechanism. In brief, bacteria are increasingly being resistant to multiple drugs, particularly antibiotics. About ten years ago this was largely so for gram positive bacteria, but this study points to this trend in gram negative bacteria like Escherichia coli and Klebsiella pneumoniae (popularly known as E.coli and K.pneumoniae respectively) because of the presence of a newly identified gene strain that is named as 'New Delhi metallo-β-lactamase 1' (NDM-1). This is serious because there are fewer drugs to address gram negative bacteria.

Further, the study also identified that these are nosocomial infections (that is, infection that are a result of treatment in hospitals), but can also inflict people outside the hospital. The bottom line is that diseases arising out of these bacteria (food poisoning or pneumonia) would be difficult to treat. There can be no two opinions about this. This is a potential global public health problem and requires international surveillance.

Additional issues for public policy discourse is the excessive use of 'antibiotics' because of avoidable and irrational prescription and use as an over-the-counter drug. Both are part of the same problem, a market based, supplier-induced demand. The excessive irrational prescription has been beautifully documented in the Indian context through a painstaking study by Anant Phadke Drug supply and use: towards a rational policy in India (1998) and also his End of drug control?, Seminar, 2000. On the unethical practices such as prescribing of drugs and diagnostic treatment being aligned with a 'cut back' method of payment, see CAK Yesudian's Behaviour of the private sector in the health market of Bombay, Health Policy and Planning, 1994.

The latter one (over-the-counter usage) comes from a personal experience. Once, our daughter Nerika was suffering from some ailment while we were traveling and we were against giving any antibiotics. A friend, without indicating the same, suggested to Nandini some tablets. Post-facto the justification given was that the child should not suffer unnecessarily. The ailment got cured by running its course or because of the antibiotic will always remain a question mark, but the antibiotic did add to our trouble as we had to ensure that it runs its course for the next five days. People do not realize that inappropriate use can be troublesome for the individual as well as the overall population in the long-run. Of course, as the paper under review points out, such epidemiological outcomes are interrelated with molecular and biological factors, but then the socio-economic factors are also important.

This brings me to a point on 'medical tourism'. It has potential to earn foreign exchange. It will provide five-star care to patients from developed at cheaper rates, and hence, the call in those countries that the bills for such medical interventions be paid by the exchequer. What is worrisome is that such 'media' news are insensitive to majority of the Indian population who cannot access medical care, forget five-star care. It forgets that if common drugs develop resistance then treatment will be further costly and this is going to hurt the poor more, as treatment in India, unlike UK, is largely out-of-pocket. It is insensitive to the fact that the developed countries like UK have four times more doctors and ten times more nurses than India for a normalized population and what is available in India is being used either in the name of 'medical tourism' or those who can pay for such treatment. In short, it is insensitive to people.

Does this mean that I am against 'medical tourism'? Well, yes and no. The reasons for 'yes' are already articulated above. The reasons for 'no' are pragmatic considerations. I know that this is not going to stop. I also know that in a globalized mobile world, restricting place of treatment would be difficult, but it does call for quality care for every one. It calls for responsibility of the developed world to millions of poor in Sub-Saharan Africa and South Asia. A suggestion is that developed countries should invest in fostering medical care in these regions including India. In particular, this should be used to develop medical colleges in rural pockets so that each and every district of India has one. This will facilitate global surveillance. This will combine pragmatism with a human touch. This can also be combined to foster 'medical tourism' with 'eco tourism'.

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An elaborate write-up Emergence of a new antibiotic resistant superbug, NDM-1 has been posted as an opinion piece in Digital Journal, 10 Octobor 2010, which is given below.

  
Emergence of the superbug New Delhi metallo-β-lactamase (NDM-1) has raised a lot of discussion on global public health in general and antibiotic usage in particular.

The infectious disease society of America highlighted the increasing public health concern of drug-resistant infections and that there is No ESKAPE (acronym for the pathogens Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species) from this clinical super-challenge of the 21st century. Recently, a new drug-resistant gene, NDM-1, was identified in a Swedish patient of Indian origin who travelled to New Delhi and acquired urinary tract infection caused by Klebsiella pneumoniae while undergoing treatment there in December 2007.

Since then, more cases have been identified. The Health Protection Agency of the United Kingdom (UK) reported 22 cases of NDM-1 in July 2009. From isolates collected between August-November 2009, a hospital in Mumbai reported 22 cases of NDM-1 with compromised treatment options. Cases have also been reported from other places and the first mortality was reported in June 2010 for a Belgian patient with prior treatment in Pakistan. All these came to public limelight after a publication in the Lancet that studies NDM-1 isolates identified in Chennai (44 cases), Haryana (26 cases), the UK (37 cases) and other cities of India and Pakistan (73 cases).

This is so because the media picked up an incidental observation indicating spread of superbug from India to Europe, potential danger to patients from the UK opting for hospitalization in India and its implication for medical tourism in India. The lead author of the Lancet paper was put in a quandary with one newspaper quoting him that the report was fudged. But, to be fair to the author, the discussion on potential danger to patients or medical tourism is not the conclusion of the paper; it is rather an observation in response to an earlier media report in the UK that highlighted the virtues of medical tourism that could save millions to the NHS (National Health Service). This discussion missed some substantive issues.

First, the spread of NDM-1, in such a short span of time, is alarming. As the paper clearly puts it there is need for integrated global surveillance and there should be no two opinions about this.

Second, this gene sequence is multidrug-resistant for gram-negative bacteria. We do not have enough drugs even in the developmental stages that could address future needs, as indicated in Bad bugs, no drugs: No ESKAPE.

Third, the UK isolates are nosocomial infections, but many of the Indian isolates were community-acquired infections indicating widespread prevalence of NDM-1 in the environment. An Indian medical journal’s editorial has written an obituary, on the death of antibiotics!

Fourth, and particularly an important concern for India, is the excessive use of antibiotics. This is on account of avoidable and irrational use. Further, unnecessary prescriptions are linked with a cut back method of payment to physicians. Along with this there are over-the-counter sale by pharmacists. These, in an economic sense, are indicative of market imperfections arising out of supplier-induced-demand that have serious implications for public health. The Indian establishment should address this at the earliest.

Fifth, a commendable aspect of this paper is that this is the result of a collaborative outcome between 31 persons spread across 13 institutions in five countries, excluding acknowledgements. Let us not trivialize this effort by stating that there is a bias against South Asia.

Last, but not the least, is designating the strain with ‘New Delhi’, which has ruffled Indian sensibilities; but this was done in an earlier paper that has some common authors. They could have been careful and, if possible, could still make a global appeal to consider replacing it with ‘New Drug-resistant’.

Having said these, one would like to comment on medical tourism. From the Indian perspective, it has the potential to earn foreign exchange. For patients from the UK, it will provide quality care at cheaper rates and reduce waiting time. However, from the point of public health in India, it is insensitive to majority of the Indian population who cannot access medical care; it forgets that if common drugs develop resistance then treatment will be further costly and this is going to hurt the poor more, as treatment in India, unlike UK, is largely out-of-pocket; it ignores the fact that the developed countries like UK have four times more doctors and ten times more nurses than India for 100,000 population. In short, the poor and the sick in India are missing.

The arguments in favour of medical tourism are pragmatic considerations. It is a reality that cannot be wished away. In a globalized mobile world, restricting place of treatment would be difficult, but it does call for quality-care for everyone. It calls for responsibility of the developed world to millions of poor in Sub-Saharan Africa and South Asia. A suggestion proposed is that developed countries should invest in fostering medical care in these regions including India, particularly, in rural areas such that each and every district has a medical college. This will facilitate global surveillance, combine pragmatism with a human touch, and foster medical tourism with eco tourism.

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