1996 Richard J. Duma/NFID Annual Press Conference and Symposium on Infectious Diseases
Please Choose a Presenter
» Frank O. Bastian, M.D.: "Late Breaker--Prions, Bovine Spongiform Encephalopathy (Mad Cow Disease) on Human Health Risk"
» Richard J. Duma, M.D., Ph.D.: Introduction Statement
» Stuart B. Levy, M.D.: "Antimicrobial Resistance: A National and Global Threat"
» David A. Relman, M.D.: "New Methods for Identification and Detection of Microbial Pathogens"
Late Breaker--Prions, Bovine Spongiform Encephalopathy (Mad Cow Disease) on Human Health Risk
By Frank O. Bastian, M.D.
The recent emergence of Bovine Spongiform Encephalopathy (BSE) and the occurrence of a new strain of Creutzfeldt-Jakob disease (CJD) has focused attention on a potential new human health hazard.
Although CJD in humans and scrapie in sheep and goats have been around for a very long time, there is surprisingly little known about the transmissible agent. For the past 15 years, the "prion" theory has drawn most of the attention and research monies. The prion protein likely represents a host response since 1) forms of the prion protein are found in unrelated diseases such as kawasaki disease and inclusion body myositis and 2) the purified prion is not infectious. The interpretation of data on this protein is not yet in, and there may be another explanation.
Spiroplasmas may also be responsible. These bacteria experimentally produce a persistent infection in rats with a spongiform pathology similar to that seen in CJD. A key piece of evidence is that spiroplasma contain fibril proteins that are morphologically identical to the unique fibrils seen in CJD and BSE; the fibrils in CJD and spiroplasma share antigenic cross-reactivity. Spiroplasmas show similarities to the transmissible agent of CJD by 1) being resistant to fixatives and heat, 2) disappearing into the tissue when looked for by electron microscopy, 3) being the same size, 4) being not culturable and 5) replicating in the spleen and lymph nodes with eventual localization to the brain.
There are some interesting peculiarities of the BSE epidemic and the new CJD cases in England. Both appear to be due to a single strain of the transmissible agent which suggests some interrelationship as proposed by the British ministry. It is possible that an enhancement of the particular strain causing BSE was facilitated by feeding cattle to cattle. The pathology of the new CJD cases in young people in England is different from the usual case of CJD. It also bears a close resemblance to the pathology of kuru reported in 1957, among the cannibals of the Fore people in the Eastern highland of New Guinea. Kuru is also caused by a single strain of the transmissible agent.
The recent BSE stories from England bring attention to the potential threat of this disease to livestock herds and the threat of related diseases to humans. An economic impact is already being felt in this country.
It is imperative that there be a new direction in research efforts including the search for a conventional agent in the transmissible spongiform encephalopathies. We must also deal with eradication of the scrapie agent which is endemic in sheep. The identification of the transmissible agent would allow the planning of various prevention strategies.
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Introduction Statement
By Richard J. Duma, M.D., Ph.D.
First, I would like to thank the National Foundation for Infectious Diseases (NFID) for associating my name with this important conference and seminar. I have always been a strong proponent of the medical and scientific fields communicating frequently and openly with the media, with those who legislate and lead our country and with the public, who not only carriers the burden of infectious diseases but also who is obviously involved in the communicability and persistence of such diseases. The public deserves and needs to know as much as possible about infectious diseases, since these diseases are often preventable, or if identified early, potentially curable.
Paul Hoeprich, a world renown infectious disease specialist and a former member of the board of directors of NFID wrote:
"Of all the diseases to which man is heir, those
- Known of etiology
- possible of cure
- capable of prevention
- are, for the most part, caused by infectious agents."
The implications of his statement, particularly as regards public health, are clear: we should prioritize infectious diseases for control and elimination, because in many instances we possess the information necessary to eliminate or prevent many of them. We cannot say that for most other diseases.
Today, our citizens receive little or no formal education about infectious or communicable disease, a sad commentary on our educational public health system. Most of what they know, they learn in later life, either from some unfortunate experiences that is an illness, or importantly from you, the media. Thank goodness for your existence.
Elementary and high schools lack curricula on the basics of immunology and infectious diseases, and most parents are ill equipped to teach the subject to their children. People graduating from high school (most of whom donıt go on to college) soon marry, have families and responsibilities, but sadly lack the necessary information to keep them and their families safe from infectious diseases. Itıs been said, "Man lives in a sea of microbes," yet our people know little about immunizations to protect them from these microbes; about food and water-borne illnesses; about the safe storage and preparation of foods; about risks of travel; about infections from pets; animals and insect vectors; about diarrheal illnesses (the leading killer of infants); about antibiotics and their limitations; about household infections; about the signs and symptoms of life threatening infectious diseases (like T.B. or meningitis); about the communicability of household infections; about sexually transmitted diseases; about blood-borne diseases; and I could go on and on.
Information about infectious diseases and our knowledge base on how our host defenses work to resist microbes are rapidly expanding. In your press kit Iıve provided you with a hastily assembled list (in no particular order and certainly incomplete) of new and emerging or re-emerging pathogens that just over the past 30 years have been identified, as well as a list of diseases that are due to, or may be triggered by, infectious agents. The list is impressive and growing every day, but it is only the beginning. It underscores the incredible growth of this subject. Yet, it was also within the past 30 years that our surgeon generals proclaimed that infectious diseases were a thing of the past and were no longer significant public health problems.
I believe NFID hopes that through conferences or seminars such as this, reaching out to the media, and legislators and opinion leaders, to help you and them understand what is taking place in the field of infectious diseases, and to keep you abreast of the changes occurring, that the public and out nation will be better served. I'm sure this conference will provide you with important insights, new knowledge and useful materials; so that you might accurately relate to your constituents where this rapidly expanding field is headed and how it will impact on all of our lives.
Again, I am very pleased to have my name associated with these efforts.
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Antimicrobial Resistance: A National and Global Threat
By Stuart B. Levy, M.D.
Many different infectious disease agents previously considered eliminated as major health problems, are reemerging. The reasons for this re-emergence are multiple, but prominent among them is the resistance to antibiotics. The resistance problem confronts patients in hospitals and in the community--it is local and global. It affects the treatment of tuberculosis, pneumonias, septicemias, ear infections, urinary tract infections, and other common diseases. Practically every major infectious disease organism is now resistant, not to one but to multiple antibiotics. The situation has been termed a major public health crisis, and many predict an impending disaster unless something is done quickly. Among the fears is that vancomycin resistance will enter the staphylococcus leaving us without any assured therapy for this pathogen. Deaths will occur if we lose vancomycin for this organism and for the pneumococcus, where it is now the relied-upon drug for meningitis, a potentially fatal illness. We stand at an important brink in antibiotic history--many bacterial disease agents are currently treatable with one or maybe two kinds of antibiotics. What happens when these are lost?
Why are we facing this problem now? We are experiencing the legacy of years of misuse of these precious therapeutics. The contributors are the prescribers and the consumers. Misconceptions about antibiotics have allowed them to be prescribed and dispensed casually, demanded and stockpiled by consumers and taken without the advice of the physician. The problem manifests itself perhaps differently in different communities, hospitals and countries depending on the antibiotic usage in that area and the disease agents present. But the consequences are worldwide, complicated by the ease by which these bacteria spread. Resistant strains in one country can travel to another country within hours. Multiple uses of antibiotics in different areas--people, animals, agriculture--continue to maintain a selection for resistant strains.
During the present decade, we are witnessing a steady increase in the numbers of multiresistant organisms as well as the appearance of new resistances in formerly susceptible strains. The problem is further complicated by the fact that a large number (estimated at 50%) of pharmaceutical companies left the antibiotic field in the mid 1980s and are only gradually coming back. Thus, at a time when bacteria are increasingly resistant to the available antibiotics, we have no new ones in the pipeline. None are expected to appear in this present decade, and there are no guarantees of any in the beginning of the next century. We must rely on the antibiotics we currently have. Both prescriber and consumer have contributed to the problem, and each can play a vital role in reversing the situation. Further basic research, funded through government and nongovernment sources, is needed in order to better understand resistance, identify new targets for therapy and new ways in which we can gain advantage again over our microbial foes.
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New Methods for Identification and Detection of Microbial Pathogens
By David A. Relman, M.D.
For nearly 100 years, clinicians and microbiologists have relied upon the ability to grow or purify microorganisms in the laboratory in order to detect or identify them. Furthermore, the traditional postulates for proof of microbial causation (Koch's postulates) have stipulated that a disease be reproduced in an experimental host with the suspected causative agent in purified form. Increasingly, throughout this last century, there have been reasons to suspect that this reliance upon microbial growth in the laboratory may have significantly limited our capacity to identify disease-causing microorganisms. The famous environmental microbiologist, Winogradsky, pointed out in 1949, that readily cultivated bacteria "draw importance to themselves," whereas those whose growth requirements are more complex and elusive "escape attention." The visible but uncultivated bacilli seen within tissues of patients with Whipple's disease, bacillary angiomatosis and cat scratch disease dramatically illustrate this point: none of these organisms could be identified until the advent of new molecular approaches and technologies during this past decade. Traditional cultivation-dependent methods are only useful for organisms whose growth requirements are understood; and we are relatively ignorant on this topic. In addition, traditional serologic diagnostic methods require purified microbial cells with which to test for specific antibodies in the blood of suspected patients. Traditional methods are often slow, insensitive and fail to discriminate between different microbial strains and species.
During the past 15 years, it has become apparent that certain genetic sequences can be used to infer the evolutionary ancestry of all living organisms. The most useful of these sequences contain interspersed regions of highly conserved and highly variable sequence. The first type of sequence allows one to target broad groups, including uncharacterized organisms; the second (variable) type creates a unique signature and allows one to identify any particular organism. Variable sequences also allow one to design highly specific detection tests for any given microbe. DNA amplification techniques [such as polymerase chain reaction (PCR)] facilitate this kind of approach and permit identification and detection of as few as one microorganism. The net result is a powerful molecular method known as consensus nucleic acid amplification. With this method, a rapidly-growing number of microbial pathogens have been identified directly from human tissue, including the agents of bacillary angiomatosis, cat scratch disease, Whipple's disease, human ehrlichiosis, hantavirus-associated pulmonary syndrome and various parasitic pathogens. A second molecular method, known as representational difference analysis (RDA), combines PCR and "subtractive" techniques to detect and isolate genes from occult microbial pathogens. The recent discovery of a new herpesvirus as the causative agent of Kaposi's sarcoma was the result of RDA. One of the first molecular methods for detecting microbial pathogens was a labor-intensive approach based upon the use of patient antibodies to detect DNA cloned from an affected clinical specimen. The method yielded the Hepatitis C Virus.
The advantages of these new molecular methods include a more rapid, sensitive and specific detection of known microbial pathogens, as well as the identification of novel, previously-uncharacterized microorganisms. Some of these methods may be automated for hospital and commercial, clinical microbiology laboratories. Widespread, organized use of these methods will surely reveal new emerging microbial pathogens, implicate microbes in the etiology of poorly-understood chronic inflammatory disease and significantly expand our understanding of microbial diversity.
