NDM-1 – is it the death knell for medical tourism?

Letters
THE MEDICAL SENTINEL

Medical tourism, long ostracized as an evil third world nations with limited health-care resources should not be dabbling in, may have finally met its fatal match. Last week, the British based, Lancet Infectious Diseases Journal reported the emergence of highly resistant bacteria carrying a new gene termed New Delhi Metallo-beta-lactamase (NDM-1) and specifically associated it with medical tourism as the bacteria seems to have originated in patients frequenting India and Pakistan for procedures such as cosmetic and transplant surgery. NDM-1 is actually an enzyme that is produced by bacteria. The ability of bacteria to produce NDM-1 is apparently the result of mobile genes that can readily jump from various different bacterial populations allowing them to incorporate these special genes into their chromosomes.

The danger of NDM-1 is that it can fight against most known antibiotics known to man, thereby rendering the human species defenseless against these superbugs. It was first discovered in December 2009 by Yong and associates who described them in a Swedish national who fell ill with an antibiotic-resistant bacterial infection that he acquired in India. The infection was unsuccessfully treated in a New Delhi hospital and after the patient’s repatriation to Sweden, the gene was identified there.

The two key authors of the Lancet paper, Karthikeyan Kumarasamy and Timothy Walsh attribute the new strain as a result of antibiotic abuse and global travel. In particular, the resistant bacteria appear to have evolved in third world nations where usage of antibiotics is poorly supervised. Further in countries like China, Indonesia, India, Bangladesh, Pakistan, Thailand, Mexico and even perhaps Malaysia all fingers appear to point to patients themselves who tend to shop around for doctors hoping for that miracle antibiotic that will cure their infection and in the process help genes like NDM -1 to evolve. Walsh pointedly, in his article anointed the blame to India and Pakistan and to medical tourism, although his postgraduate student and lead author, Kumarasamy, originally from the Medical College of Madras and now based at Cardiff appeared to want to distance himself from these inferences to avoid embarrassing his native India.

Indian medical authorities themselves are in a state of denial, ignoring the clear evidence that points to NDM-1’s origin in Indian private hospitals. The Indian medical community is up in arms for even naming the gene after the nation’s capital New Delhi, although the norm in microbiology has always been that new genes be named after the place of origin. Indian authorities are variously describing the clear impact of the Lancet article as a ‘conspiracy’ and an attack on the country’s lucrative medical tourism industry. However they are on thin ice as it turns out, that not only two of the authors were from India’s Apollo Hospital, long seen as the bastion of Indian medical tourism but in fact they had already been pre-warned by Dr K. Abdul Ghafur, himself a consultant in infectious diseases at the Apollo Hospital, Chennai.

Ghafur, in a signed article titled “An obituary-Death of Antibiotics” in the Journal of Association of Indian Physicians (JAPI) in March this year was already complaining about the Indian approach to tackling NDM-1. He observed: “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”. Let’s hope Malaysia will not adopt similar strategies. The same issue of JAPI carried a study by Dr P. Deshpande from Hinduja National Hospital, Mumbai, reporting the isolation of 22 NDM-1 producing bacteria in just three months. “If a single hospital can isolate such a significant number of bacteria with a new resistance gene in a short period of time, the data from all Indian hospitals, if available would potentially be more interesting and shocking than the human genome project data,” Ghafur wrote.

Walsh in his Lancet article himself concludes that bacteria with NDM-1 are highly resistant to many antibiotic classes and potentially herald the end of treatment with the main antibiotic classes for the treatment of infections. He further quotes Ghafur again who highlighted the widespread non-prescription use of antibiotics in India and predicts that the NDM-1 problem is likely to get substantially worse in the foreseeable future. Even more disturbing is that most of the Indian isolates from Chennai and Haryana were from community-acquired infections, suggesting that NDM-1 is widespread in the environment.

Given the historical links between India and the UK, it was unsurprising that the UK is the first western country to register the widespread presence of NDM-1-positive bacteria. However, it is not the only country affected. In addition to the first isolate from Sweden, a NDM-1-positive isolate was recovered from a patient who was an Australian resident of Indian origin and had visited Punjab in late 2009. These conclusions make one ponder if NDM-1 already exists in the many Malaysian patients who frequent India for medical treatment, the many Indonesian patients who frequent Malaysia for treatment and the many Malaysian patients who frequent Singapore for their medical therapy.

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 NDM-1 will likely spread worldwide. Walsh cautions the calls in the popular press for UK patients to opt for corrective surgery in India with the aim of saving the NHS money. Such a proposal might ultimately cost the NHS substantially more than the short-term saving and he has strongly advised 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.

Following the Lancet article, the UK’s Guardian, in their ominously titled article, “Are you ready for a world without antibiotics?” warn that in the very near future, we’re going to have to learn to live without them once again. The era of antibiotics is coming to a close and the post-antibiotic apocalypse is within sight. Since antibiotics are generally for short term use, Big Pharma has shown little enthusiasm in developing new antibiotics as there is just not much money in it.

The implications of a world without antibiotics are wide. A lot of modern medicine would become impossible if the ability to treat infections is lost. This is especially so in transplant and cancer surgery. Surgery will be thrown back to the pre Fleming era of 1928 when penicillin was discovered. Apart from NDM 1-producing bacteria, an enzyme called KPC has spread in the US (and in Israel and Greece) which also gives bacteria resistance to the carbapenems, the most powerful group of antibiotics we (once) had.

So the game now is to keep bacteria at bay. Hygiene is an obvious weapon. Better cleaning, hand gels and stern warnings to staff and public alike have helped reduce infection rates in hospitals. Beyond that, there is a real need to conserve those antibiotics we have. Walsh’s report shows that the battle to control the emergence of antibiotic-resistant superbugs through appropriate use of antibiotics must be fought at an international level. It illustrates the importance of considering health issues as a world issue – how antibiotics are prescribed and controlled in one part of the world can very rapidly have consequences elsewhere. What happens when antibiotics don’t work? The Guardian has listed the following:

• Transplant surgery becomes virtually impossible.

• Removing a burst appendix becomes a dangerous operation once again.

• Pneumonia becomes once more “the old man’s friend”.

• Gonorrhea becomes hard to treat.

• Tuberculosis becomes incurable

Malaysia which is still grappling with problems like dengue and worse still the re-emergence of “old” diseases like malaria, TB and leptospirosis, the Lancet report cannot have come at worser time. Malaysia’s nationalized but understaffed healthcare system is already lacking experienced personnel in almost every field of medicine. A world without effective antibiotics will not only sound the death knell for medical tourism right from Singapore through Malacca and Penang, but our hospitals and ICUs can potentially be flooded with patients afflicted with serious infections with surgery or any invasive procedure being virtually impossible to perform. It also highlights what a fragile world we actually live in. It may not necessarily take a tsunami, massive earthquake or a giant meteor to wipe out the human race. It may only require a single gene – like the NDM-1.