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a CANADIAN SECURITY INTELLIGENCE SERVICE publication
June 1995
Unclassified
Editors Note:
Well known diseases (such as tuberculosis) continue to kill far more people than do new ones (such as AIDS). Yet for other reasons discussed in this month's Commentary, these emerging pathogens are currently the object of careful attention by doctors and researchers, including the author, Dr. K.R. Rozee, Professor of Microbiology and Medicine, and Scientific Director at the Centre for Clinical Research, Victoria General Hospital, Dalhousie University, Halifax, N.S.
Dr. Rozee identifies a number of problems facing those engaged in the battle: new strains of virulent pathogens continue to appear; many of the traditional enemies have developed a hardy resistance to antibiotics; transmissibility is virtually impossible to prevent; financial resources are strained. Yet his review of existing facilities and counter-measures in Canada, and his prescription for further improvements, offer a strong antidote to these threats in an "epidemic era".
Disclaimer: Publication of an article in the COMMENTARY series does not imply CSIS authentication of the information nor CSIS endorsement of the author's views.
The firm principle that for every action there is a reaction applies as well to human populations and their interaction with their entrepreneurial microbial pathogens. Microbiologists have known for some time that the great contagions that have periodically ravaged humanity have occurred in the context of intricate orchestrations of biology that we only now begin dimly to comprehend. The causes of a particular outbreak or pandemic are no simple matters, as we can appreciate by only a casual familiarity with our current struggle with the AIDS epidemic. Protection of a population or a person against a particular pathogen, implying an understanding of the mechanisms that generate risks and the evolution of large numbers of diseased people, are also not simple subjects and require the interaction of many different scientific specialties.
"In the beginning" it was assumed that the great catastrophes of infectious diseases — the various plagues of recorded history and before — were either retributive visitations ordained by God or creations of the devil. (Some today would still subscribe to these views!)
Although most microbes are fortunately not pathogenic (they do not normally cause disease), several important characteristics serve them well when they do cause disease: they participate in selection phenomena in which the fittest survive in a particular environment; they also mutate so that as the environment changes as the result of developing immunity or antibiotic treatment, for example, they have the genetic versatility to change. It is said of such organisms that they are "selected out."
If this were all they could do, we would be describing a saprophytic relationship — one which harms neither parasite nor host. However, in fitting themselves for the human environment and by using their ability to survive changes in this environment, they frequently also develop characteristics that threaten their host, and hence they become pathogens. Their hosts, of course, in turn have protective adaptations designed to immunize themselves against the predations of their unwelcome guests. It is therefore in the context of this biological engagement, this competition for dominion in the human environment, that we must consider whether we in Canada are able to protect ourselves against the inevitable arrival in our midst of a new and/or mutationally regenerated microbial pathogen — the emerging pathogen.
Infective risk is any circumstance that would enhance or encourage the establishment, development and/or transmission of a particular micro-organism that causes an infectious disease. Many such circumstances are common to all pathogens (for instance, crowded human conditions, or poor hygiene), but others are specific for particular pathogens (for instance, the pre-condition that a certain insect transmit it from host to host). The investigation of any outbreak will always center on the need to discover the risk factors responsible for its occurrence in order to prevent its recurrence. This study is called epidemiology and is intimately inter-related to the science of microbiology and infectious disease.
What about an emerging pathogen? This question is better answered by giving examples from recent history. In the space of a little over two years in 1991-1993, this hemisphere witnessed the resurgence in Peru of Asiatic cholera and its permanent establishment in South America; the explosive waterborne outbreak of a once obscure intestinal parasite, Cryptosporidium, in Minnesota; an American West-coast epidemic of bloody diarrhea caused by Escherichia coli 0157:H7, described originally in Ontario a decade earlier; a mid-western outbreak of an often fatal lung infection caused by Hanta virus, first described in Korea years before and now reported from Alberta; and the progression westward and eastward in Canada of a particularly virulent strain of meningococcus which originally caused an epidemic of meningitis several years earlier in central Ontario. These North American examples, along with the continuing epidemic of HIV infection worldwide and the appearance, probably in association with the HIV epidemic, of antibiotic-resistant strains of mycobacteria that cause incurable tuberculosis; the appearance of a new strain of virulent cholera — Vibrio cholerae 0139 — in Asia; an epidemic of Rift Valley fever in Egypt; the occurrence of dengue (an infectious tropical fever) in Costa Rica; multi-drug-resistant Shigella dysenteriae in Burundi and the resurgence of diphtheria in Russia — these events illustrate and describe emerging pathogens more vividly than any definition. [Editor's Note: Since Dr. Rozee submitted his article, the Red Cross has announced it is withdrawing thousands of units of blood products which may have been contaminated from a donor with Creutzfeldt-Jakob disease. Researchers are still unsure how this disease is spread.]
All of these epidemic events, crowded into such a short time-frame, are putting tremendous pressures on our ability to react and on the very limited resources available in most areas of the world. However uncertain our ability is to cope with such an onslaught, what is certain is that we are, for unknown reasons, in an era prone to multiple epidemics, many of which can be transmitted rapidly anywhere in the world.
Information was key in the case of Hanta virus, the respiratory virus that recently appeared in the southwest United States. Hanta virus is carried by the deermouse (Peromyscus maniculatus) — whose range covers the north temperate zones of Canada — and is harboured in its excretions. These excretions dry and the dust is inhaled by humans who, on infection, become accidental hosts.
To date there are seven recorded cases and two deaths from this virus in Canada. All have come from west of Ontario, although we suspect all areas of Canada harbour this virus in their deermouse population. It is important to stress that the risk to rural Canadians and those who use our natural environment for recreation has not increased or been changed by the fact that we are now aware that such an infection can occur. In the USA where many more cases have occurred, the mortality rate seems to be about 40% of those infected. This is probably the rate we will see in Canada, although it appears to be dropping with the advent of more adequate diagnosis and treatment.
Press coverage of recent high-profile victims of the pathogenic bacterium Streptococcus pyogenes, including Canadian Lucien Bouchard, have aroused public concern. This organism, "Group A Strep" or the "flesh-eating bacteria", a name coined by the sensation-seeking press, is a frequent inhabitant of the human nasopharynx. Necrotizing fasciitis (the "flesh-eating" disease) is a known and very rare outcome of infection with this organism. Most outcomes are much less traumatic and vary from the troublesome and well known strep-throat, to inflammatory wound and skin infections, to the now infrequently seen Scarlet Fever. Perhaps the more important long-term effect related to infection is kidney damage.
Why this organism, normally a well behaved inhabitant of our nose and throat, should become so aggressively virulent is not known. Streptococci are known to acquire many toxins, and this characteristic may provide some of the answers, but there are also debilitating immunological changes in the human host which may also contribute to serious disease. Fortunately, several good antibiotics exist which, if used early, are able successfully to combat this infection. Once toxigenic damage has begun, however, these are much less effective, and surgery may be required, as in the case of Mr. Bouchard.
Is "flesh eating disease" becoming more frequent? Frankly and scientifically, we do not know. Its recent notoriety would suggest to the public that the sky is falling, but there have been no scientific studies to show that recent occurrences are any more frequent than normal. In the interim, the consensus based on anecdotal evidence (the weakest scientific data base) is that we may not be seeing an increase in streptococcal infections, but that there may be an increase in this particular outcome of streptococcal disease. With respect to remedial public health activities, most professionals would agree that most Canadians are served very well. Some requirements in molecular analysis and typing are not being met, but these do not affect our ability to serve our patients.
Perhaps of more importance to the subject of risk are several other examples of what are known in the infectious disease trade as "zoonotics". These are agents that normally affect only lower animals but to which man is sometimes susceptible. Besides the Hanta virus, others have recently been the subject of public concern; "Mad Cow" disease is one. It is caused by an agent which appears to be unrelated either to bacteria or viruses, and is called a prion. Mad Cow disease belongs to a group of central nervous system diseases called the "spongiform encephalopathies" and in all affected animals they result in progressively increasing muscular and mental deterioration. All have a very long incubation period usually measured in years. The agents (prions) have a very selective host range, and certain ones can infect only humans (and with some experimental difficulty, some closely related primates).
The public's concern with Mad Cow disease relates to the question of transmissibility: can Mad Cow prions be transmitted to humans when they consume beef or milk? The transmission of bovine prions has been traced to the use of cattle offal in packing plants as protein supplements in cattle feed. Processing of the feeds does not destroy the prion, which survives to infect other cattle.
We cannot, of course, deliberately do the appropriate experiment and infect humans with tissues from Mad Cow-infected cattle. Mother Nature has done the experiment for us. The cattle population of the United Kingdom is widely infected with Mad Cow prions, to the degree that other European Common Market countries discourage the importation of British animals and beef. However, there has never been a case of spongiform encephalitis attributed to Mad Cow prions in humans, despite the enthusiastic consumption of beef in all its forms by the British. Like other prions, it appears the bovine prions are very species-specific. Canada does not have a Mad Cow problem in its cattle population, but caution should be exercised in the source of protein supplements in our cattle feeds. A monitoring program would be reassuring in this respect.
Finally, with respect to zoonotics that are emerging, the Ebola virus is a unique case. Like the Marburg virus, it belongs to a very filamentous virus family called the Filoviridae, which in turn, belong to a large family of viruses that cause hemorrhagic fevers; most have a very high mortality rate in humans. In Western countries there is a typical story behind outbreaks of these African viruses. The source of the Ebola viruses is usually monkeys, frequently Green Monkeys (Cercophithecus aethiops) imported from Africa or Asia into laboratories for vaccine preparation or studies. If the animals are infected at source, when they arrive in either Europe or North America they become ill and infect their handlers or laboratory personnel. The important aspect of these infections is that the primary human infectees can infect their associates and families.
Originally it was thought that these viruses were always highly virulent, with human mortality rates of 40%-70%; more recently it is known that strains of greatly reduced virulence are possible. In endemic areas of Africa some 10%-20% of persons show evidence of post-infection by carrying serum antibodies. As evidence of this range of possible virulence, the recent outbreak in an animal colony in Reston, Virginia was particularly (and fortunately) very mild.
With respect to actions that would prevent these occurrences in Canada, we need only be aware of the need for care in the laboratory use of primates and observe the well known prohibitions if they are infected. If infected primates are necessary they must be held in facilities that have been designed to contain the viruses. These viruses are so-called "level-four" organisms and must be manipulated in laboratories and animal facilities with the highest level of biologic and physical containment.
What are we doing as a nation to protect our citizens in the face of these emerging pathogens? What mechanisms are possible to forewarn and protect us as a community and as individuals?
How do we position Canadians to be survivors rather than victims of these epidemics? Some of the answers are to be found in three publications [Editor's Note: these three publications are listed at the end of this issue] that report the proceedings of meetings in Washington, Quebec and Geneva at which experts provided detailed comments on the questions of surveillance, identification, remediation and the developing antibiotic resistance for known and unknown microbial pathogens.
Antibiotics are, of course, our major weapons in achieving cures when faced with infectious diseases. They are also frequently used to protect persons who have been in contact with a source of infection and are thereby used to contain the spread of an infection. On both counts the loss of an effective antibiotic due to the development of resistance in the target organism is a serious problem. In recent times, public attention has focused on antibiotic resistance as it relates to tuberculosis. Particular mycobacteria strains resistant to a dozen therapeutically important antibiotics - usually epidemiologically related to HIV infection and drug abuses — have been frequently isolated in particular areas of the United States. Fortunately, these strains have not yet appeared in Canada. As important as tuberculosis is, the situation is of wider significance. Reports of infections caused by penicillin-resistant pneumococci and gonococci, and Vancomycin resistant enterococci and others are received almost daily. These are widely used antibiotics and their exclusion from our therapeutic and protective game-plan is unfortunate and in some individual cases, tragic.
More unfortunately, it does not appear that we have the means of preventing the development of resistance, which in many circumstances is encouraged by the inappropriate clinical use and agricultural exploitation of antibiotics. We must, according to all expert advice, re-examine the way we use these drugs and stop depending as much as we do on drug companies to provide us with an unending supply of new ones. In fact, the latter assumption — that a never-ending supply of novel antibiotics is possible — is fallacious. Even now, in some circumstances, infectious disease physicians are limited to only one effective antibiotic. Action on the development of a national policy on antibiotic resistance is long overdue and will require a research-based strategy for implementation that begins with resource reallocation to expert researchers by our health authorities.
The former report contains 15 recommendations centred on disease surveillance, nosocomial (hospital based) infection, data collection and analysis, research on emergence and control, public health manpower requirements, emergency requirements for vaccines, pesticides and antibiotics, personal and public behaviour and worldwide monitors. This 1992 report followed three earlier reports prepared in the United States that documented the unready state of the American public health system to respond to the challenges of emerging pathogens and the "epidemic era". These publications together document the disarray and crisis-driven nature of the American response system and attribute it to the complacency and governmental neglect that are the root causes of the decay. These are attitudes and circumstances that could equally well describe the current state of Canadian policies and institutes of public health.
The Health Canada (1993) Report recommends remediation under four headings. The first contains recommendations for national strategy development in which the Laboratory Centre Disease Control would play an organizational role in bringing together the provincial and federal agencies that should be involved and the necessary experts from the academic community. These 13 recommendations range from the necessity to educate primary-care health professionals to reinforce and develop our diagnostic laboratory system, to evolving a national authority that avoids the contradictions and roadblocks in our provincial/federal jurisdictional situation in health and national and worldwide surveillance. Another group of recommendations deals with the important subject of communication. There are some major deficits in this regard that must be addressed if we are to satisfy both the requirement for expert dialogue and the public's need to know. Finally, the report re-commends the formation of an expert panel to examine the ethical questions related to the intrusive aspects of surveillance connected to the confidentiality of patient's data. One last recommendation deals with separate health funding for primary preventive programs, such as immunization, which are critical to the success of our efforts in infectious disease, as opposed to lumping them with programs that undertake secondary and tertiary medical therapies; i.e., transplants. From experience we know that the primary programs that are absolutely essential and have enormous pay-back potential fare very poorly if competing with the esoteric programs that have public and political "fan-clubs".
Over the last century every modern state in the world has developed a highly sophisticated, laboratory-based information and early warning system to alert public health officials and government as to infections within their borders. In conjunction with the World Health Organization and regional associations such as the Pan American Health Organization, states formally exchange information and technology. In most circumstances, however, this interaction occurs more efficiently when physicians and scientists from state laboratories, universities, medical schools and hospitals interact directly rather than through the international umbrella agencies. Here the new computer-assisted networks provide an increasingly important service, and these must become an integral part of our solution to information exchange problems, identification and control of emerging pathogens.
In Canada, the provincial systems of hospitals and laboratories responding to the requirements of practicing physicians are the backbone of our surveillance mechanism. In the provinces of British Columbia, Alberta, Saskatchewan, Manitoba, Ontario and Quebec, provincial laboratories formally provide sophisticated services to the hospital laboratories at a level required for surveillance and epidemiology, but above a level needed by the hospitals' own primary care responsibility. In the Atlantic provinces these sophisticated services are usually provided by the tertiary care hospital serving the region or a particular province. Additionally, all provinces are serviced by the federal Laboratory Centre for Disease Control (LCDC) in Ottawa.
These laboratory services in microbiology and serology must be complemented by the availability of services in epidemiology that are either provincially or federally based. The epidemiology services at the LCDC are available to any province on request, but these resources are quite limited. More realistically the Departments of Epidemiology (Preventive Medicine, Community Medicine, etc.) in the 16 medical schools across Canada can provide services that may be contracted to LCDC or to provincial governments to undertake interaction with the pathological and microbiological laboratories that may from time to time become necessary.
Is the existing network of physicians, hospitals, laboratories, university departments and central federal and provincial institutions adequate to protect us in the event of the introduction into Canada of novel pathogens? A realistic response would have to be a conditional one. We do have existing networks that are under tremendous stress on two fronts: technological and financial. One would have to rephrase the question and ask if we are capable of responding effectively in the face of current financial and personnel limitations.
Canadians now support a loose network of federal and provincial institutions that interact to examine, analyze and promote all subjects concerned with the health of the public. In the field of infectious disease this network comprises a system of laboratories and epidemiologic units that respond to the needs of the other components of the network, our physicians and hospitals.
The first line of involvement, the foot soldiers of our system, are the physicians and the laboratories and hospitals that serve them and their patients. It is here that we will first meet our emerging pathogen. Will we recognize the encounter?
In the case of the Hanta virus outbreak in the United States, discovery depended on the vigilance of a New Mexico doctor faced with two inexplicable deaths. The symptoms of this fatal respiratory illness were unlike anything he had encountered in his previous practice. This physician placed an inquiry with the Centre for Disease Control in Atlanta and the rest, as they say, is history.
Once we have identified an unusual infective event, do we in Canada have the laboratory skills and resources to identify precisely the offending organism, and persons to carry out the necessary epidemiology that will tell us how it became a problem, and what risks we can associate with it? The answer is, of course, yes, but our system must be organized for this purpose and properly resourced. Those are the issues addressed in the Lac Tremblant Declaration, 1993.
There is no doubt that there are diagnostic laboratories in Canada practicing at the required high technological level to assist us in tracing and identifying unknown emerging pathogens. These are few in number. More are required if our comfort level is to be satisfactory and, of particular importance, support for those that do exist must become more substantial and less dependent upon the vagaries of the granting agencies.
The desired laboratories, the ones that will be of most use in an emergency, operate at the fringe of knowledge and are known only to fellow microbiologists, pathologists and infectious disease epidemiologists; they are seldom in a position to make the financial and political decisions that are critical to creating and maintaining a successful response system to cope with any pathogen newly emergent in Canada. This must be changed if a prompt and suitable response system is to be developed. It is dubious whether the public will again tolerate the degree of official fumbling that occurred when the HIV threat became common knowledge in Canada. The elements of an appropriate response system are available in Canada, but they are being rapidly eroded by lack of care, a benign neglect. They can be revived only if there is political will.
The laboratories of the existing system will require dedicated research support separate from that provided for patient care (laboratory diagnosis) if they are to be ready to respond to infective emergencies. Research into applied medical microbiology, mechanisms of microbial virulence and alternative antimicrobial therapy must be all priority topics if our Canadian system is to be primed and sensitized to needs generated by the epidemic era. The appropriate research laboratories in Centres of Excellence, in partnership with federal and provincial laboratories and interested industrial enterprises, should be able to access this research support with a minimum of bureaucratic interference but with adequate peer review. To meet and develop these requirements alone will present a major challenge to those who would construct an adequate response system.
"Lac Tremblant Declaration: The Proceedings and Recommendations of the Expert Working Group on Emerging Infectious Disease Issues". Canada Communicable Disease Report 20S2, December 1993.
World Health Organization, Scientific Working Group on Monitoring and Management of Bacterial Resistance to Antimicrobial Agents. Geneva, December 1994.
"Emerging Infections, Microbial Threats to Health in the United States". Institute of Medicine, National Academy Press, Washington, DC, 1992.
The views expressed herein are those of the author, who may be contacted by writing to :
CSIS P.O.Box 9732 Postal Station T Ottawa, Ontario K1G 4G4 FAX: (613) 842-1312
ISSN 1192-277X
Catalogue JS73-1/58
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