Zoonotic diseases are a small but important part of the hazards that are
associated with the care and use of laboratory animals. The large number of
potential zoonoses in the laboratory animal facility includes organisms from
every category of causative agents and really spans the spectrum of the types
of animals that are used in biomedical research. However, what would seem to
be a continuous opportunity for zoonotic infections to occur in the
laboratory, the number of cases reported in the literature suggests that these
are, in fact, very infrequent. Most laboratory animal facilities, and many
laboratory animal veterinarians, have never had any experience with zoonotic
infections among their personnel.
The explanation for why there are so few actual reported zoonotic infections
really relates to four items. Most institutions already have a program of
integrated management for the oversight of zoonotic infections in animal
facilities. This reflects, first and foremost, the terrific progress that has
been made in the laboratory animal industry in the past 20 years to improve
the health of laboratory animals. This involves the veterinarians and other
laboratory animal specialists who are providing a very high quality laboratory
animal for most applications in biomedical research. Once the animals arrive
at the animal facility, if in fact they are not from sources which are of
excellent health, the veterinary programs are generally quite mature, and have
an interest in zoonotic infections. They pursue hem in a timely fashion, they
are aware of appropriate diagnostic techniques and methods, and they define
these new problems promptly to try to control them in the animal populations.
Where that is not possible, of course, infections may be present in the
facility. Then the health and safety professionals have to play an important
role in informing personnel and devising preventive programs which include
immunizations appropriate for the agents present in the facilities. The
importance of proper training and education of personnel must be emphasized
for the control of zoonoses. The recent passage of OSHA's Personal Protective
Devices regulation has further bolstered the need to have written plans for
the kinds of protective equipment to reduce hazards in the workplace. Under
that broad umbrella, the consideration of zoonotic hazards and the barriers to
the prevention of those hazards has made it even more unlikely that an actual
zoonotic infection would occur even when the agent is present. Finally, there
has been an evolution in the field to move towards progressively more
exclusionary caging systems and other engineering controls to prevent the
spread of infection from the animal housing environment to the individuals
working in that environment.
There are several ways of defining these hazards, several factors that one
should consider when weighing a program and trying to set priorities for the
control of zoonoses in the laboratory. The first thing to consider is animal
species. Generally, the small laboratory rodent is not of concern with
zoonoses. However, it has recently been shown that lymphocytic
choriomeningitis virus in rodents is a potential zoonotic infection in
laboratory animal facilities. But once that particular organism is discounted
with regard to rodents, there is relatively little opportunity for personnel
involved with the care of rodents to contract zoonotic infections. As one
moves to other species, the likelihood of encountering potentially zoonotic
agents increases. One such extremely important agent is, Herpes B virus.
The source of animals also needs to be considered. Laboratory rodents have
undergone their growth and development in a highly defined environment and
therefore they have little opportunity to contract unwanted infections. Other
animals coming from sources that are less regulated and less stable have more
opportunity to have acquired an infection which can subsequently be introduced
it into the workplace.
The physical environment for the animals also has a direct bearing on the
potential for acquiring an unwanted infection. Once animals are in the highly
defined laboratory environment, there is not much opportunity for them to then
acquire infections from other animals in the facility. If animals are kept in
a more naturalistic setting, and there is somewhat more emphasis on doing that
nowadays (particularly if they're housed outdoors as agricultural animals),
the risk increases. You may have looked at that animal at one point in time
and determined that it had no zoonotic risk, but that animal has had a
continual exposure to other animals which might introduce new infections. Then
you need to look at the animal on a recurring basis to determine that it's
safe to be used within the facility.
Finally, it is important to consider the intrinsic difficulties in the
characterization or identification of the hazard. For example, some hazards
are technically difficult to isolate. Agents which cause latent infections
require specialized diagnostic techniques, and this may put their detections
out of the reah of most animal facilities. You have to use specialized
resources or call upon specialized expertise to determine whether those agents
are present or not. That interacts with the last factor, namely that there are
very serious expense constraints in the detection of some of these agents. I
think there is an unstated hierarchy in the likelihood of detecting zoonoses
according to the source of the animals in your facilities. Many animals go
through a cesarean re-derivation process, and as part of the process, all the
endemic infections may have been eliminated. These populations are generally
maintained under a very high veterinary diagnostic surveillance, so that if
there are problems in the facilities, they are promptly detected and reported
to the user of the animals. Purpose-bred animals are perhaps one notch down on
the scale. These are animals which have not been through cesarean re-
derivation so they do have their native infections. Because they have been
purpose-bred and under professional care for long time, the diseases of these
populations are generally highly characterized. There has been focused efforts
to eliminate any organisms which might be problematic within the animal
facility. There has been reports in recent years of some purpose-bred
populations having serious zoonotic infection.
Further down on the list are random-source populations containing animals from
multiple points with unknown personal disease and exposure histories.
Frequently these animals are mixed in larger pools where disease is exchanged,
and a real opportunity exits to encounter zoonotic infections in these
animals. One problem that you encounter with the characterization of these
populations is expense. Imagine a program which uses hundreds of dogs a year
to look for an enteric pathogen. That would entail sampling those animals to
determine in each animal whether they harbored something which might be a
zoonotic concern for personnel. This gets to be prohibitively expensive and
requires a lot of thinking about how the institution will expend its
resources.
At the absolute bottom of the hierarchy are wild-caught animals, leaving us
open to not just infections from every source, but also a number of arcane and
unusual infections that are not usually thought of in the laboratory animal
environment. Among the zoonoses, all the major disease categories are
represented, and there generally is a hierarchy of agents by importance as
well. The top four groups, viruses, bacteria, fungi and protozoa are the ones
of most concern, and in each of those categories, there is an agent or agents
which are serious in nature and have a potential to be in the laboratory
environment. The helminth parasites are generally less problematic because the
routine sanitation that's performed on laboratory animal facilities removes
most of these organisms before they've gone through embryonation or other
important developmental steps which makes them infectious for personnel. Other
parasites are also present on occasion, and they can be vectors for other
diseases. They're important to consider, but don't rank up there with some of
the other agents. In addition to B virus, note there are other herpes viruses
carried by macaques. At least one herpes virus infecting squirrel monkeys has
been noted historically to cause a disease similar to Herpes B, although not
as severe. Individuals who are bitten develop a vesicular rash on the wound
area where the bite occurred, then a general flu-like syndrome and a non-fatal
encephalitis. This is a weaker variant, perhaps of the Herpes B. It points out
the importance of regarding any bite from a non-human primate as a very
serious incident, and clearly bites of macaques are very important. Other
important viral infections of non-human primates are hepatitis viruses A and
E, agents which are passed by the fecal oral route. There have been cases
reported where Hepatitis A has been passed from infected chimps to humans.
That has been a recognized zoonoses. Hepatitis E has not been recognized as a
zoonoses at this point, but many of the non-human primates species are
susceptible to Hepatitis E. It is also fecal-orally spread. In the recen
literature there have also been outbreaks of Hepatitis A among a colony of
young macaques. This is an agent which is still present in some of the
colonies here in the United States.
The other group under non-human primates which bear some discussion are the
pox viruses; these would mostly be seen in quarantine stations from imported
animals. Facilities which conduct that kind of activity need to look for
monkey pox. Another one that's noteworthy is simian immunodeficiency virus.
There have been several needle exposures to SIV of personnel who work with
non-human primates. One of these individuals has been shown to have sero-
converted and actually became viremic with the agent. So it's something that
warrants watching.
Among the other animal species there is a similar list of viruses. I glossed
over the arbo viruses because they require an insect vector for passage from
the animal host into the human. In the laboratory setting there are a number
of cases where humans have been infected with arbo viruses from generated
aerosols and while working with copious amounts of materials. Personnel have
been experimentlly infected with arbo viruses from infected rodents. With
wild-caught animals, each animal becomes its own experimental situation. As
shown by the recent outbreak of Hanta virus in the southwest a couple of
summers ago, we must always be on the look-out for emerging infectious
diseases. Although not present in our commercial laboratory animal stocks,
Hanta virus is one, which like lymphocytic Choriomeningitis virus or other
viruses that are tumor-associated, may be brought into a colony by tumor
passage. It might be within certain wild-caught rodents which is not uncommon
in biomedical research. Just a five minute exposure by people casually walking
through rooms that house mice infected with Hanta virus has been known to
transmit the disease. So it is a very transmissible agent. One agent with
which I had a personal and intimate relationship with is orf virus. I had this
as a veterinary student as a result of doing an oral exam on a sheep that had
a sore mouth. I was bitten on my fingers and developed these very large and
painful nodules on my hand for about the next six weeks. In some individuals
that's known to be a generalized infection with lymphadenectomy. In many of
these species, we need to consider rabies as a possibility.
Bacterial zoonoses can be split basically into the major systems that they
affect.The respiratory group is most important. Microbacteriosis is a very
important disease. The veterinary and occupational health programs work "glove
and hand" to control this agent in the animal facility. Q-fever is another
very important agent for people who work with sheep, particularly pregnant
sheep. The problem with this agent is that it is very difficult to detect
because the organism is generally latent; it is only shed in copious amounts
around the time of parturition. In other words, the serological tests for the
organism are not reliable in that there are a large number of false negatives.
So it's problematic that it will be routinely detected. In a similar vein,
chlamydiosis falls into a similar pattern, but is much less common in the
laboratory animal environment.It might be associated with laboratory housed
birds.If you're bringing in wild-caught birds for any purpose, you need to be
aware of this. There are reported cases of agricultural workers dealing with
turkeys who are infected, and this organism is very transmissible.
The enteric bacteria zoonoses are also important to consider; for the most
part these are related to non-human primates, ogs, cats, and some of the
larger animals. One does not frequently think of the rodents as a cause of
human infection. Rodents can get contaminated either through feed or through
other means and harbor agents like salmonella. For the most part, these relate
to the larger animals and frequently the younger animals within the species.
They can cause a serious problem in personnel who contract them. One of the
problems in the detection of these relates just to the money issue. It is one
thing to detect a disease which is showing clinical signs because the organism
is presumably in high number, making it fairly easy to culture, but the
difficulty is that many of these organisms can exist in a carrier state with
intermittent shedding of the organism. This requires that you do multiple
cultures on a given animal to determine whether it is there. The problem is
that with cultures costing anywhere from twenty-five to forty dollars each, it
is a very expensive proposition for the animal facility environment. The
systemic bacterial zoonoses (some are actually more regional infections with
the potential to become systemic) can be quite serious. Brucellosis is one
which has been reported in some dog breeding colonies. The organism is
available in copious amounts at the time of parturition in dogs and in other
species which harbor brucella, but it is also shed in urine so urinary contact
can cause the spread of that disease. Cat-scratch disease is better defined
now that that organism has been isolated and characterized. This is something
that is fairly common among cats, especially young cats. They have a low grade
bacteremia with continual infection; the agent is transmitted with bites and
scratches. Leptospirosis is pretty much unheard of in the laboratory animal
facility. With the great number of pigs and other animals coming directly off
farms into animal facilities for acute surgical procedures, one has to wonder
when we will see this organism again. Anecdotally, I have heard of several
technicians who contracted leptosirosis just through that means. Plague is
mostly associated with wild animals, and rat bite fever is something you would
have to consider with any rodent bite.
There are a number of different fungi that can be harbored both clinically and
subclinically. They cause a ringworm like condition. In certain rare
circumstances, individuals that are immunosuppressed have been known to
develop systemic infections. The protozoal diseases are important, mostly in
that they can infect the gastrointestinal tract and the larger animal species
which have these include the primates, dogs, cats, etc. Amebiasis has not been
reported in some time in non-human primates, but the oral reports indicate
that entameba histolytica is not uncommon in primates. It caused a disease
similar to enteritis with perforating ulcers in humans, and so primates would
need to be considered a possible point of origin. Cryptosporidium occurs in
many of the laboratory animal species; it was the celebrated cause of diarrhea
for the City of Milwaukee a couple of summers ago. You would be more inclined
to look for it in large animals coming directly off farms where you don't know
too much about the husbandry and conditions of those farms. Giardia is the
most important agent, at least from my perspective, and from the health
reports and clinical cases that I see. Its very common for non-human primates
and cats and dogs from random sources to harbor giardia lamblia, a zoonotic
organism which is spread by the fecal oral route. We need to make people aware
of it when it's in the environment and treat those animals in a timely
fashion. Toxoplasmosis is mostly related to cats. They are the definitive
hosts in which the organisms replicating in the gut are shed in high amounts
in the environment. There are many other laboratory animals which can be
infected with toxoplasmosis. If you are working inappropriately with tissues
from those animals, there would be some chance that you could get the
infection through contamination of the hands, ingesting the organism, or
inoculation of small lesions on your hands.
Zoonoses in Animal Care Facilities
Breakout Session
Rapporteur: David Dreesen, MPVM
Medical Microbiology
Rm 346, College of Veterinary Medicine
University of Georgia
Athens, GA 30602-1386
706-542-4979