Jeff Hankey

BIOBD 495

Summer/Fall 2002

 

Immunology Research and the Availability of Standard Observation Guidelines for the Rabies Virus in Domestic Animals and Terrestrial Wildlife

 

 

          The rabies virus belongs to the family Rhabdoviridae and causes acute encephalitis and myelitis in all warm-blooded animals (United States. CDC – Rabies: The Virus). Without treatment, rabies is almost always fatal in all animals (Rabies. Westport Weston Health District). The virus is bullet-shaped, with an average size of 75nm by 180nm, and is composed of RNA enclosed by nucleoprotein and a layer of glycoprotein on the exterior that is believed to aid in the attachment to host cells (General Information Page). The infected animal is only capable of transmitting the disease when it is in the final stages of illness (Nadzam, Jill). Although infection has been documented through aerosol transmission and eight corneal transplants (in humans), the most common way for the disease to be spread is through a bite of an infected animal (United States. Human Rabies Prevention).

In theory, any warm-blooded animal can contract and spread the virus. Four species of terrestrial mammals (known as rabies-vector species), however, including foxes, coyotes, raccoons, and skunks have become definitive reservoirs for the rabies virus.  Even though the majority of recent human rabies-related deaths were the result of an exposure to a rabid bat, bats will not be discussed in this paper because the bat strain of rabies is fairly new and not well understood (United States. CDC – Rabies: Epidemiology).  Among domestic animals, only dogs, cats, and ferrets seem to be especially susceptible to the disease. These three domestic animals are required by law to have an up-to-date vaccination against rabies and, because of this law, the majority of rabies cases each year in the United States (as well as most other developed countries) come from wildlife (Model Rabies Control Ordinance).  With an average of 92% of rabies cases reported to the Centers for Disease Control and Prevention each year occurring in wild animals, it is somewhat surprising to find out that there is much more known about rabies in domestic animals than in wildlife (United States. CDC – Rabies: Epidemiology and Krebs, John).

            Upon entering a new host, the rabies virus sits in a seemingly dormant state (known as the incubation period), at which time the animal is not capable of transmitting the virus.  The incubation period is a key factor in the survival of an infected animal because it can range from just a few days to as long as nineteen years (Health: Rabies Information). Because rabies vaccinations can be given after the initial exposure to the virus, the survival rate among exposed patients is extremely high (United States. CDC – Rabies: Questions and Answers).   The incubation period, however, is never a certain length of time because it is influenced by a number of factors including the amount of the virus transmitted, the age of the victim, and the location of the bite.  To begin affecting the host animal, the virus must go against the axioplasmic flow of the peripheral nerves in order to invade the central nervous system and begin its rapid reproduction. If the bite occurs in a largely muscular area of the body, the incubation period is extended because there are fewer nerves, so it takes the virus a considerably longer time to travel to the central nervous system (United States. CDC – Rabies: Natural History).

Some animals are far less likely to contract rabies. The opossum, for example, rarely carries the disease because its body temperature is too low to provide a stable environment for the virus (General Information Page). Also, rodents (with the exception of the woodchuck) almost never found to carry rabies because they are so small that are almost always killed during an attack by an infected animal (Wildlife).

Once an animal has contracted the virus, there are three phases of illness that precede the death of the victim. Each phase follows a trend as to how long it persists, although there are exceptions to every generalization.  The first phase, the prodromal phase, usually lasts from one to three days after the onset of symptoms.   The second and third phases are referred to as either “paralytic” or “excitative” phases. Usually an animal will go through periods of both phases, but some animals are more prone to demonstrate an extreme occurrence of one phase and almost none of the other.  By the time these two phases become obvious, the host is already shedding large amounts of the virus and death is almost certain within ten days of the onset of these symptoms (Merck Vet Edition – Rabies: Introduction). 

            In the United States and most other developed countries, less than 10% of the reported rabies cases come from domestic animals (United States. CDC – Rabies: Epidemiology).  Even though the vast majority of rabies cases occur in wildlife, there is a surprisingly great amount of information that is known about the rabies epizootic in domestic animals (Krebs, John).   For instance, if a domestic dog bites a human, there is a set time period in which the dog is isolated and observed. If it is not known whether the dog has rabies, it is kept in quarantine for ten days (remember that animals are only able to transmit the disease after symptoms first appear and they almost certainly die within ten days of the first symptom). If the dog is currently vaccinated, it is kept under observation for 45 days, and if the dog is known not to be vaccinated, it can be kept in quarantine for 6 months (the quarantine time is lengthened due to the incubation period of the virus) or it can be euthanized and submitted for testing (United States. CDC – Rabies: Questions and Answers).   Guidelines such as these exist because rabies is viewed as a threat to human health. A human victim cannot be adequately treated if nothing is known about the virus; therefore great lengths are taken to understand the risk to human life. 

The aforementioned guidelines, however, do not exist for wild animals (Krebs, John).  There are at least three possible reasons as to why guidelines exist only for domestic animals: 1) Human exposure to domestic animals vs. human exposure to wildlife, 2) Availability of wild and domestic test specimens, and 3) The cost of research.  Put together, these factors dictate the priority of understanding the rabies virus in domestic animals:

 

            1. Human Exposure to Domestic Animals vs. Human Exposure to Wildlife

            Wildlife, for the most part, is very elusive. Most wild animals avoid human contact at all costs and human-animal interaction is minimized because the majority of mammals are at least semi-nocturnal.  When this as well as other mammalian behavior is taken into account, it comes as no surprise that the average person taking a walk in the woods for a few hours on the weekend rarely see mammals of any kind – especially rabies-vector species (Stokes and Stokes 3). 

On the other hand, one estimate suggests that there are 60 million dogs living in homes in the United States alone (It’s Estimated). Clearly there is a far greater interaction between humans and domestic animals than there is between humans and wildlife. Because most dogs (as well as cats and ferrets) live in close quarters with their owners, there is a far greater risk of a person contracting the rabies virus from a bite from someone’s pet than from a wild animal.  In most underdeveloped countries, dogs are by far the most common carriers of rabies and, as a result, there are a high number of rabies-related human deaths each year in those areas (Merck Vet Edition – Rabies: Introduction). 

To combat this problem in the United States, rabies in dogs was studied, and in 1885 Lewis Pasteur developed the first post-exposure prophylaxis treatment, which consisted of rabies virus immune globulin (United States. Historical Perspectives).  This method of post-exposure treatment has proven more effective with every year because there has been an overall downward trend of domestic rabies cases since the 1940’s when organized vaccination programs were initiated (United States. CDC – Rabies: Epidemiology).  As research continued, the observation guidelines were formed for domestic animals as another means to ensure that any exposed humans would get the required treatment.  For example, if the biting animal survives the 10-day observation period, then it can be assumed it wasn’t infectious when the bite occurred, and the victim no longer needs to complete the 28-day post-exposure prophylaxis treatment (United States. CDC – Rabies: Questions and Answers).

 

            2. Availability of Wild and Domestic Test Specimens

            Much is known about the fundamentals of how the rabies virus infects the central nervous system of its victims. This, however, is not enough to fully understand the intricate course of the virus on a species-by-species basis.  Rabies affects different species in slightly different ways (Krebs, John). This number of ways is exponentially magnified by the fairly recent discovery of different genetic strains of the virus.  To completely understand a disease, research must be conducted on it, but to conduct the research, there must be an ample supply of test specimens.

According to one estimate by the Humane Society of the United States, around 9 million dogs and cats are put into shelters each year, and 4 to 5 million of those animals are euthanized because homes are not found for them (The Crisis of Pet Overpopulation).  With this many healthy animals being euthanized every year, a reservoir of domestic animals is created that could potentially be used for research of the rabies virus.  The only reservoir of test specimens for rabies-vector wildlife is the natural population, which is inherently far less than the population of domestic animals that are susceptible to rabies.  The Pennsylvania coyote population, for example, is estimated to be about 25,000 individuals (More About the Eastern Coyote). Assuming that coyotes had an even distribution throughout all 50 states, the overall coyote population would only add up to 1.25 million individuals; a far less number than their domestic dog counterpart.

In addition to the relatively low population of rabies-vector species, a large-scale rabies study would have the potential to severely alter the balance of the local ecosystem even if only two or three individuals were taken from any given location. Mammals are at the top of the food chain; they keep the populations of prey animals at a reasonable level and are a necessity for a stable environment.

 

            3) The cost of research

            The cost of rabies prevention in this country is enormous. Prevention includes pet vaccinations, pre- and post-exposure prophylaxis treatments, research, and (within the past year) a plan to “air drop” vaccinations to cut down on the incidence of the virus in wildlife.  Annually, approximately $300 million is spent on rabies prevention in this country alone, with a majority of that money used to fund vaccination programs for domestic animals (United States. CDC – Rabies: Introduction).  With such a large amount of money already being spent on rabies-related endeavors each year, it makes more financial sense to spend the money on the main source of the problem. As previously discussed, there is a far greater chance of contracting rabies from a domestic animal due to the sheer number of them and the amount of human interaction with pets, so it only makes sense to begin to solve the problem of rabies by researching the virus in domestic animals before researching it in wildlife.

For now, a fairly inexpensive to researching the finer points of the virus in rabies-vector species has been proposed. Over the past 10 years, an oral rabies vaccine has been tested on wildlife with promising results (Rabies Vaccines). It is very cheap to make, averaging less than $1 per vaccine and, when compared to the $40 million post-exposure prophylaxis tab in the United States, it seems to be an effective means to hold off the spread of the rabies epizootic until more research is carried out on the virus in wildlife (Rabies and Feral Cats).

            Rabies is not inherently a human disease per-se because humans are not a reservoir of the virus. However, virtually everything that is known about rabies is known because it must be understood to preserve human health.  Rabies in domestic animals is the primary way it is transmitted to people, so the course of the disease in these animals is far better known than it is in wildlife. Frequency of human exposure, availability of wild specimens, and cost of research all have a direct effect on which animals are studied and to what degree.  But until there is a major impact on human health by rabies in wildlife, there is not likely to be any in-depth research on the course of the virus in rabies-vector species.

 

 

Works Cited:

General Information Page. 9 Dec. 2002 <http://duke.usask.ca/~misra/virology/stud2002/rabies/general.html#virus%20structure>

Health: Rabies Information. 9 Sept. 2002. Pennsylvania Department of Health. 9 Dec. 2002 <http://webserver.health.state.pa.us/health/cwp/view.asp?a=171&Q=230513&healthPNav=|#4495>

It’s Estimated. 9 Dec. 2002 <http://dogbitealternatives.com/transcript.htm>

Krebs, John. Telephone interview. 3 Oct. 2002.

Merck Vet Edition – Rabies: Introduction. The Merck Veterinary Manual. 9 Dec. 2002 <http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/102200.htm>

Model Rabies Control Ordinance. American Veterinary Medical Association. 9 Dec. 2002 <http://www.avma.org/pubhlth/rabord.asp>

More About the Eastern Coyote. 2 Dec. 2002. The Pennsylvania Game Commission. 9 Dec. 2002 <http://sites.state.pa.us/PA_Exec/PGC/wildlife/coyoteknow.htm>

Nadzam, Jill. 29 Oct. 2002. Email to the author. 29 Oct. 2002.

Rabies and Feral Cats. 31 Jan. 1997. 9 Dec. 2002 <http://www.feralcat.com/acarafc.html>

Rabies Vaccines. 9 Dec. 2002 <http://www.brown.edu/Courses/Bio_160/Projects1999/rabies/vacc.html>

Rabies. 9 Feb. 2000. Westport Weston Health District. 9 Dec. 2002 <http://www.wwhd.org/rabies.htm>

Stokes, Donald, and Lillian Stokes. Guide to Animal Tracking and Behavior. New York: Little, Brown and Company, 1986.

The Crisis of Pet Overpopulation. The Humane Society of the United States. 9 Dec. 2002 < http://www.hsus.org/ace/11864>

United States. Centers for Disease Control and Prevention. CDC – Rabies: The Virus. 7 Sept. 2000. 9 Dec. 2002 <http://www.cdc.gov/ncidod/dvrd/rabies/the_virus/virus.htm>

United States. Centers for Disease Control and Prevention. CDC – Rabies: Epidemiology. 6 Feb. 2000. 9 Dec. 2002 <http://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm>

United States. Centers for Disease Control and Prevention. CDC – Rabies: Questions and Answers. 14 Feb. 2000. 9 Dec. 2002 <http://www.cdc.gov/ncidod/dvrd/rabies/ques&ans/q&a.htm>

United States. Centers for Disease Control and Prevention. CDC – Rabies: Natural History. 26 Nov. 2001. 9 Dec. 2002 <http://www.cdc.gov/ncidod/dvrd/rabies/natural_history/nathist.htm>

United States. Centers for Disease Control and Prevention. CDC – Rabies: Introduction. 7 Sept. 200. 9 Dec. 2002 <http://www.cdc.gov/ncidod/dvrd/rabies/Introduction/intro.htm>

United States. Historical Perspectives A Centennial Celebration: Pasteur and the Modern Era of Immunization. 2 May 2001. 9 Dec. 2002 <http://www.cdc.gov/mmwr/preview/mmwrhtml/00000572.htm>

United States. Human Rabies Prevention - United States, 1999 Recommendations of the Advisory Committee on Immunization Practices (ACIP). 2 May 2001. 9 Dec. 2002 <http://www.cdc.gov/mmwr/preview/mmwrhtml/00056176.htm>

Wildlife. 9 Dec. 2002 <http://duke.usask.ca/~misra/virology/stud2002/rabies/wildlife.html>

 

Bibliography:

Altmeyer, Jr. Robert M. DMV. Telephone interview. 16 Oct. 2002

Animal Rabies: 1998-February 2000. State of Alaska Department of Health and Social Services. 9 Dec. 2002 <http://www.epi.hss.state.ak.us/bulletins/docs/b2000_05.htm>

ASM | Mammals of Pennsylvania. The American Society of Mammologists.9 Dec. 2002 <http://www.mammalsociety.org/statelists/pamammals.html>

Campbell, Gerald DMV. Telephone interview. 3 Oct. 2002

eNature.com – Nature and Wildlife Field Guides. eNature.com. 9 Dec. 2002 <http://www.enature.com/fieldguide/showSpeciesGS.asp?sort=1&curGroupID=99&display=1&area=99&searchText=fox&curPageNum=8&recnum=MA0021>

Fact Sheets – What is Rabies. The University of Iowa – Hygienic Laboratory. 9 Dec. 2002 <http://www.uhl.uiowa.edu/Publications/Facts/rabies.html>

Felix, Kenneth DMV. Telephone interview. 3 Oct. 2002

Kester, Richard DMV. Telephone interview. 4 Oct. 2002

Lutz, Doborah DMV. Telephone interview. 4 Oct. 2002

McClain, Tom DMV. Telephone interview. 3 Oct. 2002

Occupational Health – Zoonotic Disease Fact Sheets #3. 30 Oct. 1998. 9 Dec. 2002 <www.ksu.edu/research/animal/occhs/fact03.htm>

PAWS Animal Shelter: Placing Animals Within Society. P.A.W.S Animal Shelter. 9 Dec. 2002 <http://www.main.nc.us/paws/>

Questions About Rabies. 9 Dec. 2002 <http://www.broward.org/Questions>

RabAvert Rabies Vaccine: Total Cases Rabies in the U.S.. 9 Dec. 2002 <http://www.rabavert.com/casesall.html>

Rabies Fact Sheet. 22 Dec. 2000. Grant County Health District. 9 Dec. 2002 <http://www.granthealth.org/rabies.htm>

Rabies Testing Methods. 16 Nov. 2000. Texas State Department of Health. 9 Dec. 2002 <http://www.tdh.state.tx.us/lab/rabies_testing.htm>

Rabies. 9 Dec. 2002 <http://www.ccm.lsuhsc-s.edu/BugBytes/Volume2/bb-v2n7.htm>

Rabies. 9 Dec. 2002 <http://www.maxshouse.com/rabies.htm>

Report 1/97 – I.1. Rabies. 9 Dec. 2002 <http://www.bats.ch/abstr/197k1.htm>

THE NORTH AMERICAN RACCOON RABIES EPIZOOTIC. 18 Dec. 1998. Agricultural Research Service. 9 Dec. 2002 <http://www.nal.usda.gov/ttic/tektran/data/000009/74/0000097419.html>

United States. Centers for Disease Control and Prevention. CDC – Rabies: Diagnosis. 7 Sept. 2000. 9 Dec. 2002 <http://www.cdc.gov/ncidod/dvrd/rabies/diagnosis/diagnosi.htm>

United States. Centers for Disease Control and Prevention. Compendium of Animal Rabies Control,1998. 29 May. 1998. 9 Dec. 2002 <http://www.cdc.gov/ncidod/dvrd/rabies/Professional/Compendium/compen98.htm>

United States. Centers for Disease Control and Prevention. Rabies Surveillance in the United States During 2000. 9 Dec. 2002 <http://www.cdc.gov/ncidod/dvrd/rabies/Professional/Surveillance00/text00.htm>

United States. Centers for Disease Control and Prevention. Rabies Surveillance in the United States During 1996. 9 Dec. 2002 <http://www.cdc.gov/ncidod/dvrd/rabies/Professional/Surveillance96/surv96.htm>

United States. Centers for Disease Control and Prevention. Rabies Surveillance in the United States During 1998. 9 Dec. 2002 <http://www.wildifemanagement.info/publications/rabies_7.htm>

United States. Centers for Disease Control and Prevention. Rabies Surveillance in the United States During 1999. 9 Dec. 2002 <http://www.inno-vet.com/articles/2002/0201/56.html>

United States. Centers for Disease Control and Prevention. Rabies Prevention -- United States, 1991 Recommendations of the Immunization Practices Advisory Committee (ACIP). 22 Mar. 1991. 9 Dec. 2002 <http://www.cdc.gov/ncidod/dvrd/rabies/Professional/ACIP/ACIP91.htm>

Urban Population Continues to Grow. 21 Jun. 2001. Pennsylvania State University. 9 Dec. 2002 <http://www.ems.psu.edu/info/explore/UrbanPop.html>

-ve ssRNA Rhaddo -. 9 Dec. 2002 <http://athena.bioc.uvic.ca/bioc/courses/402/402.21.html>

Wavelength 16 – A Brush with Death. 16 June 1998. 9 Dec. 2002 <http://www.uwe.ac.uk/fas/wavelength/wave16/nelmes.html>

Zoonosis Control Division. 29 Aug. 2001. Texas State Department of Health. 9 Dec. 2002 <http://www.tdh.state.tx.us/zoonosis/diseases/RABIES/lab/genetic.asp>

 

Hosted by www.Geocities.ws

1