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Laboratory Animal Science Copyright 1998 by the American Association for Laboratory Animal Science Vol 48, No 3 June 1998 Meeting Report International Conference on Emerging Infectious Diseases Abigail L. Smith The meeting was organized by the Centers for Disease Control (CDC) and Prevention, the Council of State and Territorial Epidemiologists, the American Society of Microbiology (ASM), and the National Foundation for CDC. Manuscripts submitted by plenary session speakers will be published in Emerging Infectious Diseases, a peer-reviewed journal published by the National Center for Infectious Diseases. The journal is distributed electronically and in hard copy at no charge. Retrieve on the World Wide Web at http://www.cdc.gov/ncidod/EID/eid.htm or from the CDC home page (http://www.cdc.gov). Twenty-six hundred attendees from 91 countries congregated in Atlanta, Georgia, to hear about emerging infectious diseases. Central issues addressed at the meeting were: “Which infectious diseases are emerging? Whom are they affecting? Why are they emerging now? What can we do to prevent and control them?” The Opening General Session on Sunday afternoon featured remarks by James Hughes (National Center for Infectious Diseases [NCID], CDC), Anthony Fauci (National Institute of Allergy and Infectious Diseases, National Institutes of Health), Claire Broome (Acting Director, CDC), David Heymann (World Health Organization), Karen Hein (Institute of Medicine), and Joshua Lederberg (Nobel Laureate, Rockefeller University). These talks set the stage for the next three days. For instance, the speakers pointed out that there was a 39% rise in mortality due to infectious diseases between 1980 and 1992 and that infectious diseases are the third leading cause of death in the United States. Emerging Infections Programs have been established as cooperative agreements between the CDC and seven locales in the U.S. Monday, 9 March: Duane Gubler (Division of VectorBorne Infectious Diseases, NCID, CDC, Fort Collins, Colo.) spoke at one of the Monday morning plenary sessions and reminded the audience that vector-borne infectious diseases, including malaria, Lyme borreliosis, plague, dengue fever and dengue hemorrhagic fever, and yellow fever, remain huge problems throughout the world. Factors contributing to the continued presence and/or re-emergence of these diseases include insecticide resistance, drug resistance, and declining economic and political support for control programs. Gail Cassell (Eli Lilly; former president of ASM) spoke about the potential for chronicity of infectious diseases. She highlighted mycoplasmosis and chlamydial infections as examples and emphasized the importance of animal models of human diseases. Invited panels addressed issues of surveillance and control of food-borne diseases, international cooperation, opportunistic infections in immunodeficient populations, vaccine-preventable diseases, and the role of host genetics in susceptibility to hantaviruses, tuberculosis, Lyme borreliosis, and the human immunodeficiency virus (HIV). A special session on disease eradication emphasized lessons from the smallpox experience and common-sense measures that can be applied to parasite eradication programs. Afternoon sessions dealt with global climate change, sentinel networks, molecular epidemiology, food safety and surveillance programs for same, vector-borne diseases, detection of novel agents, vaccine development, international cooperation, and bacterial and mycotic diseases. Tuesday, 10 March: D. A. Henderson (Johns Hopkins University) emphasized that the U.S. is ill prepared to deal with incidents involving the use of biological weapons (“bioterrorism”) and that we do not discuss the ramifications because we find the subject morally repugnant. An accident at a Soviet facility in 1979 resulted in the deaths from anthrax of 66 of 77 human cases and mortality among sheep and cows as far away as 40 to 50 km. Since virtually no U.S. physicians have ever observed inhalation anthrax, the likelihood is remote that a laboratory in this country would process and report promptly a correct diagnosis. Robert Webster (St. Jude Medical Center) presented an overview of the world experience with influenza and pointed out that the 20 million deaths resulting from the 1918 pandemic actually reduced the life expectancy in the United States by 10 years. The recent emergence of monkeypox (something of a misnomer since the major reservoir appears to be squirrels) in the Democratic Republic of the Congo (formerly Zaire) was reviewed. Civil war and a concurrent outbreak of chickenpox among children less than 16 years of age complicated the situation in which 92 clinically defined cases were recognized over a one-year period. Encephalitozoon hellum was isolated by John Shadduck in 1991 and subsequently was isolated from several psitticines, including love birds, parrots, and budgerigars. 225 Vol 48, No 3 Laboratory Animal Science June 1998 A case involving an eclectus parrot was presented, and the issue of whether immunosuppressed humans might be a risk for infection was discussed. A presentation from the Animal Research Institute and the University of Queensland revealed that fruit bats of the genus Pteropus harbor not only the equine morbillivirus (see below) that killed several horses and three humans in Australia during 1994 to 1995, but also a lyssavirus (rabies-related virus) and a paramyxovirus, tentatively named Mananglevirus. The last agent was isolated from pigs in New South Wales and causes no clinical signs in adult animals, but, like Akabane virus, does affect porcine fetuses. There is speculation that fruit bats are becoming reservoirs for zoonotic diseases due to human pressures on their habitat that are resulting in movements into peri-urban areas. Another talk revealed that genetic and protein analysis performed at the CDC forms the basis for removal of equine morbillivirus from that taxon; based on the most recent findings, the name “Hendravirus” (based on the location of the 1994 outbreak) has been suggested. Wednesday, 11 March: Sir John Pattison reviewed the history of bovine spongiform encephalopathy (BSE; “mad cow disease”) from its recognition in 1986 until the present day. There have been 170,000 cases to date, 36,000 of which were born after the feed ban went into effect. Because beef cattle are slaughtered when young, a mathematical model was devised that estimated one million actual infections would be required to recognize 170,000 clinical cases. The syndrome was recognized in several exotic (zoo) species, including kudu, nyala, oryx, and eland; these cases were also the direct result of including rendered meat products in feed. There were grave concerns about transmission of the agent through the food chain, so further surveillance has included farmers, veterinarians, and abattoir workers; dogs that had fed on downed cattle; and domestic cats. Four cases were identified between 1990 and 1995 in farmers, who were referred to as sentinels. No evidence for transmission to dogs was found, but several positive cats were identified. Zoo-maintained big cats that had been fed raw meat were tested, and cheetahs, pumas, ocelots, and tigers were identified as carriers. Although no further cases in farmers have been identified since 1995, several cases of so-called “new variant Creutzfeld-Jacob disease” (nvCJD) have been identified in individuals ranging in age from the teens to early 50s. The hallmarks are disease in patients who are young(ish) and who manifest behavioral changes, have atypical EEGs and atypical pathology, and who generally have a long clinical course (although some cases have died less than one year after onset of clinical signs). Compared to “traditional” CJD cases, these victims have huge accumulations of prion protein (PrP) that can be visualized by immunohistochemistry. The distribution of PrP is also different: for example, tonsils of nvCJD cases, but not traditional CJD cases, have large amounts of PrP. The precise vehicle of transmission to human cases remains a mystery, but brain, spinal cord, ileum, dorsal root ganglia, retina, and spleen must all be considered based on PrP localization studies; as a result, these materials may no longer 226 be included in pies or sausages in the U.K. Attempts have been made to predict the ultimate number of human nvCJD cases; however, accuracy of the models relies in part on the actual incubation period. Based on several assumptions, the model predicts a total of 100 to 200 cases if the incubation period is 10 years, and 35,000 to 80,000 cases if the incubation period is 25 years. Intensive surveillance is now directed at sheep flocks because these animals were fed the same rendered products as the cows. There are also concerns about possible contamination of the international blood supply (see below). This BSE presentation generated the most discussion of any of the plenary sessions. Questions relating to dose-response effects and processing mechanisms that may be most effective in eliminating offending organs from the food supply were raised. It has been shown that 1 g of infected cow brain is sufficient to transmit orally to a cow, and that 0.5 g can transmit orally to sheep. Obviously, similar data were not available for Homo sapiens, and it is not known whether thorough cooking might reduce the risk of transmission, although experimental data with traditional CJD suggest that would not be the case. Since there have been very few “occupational” transmissions, aerosols are not thought to present much risk. The issue of why cases have not been reported in the U.S., especially in view of the fact that the identical rendering process was used here, remains puzzling. The U.K. is home to 9.5 million cattle; although the public will not tolerate clinically evident BSE, they cannot and do not wish to slaughter that huge number of animals. An invited panel that included a speaker from the National Creutzfeld-Jacob Disease Surveillance Unit in Edinburgh, a Red Cross representative, and one from the Mayo Clinic discussed infection risks to the international blood supply. CJD is known to be associated with viremia for up to one-third of the long incubation period, thought to be 1.5 to 6 years when iatrogenically acquired and 12 to 13 years after peripheral exposure (such as through growth hormone injections). The issue of transmission of CJD to animal models via blood or buffy coat remains controversial, as successful transmission to primates (which are more sensitive hosts than rodents) has not been documented, and transmissions to rodents have met with variable success. Four transfusion transmissions in Australia have not been substantiated. Although the jury remains out, the consensus appears to be that the risks of transfusion-related CJD are quite low. Rare cases of malaria and Chagas disease transmission have been associated with blood transfusions. Dave Persing addressed the issue of blood-borne diseases transmitted by ticks, dealing specifically with babesiosis, ehrlichiosis, and Lyme borreliosis, the emergence of which has been associated largely with expansions of tick ranges. There have been 21 transfusion-associated cases of babesiosis and no such cases of ehrlichia or borrelia transmission. Seven talks were given on the H5N1 influenza outbreak in Hong Kong. Affected chickens were observed to have blood draining from their cloacae and to die suddenly, so the preliminary descriptor was “chicken Ebola.” More than Meeting Report 100,00 domestic fowl may be found in the Hong Kong markets every day. Seventy-five percent of them are imported from the mainland, and there are 1,000 markets, shops, and stalls selling the birds. They are held in wooden slatted crates that are virtually impossible to disinfect. Some farms raise both pigs and chickens, a lethal combination for an area in which most new influenza types are projected to emerge. There are approximately 700 farms within a 20-km radius of Hong Kong, and some are separated by only narrow moats. Between March and May of 1997, three chicken farms sustained 100% mortality, but serologic evidence for circulation of H5 was lacking. A second wave of mortality was noted in December, but H5 virus was still not detected serologically. By December 29, there was widespread chicken mortality, and H5 virus was isolated from chickens at one of the local farms. Despite the fact that all the data were not yet available, the order was given to depopulate. Imported birds continue to be tested prior to shipment and on arrival in Hong Kong, and they may be sold only if they are H5-free. The point was made that it was “lucky” that the H5 virus emerged in Hong Kong—the surveillance, response time, and cooperation were all outstanding, and Hong Kong is very wealthy and could afford to offer much more than market value in compensation for the chickens that were culled. It was speculated that the outcome would likely have been far different had the new virus arisen in a remote, rural area of China or elsewhere. The closing session featured remarks by Sir George Alleyne, Director of the Pan American Health Organization; Stanley Falkow, President, American Society for Microbiology; and Laurie Garrett, Pulitzer prize-winning author and journalist. Among the past and present challenges mentioned are diseases that reflect human “progress,” such as Legionnaire’s disease, toxic shock syndrome, and Lyme borreliosis. Laurie Garrett detailed the history of syringe transmission, beginning with transmission of malaria in the early 1930s. The former Soviet States had essentially no HIV infection until recent years, when intravenous drug abuse soared to epidemic proportions. As of 1996, 40,000 HIV infections had been recorded in Odessa alone. inflation. Support for the infrastructure that supports biomedical research needs to be bolstered so that we may understand the implications and consequences of genetic alterations. A major factor in the emergence of some human diseases has been immunosuppression, either as the result of infection (such as HIV) or of treatments accompanying organ transplantation. Likewise, laboratory animal specialists are seeing increasing numbers of opportunistic infections, such as pneumocystosis, in genetically altered rodents, suggesting that at least some of these animals are immunosuppressed. As stated by Brownstein in his recent editorial (1), understanding of genetically altered laboratory animals should be a priority of laboratory animal scientists. The common theme of immunosuppression was extended in a meeting report in the same volume of Laboratory Animal Science (2). The meeting synopsis emphasized opportunistic infections resulting from retrovirus infections of nonhuman primates and developing models of AIDS-associated neoplasia in primates. Only through the conscientious efforts of a well-supported laboratory animal medicine community can both genetically manipulated laboratory animals and primate models of human disease continue to make meaningful contributions to human health. This should be viewed as an investment in our future. References 1. Brownstein, D. G. 1998. Genetically engineered mice: the holes in the sum of their parts. Lab. Anim. Sci. 48:121–122. 2. Birkebak, T. A. 1998. Synopsis: primary and opportunistic infections in retroviral induced immunosuppression in nonhuman primates. Lab. Anim. Sci. 48:123. Submitted by: Abigail L. Smith Professor of Pathology Loyola University Medical Center Maywood, Illinois Commentary Although very few of the presentations at this meeting focused on laboratory animal diseases per se, there was certainly a perceived, and sometimes stated, link to comparative medicine. Animal models of human disease and zoonotic agents were addressed by several speakers. In the broadest sense, we in the laboratory animal/comparative medicine community are dealing with some of the same issues facing human medicine in this era of global travel: the advent of genetically altered rodents and rabbits has precipitated unprecedented movement of animals both nationally and internationally. Genetic manipulations have resulted in the emergence and re-emergence of diseases and syndromes at a time when resources available for their study are diminishing. Government support of public health initiatives and basic science research is, after years of decline or plateau, finally increasing at a rate that will outpace anticipated 227