Sunday, April 17, 2011

New Delhi Metallo beta lactamase: Many questions but a few answers to the problem called superbugs

By Syed Akbar
Does there exist a superbug called New Delhi Metallo beta lactamase? Or is it one of the many beta lactamases that thrive in hospitals, particularly the intensive care units, around the world including those
in the USA and Europe? If there's a new mutant by name New Delhi Metallo beta lactamase, is it really a potential medical hazard? And if it is a major potential health hazard, then how different is the NDM-1
with other beta lactamases? Did NDM-1 really evolve in India, or was it introduced into the country by one of the infected foreign patients?
These are some of the questions haunting the mind of the common man and health planners alike ever since newspapers and TV channels started giving wide publicity to a research finding, published first in August 2010 and in April this year, by the UK-based medical journal, the Lancet. The common man in India is really worried after the Lancet's revelation that the NDM-1 has spread out of the hospital setting to the free environment - drinking water and open water bodies in New Delhi. This in other words means, as against the earlier threat of NDM-1 infection limited to just those who receive treatment in hospitals, it's now an "open infection"; everyone who drinks NDM-1 contaminated water runs the risk of superbug infection.
The Central government, as usual, played its part to further confound the doubts in the public mind by first rejecting the very existence of the superbug. Doubts have been expressed that the super bug theory is invented to make a dent into India's nascent medical tourism sector.
The government even went to the extent of supporting a "conspiracy" theory aimed at belittling the sanitation capabilities of the country. But when Lancet confronted the Centre's contention, it agreed for a
scientific study to find out whether such a superbug exists; and if so, to what extent; its health implications and the remedial measures needed to stop this superbug from proliferating into the atmosphere, and in hospitals.
Doctors, antibiotics, the culprit
Bacteriologists argue that beta lactamases have been in existence around the world for many, many years. They have been triggered by abuse of antibiotics. Beta lactamase is an enzyme released by certain bacteria. This enzyme is capable of crossing over to other bacterial species. And when this happens, the otherwise relatively harmless bacteria becomes a powerful organism or superbug. In short, a superbug does not respond to ordinary antibiotics. Even top class antibiotics often fail to kill the super bugs. In this background, the
discovery of the so-called NDM-1 in New Delhi's drinking water and in Indian hospitals comes as a major challenge to health planners, doctors and scientists alike.
Whether Lancet's study is true or a mere medical accusation will be known only after a thorough investigation by the teams appointed by the Central government. But it remains a fact that India is one of the few countries where antibiotics are misused, rather abused to the fullest. India has the dubious distinction of a nation consuming the highest quantity and number of antibiotics, even for simple problems that need no medicare at all. The sanitation in many hospitals, including those termed as Corporate, is bad if not worse. Nosocomial
or hospital acquired infections are quite common in the country. Hospital ICUs are colonised by bacteria that are capable of using antibiotics like penicillin as nutrition or food.
The sanitation scenario in the country is grim. Potable drinking water continues to be a dream for a vast majority of our populations. Our municipal sanitation and health staff test water samples for bacteria, but
they do not have the mechanism to find out whether the bacteria are carrying the super bug gene, NDM-1 or any beta lactamase enzyme. In the absence of sophisticated culture tests, it will never be known whether the water we drink is contaminated by the simple bacteria or the super bug.
Then there's the issue of overdose of antibiotics in veterinary field. Dairy milk and meat have been found to be contaminated by antibiotic residues. Animal hormones are used for artificial ripening and increasing the size and texture of fruits like mangoes, bananas and papaya.
The abuse of antibiotics, scientists cite, is one of the contributory factors for the emergence of super bugs, time and again. "There should be check on the use of broadspectrum antibiotics. Doctors prescribe broadspectrum antibiotics for problems, which require just pathogen-
specific antibiotic. Broadsprectrum antibiotics create immunity in a person against health problems which he had not yet faced. And when he faces the problem, the antibiotics do not work. In a way we ourselves are responsible for the emergence of super bugs," argues senior geneticist Dr MN Khaja.
Unfortunately, due to lack of updation of medical knowledge and regular conduct of Continuing Medical Education (CME) courses, many doctors fail to recognise the problem when patients approach them for medical help. Medical knowledge is undergoing a sea change  thanks to discovery of new pathogens, change in the way diseases are manifest, and emergence of drug-resistance ailments. The Medical Council of India had long ago proposed holding regular refresher courses for doctors to keep them abreast of the  developments in the medical world. It had also proposed that only those who attend the refresher course and pass the examination conducted after the course will be eligible for re-registration. But these proposals have been kept in cold storage and many doctors, who had passed even 10 years ago, are not informed of the newest medical sciences.
"Updation of medical knowledge should be made compulsory for doctors. It is irony that 90 per cent of doctors do not know about new diseases like Crimean Congo Haemorrhagic Fever. When Chikungunya
first broke out five years ago, doctors could not recognise it. Dengue has been here for many years, and yet doctors grapple with medicines. The trend is to first administer an antibiotic and if it does not work, change it. In a way doctors experiment with antibiotics and other medicines, indirectly giving birth to super bugs," observes senior health activist V Satyanarayana.
The Central government has finally woken up to the problem of antibiotics abuse in the backdrop the Lancet's revelation, to study the need to bar sale of powerful antibiotics to all and sundry. If the Centre has its way, tertiary antibiotics will now be available only to a few important hospitals in the country. Some of the powerful drugs listed under Schedule H will be shifted to a new Schedule to be created (Schedule H1). Common doctors, small hospitals and the general public will not have access to these antibiotics. This will to some extend check the menace of over the counter sale of powerful medicines.
The Name Game
The naming of the latest super bug after New Delhi has been mired in controversy. While the Indian government criticises Lancet for the "name blame game", Lancet conveniently passes on the buck to American scientists, who had named the super bug after New Delhi, two years before the Lancet publication in August 2010. In fact, Lancet has apologised for attaching the New Delhi tag to the super bug.
Scientists argue that it is difficult to pinpoint the origin of a pathogen. If the pathogen has originated in New Delhi, there's nothing wrong in naming it, argues infectious diseases expert from Apollo Health City Dr Suneetha Narreddy. "If the super bug bacteria had its birth in New Delhi, naming it after the city of its origin is not wrong".
But, there are others like Dr Niyaz Ahmed, professor of bacterial genomics at the Institute of Life Sciences, University of Hyderabad, who point out that NDM-1 is not the only super bug or bacteria that have developed resistance to powerful antibiotics like penicillins, cephamycins and carbapenems. Since these super bugs are resistant to carbapenems, they are called carbapenemases.
"NDM-1 is a world-wide problem although much caution is warranted as it is a worrisome situation for India due to the current stigmatisation by the Lancet studies. But, what about all other metallo beta-lactamases
circulating around the world since many years - why didn’t these carbapenemases evoke such a hype," he wonders.
According to Dr Niyaz Ahmed, who also edits PLoSONE, a leading biomedical journal published from San Francisco, USA, super bugs like bla-VIM, bla-KPC and some OXA types (in Germany and Europe,
for example, the prevalent type is OXA-48) are known for several years and their worldwide distribution is much higher than that of NDM-1 (estimated prevalence of NDM-1 less than 0.1 per cent in Europe/Germany as compared to other carbapenemases whose occurrence is about 10 to 100 times higher in countries such as Cyprus and Greece. And this is not only true for Europe, but also for other developed countries such as Japan and the United States.
Study flawed?
Did those involve in the Lancet study adopted a different yardstick when it came to discovering NDM-1? Indian scientists believe so.
Stating that faecal-oral route of the transmission of enteric bacteria is not novel, Dr Niyaz Ahmed said it has always posed health risks for centuries, throughout the world. When these phenotypes are seen in
Germany, Japan, China and Taiwan, Indian cities can’t remain an exception.
However, the prevalence in environment and in hospitals constitutes two different issues. Unfortunately, all the published reports on NDM- 1 including the Lancet study based on Delhi water samples are based
on ‘convenience sampling’.
"When conveniently spotted and potentially suspected sources are picked up as first choice and tested with highly sensitive tools such as PCR and real time PCR, it is possible to get positivity even for places
such as Switzerland. However, culture or PCR positivity does not mean that a potential epidemic is brewing," he adds.
A senior scientist at the Centre for Cellular and Molecular Biology argues that had the Lancet team been sincere and really scientific in its approach, it would not have compared potable water from India and
sewage water from Cardiff, UK, for the NDM-1 study. "If they want to say sewage water in Europe is better than drinking water in India, it's a different story. But justice and fairness demands that the samples
should be identical. They should have first compared Indian drinking water with drinking water samples from Europe, and then after ruling out the presence of NDM-1 in European water samples, they should
have gone for sewage effluent sampling," the CCMB scientist told this correspondent on condition of anonymity.
NDM-1, its implications
What does it mean to have drinking water and hospitals infested by NDM-1? If what Lancet says is true, then NDM-1 has entered as many as 20 bacterial species including the ones that cause simple loose
motions, gastroenteritis and cholera.
According to senior physician Dr Aftab Ahmed, it will be a difficult task to treat health problems created by super bugs, since they do not respond even to some powerful antibiotics. They, however, are susceptible to a couple of antibiotics at present. If these super bugs become resistant to these antibiotics too, then it will be an Herculean task indeed.
"If we do not kill the cholera bacteria (Vibrio cholerae) or E coli (gastroenteritis) in the stomach itself, it will spread to other parts of the body like blood, bones, lungs, heart and kidneys. Even simple loose motions caused by super bugs will become harder to treat," he warns.
Dr Suneetha Narreddy points out that the problem of super bug can be tackled by judicious use of antibiotics. "Though NDM-1 is not the only superbug in the world, one should be extra cautious about this bacteria
since the New Delhi name tag is attached to it," she warns.
Coming to the "conspiracy" part of the NDM-1 discovery, scientists argue that multinational bottled water industry will flourish as more and more people will lose faith in the drinking water supplied by civic
bodies and water boards. The multinational pharma companies may also stand to benefit.

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