martes, 27 de agosto de 2013

RABIA

Rabies is a fatal viral zoonosis and a serious public health problem (1). All mammals are believed to be
susceptible to the disease, and for purposes of this document, use of the term “animal” refers to mammals. The
disease is an acute, progressive encephalitis caused by a lyssavirus. Rabies virus is the most important
lyssavirus globally. In the United States, multiple rabies virus variants are maintained in wild mammalian
reservoir populations such as raccoons, skunks, foxes, and bats. Although the U.S. has been declared free of
canine rabies virus variant transmission, there is always a risk of reintroduction of these variants (2-6).
The virus is usually transmitted from animal to animal through bites. The incubation period is highly variable.
In domestic animals it is generally 3-12 weeks, but can range from several days to months, rarely exceeding 6
months (7). Rabies is communicable during the period of salivary shedding of rabies virus. Experimental and
historic evidence document that dogs, cats, and ferrets shed virus a few days prior to clinical onset and during
illness. Clinical signs of rabies are variable and include inappetance, dysphagia, cranial nerve deficits, abnormal
behavior, ataxia, paralysis, altered vocalization, and seizures. Progression to death is rapid. There are currently
no known effective rabies antiviral drugs.
The recommendations in this compendium serve as a basis for animal rabies prevention and control programs
throughout the United States and facilitate standardization of procedures among jurisdictions, thereby
contributing to an effective national rabies control program. This document is reviewed and revised as
necessary. The most current version replaces all previous versions. These recommendations do not supersede
state and local laws or requirements. Principles of rabies prevention and control are detailed in Part I;
recommendations for parenteral vaccination procedures are presented in Part II; and all animal rabies vaccines
licensed by the United States Department of Agriculture (USDA) and marketed in the United States are listed
and described in Part III.
The NASPHV Committee
Catherine M. Brown, DVM, MSc, MPH, Chair
Lisa Conti, DVM, MPH
Paul Ettestad, DVM, MS
Mira J. Leslie, DVM, MPH
Faye E. Sorhage, VMD, MPH
Ben Sun, DVM, MPVM
*Address all correspondence to:
Catherine M. Brown, DVM, MSc, MPH
State Public Health Veterinarian
Massachusetts Department of Public Health
Hinton State Laboratory Institute,
305 South St.
Jamaica Plain, MA 02130
Consultants to the Committee
Donald Hoenig, VMD; AVMA
Donna M. Gatewood, DVM, MS; USDA Center for
Veterinary Biologics
Lorraine Moule; NACA
Barbara Nay; Animal Health Institute
Raoult Ratard, MD, MS, MPH; CSTE
Charles E. Rupprecht, VMD, MS, PhD; CDC
Dennis Slate, MS, PhD; USDA Wildlife Services
James Powell, MS; APHL
Burton Wilcke, Jr., PhD; APHA
Endorsed by:
American Public Health Association (APHA)
American Veterinary Medical Association (AVMA)
Association of Public Health Laboratories (APHL)
Council of State and Territorial Epidemiologists (CSTE)
National Animal Control Association (NACA)
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Part I. Rabies Prevention and Control
A. PRINCIPLES OF RABIES PREVENTION AND CONTROL
1. CASE DEFINITION: An animal is determined to be rabid after diagnosis by a qualified laboratory as
specified in Part I.A.9. The national case definition for animal rabies requires laboratory confirmation by
either:
• A positive direct fluorescent antibody test (preferably performed on central nervous system
tissue); or
• Isolation of rabies virus (in cell culture or in a laboratory animal (8).
2. RABIES EXPOSURE: Rabies is transmitted when the virus is introduced into bite wounds, open cuts
in skin, or onto mucous membranes from saliva or other potentially infectious material such as neural tissue
(9). Questions regarding possible exposures should be directed promptly to state or local public health
authorities.
3. PUBLIC HEALTH EDUCATION: Essential components of rabies prevention and control include
ongoing public education, responsible pet ownership, routine veterinary care and vaccination, and
professional continuing education. The majority of animal and human exposures to rabies can be prevented
by raising awareness concerning: rabies transmission routes, avoiding contact with wildlife, and following
appropriate veterinary care. Prompt recognition and reporting of possible exposures to medical professionals
and local public health authorities is critical.
4. HUMAN RABIES PREVENTION: Rabies in humans can be prevented either by eliminating
exposures to rabid animals or by providing exposed persons with prompt local treatment of wounds
combined with the appropriate administration of human rabies immune globulin and vaccine. Exposure
assessment should occur before postexposure rabies prophylaxis (PEP) is initiated and should include
discussion between medical providers and public health officials. The rationale for recommending
preexposure prophylaxis and details of both pre- and post-exposure prophylaxis administration can be found
in the current recommendations of the Advisory Committee on Immunization Practices (ACIP) (9,10).
These recommendations, along with information concerning the current local and regional epidemiology of
animal rabies and the availability of human rabies biologics, are available from state health departments.
5. DOMESTIC ANIMAL VACCINATION: Multiple vaccines are licensed for use in domestic animal
species. Vaccines available include: inactivated or modified live virus vectored products; products for
intramuscular and subcutaneous administration; products with durations of immunity from one to 4 years;
and products with varying minimum age of vaccination. The recommended vaccination procedures and the
licensed animal vaccines are specified in Parts II and III of this compendium, respectively. Local
governments should initiate and maintain effective programs to ensure vaccination of all dogs, cats, and
ferrets and to remove strays and unwanted animals. Such procedures in the United States have reduced
laboratory confirmed cases of rabies in dogs from 6,949 in 1947 to 93 in 2009 (2). Because more rabies
cases are reported annually involving cats (274 in 2009) than dogs, vaccination of cats should be required
(2). Animal shelters and animal control authorities should establish policies to ensure that adopted animals
are vaccinated against rabies.
6. RABIES IN VACCINATED ANIMALS: Rabies is rare in vaccinated animals (11-13). If such an
event is suspected, it should be reported to public health officials; the vaccine manufacturer; and USDA,
Animal and Plant Health Inspection Service, Center for Veterinary Biologics (Internet:
http://www.aphis.usda.gov/animal_health/vet_biologics/vb_adverse_event.shtml; telephone: 800-752-
6255). The laboratory diagnosis should be confirmed and the virus variant characterized by the Centers for
Disease Control and Prevention (CDC) rabies reference laboratory. A thorough epidemiologic investigation
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including documentation of the animal’s vaccination history and a description of potential rabies exposures
should be conducted.
7. RABIES IN WILDLIFE: The control of rabies among wildlife reservoirs is difficult (14). Vaccination
of free-ranging wildlife or selective population reduction is useful in some situations (15), but the success of
such procedures depends on the circumstances surrounding each rabies outbreak (see Part I. C.). Because of
the risk of rabies in wild animals (especially raccoons, skunks, coyotes, foxes, and bats), the American
Veterinary Medical Association, American Public Health Association, Council of State and Territorial
Epidemiologists, National Animal Control Association and the National Association of State Public Health
Veterinarians strongly recommend the enactment and enforcement of state laws prohibiting their
importation, distribution, translocation, and private ownership.
8. RABIES SURVEILLANCE: Enhanced laboratory-based rabies surveillance and variant typing are
essential components of rabies prevention and control programs. Accurate and timely information and
reporting is necessary to: guide human PEP decisions; determine the management of potentially exposed
animals; aid in emerging pathogen discovery; describe the epidemiology of the disease; and assess the need
for and effectiveness of vaccination programs for domestic animals and wildlife. Every animal submitted for
rabies testing should be reported to CDC to evaluate surveillance trends. Electronic laboratory reporting and
notification of animal rabies surveillance data should be implemented (16). Optimal information on animals
submitted for rabies testing should include species, point location, vaccination history, rabies virus variant
(if rabid), and human or domestic animal exposures. Rabid animals with a history of importation within 60
days into the United States are immediately notifiable by state health departments to CDC; all indigenous
cases should follow standard notification protocols (17). Integration with standard public health reporting
and notification systems should facilitate the transmission of the above data elements.
9. RABIES DIAGNOSIS:
a) The direct fluorescent antibody (DFA) test is the gold standard for rabies diagnosis. The DFA test
should be performed in accordance with the established national standardized protocol
(http://www.cdc.gov/rabies/docs/standard_dfa_protocol_rabies.pdf) by a qualified laboratory that has
been designated by the local or state health department (18,19). Animals submitted for rabies testing
should be euthanized (20,21) in such a way as to maintain the integrity of the brain so that the laboratory
can recognize the anatomical parts. Except in the case of very small animals, such as bats, only the head
or brain (including brain stem) should be submitted to the laboratory. To facilitate prompt laboratory
testing, submitted specimens should be stored and shipped under refrigeration without delay. The need
to thaw frozen specimens will delay testing. Chemical fixation of tissues should be avoided to prevent
significant testing delays and because it might preclude reliable testing. Questions about testing of fixed
tissues should be directed to the local rabies laboratory or public health department.
b) Rabies testing should be available on an emergency basis to expedite exposure management
decisions (18). When confirmatory testing is needed by state health departments (e.g., inconclusive
results, unusual species, mass exposures), the CDC rabies laboratory can provide results within 24 hours
of submission (22).
c) A direct rapid immunohistochemical test (DRIT) is being used by trained field personnel in
surveillance programs for specimens not involved in human or domestic animal exposures (23-26). All
positive DRIT results need to be confirmed by DFA testing at a qualified laboratory.
d) Currently, there are no USDA licensed rapid test kits commercially available for rabies diagnosis.
Unlicensed tests should not be used due to several concerns: the sensitivity/specificity are not known;
the tests have not been validated against current standard methods; the excretion of virus in the saliva is
intermittent and the amount varies over time; any test result would need to be confirmed by more
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reliable methods such as DFA testing on brain tissue; and the interpretation of results may place exposed
animals and persons at risk.
10. RABIES SEROLOGY: Some jurisdictions require evidence of vaccination and rabies virus antibodies
for animal importation purposes. Rabies virus antibody titers are indicative of a response to vaccine or
infection. Titers do not directly correlate with protection because other immunologic factors also play a role
in preventing rabies, and our abilities to measure and interpret those other factors are not well-developed.
Therefore, evidence of circulating rabies virus antibodies in animals should not be used as a substitute for
current vaccination in managing rabies exposures or determining the need for booster vaccinations (27-30).
11. RABIES RESEARCH: Information derived from well-designed studies is essential for the
development of science-based recommendations. Data are needed in several areas including: viral shedding
periods for domestic livestock and lagomorphs; potential shedding of virus in milk; earliest age at which
rabies vaccination is effective and protective effect of maternal antibody; duration of immunity;
postexposure prophylaxis protocols for domestic animals; models for treatment of clinical rabies; extra label
vaccine use in domestic animals and wildlife rabies reservoirs; host-pathogen adaptations and dynamics;
and the ecology of wildlife rabies reservoir species, especially in relation to the use of oral rabies vaccines.
B. PREVENTION AND CONTROL METHODS IN DOMESTIC AND CONFINED ANIMALS
1. PREEXPOSURE VACCINATION AND MANAGEMENT: Parenteral animal rabies vaccines
should be administered only by or under the direct supervision of a licensed veterinarian on premises.
Rabies vaccinations may also be administered under the supervision of a licensed veterinarian to animals
held in animal control shelters before release. The veterinarian signing a rabies vaccination certificate must
ensure that the person administering vaccine is identified on the certificate and is appropriately trained in
vaccine storage, handling, administration, and in the management of adverse events. This practice assures
that a qualified and responsible person can be held accountable for properly vaccinating the animal. Within
28 days after initial vaccination, a peak rabies virus antibody titer is reached, and the animal can be
considered immunized (29,31-33). An animal is currently vaccinated and is considered immunized if the
initial vaccination was administered at least 28 days previously or booster vaccinations have been
administered in accordance with this compendium.
Regardless of the age of the animal at initial vaccination, a booster vaccination should be administered 1
year later (see Parts II and III for vaccines and procedures). No laboratory or epidemiologic data exist to
support the annual or biennial administration of 3- or 4-year vaccines after the initial series. Because a rapid
anamnestic response is expected, an animal is considered currently vaccinated immediately after a booster
vaccination (34).
a) DOGS, CATS AND FERRETS
All dogs, cats, and ferrets should be vaccinated against rabies and revaccinated in accordance with
Part III of this compendium. If a previously vaccinated animal is overdue for a booster, it should
be revaccinated. Immediately after the booster, the animal is considered currently vaccinated and
should be placed on a booster schedule, depending on the labeled duration of the vaccine used.
b) LIVESTOCK
All horses should be vaccinated against rabies (35). Livestock, including species for which
licensed vaccines are not available, that have frequent contact with humans (e.g., in petting zoos,
fairs, and other public exhibitions) should be vaccinated against rabies (36,37). Consideration
should also be given to vaccinating livestock that are particularly valuable.
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c) CAPTIVE WILD ANIMALS AND HYBRIDS (the offspring of wild animals crossbred to
domestic animals).
(1) Wild animals or hybrids should not be kept as pets (38-40). No parenteral rabies vaccines are
licensed for use in wild animals or hybrids (41).
(2) Animals that are maintained in exhibits and in zoological parks and are not completely
excluded from all contact with rabies vectors can become infected. Moreover, wild animals might
be incubating rabies when initially captured; therefore, wild-caught animals susceptible to rabies
should be quarantined for a minimum of 6 months. Employees who work with animals at such
facilities should receive preexposure rabies vaccination. The use of pre- or postexposure rabies
vaccinations for handlers who work with animals at such facilities might reduce the need for
euthanasia of captive animals that expose handlers. Carnivores and bats should be housed in a
manner that precludes direct contact with the public (36,37).
2. STRAY ANIMALS: Stray dogs, cats, and ferrets should be removed from the community. Local health
departments and animal control officials can enforce the removal of strays more effectively if owned
animals are required to have identification and are confined or kept on leash. Strays should be impounded
for at least 3 business days to determine if human exposure has occurred and to give owners sufficient time
to reclaim animals.
3. IMPORTATION AND INTERSTATE MOVEMENT OF ANIMALS:
a) INTERNATIONAL. CDC regulates the importation of dogs and cats into the United States (5).
Importers of dogs must comply with rabies vaccination requirements (42 CFR, Part 71.51[c]
[http://www.cdc.gov/animalimportation/dogs.html]) and complete CDC form 75.37
(http://www.cdc.gov/animalimportation/pdf/dog-import.pdf). These regulations require dogs imported
from rabies endemic countries to be vaccinated for rabies and confined for varying timeframes
depending on age, prior vaccination status, and country of origin. The appropriate health official of
the state of destination should be notified within 72 hours of the arrival of any imported dog required
to be placed in confinement under these regulations. Failure of the owner to comply with these
confinement requirements should be promptly reported to the Division of Global Migration and
Quarantine, CDC (telephone: 404-639-4528 or 404-639-4537).
Federal regulations alone are insufficient to prevent the introduction of rabid animals into the United
States (3,4,42,43). All imported dogs and cats are subject to state and local laws governing rabies and
should be currently vaccinated against rabies in accordance with this compendium. Failure of the
owner to comply with state or local requirements should be referred to the appropriate state or local
official.
b) AREAS WITH DOG-TO-DOG RABIES TRANSMISSION. Canine rabies virus variants have
been eliminated in the United States (2,6). Rabid dogs have been introduced into the continental
United States from areas with dog-to-dog rabies transmission (3,4,42,43). The movement of dogs for
the purposes of adoption or sale from areas with dog-dog rabies transmission increases the risk of
introducing canine-transmitted rabies to areas where it does not currently exist and should be
prohibited.
c) INTERSTATE. Before interstate (including commonwealths and territories) movement, dogs, cats,
ferrets, and horses should be currently vaccinated against rabies in accordance with this compendium’s
recommendations (see Part I. B.1.). Animals in transit should be accompanied by a currently valid
NASPHV Form 51, Rabies Vaccination Certificate
(http://www.nasphv.org/Documents/RabiesVacCert.pdf). When an interstate health certificate or
certificate of veterinary inspection is required, it should contain the same rabies vaccination
information as Form 51.
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4. ADJUNCT PROCEDURES: Methods or procedures that enhance rabies control include the following
(http://www.rabiesblueprint.com/spip.php?article119):
a) IDENTIFICATION. Dogs, cats, and ferrets should be identified (e.g., metal or plastic tags or
microchips) to allow for verification of rabies vaccination status.
b) LICENSURE. Registration or licensure of all dogs, cats, and ferrets is an integral component of an
effective rabies control program. A fee is frequently charged for such licensure, and revenues collected
are used to maintain rabies or animal control activities. Evidence of current vaccination should be an
essential prerequisite to licensure.
c) CANVASSING. House-to-house canvassing by animal control officials facilitates enforcement of
vaccination and licensure requirements.
d) CITATIONS. Citations are legal summonses issued to owners for violations, including the failure
to vaccinate or license their animals. The authority for officers to issue citations should be an integral
part of each animal control program.
e) ANIMAL CONTROL. All local jurisdictions should incorporate stray animal control, leash laws,
animal bite prevention, and training of personnel in their programs.
f) PUBLIC EDUCATION. All local jurisdictions should incorporate education covering responsible
pet ownership, bite prevention, and appropriate veterinary care in their programs.
5. POSTEXPOSURE MANAGEMENT: This section refers to any animal exposed (see Part I.A.2.) to a
confirmed or suspected rabid animal. Wild mammalian carnivores or bats that are not available or suitable
for testing should be regarded as rabid animals.
a) DOGS, CATS AND FERRETS. Any illness in an exposed animal should be reported immediately
to the local health department. If signs suggestive of rabies develop (e.g., paralysis, seizures, etc.), the
animal should be euthanized and the head shipped for testing as described in Part I.A.9.
(1) Dogs, cats, and ferrets that have never been vaccinated and are exposed to a rabid animal
should be euthanized immediately. If the owner is unwilling to have this done, the animal should
be placed in strict isolation for 6 months. Isolation in this context refers to confinement in an
enclosure that precludes direct contact with people and other animals. Rabies vaccine should be
administered upon entry into isolation or up to 28 days before release to comply with preexposure
vaccination recommendations (see Part I.B.1.a.). There are currently no USDA licensed biologics
for postexposure prophylaxis of previously unvaccinated domestic animals, and there is evidence
that the use of vaccine alone will not reliably prevent the disease in these animals (44).
(2) Animals overdue for a booster vaccination should be evaluated on a case-by-case basis based
upon severity of exposure, time elapsed since last vaccination, number of previous vaccinations,
current health status, and local rabies epidemiology to determine need for euthanasia or immediate
revaccination and observation/isolation.
(3) Dogs, cats, and ferrets that are currently vaccinated should be revaccinated immediately, kept
under the owner’s control, and observed for 45 days. The rationale for an observation period is
based in part on the potential for: overwhelming viral challenge, incomplete vaccine efficacy,
improper vaccine administration, variable host immunocompetence, and immune-mediated fatality
(i.e., early death phenomenon) (12,45-47).
b) LIVESTOCK. All species of livestock are susceptible to rabies; cattle and horses are the most
frequently reported infected species (2). Any illness in an exposed animal should be reported
immediately to the local health and agriculture officials. If signs suggestive of rabies develop, the
animal should be euthanized and the head shipped for testing as described in Part I.A.9.
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(1) Unvaccinated livestock should be euthanized immediately. If the animal is not euthanized, it
should be observed and confined on a case-by-case basis for 6 months.
(2) Livestock exposed to a rabid animal and currently vaccinated with a vaccine approved by
USDA for that species should be revaccinated immediately and observed for 45 days.
(3) Multiple rabid animals in a herd or herbivore-to-herbivore transmission are uncommon (48);
therefore, restricting the rest of the herd if a single animal has been exposed to or infected by
rabies is usually not necessary.
(4) Handling and consumption of tissues from exposed animals might carry a risk for rabies
transmission. Risk factors depend in part on the site(s) of exposure, amount of virus present,
severity of wounds, and whether sufficient contaminated tissue has been excised. If an exposed
animal is to be custom or home-slaughtered for consumption, it should be done immediately after
exposure, and all tissues should be cooked thoroughly. Persons handling exposed animals,
carcasses, and tissues should use barrier precautions (49,50). Historically, federal guidelines for
meat inspectors required that any animal known to have been exposed to rabies within 8 months be
rejected for slaughter (51). USDA Food and Inspection Service (FSIS) and state meat inspectors
should be notified if such exposures occur in food animals before slaughter.
Rabies virus is widely distributed in tissues of rabid animals (52-54). Tissues and products from a
rabid animal should not be used for human or animal consumption (55,56) or transplantation (57).
Pasteurization and cooking will inactivate rabies virus (58); therefore, inadvertently drinking
pasteurized milk or eating thoroughly cooked animal products does not constitute a rabies
exposure.
c) OTHER ANIMALS. Other mammals exposed to a rabid animal should be euthanized
immediately. Animals maintained in USDA-licensed research facilities or accredited zoological parks
should be evaluated on a case-by-case basis in consultation with public health authorities.
Management options may include isolation, observation, or administration of rabies biologics.
6. MANAGEMENT OF ANIMALS THAT BITE HUMANS:
a) Dogs, Cats, and Ferrets. Rabies virus is excreted in the saliva of infected dogs, cats, and ferrets
during illness and/or for only a few days before illness or death (59-61). Regardless of rabies
vaccination status, a healthy dog, cat, or ferret that exposes a person should be confined and observed
daily for 10 days from the time of the exposure (62); administration of rabies vaccine to the animal is
not recommended during the observation period to avoid confusing signs of rabies with rare adverse
reactions (13). Any illness in the animal should be reported immediately to the local health
department. Such animals should be evaluated by a veterinarian at the first sign of illness during
confinement. If signs suggestive of rabies develop, the animal should be euthanized and the head
submitted for testing as described in Part I.A.9. Any stray or unwanted dog, cat, or ferret that exposes
a person may be euthanized immediately and the head submitted for rabies examination.
b) Other Animals. Other animals that might have exposed a person to rabies should be reported
immediately to the local health department. Management of animals other than dogs, cats, and ferrets
depends on the species, the circumstances of the exposure, the epidemiology of rabies in the area, the
exposing animal’s history, current health status, and the animal’s potential for exposure to rabies. The
shedding period for rabies virus is undetermined for most species. Previous vaccination of these
animals might not preclude the necessity for euthanasia and testing.
7. OUTBREAK PREVENTION AND CONTROL. The emergence of new rabies virus variants or the
introduction of non-indigenous viruses poses a significant risk to humans, domestic animals, and wildlife
(63-70). A rapid and comprehensive response includes the following measures (71):
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a) Characterize the virus at the national reference laboratory.
b) Identify and control the source of the introduction.
c) Enhance laboratory-based surveillance in wild and domestic animals.
d) Increase animal rabies vaccination rates.
e) Restrict the movement of animals.
f) Evaluate the need for vector population reduction.
g) Coordinate a multiagency response.
h) Provide public and professional outreach and education.
8. DISASTER RESPONSE: Animals might be displaced during and after man-made or natural disasters
and require emergency sheltering (http://www.bt.cdc.gov/disasters/petshelters.asp and
http://www.avma.org/disaster/default.asp) (72). Animal rabies vaccination and exposure histories often are
not available for displaced animals. Disaster response creates situations where animal caretakers might lack
appropriate training and preexposure vaccination. In such situations, it is critical to implement and
coordinate rabies prevention and control measures to reduce the risk of rabies transmission and the need for
human PEP. Such measures include actions to:
a) Coordinate relief efforts of individuals and organizations with the local emergency operations
center before deployment.
b) Examine each animal at a triage site for possible bite injuries or signs of rabies.
c) Isolate animals exhibiting signs of rabies, pending evaluation by a veterinarian.
d) Ensure that all animals have a unique identifier.
e) Administer a rabies vaccination to all dogs, cats and ferrets unless reliable proof of vaccination
exists.
f) Adopt minimum standards for animal caretakers as feasible, including personal protective
equipment, preexposure rabies vaccination, and appropriate training in animal handling (73).
g) Maintain documentation of animal disposition and location (e.g., returned to owner, died or
euthanized, adopted, relocated to another shelter, and address of new location).
h) Provide facilities to confine and observe animals involved in exposures (see Part I.B.6.).
i) Report human exposures to appropriate public health authorities (see Part I.A.3.).
C. PREVENTION AND CONTROL METHODS RELATED TO WILDLIFE
The public should be warned not to handle or feed wild mammals. Wild mammals and hybrids that expose
persons, pets, or livestock should be considered for euthanasia and rabies diagnosis. A person exposed by
any wild mammal should immediately report the incident to a healthcare provider who, in consultation with
public health authorities, can evaluate the need for PEP (9,10).
Translocation of infected wildlife has contributed to the spread of rabies (63-68,74); therefore, the
translocation of known terrestrial rabies reservoir species should be prohibited. Whereas state regulated
wildlife rehabilitators and nuisance wildlife control operators may play a role in a comprehensive rabies
control program, minimum standards for persons who handle wild mammals should include rabies
vaccination, appropriate training, and continuing education.
1. CARNIVORES: The use of oral rabies vaccines (ORV) for the mass vaccination of free-ranging
wildlife should be considered in selected situations, with the approval of the appropriate state agencies
(14,75). There have been documented successes using ORV to control rabies in wildlife in North America
(75-78). The currently licensed vaccinia-vectored ORV is labeled for use in raccoons and coyotes. The
distribution of ORV should be based on scientific assessments of the target species and followed by timely
and appropriate analysis of surveillance data; such results should be provided to all stakeholders. In
addition, parenteral vaccination (trap-vaccinate-release) of wildlife rabies reservoirs may be integrated into
coordinated ORV programs to enhance their effectiveness. Continuous and persistent programs for trapping
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or poisoning wildlife are not effective in reducing wildlife rabies reservoirs on a statewide basis. However,
limited population control in high-contact areas (e.g., picnic grounds, camps, and suburban areas) might be
indicated for the removal of selected high-risk species of wildlife. State agriculture, public health, and
wildlife agencies should be consulted for planning, coordination, and evaluation of vaccination or
population reduction programs (14).
2. BATS: From the 1950’s to date, indigenous rabid bats have been reported from every state except
Hawaii and have caused rabies in at least 43 humans in the United States (79-92). Bats should be excluded
appropriately from houses, public buildings, and adjacent structures to prevent direct association with
humans (93,94). Such structures should then be made bat-proof by sealing entrances used by bats.
Controlling rabies in bats through programs designed to reduce bat populations is neither feasible nor
desirable.
Part II. Recommendations for Parenteral Rabies Vaccination Procedures
A. VACCINE ADMINISTRATION: All animal rabies vaccines should be restricted to use by or under the
direct supervision of a veterinarian (95), except as recommended in Part I.B.1.
B. VACCINE SELECTION: Part III lists all vaccines licensed by USDA and marketed in the United States at
the time of publication. New vaccine approvals or changes in label specifications made subsequent to
publication should be considered as part of this list. Any of the listed vaccines can be used for revaccination,
even if the product is not the same as previously administered. Vaccines used in state and local rabies control
programs should have at least a 3-year duration of immunity. This constitutes the most effective method of
increasing the proportion of immunized dogs and cats in any population (96). No laboratory or epidemiologic
data exist to support the annual or biennial administration of 3- or 4-year vaccines following the initial series.
C. ADVERSE EVENTS: Currently, no epidemiologic association exists between a particular licensed vaccine
product and adverse events (13,97-98). Although rare, adverse events including vomiting, injection site
swelling, lethargy, hypersensitivity, and rabies in a previously vaccinated animal have been reported. Adverse
events should be reported to the vaccine manufacturer and to USDA, Animal and Plant Health Inspection
Service, Center for Veterinary Biologics (Internet:
http://www.aphis.usda.gov/animal_health/vet_biologics/vb_adverse_event.shtml; telephone: 800-752-6255). No
contraindication to rabies vaccination exists. Animals with a previous history of anaphylaxis can be medically
managed and observed after vaccination (46).
D. WILDLIFE AND HYBRID ANIMAL VACCINATION: The safety and efficacy of parenteral rabies
vaccination of wildlife and hybrids have not been established, and no rabies vaccines are licensed for these
animals. Zoos or research institutions may establish vaccination programs to attempt to protect valuable
animals, but these should not replace appropriate public health activities that protect humans (see Part
I.B.1.c.2).
E. ACCIDENTAL HUMAN EXPOSURE TO VACCINE: Human exposure to parenteral animal rabies
vaccines listed in Part III does not constitute a risk for rabies virus infection. Human exposure to vacciniavectored
oral rabies vaccines should be reported to state health officials (100,101).
F. RABIES CERTIFICATE: All agencies and veterinarians should use NASPHV Form 51 (revised 2007),
Rabies Vaccination Certificate, or an equivalent. This form can be obtained from vaccine manufacturers,
NASPHV (http://www.nasphv.org/Documents/RabiesVacCert.pdf), or CDC
(http://www.cdc.gov/rabies/pdf/nasphv_form51.pdf). The form must be completed in full and signed by the
administering or supervising veterinarian. Computer generated forms containing the same information are also
acceptable.
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III.Rabies Vaccines Licensed and Marketed in the U.S., 2011
Age at Primary Booster Route of
Product Name Produced by Marketed by For Use In Dosage Vaccinationa Recommended Inoculation
A) MONOVALENT (Inactivated)
RABVAC 1 Boehringer Ingelheim
Vetmedica, Inc.
License No. 112
Boehringer Ingelheim
Vetmedica, Inc.
Dogs
Cats
1 ml
1 ml
3 monthsb
3 months
Annually
Annually
IMc or SCd
IM or SC
RABVAC 3 Boehringer Ingelheim
Vetmedica, Inc.
License No. 112
Boehringer Ingelheim
Vetmedica, Inc.
Dogs
Cats
Horses
1 ml
1 ml
2 ml
3 months
3 months
3 months
1 year later & triennially
1 year later & triennially
Annually
IM or SC
IM or SC
IM
RABVAC 3 TF Boehringer Ingelheim
Vetmedica, Inc.
License No. 112
Boehringer Ingelheim
Vetmedica, Inc.
Dogs
Cats
Horses
1 ml
1 ml
2 ml
3 months
3 months
3 months
1 year later & triennially
1 year later & triennially
Annually
IM or SC
IM or SC
IM
CONTINUUM RABIES Intervet, Incorporated
License No. 165A
Intervet, Incorporated Dogs
Cats
1 ml
1 ml
3 months
3 months
1 year later & triennially
1 year later & quadrennially
SC
SC
EQUI-RAB Intervet, Incorporated
License No. 165A
Intervet, Incorporated Horses 1 ml 4 months Annually IM
PRORAB-1 Intervet, Incorporated
License No. 165A
Intervet, Incorporated Dogs
Cats
Sheep
1 ml
1 ml
2 ml
3 months
3 months
3 months
Annually
Annually
Annually
IM or SC
IM or SC
IM
DEFENSOR 1 Pfizer, Incorporated
License No. 189
Pfizer, Incorporated Dogs
Cats
1 ml
1 ml
3 months
3 months
Annually
Annually
IM or SC
SC
DEFENSOR 3 Pfizer, Incorporated
License No. 189
Pfizer, Incorporated Dogs
Cats
Sheep
Cattle
1 ml
1 ml
2 ml
2 ml
3 months
3 months
3 months
3 months
1 year later & triennially
1 year later & triennially
Annually
Annually
IM or SC
SC
IM
IM
RABDOMUN Pfizer, Incorporated
License No. 189
Schering-Plough Animal
Health
Dogs
Cats
Sheep
Cattle
1 ml
1 ml
2 ml
2 ml
3 months
3 months
3 months
3 months
1 year later & triennially
1 year later & triennially
Annually
Annually
IM or SC
SC
IM
IM
RABDOMUN 1 Pfizer, Incorporated
License No. 189
Schering-Plough Animal
Health
Dogs
Cats
1 ml
1 ml
3 months
3 months
Annually
Annually
IM or SC
SC
IMRAB 1 Merial, Incorporated
License No. 298
Merial, Incorporated Dogs
Cats
1 ml
1 ml
3 months
3 months
Annually
Annually
SC
SC
IMRAB 1 TF Merial, Incorporated
License No. 298
Merial, Incorporated Dogs
Cats
1 ml
1 ml
3 months
3 months
Annually
Annually
SC
SC
IMRAB 3 Merial, Incorporated
License No. 298
Merial, Incorporated Dogs
Cats
Sheep
Cattle
Horses
Ferrets
1 ml
1 ml
2 ml
2 ml
2 ml
1 ml
3 months
3 months
3 months
3 months
3 months
3 months
1 year later & triennially
1 year later & triennially
1 year later & triennially
Annually
Annually
Annually
IM or SC
IM or SC
IM or SC
IM or SC
IM or SC
SC
IMRAB 3 TF Merial, Incorporated
License No. 298
Merial, Incorporated Dogs
Cats
Ferrets
1 ml
1 ml
1 ml
3 months
3 months
3 months
1 year later & triennially
1 year later & triennially
Annually
IM or SC
IM or SC
SC
IMRAB
Large Animal
Merial, Incorporated
License No. 298
Merial, Incorporated Cattle
Horses
Sheep
2 ml
2 ml
2 ml
3 months
3 months
3 months
Annually
Annually
1 year later & triennially
IM or SC
IM or SC
IM or SC
B) MONOVALENT (Rabies glycoprotein, live canary pox vector)
PUREVAX Feline
Rabies
Merial, Incorporated
License No. 298
Merial, Incorporated Cats 1ml 3 months Annually SC
C) COMBINATION (Inactivated rabies)
CONTINUUM DAP-R Intervet, Incorporated
License No. 165A
Intervet, Incorporated Dogs 1 ml 3 months 1 year later & triennially SC
CONTINUUM Feline
HCP-R
Intervet, Incorporated
License No. 165A
Intervet, Incorporated Cats 1 ml 3 months 1 year later & triennially SC
Equine POTOMAVAC +
IMRAB
Merial, Incorporated
License No. 298
Merial, Incorporated Horses 1 ml 3 months Annually IM
D) COMBINATION (Rabies glycoprotein, live canary pox vector)
PUREVAX Feline 3/
Rabies
Merial, Incorporated
License No. 298
Merial, Incorporated Cats 1ml 8 weeks
3 months
Every 3 weeks until 3 months &
annually
3 weeks later & annually
SC
PUREVAX Feline 4/
Rabies
Merial, Incorporated
License No. 298
Merial, Incorporated Cats 1ml 8 weeks
3 months
Every 3 weeks until 3 months &
annually
3 weeks later & annually
SC
E) ORAL (Rabies glycoprotein, live vaccinia vector) - RESTRICTED TO USE IN STATE AND FEDERAL RABIES CONTROL PROGRAMS
RABORAL V-RG Merial, Incorporated
License No. 298
Merial, Incorporated Coyotes
Raccoons
N/A N/A As determined by local
authorities
Oral
a. Minimum age (or older) and revaccinated one year later
b. One month = 28 days
c. Intramuscularly
d. Subcutaneously
e. Fort Dodge Animal Health was recently acquired by Boehringer Ingelheim Vetmedica, Inc.
13
Rabies Vaccine Manufacturer Contact Information
Manufacturer Phone Number Internet Address
Boehringer Ingelheim Vetmedica, Inc. 800-638-2226 Not available
Intervet, Inc. 800-441-8272 http://www.intervetusa.com
Merial, Inc. 888-637-4251 http://us.merial.com
Pfizer, Inc. 800-366-5288 http://www.pfizerah.com
ADVERSE EVENTS: Adverse events should be reported to the vaccine manufacturer and to USDA, Animal and Plant Health Inspection Service,
Center for Veterinary Biologics (Internet: http://www.aphis.usda.gov/animal_health/vet_biologics/vb_adverse_event.shtml; telephone: 800-
752-6255;).
REFERENCES:
1. Rabies. In: Heymann D, ed. Control of communicable diseases manual. 19th ed. Washington, DC: American Public Health
Association; 2008:498-508.
2. Blanton JD, Palmer D, Christian KA, Rupprecht CE. Rabies surveillance in the United States during 2009. J Am Vet Med Assn
2010;237(6):646-657. Available at: http://www.cdc.gov/rabies/resources/publications/index.html.
3. Castrodale L, Walker V, Baldwin J, Hofmann J, Hanlon C. Rabies in a puppy imported from India to the USA, March 2007.
Zoonoses Public Health 2008;55(8-10):427-430.
4. CDC. Rabies in a Dog Imported from Iraq -- New Jersey, June 2008. MMWR 2008; 57:1076-1078. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5739a3.htm.
5. McQuiston JH, Wilson T, Harris S, et al. Importation of dogs into the United States: risks from rabies and other zoonotic diseases.
Zoonoses Public Health 2008;55(8-10):421-426.
6. Velasco-Villa A, Reeder SA, Orciari LA, et al. Enzootic rabies elimination from dogs and reemergence in wild terrestrial
carnivores, United States. Emerg Infect Dis 2008;14(12):1849-1854. Available at:
http://www.cdc.gov/EID/content/14/12/1849.htm.
7. Beran GW. Rabies and infections by rabies-related viruses. In: Beran GW (ed.) Handbook of zoonoses section B: Viral, second
ed. Boca Raton, FL: CRC Press; 1994:307-57.
8. Council of State and Territorial Epidemiologists. Public Health Reporting and National Notification for Animal Rabies. Infectious
Disease Positions Statements, June 2009. CSTE, Atlanta, GA. Available at: http://www.cste.org/ps2009/09-ID-12.pdf.
9. CDC. Human rabies prevention—United States, 2008. Recommendations of the Advisory Committee on Immunization Practices
(ACIP). MMWR 2008;57(No. RR-3):1-28. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e507a1.htm.
10. CDC. Use of reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies. Recommendations of the
Advisory Committee on Immunization Practices (ACIP). MMWR 2010;59(No. RR-2):1-12. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5902a1.htm.
11. McQuiston J, Yager PA, Smith JS, Rupprecht CE. Epidemiologic characteristics of rabies virus variants in dogs and cats in the
United States, 1999. J Am Vet Med Assoc 2001;218:1939–42.
12. Murray KO, Holmes KC, Hanlon CA. Rabies in vaccinated dogs and cats in the United States, 1997-2001. J Am Vet Med Assoc
2009;235:691-695.
13. Frana TS, Clough NE, Gatewood DM, Rupprecht CE. Postmarketing surveillance of rabies vaccines for dogs to evaluate safety
and efficacy. J Am Vet Med Assoc 2008;232:1000-1002.
14. Hanlon CA, Childs JE, Nettles VF, et al. Recommendations of the Working Group on Rabies. Article III: rabies in wildlife. J Am
Vet Med Assoc 1999;215:1612–8.
15. Slate D, Algeo TD, Nelson KM, et al. Oral rabies vaccination in North America: opportunities, complexities, and challenges.
PLoS Negl Trop Dis 2009;3(12):1-9
16. Council of State and Territorial Epidemiologists. Electronic laboratory reporting in the US: underfunded and under potential, or,
recommendations for the implementation of ELR in the US. Policy Positions Statements, June 2009. CSTE, Atlanta, GA.
Available at: http://www.cste.org/ps2009/09-SI-03.pdf.
17. Council of State and Territorial Epidemiologists. Process statement for immediately nationally notifiable conditions. Policy
Positions Statements, June 2009. CSTE, Atlanta, GA. Available at: http://www.cste.org/ps2009/09-SI-04.pdf.
18. Hanlon CA, Smith JS, Anderson GR, et al. Recommendations of the Working Group on Rabies. Article II: laboratory diagnosis of
rabies. J Am Vet Med Assoc 1999;215:1444–6.
19. Rudd RJ, Smith JS, Yager PA, et al. A need for standardized rabies-virus diagnostic procedures: effect of cover-glass mountant
on the reliability of antigen detection by the fluorescent antibody test. Virus Res 2005;111:83–8.
20. American Veterinary Medical Association. AVMA guidelines on euthanasia, June2007. Schaumburg, IL: American Veterinary
Medical Association; 2007. Available at: http://www.avma.org/issues/animal_welfare/euthanasia.pdf.
21. Michigan Rabies Working Group. Humane euthanasia of bats for public health rabies testing. 2008. Available at:
http://www.michigan.gov/documents/emergingdiseases/Humane_Euthanasia_of_Bats-Final_244979_7.pdf.
22. CDC. Public health response to a potentially rabid bear cub -- Iowa, 1999. MMWR 1999;48:971-3. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4842a5.htm.
14
23. Niezgoda M, Rupprecht CE. Atlanta: US Department of Health and Human Services, Centers for Disease Control and Prevention
1-16; 2006. Standard operating procedure for the direct rapid immunohistochemistry test for the detection of rabies virus antigen.
National Laboratory Training Network Course. Available at: http://www.rabiesblueprint.com/IMG/pdf/DRIT_SOP.pdf.
24. Lembo T, Niezgoda M, Velasco-Villa A, Cleaveland S, Ernest E, Rupprecht CE. Evaluation of a direct, rapid
immunohistochemical test for rabies diagnosis. Emerg Infect Dis. 2006. Feb;12(2):310-3.
25. Dürr S, Naïssengar S, Mindekem R, et al. Rabies diagnosis for developing countries. PLoS Negl Trop Dis. 2008. Mar
26;2(3):e206.
26. Saturday GA, King R, Fuhrmann L. Validation and operational application of a rapid method for rabies antigen detection. US
Army Med Dep J. 2009. Jan-Mar:42-5.
27. Tizard I, Ni Y. Use of serologic testing to assess immune status of companion animals. J Am Vet Med Assoc 1998;213:54–60.
28. Greene CE, ed. Rabies and other lyssavirus infections. In: Infectious diseases of the dog and cat. 3rd ed. London, England:
Saunders Elsevier; 2006;167–83.
29. Rupprecht CE, Gilbert J, Pitts R, Marshall K, Koprowski H. Evaluation of an inactivated rabies virus vaccine in domestic ferrets.
J Am Vet Med Assoc 1990;196:1614–6.
30. Moore SM, Hanlon CA. Rabies-specific antibodies: measuring surrogates of protection against a fatal disease. PLoS Negl Trop
Dis. 2010. Mar 9;4(3):e595.
31. Aubert MF. Practical significance of rabies antibodies in cats and dogs. Rev Sci Tech 1992;11:735–60.
32. Muirhead TL, McClure JT, Wichtel JJ, et al. The effect of age on serum antibody titers after rabies and influenza vaccination in
healthy horses. J Vet Intern Med 2008;22:654-661.
33. Shimazaki Y, Inoue S, Takahashi C, et al. Immune response to Japanese rabies vaccine in domestic dogs. J Vet Med B
2003;50:95-8.
34. Cliquet F, Verdier Y, Sagné L, et al. Neutralising antibody titration in 25,000 sera of dogs and cats vaccinated against rabies in
France, in the framework of the new regulations that offer an alternative to quarantine. Rev Sci Tech 2003;22:857–66.
35. Rabies. In: Guidelines for the vaccination of horses. American Association of Equine Practitioners; 2009. Available at:
http://www.aaep.org/rabies.htm.
36. National Association of State Public Health Veterinarians. Compendium of measures to prevent disease and injury associated
with animals in public settings, 2007. MMWR 2007;56(RR05);1-13. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5805a1.htm.
37. Bender J, Schulman S. Reports of zoonotic disease outbreaks associated with animal exhibits and availability of
recommendations for preventing zoonotic disease transmission from animals to people in such settings. J Am Vet Med Assoc
2004;224:1105–9.
38. American Veterinary Medical Association. Private ownership of wild animals. Schaumburg, IL: American Veterinary Medical
Association; 2006. Available at: http://www.avma.org/issues/policy/wild_animal_ownership.asp.
39. American Veterinary Medical Association. Position on canine hybrids. Schaumburg, IL: American Veterinary Medical
Association; 2008. Available at: http://www.avma.org/issues/policy/canine_hybrids.asp.
40. Siino BS. Crossing the line: the case against hybrids. American Society for the Prevention of Cruelty to Animals, Animal Watch;
2000:22–9. Available at: http://www.petfinder.com/before-pet-adoption/case-against-hybrids.html?page-index=1&query=hybrids.
41. Jay MT, Reilly KF, DeBess EE, Haynes EH, Bader DR, Barrett LR. Rabies in a vaccinated wolf-dog hybrid. J Am Vet Med
Assoc 1994;205:1729–32.
42. CDC. An imported case of rabies in an immunized dog. MMWR 1987;36:94–6. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/00000874.htm.
43. CDC. Imported dog and cat rabies—New Hampshire, California. MMWR 1988;37:559–60. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/00001275.htm.
44. Hanlon CA, Niezgoda MN, Rupprecht CE. Postexposure prophylaxis for prevention of rabies in dogs. Am J Vet Res
2002;63:1096–100.
45. US Government Printing Office. 9CFR113.209. Available at: http://edocket.access.gpo.gov/cfr_2003/9cfr113.209.htm.
46. Greene CE, ed. Immunoprophylaxis. In: Infectious diseases of the dog and cat. 3rd ed. London, England: Saunders Elsevier;
2006;1069-1119.
47. Willoughby, RE. “early death” and the contraindication of vaccine during rabies treatment. Vaccine 2009;27:7173-7177.
48. Mansfield K, McElhinney L, Hübschle O, et al. A molecular epidemiological study of rabies epizootics in kudu (Tragelaphus
strepsiceros) in Namibia. BMC Vet Res 2006;2:2.
49. Viral agents. In: U.S. Department of Health and Human Services. Biosafety in Microbiological and Biomedical Laboratories. 5th
edition. Washington, D.C.: U.S. Government Printing Office; 2007:234-235. Available at:
http://www.cdc.gov/biosafety/publications/bmbl5/BMBL5_sect_VIII_e.pdf.
50. Wertheim HFL, Nguyen TQ, Nguyen KAT, et al. Furious rabies after an atypical exposure. PLoS Med 2009;6(3):0264-8.
51. Ante-mortem inspection. In: U.S. Meat and Poultry Inspection Program. Meat and poultry inspection manual. Washington, D.C.:
U.S. Government Printing Office; 1973:314 p.
52. Debbie JG, Trimarchi CV. Pantropism of rabies virus in free-ranging rabid red fox (Vulpes fulva). J Wildl Dis 1970;6(4):500-6.
53. Fekadu M, Shaddock JH. Peripheral distribution of virus in dogs inoculated with two strains of rabies virus. Am J Vet Res
1984;45(4):724-729.
15
54. Charlton, KM. The pathogenesis of rabies and other lyssaviral infections: recent studies. Curr Top Microbiol Immunol
1994;187:95–119.
55. Afshar, A. A review of non-bite transmission of rabies virus infection. Br Vet J 1979;135:142-8.
56. CDC. Mass treatment of humans who drank unpasteurized milk from rabid cows—Massachusetts, 1996–1998. MMWR
1999;48:228–9. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/00056759.htm.
57. CDC. Public health service guideline on infectious disease issues in xenotransplantation. MMWR 2001;50(No. RR-15):1-56.
58. Turner GS, Kaplan C. Some properties of fixed rabies virus. J Gen Virol 1967;1:537-551.
59. Vaughn JB, Gerhardt P, Paterson J. Excretion of street rabies virus in saliva of cats. J Am Med Assoc 1963;184:705.
60. Vaughn JB, Gerhardt P, Newell KW. Excretion of street rabies virus in saliva of dogs. J Am Med Assoc 1965;193:363–8.
61. Niezgoda M, Briggs DJ, Shaddock J, Rupprecht CE. Viral excretion in domestic ferrets (Mustela putorius furo) inoculated with a
raccoon rabies isolate. Am J Vet Res 1998;59:1629–32.
62. Tepsumethanon V, Lumlertdacha B, Mitmoonpitak C, Sitprija V, Meslin FX, Wilde H. Survival of naturally infected rabid dogs
and cats. Clin Infect Dis 2004;39:278–80.
63. Jenkins SR, Perry BD, Winkler WG. Ecology and epidemiology of raccoon rabies. Rev Infect Dis 1988;10(Suppl 4):S620–5.
64. CDC. Translocation of coyote rabies—Florida, 1994. MMWR 1995;44:580–7. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/00038451.htm.
65. Rupprecht CE, Smith JS, Fekadu M, Childs JE. The ascension of wildlife rabies: a cause for public health concern or
intervention? Emerg Infect Dis 1995;1:107–14. Available at: http://www.cdc.gov/ncidod/eid/vol1no4/rupprech.htm.
66. Constantine DG. Geographic translocation of bats: known and potential problems. Emerg Infect Dis 2003;9:17–21. Available at:
http://www.cdc.gov/ncidod/EID/vol9no1/02-0104.htm.
67. Krebs JW, Strine TW, Smith JS, Rupprecht CE, Childs JE. Rabies surveillance in the United States during 1993. J Am Vet Med
Assoc 1994;2051695–709.
68. VF Nettles, JH Shaddock, RK Sikes, CR Reyes. Rabies in translocated raccoons. Am J Public Health 1979;69:601–2.
69. RM Engeman, KL Christensen, MJ Pipas, DL Bergman. Population monitoring in support of a rabies vaccination program for
skunks in Arizona. J Wildl Dis 2003;39:746–50.
70. Leslie MJ, Messenger S, Rohde RE, et al. Bat-associated rabies virus in skunks. Emerg Infect Dis 2006;12:1274–7. Available at:
http://www.cdc.gov/ncidod/EID/vol12no08/05-1526.htm.
71. Rupprecht CE, Hanlon CA, Slate D. Control and prevention of rabies in animals: paradigm shifts. Dev Biol (Basel).
2006;125:103-11.
72. Pets Evacuation and Transportations Standards Act of 2006. Available at: http://frwebgate.access.gpo.gov/cgibin/
getdoc.cgi?dbname=109_cong_public_laws&docid=f:publ308.109.pdf.
73. National Animal Control Association guidelines. Available at: http://www.nacanet.org/guidelines.html.
74. Chipman R, Slate D, Rupprecht C, Mendoza M. Downside Risk of Translocation. Dodet B, Fooks AR, Muller T, Tordo N, and
the Scientific & Technical Department of the OIE (eds): Towards the Elimination of Rabies in Eurasia. Dev Biol. Basel, Karger
2008;131:223-232.
75. Slate D, Rupprecht CE, Rooney JA, Donovan D, Lein DH, Chipman RB. Status of oral rabies vaccination in wild carnivores in
the United States. Virus Res 2005;111:68–76.
76. Sidwa TJ, Wilson PJ, Moore GM, et al. Evaluation of oral rabies vaccination programs for control of rabies epizootics in coyotes
and gray foxes: 1995-2003. J Am Vet Med Assoc 2005;227:785-792.
77. MacInnes CD, Smith SM, Tinline RR, et al. Elimination of rabies from red foxes in eastern Ontario. J Wildl Dis 2001;37:119-
132.
78. Rosatte RC, Power MJ, Donovan D, et al. Elimination of arctic variant of rabies in red foxes, metropolitan Toronto. Emerg Infect
Dis 2007;13(1)25-27. Available at: http://www.cdc.gov/ncidod/EID/13/1/25.htm.
79. Messenger SL, Smith JS, Rupprecht CE. Emerging epidemiology of bat-associated cryptic cases of rabies in humans in the United
States. Clin Infect Dis 2002;35:738–47.
80. CDC. Human rabies—California, 2002. MMWR 2002;51:686–8. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5131a4.htm.
81. CDC. Human rabies—Tennessee, 2002. MMWR 2002;51:828–9. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5137a2.htm.
82. CDC. Human rabies—Iowa, 2002. MMWR 2003;52:47–8. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5203a3.htm.
83. CDC. Human death associated with bat rabies—California, 2003. MMWR 2004;53:33–5. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5302a4.htm.
84. CDC. Recovery of a patient from clinical rabies, Wisconsin, 2004. MMWR 2004;53:1171–3. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5350a1.htm.
85. CDC. Human rabies—Mississippi, 2005. MMWR 2006;55:207–8. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5508a4.htm.
86. CDC. Human rabies—Indiana and California, 2006. MMWR 2007;56:361–5. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5615a1.htm.
87. CDC. Human rabies—Minnesota, 2007. MMWR 2008;57:460-462. Available at:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5717a3.htm.

miércoles, 14 de agosto de 2013

Rabia en Chile. Murciélagos insectívoros. Miriam Favi et al. 1999

Archivos de medicina veterinaria

versión impresa ISSN 0301-732X

Arch. med. vet. v.31 n.2 Valdivia  1999

http://dx.doi.org/10.4067/S0301-732X1999000200002 



Rol de los murciélagos insectívoros en la transmisión
de la rabia en Chile

Role of insectivorous bats in the transmission
of Rabies in Chile

MYRIAM FAVIC.1, M.V.; VERÓNICA YUNG P.1, T.M.; CARLOS PAVLETIC B.2, M.V.;
EUGENIO RAMIREZ V.1, B.Q.; CECILIA DE MATTOS3, M.V.; CARLOS A. DE MATTOS3, M.V.

1Instituto de Salud Pública de Chile, Marathon 1000, Ñuñoa, Casilla 48, Santiago, Chile.
Fax: 2-239-6966, Correo electrónico: virología@ispch.cl.
2Ministerio de Salud de Chile, Estado N° 360, Oficina 602, Santiago, Chile.
3Viral and Ricketsial Zoonosis Branch, Division of Viral and Ricketsial Disease, National Center for Infectious Disease, 1600 Clifton Road, N.E., Atlanta, Georgia 30333, USA.

SUMMARY

The importance of wild animals in the epidemiology of rabies in Chile was not recognized until 1985. Since then the epidemiology of rabies has been characterized by the presence of an endemic cycle in the species of the Order Chiroptera. In 1996, after 24 years without human rabies cases, a child died of the disease. The victim was infected with an antigenic variant 4 (AgV4) virus whose reservoir is the non-hematophagous bats Tadarida brasiliensis. This event emphatized the need for a better characterization of rabies selvatic cycles, their geographical distribution, and the risk factors that influence the virus transmission to humans and domestic animals in the country.
From a total of 250 isolates obtained between 1977 and 1997, 119 were reactived. These samples were antigenically characterized by the indirect inmunofluorescence technique using a panel of 8 monoclonal antibodies direct against epitopes of the viral nucleoprotein produced by the Centers of Disease Control and Prevention, Atlanta, Georgia, USA. The analysis showed that all the viruses obtained from non-hematophagous bats were AgV4 seven out of 10 canine isolates were AgV4. The other 3 canine viruses were AgV1, whose reservoir is the dog. Of the 3 bovine isolates, 2 was AgV1 and 1 AgV4. Three feline and one porcine viruses was caracterized as AgV4. It was determined that a bovine rabies case reported in 1977 and all the viruses isolated from domestic animals since 1990 were AgV4.
These results allowed to conclude that, in Chile, the non-hematophagous bats Tadarida brasiliensis was a rabies selvatic reservoir before 1985, and since then it has been the only wild reservoir know responsible for rabies sporadic cases in human and domestic animals.
Palabras claves: Anticuerpos monoclonales, Variantes antigénicas, Rabia.
Key Words: Monoclonal Anbitodies, Antigenic Variant, Rabies.

INTRODUCCION

La rabia en América Latina se presenta en sus dos ciclos epidemiológicos, el urbano y el silvestre. El perro es el reservorio y transmisor del ciclo urbano y los reservorios más importantes del ciclo silvestre son el murciélago vampiro Desmodus rotundus,y la mangosta Herpestes auropucntatus (WHO, 1992).
En Chile la rabia urbana fue endémica entre los años 1950 y 1960, registrándose numerosos casos humanos y animales durante dicho período. Esto llevó a la instauración en 1960 de un programa de control y prevención de la rabia en el país. Este programa fue orientado a tres importantes objetivos: primero, reducir la población canina; segundo inmunizar masivamente a los perros y finalmente aumentar la cobertura del diagnóstico de rabia, tanto en animales sospechosos como a través de la vigilancia epidemiológica activa. (Favi y Catalán, 1986) La efectividad de las medidas adoptadas se hizo evidente a partir de 1962, al producirse una disminución drástica de los casos de rabia, y detectándose casos humanos hasta el año 1972 (Favi y Durán, 1991).
Desde el año 1980 se presentaron casos de rabia en forma esporádica en animales domésticos sin que su fuente de infección pudiera ser identificada. Estos casos tuvieron la particularidad de ser de bajo poder epidémico, presentándose incluso un silencio epidemiológico en los años 1982 y 1984. Este cuadro epidemiológico sugirió que la fuente de infección en estos eventos podía ser de origen silvestre (Nieto, 1985).
La importancia de los animales silvestres en la transmisión de la rabia fue reconocida en Chile en 1985, cuando se detectó por primera vez rabia en murciélagos insectívoros de la especie Tadarida brasiliensis (Favi y Catalán, 1986Nuñez y col., 1987). Hasta ese momento todas las acciones del Programa de Control y Prevención de Rabia estaban focalizadas sobre las especies domésticas, principalmente sobre los perros, existiendo un total desconocimiento de la presencia de la rabia en la fauna silvestre. El reconocimiento de los murciélagos como reservorios de la enfermedad en Chile hizo que se ampliaran las acciones de vigilancia epidemiológica hacia esas especies. A partir de entonces el patrón epidemiológico de la rabia en Chile se ha caracterizado por una endemia en quirópteros. La importancia de esta nueva situación epidemiológica alcanza su mayor relevancia en el país al reportarse el primer caso humano después de 24 años. Este ocurre en un niño de siete años de edad, sin antecedentes de mordeduras o exposición al virus, sospechándose de un murciélago no hematófago como su fuente de infección (Favi y Ramírez, 1996).
El primer caso de rabia en murciélagos no hematófagos fue reportado en Estados Unidos en 1953 (Scatterday y Galton, 1954Venters y cols.,1954). En este país, 30 de las 39 especies presentes, están infectadas con el virus rábico y 21 de los 36 casos humanos registrados, entre 1981 y octubre de 1997, fueron debidos a variantes virales circulando en murciélagos no hematófagos (Constantine 1979Krebs y col., 1996). Estas variantes fueron diferenciadas a través de su caracterización antigénica y genética (Smith, 1989Smith y col.,1995). Se demostró que en este país, la especie migratoria Tadarida brasiliensis mantiene un ciclo endémico independiente, cuya variante viral es diferente a la VAg4 que circula en Chile (Smith, 1989Díaz y col., 1994).
La caracterización de aislamientos por anticuerpos monoclonales es un elemento de apoyo muy valioso a los sistemas de vigilancia epidemiológica de la enfermedad. Esta caracterización ayuda a identificar las especies reservorias presentes en una determinada área geográfica, a elaborar estrategias de control y prevención más eficientes y a mejorar el monitoreo de los programas de control correspondientes (Smith, 1989).
El objetivo del presente trabajo fue caracterizar antigénicamente los aislamientos del virus rábico efectuados en el Centro Nacional de Referencia de Rabia del Instituto de Salud Pública de Chile, desde 1977, hasta abril de 1997 con el fin de lograr un mejor entendimiento de la epidemiología de la rabia silvestre en murciélagos no hematófagos en Chile.

MATERIALES Y METODOS

Reactivación de las muestras. Un total de 250 muestras con diagnóstico previo positivo al virus de la rabia, obtenidas entre 1977 y abril de 1997, y mantenidas en congelación a -70°C, fueron inoculadas en ratones lactantes con el fin de ser reactivadas (Koprowsky, 1976) y para que el antígeno rábico se encuentre presente en el 75% al 100% de los campos microscópicos, a ser observados por la técnica de inmunofluorescencia indirecta usando anticuerpos monoclonales (Smith y col., 1986). Diez microlitros de una suspensión al 20% en PBS de cada una de ellas fue inoculada intracerebralmente en un grupo de 10 ratones lactantes (Albino swiss) de uno a tres días de edad. Los animales fueron observados diariamente por un período de 28 días. A partir del quinto día post-inoculación un animal de cada grupo fue sacrificado diariamente, sus cerebros extraídos e improntas de los mismos observadas por la técnica de inmunofluorescencia directa para determinar la presencia de antígeno rábico y así ser consideradas reactivadas (Larghi,1975; Dean y col., 1996).
Caracterización antigénica. Las muestras reactivadas fueron analizadas por la técnica de inmunofluorescencia indirecta (Smith y col., 1989Smith, 1988). En esta caracterización se incluyó, también, la muestra humana obtenida en 1996, cuya reactivación no fue necesaria.
Para la tipificación antigénica se utilizó un panel reducido de anticuerpos monoclonales producidos contra la ribonucleoproteína viral reconocido por el Consorcio Institucional Multinacional Subregional de Laboratorios de Referencia para el diagnóstico y caracterización de variantes de virus rábico en América Latina, y producido por el Centers for Disease Control and Prevention de Atlanta, Georgia, Estados Unidos. La reactividad de estos anticuerpos monoclonales para muestras del virus rábico obtenidas en América Latina fue determinada en estudios previos (Díaz y col., 1994De Mattos y col., 1996). El cuadro 1 muestra el panel de anticuerpos monoclonales utilizados.

CUADRO 1. Patrones de reacción de las diferentes variantes antigénicas con los anticuerpos monoclonales.
Reaction patterns of different antigenic variants to monoclonal antibodies.

 C1C4C9C10C12C15C18C19AgV

CVS/ERA-SAD/PAST++++++++Lab
Perro/mangosta++++++-+1
Perro
+
+
-
+
+
+
-
+
2
Desmodus rotundus
-
+
+
+
+
-
-
+
3
Tadarida brasiliensis-
+
+
+
+
---4
Desmodus rotundus-
+
v
+
+
v-v5
Lasiurus cineriusv
+
+
+
+
---6
Zorro de Arizona
+
+
+
-
+
+
-
+
7
Zorrillo Centro/Sur-
+
+
+
+
+
+
+
8
Tadarida brasiliensis
+
+
+
+
+
---9

RESULTADOS
De las 250 muestras iniciales, sólo 119 pudieron ser reactivadas y éstas junto con la muestra del caso humano fueron analizadas antigénicamente. El cuadro 2 muestra la especie y la región geográfica de origen de las muestras reactivadas, el número de las mismas por especie y el año de aislamiento.
Sobre la base de la reacción con el panel de anticuerpos monoclonales, se identificaron 2 patrones antigénicos: VAg1 (canina) y VAg4 (Tadarida brasiliensis). La VAg1 se observó en cuatro aislamientos. Tres en perros, en los años 1977, 1981 y 1990, respectivamente, y un caso en bovino de la Región Metropolitana en 1983. La VAg4 se observó en los 115 aislamientos restantes; 102 fueron aislamientos efectuados a partir de murciélagos de la especie Tadarida brasiliensis en las regiones IV a la X y en la Región Metropolitana, y 17 fueron virus rábicos obtenidos de 3 bovinos, 3 felinos, 10 caninos y 1 porcino en las regiones IX, V, X, I y Región Metropolitana (cuadro 2).

CUADRO 2. Caracterización antigénica de las muestras reactivadas por pasaje en ratón,
según su año de aislamiento, especie animal y región geográfica.
Antigenic characterization of samples reactivated by passage in mice, according to year of isolation,
animal species and geographic location.
 
Año Nº de muestrasVarianteRegión Geográfica
   Antigénica 

1977Canino11I
 Bovino14IX

1981Canino11VIII

1983Bovino11RM*

1985Felino14V
 T. brasiliensis144RM (11)**, V (3)

1986Canino24RM
 Felino14RM
 T. brasiliensis54RM

1987Canino14RM
 Bovino14RM
 Porcino14RM
 T. brasiliensis134RM (11), V (2)

1988T. brasiliensis14RM

1989T. brasiliensis24VII

1990T. brasiliensis84RM (5), V (1); VII
 Canino14RM
 Canino11VI

1991T. brasiliensis14RM

1992T. brasiliensis14RM

1993T. brasiliensis64VI (1), VIII (3), RM (2)

1996T. brasiliensis444IV (4), V (5), VI (10), VII (3),
    VIII (3), IX (1), RM (18)
 Humano14VI

1997Canino14I
 Felino14X
 T. brasiliensis94V (2), VI (2), VII (1), VIII (1),
    IX (1), X (1), RM 5.RM (5)

* Región Metropolitana.
** Número de muestras obtenidas en esa región geográfica.

DISCUSION

La caracterización antigénica de 119 aislamientos del virus rábico obtenidos de diferentes especies animales y un humano en Chile entre 1977 y 1997 confirmó que actualmente la especie Tadarida brasiliensis es el reservorio más importante de la rabia en los centros urbanos y rurales del país. La relevancia de los murciélagos no hematófagos en la epidemiología de la rabia en los centros urbanos de América del Sur ha sido sugerida previamente (Lord, 1976De Mattos y cols., 1996). Las características poblacionales y de diversidad de estas especies en América Latina hacen que su infección con el virus rábico, aún con una baja incidencia, sea una fuente de infección muy importante para los humanos y animales domésticos (Lord, 1976De Mattos y cols., 1996).
El control de la rabia urbana permite que se haga evidente la presencia de ciclos silvestres en áreas geográficas donde previamente eran inadvertidos (Ruíz y Arambulo III, 1994). Esta situación es la que actualmente caracteriza el cuadro epidemiológico en Chile, donde, según nuestros datos aquí lo demuestran, el último caso producido por la variante VAg1 se registra en un perro en el año 1990, después de que el único caso de variante Vag1 se presentó en 1983 en un bovino. Esto indica la interrupción de la circulación de la variante canina desde esta fecha hasta abril de 1997.
En el período 1985-1997 se registra un promedio anual de 25 casos de rabia en quirópteros, reportándose también casos esporádicos en animales domésticos y el caso humano en 1996 (Favi y Ramírez,1996). La caracterización antigénica del aislamiento humano como VAg4 indica que la fuente de infección fue un Tadarida brasiliensis. Este evento epidemiológico es similar a numerosos casos de rabia humana ocurridos en Estados Unidos durante las últimas dos décadas. En algunos casos, asociados a variantes virales circulantes en poblaciones de murciélagos no hematófagos. Tampoco se pudo determinar la forma de exposición al virus o comprobar historia alguna de mordedura (Krebs y cols.. 1996Weekly Epidemiological, 1997). Nuestros hallazgos demuestran la necesidad de disponer de la tecnología adecuada que permita determinar con la mayor resolución posible el origen de la fuente de infección en cuadros epidemiológicos complejos y caracterizar las variantes del virus rábico circulando en distintas zonas geográficas de Chile.
En relación a la distribución geográfica de los casos de rabia en murciélago en Chile (Mapa 12 y 3), el primero se detectó en la Región Metropolitana en el año 1985, seguido a la brevedad por la aparición de nuevos casos en las regiones V, hacia el norte y VI, VII y VIII hacia el sur entre los años 1985 y 1995. En 1996 se amplía esta distribución con la detección de casos en la IV región después de más de 20 años de silencio epidemiológico en la zona. En el año 1997, la distribución geográfica de las VAg4 se extiende a las regiones III y X, con el aislamiento del virus a partir de un murciélago y un gato doméstico respectivamente. En este mismo año se reporta un caso de rabia en un perro en la ciudad de Arica (I Región), donde no se presentaban casos desde el año 1986. En esta zona se realiza vigilancia epidemiológica exclusivamente en animales domésticos, con vacunaciones antirrábicas masivas una vez al año en perros y gatos. En circunstancias como esta, la correcta y pronta identificación de la variante antigénica implicada, y en algunos casos su caracterización genética, permiten la pronta definición del cuadro epidemiológico que, a su vez, se traduce inmediatamente en medidas de vigilancia epidemiológica y control más eficaces.
Mapa 1. Distribución de variantes antigénicas en cepas reactivadas de virus rábico.
Distribution of antigenic patterns in reactivated strains of rabies virus.
Chile 1977 - 1983.
Mapa 2. Distribución de variantes antigénicas en cepas reactivadas de virus rábico.
Distribution of antigenic patterns in reactivated strains of rabies virus.
Chile 1985-1990.
Mapa 3. Distribución de variantes antigénicas en cepas reactivadas de virus rábico.
Distribution of antigenic patterns in reactivated strains of rabies virus.
Chile 1991 - 1997.
La distribución geográfica de los casos coincide con la del murciélago insectívoro Tadarida brasiliensis que abarca desde la zona desértica de Tarapacá hasta la región de los bosques lluviosos de la ciudad de Valdivia, demostrando su extraordinaria capacidad de adaptación frente a las más variadas condiciones climáticas (Redford y Eiseberg, 1992Mann, 1978). Aparentemente estos animales migran estacionalmente y comúnmente se refugian en edificios y cavidades naturales (Redford y Eiseberg, 1992).
Además del Tadarida brasiliensis, existen en Chile al menos 8 especies de murciélagos no hematófagos distribuidos del norte al sur del país, entre ellas se encuentra el Lasiurus cinereus y el Lasiurus borealis (Mann, 1978), dos especies identificadas como reservorios de la rabia en otros países (Redford y Eiseberg, 1992).
Esto sugiere la posible presencia de otros ciclos endémicos silvestres en otras especies de quirópteros manteniendo otras variantes virales en el país.
Dada la posible complejidad del ciclo silvestre de la rabia en Chile, que ya ha cobrado una vida humana en uno de sus centros urbanos más importantes, es imperioso continuar con la caracterización antigénica y genética de las variantes existentes en conjunción con los programas de vigilancia epidemiológica en todas aquellas regiones donde existan posibles reservorios.
Los murciélagos por sus hábitos antropofílicos representan un riesgo para el hombre, por lo cual es también necesario intensificar la educación de la población en relación a su comportamiento frente a estos animales para su propia protección y para la conservación de estas especies quirópteras de enorme valor ecológico.

RESUMEN

La importancia de los animales silvestres en la trasmisión de la rabia en Chile no fue reconocida hasta 1985. A partir de entonces el patrón epidemiológico de la rabia se ha caracterizado por una endemia en quirópteros.
En el año 1996, después de 24 años sin registrarse casos de rabia en humanos, se reporta un caso en un niño infectado con la variante antigénica 4 (VAg4), cuyo reservorio es el murciélago no hematófago Tadarida brasiliensis. Esta situación determinó la necesidad de identificar con mayor precisión los ciclos silvestres del virus rábico, su dispersión territorial y los factores de riesgo que condicionan su trasmisión en el país.
De un total de 250 cepas aisladas entre los años 1977 y 1997 se reactivaron 119. Estas fueron analizadas por la técnica de inmunofluorescencia indirecta con un panel de ocho anticuerpos monoclonales producido por el Centers for Disease Control and Prevention en Atlanta, Georgia, Estados Unidos.
El análisis determinó que todos los virus de murciélagos pertenecen a la variante antigénica 4 (VAg4). De los 10 aislamientos caninos, siete corresponden a la VAg4 y tres a la VAg1, cuyo reservorio es el perro. De los aislamientos de bovinos uno fue VAg1 y dos VAg4 y aquellos de tres felinos y un porcino también fueron VAg4. Se determinó que un caso bovino reportado en 1977 y los virus aislados de animales domésticos desde 1990 corresponden a la Variante 4.
Estos resultados permiten concluir que, en Chile los murciélagos no hematófagos han actuado como reservorio de la rabia silvestre con anterioridad a 1985 y que posteriormente a este año son los únicos reservorios, conocidos hasta el momento, que han originado casos esporádicos de rabia en el hombre y los animales domésticos.

AGRADECIMIENTOS
Agradecemos al personal del Laboratorio de Diagnóstico de Rabia del Instituto de Salud Pública de Chile, especialmente a la Sra. Cristina Toledo y Sra. Beatriz Sanhueza por su valiosa colaboración
Aceptado: 04.05.99.

REFERENCIAS

CONSTANTINE, D. G. 1979. An undated list of rabies infected bats in North America, J. Wild Dis. 15: 347 - 349.         [ Links ]
DEAN, JJ., M. K. ABELSTH, P. ATANASIU. 1996. The fluorescent antibody test. /In Laboratory Techniques in Rabies (4th ed.), Meslin F-X, Kaplan MM, Koprowsky, H. (eds.). World Health Organization, Geneve, pp. 86 -96.         [ Links ]
De MATTOS, C.A., C.C. De MATTOS, J.S. SMITH, E.T. MILLER, S. PAPO, A. UTRERA, B. I. OSBURN. 1996. Genetic characterization of rabies field isolates from Venezuela, J. Clin. Microbiol. 34: 1553 - 1558.         [ Links ]
DIAZ, A.M., S. PAPO, A. RODRIGUEZ, J.S. SMITH. 1994. Antigenic analysis of rabies virus isolated from Latin America and the Caribbean, Zentralbl. Veterinaer med Reihe B 41: 153 - 160.         [ Links ]
FAVI, M.; R. CATALAN. 1986. Rabia en murciélagos en Chile, Av. Cs. Vet. 1: 73-76.         [ Links ]
FAVI, M., J. C. DURAN. 1991. Epidemiología de la rabia en Chile (1929 - 1988) y perpectivas en mamíferos silvestres, Av. Cs. Vet. 6: 13 - 21.         [ Links ]
FAVI, M., E. RAMIREZ. 1996. Rabia humana en Chile. Laboratorio al día. Instituto de Salud Pública de Chile, Vol. XII N° 2, pp 7.
FAVI, M., V. YUNG, C. PAVLETIC. 1997. Programa de vigilancia de rabia. Laboratorio al día, Instituto de Salud Pública de Chile, Vol. XIII N° 1, p 18.
KREBS, J.W., J.S. SMITH, C.E. RUPPRECHT, J.E. CHILDS. 1996. Rabies Surveillance in the US during 1966, JAVMA.211:1525 - 1539.         [ Links ]
KOPROWSKY, H. 1976. Prueba de inoculación en ratón. En: La Rabia. Técnica de Laboratorio. (3ª ed.) Kaplan, M.N; Koprowsky, H. Ginebra, OMS., pp 88- 97.
LARGHI, O.P. 1975. Anticuerpos fluorescentes para rabia. Centro Panamericano de Zoonosis (Buenos Aires). Oficina Sanitaria Panamericana (Nota técnica N° 8).
LORD. R. 1976. Importancia de los murciélagos en la epidemiología de las zoonosis con énfasis en la rabia bovina. Publ. Cient. Org. Panam. Salud. 334: 89-97 .         [ Links ]
MANN, G. 1978. Los pequeños mamíferos de Chile, Gayana Zoología 40: 40 - 105. Universidad de Concepción, Chile.         [ Links ]
NIETO, D.A. 1985. Antecedentes sobre rabia silvestre en la comunidad de Pirque. Tesis.Santiago, Escuela de Medicina Veterinaria, Universidad de Chile.         [ Links ]
NUÑEZ,S.F., M. FAVI, V.S. URCELAY, C. SEPULVEDA, G.F. FABREGA. 1987. Rabia silvestre en murciélagos insectívoros en Chile, Bol. Of. Sanit. Panam.103(2):140-145 (English traslation in Wild. Dis. Rev. VI(2): 88-93.         [ Links ]
REDFORD K.H., J.F. EISENBERG. 1992. Orden quiroptera. In Mamals of the Neurotropics.The Southern cone . The University of Chicago Press, Chicago, London. Vol. 2, Chapter 4, pp 69-133.         [ Links ]
RUIZ A., P. ARAMBULO III. 1994. Program for the elimination of rabies in Latin America. 131 AVMA Annual Meeting, San Francisco, July 9-13.         [ Links ]
SMITH J.S., F.R. REID-SANDEN. L.F. ROUMILLAT, C. TRIMARCHI, A. CLARK, G.M. BAER, W.G. WINKLER. 1986. Demostration of antigenic variation among rabies virus isolated by using monoclonal antibodies to nucleocapsid proteins, J. Clin. Microbiol. 24 : 573-580.         [ Links ]
SMITH J.S. 1988. Monoclonal Antibody Studies in insectivorous bats of the United States, Rev. Infect. Dis. 10 (Sppl. 4): 5637-5643.         [ Links ]
SMITH J.S., L.A. ORCIARI, P.A. YAGER. 1995. Molecular epidemiology of rabies in the United States, Seminars in Virol. 6: 387-400.         [ Links ]
SMITH J.S. 1989. Rabies virus epitope variation use in ecologic studies, Adv. Vi. Res. 36: 215-253.         [ Links ]
SCATTERDAY J.E., M.M. GALTON. 1954. Bat rabies in Florida; Vet. Med. 49:133.         [ Links ]
VENTERS H.D., W.R. HOFFERT, J.E. SCATTERDAY, A. V. HARDY. 1954. Rabies in bats in Florida, Am. J. Public. Health 44: 182.         [ Links ]
WEEKLY EPIDEMIOLOGICAL REPORT. 1997. Human rabies,Kentucky and Montana, 1996, N°29, julio.
WHO. 1992. Expert Commitee on Rabies, Eigth Report. WHO Technical Report Series 824, Geneva.         [ Links ]