4th World Melioidosis Congress

16 Sep 2004

By Prof K Satkunanantham, Director of Medical Services

Venue: Novotel Apollo Hotel

4th World Melioidosis Congress, Singapore 16-18 September 2004

Key Plenary Address - MOH's Efforts In Combating Infectious Diseases

Dr. Tan Kim Siew, 2nd Permanent Secretary for Defence

Mr Quek Gim Pew, CEO, DSO National Laboratories

A/Prof Lionel Lee, Director, Defence Medical and Environmental Research Institute (DMERI) at DSO

Distinguished Guests

Ladies and Gentlemen

It gives me great pleasure to join you all this morning at the opening of the 4th World Melioidosis Congress. I would like to begin by thanking the organizers for inviting me to give this key plenary address. I will focus my talk on the challenges that infectious diseases, particularly those that are emerging and re-emerging, pose to Singapore.

History of infectious diseases in Singapore

When Singapore became an independent nation some 40 years ago, we were then a developing country. The standard of housing was generally poor and the living conditions cramped. This coupled with poor hygiene and sanitation was conducive for the spread of infectious agents. The incidence of tuberculosis, for example, was close to 400 cases per 100,000 population in 1961. With the improvements in our housing, hygiene and sanitation standards, the incidence of TB gradually declined to 41 cases per 100,000 population last year, almost a ten fold reduction.

These economic developments and the provision of childhood vaccination in Singapore also contributed to the reduction in the incidence of debilitating childhood diseases. The last indigenous case of poliomyelitis here was reported in 1973 and Singapore was certified polio-free in December 2000. No local cases of diphtheria have been reported since 1992. The incidence of measles has dropped from 83 per 100,000 in 1982 to 0.8 per 100,000 last year. With containment of the infectious diseases and increasing affluence and changes in lifestyle, the incidence of non communicable diseases in particular cancer and cardiovascular diseases, steadily rose. These diseases have now become the predominant causes of morbidity and mortality in Singapore.

The rapidly diminishing trends in the incidence of TB and childhood diseases like polio can lead one to be complacent about the public health burden that infectious diseases pose. Indeed, the Nobel laureate, MacFarlane Burnet has been quoted many times now as having said, "One can think of the middle of the twentieth century as the end of one of the most important social revolutions in history, the virtual elimination of the infectious disease as a significant factor in social life". He lived in a time of great optimism with the discovery of antimicrobial drugs and declining trends in infectious diseases incidence.

The reality, unfortunately, is that infectious diseases are not only here to stay but we face even more diverse pathogens than we did in the 1960s. In the last 20 years, more than 20 different pathogens have emerged and in some instances, resulted in devastating outbreaks. Viruses like ebola, west nile, nipah and, more recently, SARS are among the many pathogens that have emerged in recent times. Each presents a daunting challenge to us in public health, in our efforts to prevent and contain them.

Factors for emerging infectious diseases

In a recent publication entitled "Microbial Threats to Health- Emergence, Detection and Response" by the Institute of Medicine of the National Academies in the United States, the factors that contribute to the emergence of pathogens are listed and include; microbial adaptation and change; human susceptibility to infection; climate and weather; changing ecosystems, economic development and land use; human demographics and behaviour; technology and industry; international travel and commerce; breakdown of public health measures; poverty and social inequality; war and famine; lack of political will; and intent to harm.

While Singapore enjoys peace, economic prosperity and political will, many of the factors listed by this report are true for emerging diseases in Singapore. These factors present themselves as challenges to us in public health and we need to address them in order to fulfill our responsibility to the public.

That microbes emerge and reemerge should not be surprising to many of us. Microbes live in every conceivable ecological niche and may be the most abundant life form by mass on our planet. In evolutionary terms, they have been around longer than us humans, and are also highly adaptable to external forces. While most microbes do us no harm and may even be essential to our health, some can have devastating effects.

Emerging infectious diseases in Singapore

Singapore has experienced several outbreaks in recent times despite our effort in maintaining a high standard of hygiene, high rates of childhood vaccination and strict import control of our food and livestock. Vibrio cholerae O139, was isolated from 5 imported cases, soon after it caused a massive epidemic in the Indian subcontinent in October 1992. Multi-drug resistant Salmonella enterica serotype Typhimurium DT 104 L was responsible for a three-month long outbreak in 2000. A total of 33 cases, involving mainly infants and toddlers, were reported. The vehicle of transmission was imported dried anchovy, what is known locally as 'ikan bilis'. In 2003, a nationwide outbreak of gastroenteritis caused by norovirus was associated with the consumption of frozen half-shell imported oysters, thawed and served raw.

In March 1999, 11 abattoir workers contracted nipah virus associated encephalitis or pneumonia, resulting in one death. The source of the virus in Singapore was the infected live pigs that were transported across the causeway and cessation of this import, stopped further cases from appearing. More recently, we were one of the many countries where the newly discovered SARS coronavirus caused an epidemic of severe acute respiratory syndrome. These are but some examples of what we faced in Singapore in recent times.

Right now, we are keeping an eye on the H5N1 influenza virus which was first discovered to be capable of transmission from poultry to human in 1997 in Hong Kong. Early this year, human cases appeared again in the region resulting in a considerable level of mortality rate among the small number of cases. Perhaps of greater concern, the finding of H5N1 influenza virus in pigs in China, giving rise to the possibility that this virus, hitherto unable to spread efficiently from man-to-man, could re-assort with a human influenza virus, acquiring the necessary genetic information that could result in a H5N1 influenza pandemic. We are a far cry from the vision voiced by MacFarlane Burnet.

Preventing emerging infectious diseases - the example of melioidosis

What then do we need to do to protect our population from these infectious diseases? What are the tools we need to prevent its transmission? What resources do we need, to carry out our job efficiently? These are some of the questions we are asking ourselves in public health and I will illustrate our response with our efforts to understand and control melioidosis in Singapore.

Background information of melioidosis in Singapore

Melioidosis was first documented in Singapore in 1920. Its causative agent is a soil commensal that can be found in certain parts of the island. From time to time, sporadic cases of melioidosis present to our acute care hospitals. The presentations range from abscesses to pneumonia and septicaemia. The outcomes of pneumonia and septicaemia are generally poor. In 1989, in an effort to understand the magnitude of the problem laboratories were required to notify the Ministry of Health if the causative bacterium was isolated from patient specimens. Since then, the reported incidence has been increasing gradually. Over the last 10 years, an average of 67 cases was reported annually, ranging from 36-114 cases. The average mortality rate was 18%. Infrequently, a number of cases are reported within a short space of time. An example of such a cluster occurred earlier in March this year, after a period of an unusually heavy rainfall, with 11 reported cases in the space of 1 week. From January to July of this year, 57 cases were reported to the Ministry of Health. 49 of them or 86% presented with pneumonia and/or septicaemia. 23 have succumbed to the disease despite aggressive antimicrobial therapy giving a mortality rate of 47%. This rate, is more than 3 fold greater than what was reported for SARS.

(Addendum : The mortality rate of 47% quoted refers to the 49 cases with pneumonia and or septicaemia. The mortality rate for the 57 cases overall reported during the period January to July 2004 is 40%)

Epidemiological data on the melioidosis cases from Jan to Jul 2004

The Ministry carried out epidemiological investigations of every reported case. The aim was to identify how and where these unfortunate individuals acquired the infection. We sought to institute the appropriate disease control measures. As my colleague will show you, in their presentation at this conference, the majority, 81% of the fatal cases had underlying chronic illnesses such as diabetes mellitus, hypertension and chronic renal failure. A strong correlation was also found with the high rainfall that preceded the onset of illness in the cases. We also sampled the soil in the places where the patients lived or reported to have visited in their clinical history and sent these for culture but no Burkholderia pseudomallei was isolated.

Aside from looking at the possible places where infection could have been acquired, we also considered the possibility, although remote, that the cluster of cases had been intentionally caused. As you know, Burkholderia pseudomallei has been classified by many countries, including the United States, Britain and Australia, to be a potential biological weapon. All the isolates we obtained from the patients with melioidosis during this period were sent from the diagnostic laboratories to our Defence Medical and Environmental Research Institute for genetic fingerprinting using multi-locus fragment length polymorphism. Results were rapid and obtained within 2 days and happily, the isolates obtained during this time was not clonal and were genetically disparate.

The challenge of controlling an environmental microbe

This recent experience with melioidosis exemplifies the challenges we face in public health. While some pathogens can replicate exclusive only in the human host, such as smallpox, many of the pathogens that cause significant public health problems are also found in the environment or other animals. Isolation of human cases alone would not completely halt disease transmission unless the environmental or animal reservoirs are also addressed in the control measures.

Singapore has managed to control malaria by reducing the habitats of the Anopheles mosquitoes. Each year, of the 300 cases of malaria notified to the Ministry of Health about 1% or less is acquired from within Singapore. Unfortunately, a story similar to malaria cannot be told today of melioidosis. No satisfactory measures can be employed to eliminate this pathogen from our environment.

Tracing the source of the outbreak - a case for investment in training

We had focused our environmental investigations into the spate of melioidosis cases earlier this year on the soil. Although direct exposure to contaminated soil is probably the most likely explanation for our cases, it is not the only way this bacterium could get into man. The investigation by Tim Inglis, who will be presenting a paper in this conference, and his colleagues in Western Australia implicated a soil-contaminated water tank in a rural community as the source of the infection. While I am not personally an expert in melioidosis, I dare hazard a guess that we have not exhausted the ways in which this bacterium can be transmitted to man. The more unusual the mode of transmission, the harder it would be to implicate it.

The best way to deal with this challenge is to train our epidemiologists to carry out as thorough an investigation as possible. Hence, the Ministry of Health has been sending its staff to centres like the London School of Hygiene and Tropical Medicine and the Bloomberg School of Public Health in Johns Hopkin for postgraduate training. We have also sent one of our staff to be trained under the Epidemic Intelligence Service Programme, conducted by the Centers for Disease Control and Prevention, headquatered in Atlanta. In addition, the Regional Emerging Diseases Intervention or REDI Centre, a collaboration between the Ministry of Health Singapore and the Department of Health and Human Services of the United States, was officially launched in May this year. One of the objectives of the REDI Centre is to provide training for regional public health officials, researchers, clinicians and other health professionals, especially on surveillance and rapid response to the threat of emerging diseases.

Another important function of the REDI Centre is to catalyze bilateral and regional collaboration in infectious disease research of relevance to the Asia-Pacific region, including SARS, influenza, dengue and West Nile fever. Proposed training activities include the development of field epidemiology training activities, a biosafety workshop, and pandemic influenza preparedness. The REDI Center will invite participation from regional countries in the coming months.

Some get ill, some do not - elucidating host factors

Our experience with melioidosis this year also highlights another aspect that could be a subject of research, namely host susceptibility. For example, Singapore is a sport-loving nation. Many of our children and youths play football, some call it soccer, and invariably they get very dirtied by the soil and mud. Despite this, we have had only a very small number of patients with melioidosis who gave a history of having played football in a field.

This epidemiological observation indicates that host factors play a significant role in the manifestations and outcome of an infection. In the case of melioidosis, chronic illnesses, such as diabetes, are associated with increased susceptibility and poor outcome but could there be other genetic factors of the host that modulate the outcome of the infection? If there is, what are they? Identifying host susceptibility markers may allow us to provide a more targeted disease control measure there by being more effective.

Improving therapeutic outcome - the Clinician Scientist Investigator Award

Prevention is better than cure. But if you cannot prevent them all, you must at least try and cure them. Many patients with melioidosis die despite aggressive treatment with antimicrobials. Two questions need to be raised here: Can we diagnose these cases earlier than we are doing now so that therapy can be started sooner? Are there any other approaches we could take to treat these patients? I am pleased to note that these will be subjects of discussion over the course of this conference.

The need to push the boundaries of therapeutics also underscores the role clinical research has in advancing our effort to enable more effective treatment to be delivered to our patients. Hence, together with the Biomedical Research Council, the National Medical Research Council of the Ministry of Health recently launched the Clinician Scientist Investigator Award and applications are right now being invited. The objective of this award is to nurture researchers who can bridge the gap between basic scientific research and clinical applications, bench to bedside, thereby bringing the rigors of scientific investigation into the patient care arena. They can also thrust clinically-relevant questions back into the basic research laboratories - bedside to bench. Under this scheme, the Research Councils will fund part of the salaries of the selected clinicians in order to free up their time for clinical research. This thus allows the hospitals to hire additional staff to cover their clinical workload. It is envisaged that this award will drive investigations into pathogenesis, prevention, diagnosis, prognosis and treatment of diseases. The endeavours of the clinician-scientists will contribute to the body of knowledge that will ultimately make a difference in patient outcomes, improve healthcare and save lives.

Laboratory approach to infectious diseases - a case for collaboration

Our effort, to rule out the possibility that the spate of melioidosis was intentionally caused, also illustrated the need for laboratories to collaborate closely with one another. Singapore has invested heavily in the life sciences. Several institutes apart from the Defence Medical and Environmental Research Institute, such as the Institute of Molecular and Cell Biology, and the Genome Institute of Singapore, now carry out investigations into the many facets of infectious diseases, from the host to the pathogen. However, no single laboratory has all the capabilities, both the hardware such as equipment, or the software, such as the microbiologists, to deal with all the questions infectious diseases and public health pose. Trying to house everything under one roof may also not be cost-effective. Collaboration, on the other hand, brings both technology and the know-how together and I believe this is the direction Singapore should take. To this end, the Ministry of Health is in the final stages of putting together a collaborative network of public health laboratories to facilitate infectious diseases surveillance and research.

Infectious diseases without borders

Finally, the fight against infectious diseases like melioidosis cannot be won unilaterally. The experience of SARS and its rapid spread globally indicate that countries will have to work together, exchanging epidemiological data and other information in order to halt the spread of diseases. During the initial stages of the SARS outbreak, epidemiologists, clinicians and virologists from many different countries held daily teleconference, facilitated by their governments and WHO, to update one another on their findings and discuss their implications. Microbes do not respect international boundaries and international cooperation will be needed to deal with them. I am thus heartened to note, the many international participants here with us at this conference. I hope that this conference will serve as a platform for our public health officers, our scientists and our guests from abroad to forge collaborations and build a network without the constraints of a geographical border.

Conclusion

Summing up, infectious diseases pose a constant threat to our Nation and a daunting challenge to our public health professionals. Our approach must incorporate, improving surveillance, facilitating research, fostering collaboration within and beyond our borders, and securing excellent epidemiological capabilities.

This conference will certainly contribute to this goal. I wish to congratulate the organizing committee for their hard work in preparing a stimulating scientific agenda. Finally to our foreign guests, I wish to express my warmest welcome to you and I hope you have a wonderful time in unique Singapore. To all delegates, I wish you an exciting and enjoyable 3 days at the conference.

Thank You.

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