Download International Conference on Emerging Infectious Diseases

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.
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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
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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
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