Urgent need to work together to fight new and old bugs

Paul Tambyah, Straits Times 24 Nov 07;

The economic impact of these emerging infections was considerable and the impact of the next will be greater. Singapore, one of the world's most globalised cities, is extremely vulnerable to new emerging pathogens.

THERE has been a lot of interest in infectious diseases in the past few weeks. Academic circles are abuzz with the news of an unprecedented $25 million grant call for research in the field, that closes this month.

Why is Singapore investing so much in infectious diseases when the major killers in Singapore for the past 50 years have been cancer and heart disease?

On a personal note, people have often asked me: 'Why did you go into infectious diseases?'

When I was a young doctor in training, one of my teachers encouraged me to take up a career in cardiology. 'Too few diagnoses,' I replied with youthful thoughtlessness. His quick retort: 'Then you should do infectious diseases, there are thousands of diagnoses there!'

On the advice of one of Singapore's most respected clinicians, Dr John Tambyah, a consultant endocrinologist who happens to be my father, I took off to the United States for postgraduate training in infectious diseases in 1993, as the local training programmes were just getting established.

For the next six years, I was immersed in the world of bugs and bug doctors. I learnt some of the science of infectious diseases, from the molecular characteristics of antibiotic resistant bacteria to the mathematical models that go into predicting antibiotic effectiveness.

I learnt the core epidemiologic skills to identify new clinical syndromes caused by emerging pathogens, and the social and clinical challenges of helping HIV/Aids patients at the start of the treatment era.

Having been back in Singapore for nearly a decade, it is exciting to see the infectious diseases field turn from a Cinderella speciality to a prestigious research arena with fierce competition among top scientists for research dollars.

What happened? The often misquoted US Surgeon-General William Stewart is alleged to have said in the late 1960s that we could 'close the book on infectious diseases'. However, as we all know, recent history changed all that.

The Severe Acute Respiratory Syndrome (Sars) epidemic was a wake-up call. It reminded all that we live in a globally interlinked world, that we ignore the interaction between humans and the other inhabitants of this planet at our peril and that collaboration and science can help control the plagues of today and tomorrow.

First, the Nipah virus which appeared in 1999, then Sars and later, the spectre of pandemic influenza, have pushed emerging infectious diseases to the front pages.

Some have already begun to forget the 'ghost town' eeriness of Orchard Road in April 2003.

The economic impact of these emerging infections was considerable and the impact of the next will be greater. Singapore, one of the world's most globalised cities, is extremely vulnerable to new emerging pathogens.

With global changes in agriculture, industry and population movements all around us and the effects of global climate change, the scene is set for new viruses or bacteria to appear.

Singapore can ill afford to be unprepared for the next pathogen and steps have been taken with the Regional Emerging Diseases Intervention Centre (Redi), the emerging infectious diseases research programmes at the universities, Ministry of Health, and the Communicable Disease Centre, Tan Tock Seng Hospital (CDC-TTSH) to try to prevent that from happening.

On a more mundane level, infectious diseases account for a disproportionate share of the complications of medical care and modern medical conditions. Foremost, are hospital-acquired infections and the complications from diabetes.

The former is an unpleasant reality worldwide and a recognised complication of modern medical care. Understanding the scope of the problem is the first step to adequately dealing with it.

Globally, hospitals are understaffed and overcrowded with patients needing invasive devices such as drips and tubes for the latest wonder drugs and therapies.

These, unfortunately, also allow germs that live on our skin and mucous surfaces to get into the weakened bodies of these patients. While medical advances have changed the face of many diseases including cancer, these new therapies can carry with them the cost of new and more resistant infections.

Today's patients are more and more vulnerable to these infections which are often multi-resistant as they are also receiving more antibiotics, and this is a major challenge in our hospitals worldwide.

Again, the first steps have been taken by research consortia from across the public hospitals and universities here to begin to address this pressing problem.

The 'antibiotic pipeline' seems to have dried up and there are now fewer new antibiotics. These bacteria seem to be one step ahead of us.

The old strategy of depending on the pharmaceutical industry may not work any more as some of the firms appear to be more focused on lifestyle drugs.

There is an urgent need for basic scientists to collaborate with clinicians to develop novel targets for antibiotic therapies and to work together to understand how to control these often deadly infections.

The newly formed Consortium on Antimicrobial Resistance is one such collaboration that brings together clinicians, public health specialists and basic scientists from four key agencies, the National University of Singapore (NUS), the National Healthcare Group, SingHealth and the Institute of Molecular and Cell Biology, to try and outfox the wily bacteria.

Singapore has one of the world's highest rates of diabetes. Foot infections in diabetic patients result in 700 amputations a year. Singapore has the opportunity to take a regional leadership role in this growing global problem.

Almost every one of us has a relative or friend with diabetes and this is clearly a fertile field for research that can benefit Singapore and beyond. This is a major public health crisis and one that demands a multi-disciplinary approach.

At the National University Hospital (NUH), the multi-disciplinary team - comprising an endocrinologist, an orthopaedic surgeon, a podiatrist, specialist nurse and microvascular reconstructive surgeon, and an infectious disease specialist - works to reduce the morbidity and mortality rates of patients with diabetic foot problems.

Finally, mention infectious diseases and everyone thinks of dengue, malaria, tuberculosis and typhoid. These are the 'classic infectious diseases' of old in which Singapore has a strong track record in clinical and basic science research.

Singapore has a dengue consortium probably among the world's largest collection of dengue researchers, in an innovative collaboration between industry, hospital-based clinicians and basic scientists from universities and research institutes here.

The newly formed Singapore malaria network, comprising members from the NUS, Nanyang Technological University and the Singapore Immunology Network, is another exceptional collaborative effort between scientists and engineers looking at new ways to diagnose and treat one of the world's deadliest infections, albeit a distant memory for most Singaporeans.

Tuberculosis is another area where Singapore has a long and distinguished history in research. The early UK Medical Research Council led trials conducted in Singapore General Hospital and Tan Tock Seng Hospital in the 1960s and 1970s which helped establish the basis for regimes used to treat tuberculosis worldwide today.

With the advent of extremely drug resistant tuberculosis (or XDR-TB), scientists and clinical researchers are facing new challenges from this very old disease.

The modern equivalent of the old infectious diseases which were 'hidden away' in sanatoria and lazarettos is HIV/Aids. We have excellent HIV/Aids clinical researchers at CDC-TTSH and the other hospitals but we need more basic scientists to step up to the challenge of HIV research.

This is a growing problem here and in the region. HIV/Aids is a microcosm of the challenges facing infectious disease researchers.

While there has been much progress since the identification of the virus which came to Singapore within a few years after the initial US reports, there are huge scientific questions yet to be answered in terms of the virus and its biology.

There are also major health services research questions as we try to deliver the therapeutic advances made elsewhere to our fellow Singaporeans, and even more challenging humanitarian questions as we examine our own personal prejudices, fears, anxieties and hopes.

The writer is Associate Professor, Department of Medicine, Yong Loo Lin School of Medicine, NUS, and Head, Division of Infectious Diseases, Department of Medicine, NUH