Rabies; cause, symptom, zoonotic risk and prevention in dogs

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Rabies; cause, symptom, zoonotic risk and prevention in dogs Rabies Vaccine
A regimen of four 1-mL doses of HDCV or PCEC vaccines should be administered intramus What is Rabies? Rabies is an RNA virus.

Rabies is a preventable viral disease most often transmitted through the bite of a rabid animal. The rabies virus infects the central nervous system of mammals, ultimately causing disease in the brain and death. The vast majority of rabies cases reported to the Centers for Disease Control and Prevention (CDC) each year occur in wild animals like bats, raccoons, skunks, and foxes, although any mamm

al can get rabies. The Rabies Virus
Rabies virus belongs to the order Mononegavirales, viruses with a nonsegmented, negative-stranded RNA genomes. Within this group, viruses with a distinct “bullet” shape are classified in the Rhabdoviridae family, which includes at least three genera of animal viruses, Lyssavirus, Ephemerovirus, and Vesiculovirus. The genus Lyssavirus includes rabies virus, Lagos bat, Mokola virus, Duvenhage virus, European bat virus 1 & 2 and Australian bat virus. Structure
Rhabdoviruses are approximately 180 nm long and 75 nm wide. The rabies genome encodes five proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and polymerase (L). All rhabdoviruses have two major structural components: a helical ribonucleoprotein core (RNP) and a surrounding envelope. In the RNP, genomic RNA is tightly encased by the nucleoprotein. Two other viral proteins, the phospoprotein and the large protein (L-protein or polymerase) are associated with the RNP. The glycoprotein forms approximately 400 trimeric spikes which are tightly arranged on the surface of the virus. The M protein is associated both with the envelope and the RNP and may be the central protein of rhabdovirus assembly. The basic structure and composition of rabies virus is depicted in the longitudinal diagram below. The genome encodes 5 proteins designated as N, P, M, G, and L. The order and relative size of the genes in the genome are shown in the figure below. The arrangement of these proteins and the RNA genome determine the structure of the rabies virus
Replication
The fusion of the rabies virus envelope to the host cell membrane (adsorption) initiates the infection process. The interaction of the G protein and specific cell surface receptors may be involved. After adsorption, the virus penetrates the host cell and enters the cytoplasm. The virions aggregate in the large endosomes (cytoplasmic vesicles). The viral membranes fuse to the endosomal membranes, causing the release of viral RNP into the cytoplasm (uncoating). Because lyssaviruses have a linear single-negative-stranded ribonucleic acid (RNA) genome, messenger RNAs (mRNAs) must be transcribed to permit virus replication. A viral-encoded polymerase (L gene) transcribes the genomic strand of rabies RNA into leader RNA and five capped and polyadenylated mRNAs, which are translated into proteins. Translation, which involves the synthesis of the N, P, M, G and L proteins, occurs on free ribosomes in the cytoplasm. Although G protein synthesis is initiated on free ribosomes, completion of synthesis and glycosylation (processing of the glycoprotein), occurs in the endoplamsic reticulum (ER) and Golgi apparatus. The intracellular ratio of leader RNA to N protein regulates the switch from transcription to replication. When this switch is activated, replication of the viral genome begins. The first step in viral replication is synthesis of full-length copies (postive strands) of the viral genome. When the switch to replication occurs, RNA transcription becomes “non-stop” and stop codons are ignored. The viral polymerase enters a single site on the 3’ end of the genome, and proceeds to synthesize full-length copies of the genome. These positive strands of rabies RNA serve as templates for synthesis of full-length negative strands of the viral genome. During the assembly process, the N-P-L complex encapsulates negative-stranded genomic RNA to form the RNP core, and the M protein forms a capsule, or matrix, around the RNP. The RNP-M complex migrates to an area of the plasma membrane containing glycoprotein inserts, and the M-protein initiates coiling. The M-RNP complex binds with the glycoprotein, and the completed virus buds from the plasma membrane. Within the central nervous system (CNS), there is preferential viral budding from plasma membranes. Conversely, virus in the salivary glands buds primarily from the cell membrane into the acinar lumen. Viral budding into the salivary gland and virus-induced aggressive biting-behavior in the host animal maximize chances of viral infection of a new host.

Rabies VaccinesVaccines stimulate adaptive immunity, which is antigen-dependent and antigen-specific; therefore, rabies ...
05/10/2022

Rabies Vaccines
Vaccines stimulate adaptive immunity, which is antigen-dependent and antigen-specific; therefore, rabies vaccination provides protection specifically from rabies infection. To be licensed in the United States, vaccines must protect at least 88% of vaccinated animals against challenge with virulent virus.5 Multiple vaccines are licensed for use in domestic animals, and inactivated (killed) vaccines are available for use in dogs . Recombinant virus-vectored products are available for cats, and oral modified live vaccines are available for wild animals, but these options are not superior to the inactivated vaccine for dogs.
Rabies Vaccination Recommendations
Rabies vaccine is a core vaccine according to the American Animal Hospital Association (AAHA) and is the only companion animal vaccine required by law in most states.6 In Canada, rabies vaccination of dogs is only required in the province of Ontario.6 Licensed veterinarians are legally required to vaccinate dogs for rabies in most U.S. states. Some states also allow canine rabies vaccines to be administered by licensed or certified veterinary technicians or lay people working under the direct supervision of a licensed veterinarian.3 After vaccination, a rabies vaccination certificate verifying the vaccinate, the health of the vaccinate, the product used, the booster interval, and the administering veterinarian is issued to identify vaccinated dogs.
While there are no clearly defined vaccination site recommendations for dogs as there are in cats, noting which vaccines are administered where is important in case of an adverse reaction. Inactivated rabies virus vaccines can be administered either intramuscularly or subcutaneously. The first vaccination is given per label recommendations at a minimum of 3 months of age due to the potential interference by maternally derived antibodies and a relatively poor immune response in the young.2,5 Regardless of the age of the first vaccination, a booster vaccine is repeated 1 year after the initial vaccine, with subsequent boosters given annually or triennially depending on the labeled duration of immunity of the vaccine used and local public health regulations.2,3,5 A recently published challenge study with virulent rabies virus demonstrated that the duration of immunity conferred by rabies vaccine extends beyond the 3-year label, which may change vaccination schedules in the future.7

Regardless of booster interval, within 28 days after initial vaccination, a peak rabies virus antibody titer is expected, and the animal can be considered immunized.3 The initial vaccine schedule (1 vaccine followed by a booster 1 year later) is inconsistent with other inactivated vaccine protocols, in which 2 sequential doses administered 2 to 4 weeks apart are required to stimulate adequate immunity. Like other inactivated vaccines, the initial dose of a rabies vaccine serves as the “priming” dose. If a dog, after having received only 1 dose of rabies vaccine, is subsequently exposed to virulent rabies virus, exposure to the virulent virus then serves as the second, or immunizing, “dose.” Because the onset of signs of rabies is slow after exposure, there is adequate time for a protective, humoral immune response to develop.6

While no vaccine is 100% effective, rabies infection is rare in vaccinated dogs. In one study, 4.9% of cases of rabid dogs had a history of prior rabies vaccination.8 Vaccination efforts can provide protection for dogs exposed to potentially rabid animals even if they are overdue for a rabies booster vaccine. Results comparing the anamnestic response rate in currently vaccinated animals versus overdue animals indicated that dogs with an out-of-date vaccination status were not inferior in their antibody response following booster rabies vaccination compared with dogs with a current vaccination status.9 The findings of this study led to changes in recommendations for postexposure management of dogs exposed to an animal confirmed or suspected to be rabid, and to advisement that an animal is currently vaccinated and considered immunized immediately after any booster vaccination.3
Rabies Postexposure Management
A dog that has been exposed to a confirmed or suspected rabid animal should immediately receive veterinary medical care for assessment, wound cleansing, and booster vaccination.3 If the exposed dog is current on rabies vaccination, it should be quarantined and observed by the owner for 45 days.3 An exposed dog that is overdue for a rabies vaccine and has documentation of a past vaccine can also be quarantined and observed by the owner for 45 days. If the exposed dog is overdue for a booster vaccine without appropriate documentation, local public health authorities should be consulted to determine the quarantine period and the utility of serologic testing to provide proof of an anamnestic response
If the exposed dog has never been vaccinated for rabies, it should be euthanized immediately; however, if the owner is unwilling to euthanize, strict quarantine for 4 months or longer without direct contact with people may be an option after consultation with local public health authorities.3

For any of these situations, if at any time during the quarantine period signs suggestive of rabies develop (e.g., paralysis or seizures), the animal should be euthanized and submitted for rabies testing.3

Adverse Rabies Vaccine Reactions
Concerns about adverse vaccine reactions and overvaccination have occasionally caused reluctance to vaccinate dogs. The following are potential vaccine adverse reactions described in dogs and cats:4
Injection-site reactions
Allergic or immune-mediated reactions
Tumorigenesis
Vaccine-induced immunosuppression
Anaphylaxis
Injection-site sarcomas
The most common vaccine-associated adverse events reported in dogs in one study were allergic reactions, local vaccine-site reactions, and nonspecific systemic signs (fever, lethargy, or anorexia).10 In the same study, the reported rate of adverse events within 3 days of vaccination was 38.2 of 10 000 dogs, although it was noted that adverse events are likely underreported.10 If an acute adverse vaccine reaction is suspected, treatment may include antihistamines (e.g., diphenhydramine), anti-inflammatories (steroids or nonsteroidal anti-inflammatory drugs, depending on the reaction), or more targeted therapy (e.g., fluids and epinephrine for anaphylaxis). All adverse vaccine events should be reported to the vaccine manufacturer and the U.S. Department of Agriculture (USDA) Animal and Plant Health Inspection Service Center for Veterinary Biologics

Clinical Signs of RabiesRabies virus infection has classically been divided into 2 main clinical manifestations: the exc...
05/10/2022

Clinical Signs of Rabies
Rabies virus infection has classically been divided into 2 main clinical manifestations: the excitatory (“furious”) and the paralytic (“dumb”) forms.2,5 This classification system is arbitrary because rabies can be quite variable in its presentation, and not all animals progress through all 3 clinical stages: prodromal, excitatory, and paralytic.2,5
Initial clinical signs (the prodromal period) are nonspecific and can include minor behavioral changes. These signs, if recognized, usually last 2 to 3 days in dogs.2,5 During the excitatory phase, dogs suddenly become vicious and behave erratically. They may become restless and irritable and have heightened sensitivities to visual and auditory stimuli.5 This stage usually lasts 1 to 7 days; however, some dogs may progress directly from the prodromal stage to the paralytic stage.2 This final stage is characterized initially by weakness and eventually by paralysis. The limb where the wound occurred is initially affected, followed by progression of paralysis to the neck and head. The paralytic phase usually lasts 2 to 4 days and ends in death from respiratory failure.2,5 The course of rabies typically lasts 3 to 8 days in dogs.2
Diagnosis and Treatment of Rabies
There is no premortem test or effective treatment for rabies in dogs. Dogs that have sustained a bite from an unknown or unvaccinated animal should be immediately vaccinated and quarantined or euthanized, as recommended (TABLE 1).3 Elimination of feral animals or wildlife populations that harbor rabies is not economically feasible, nor is it socially or ecologically acceptable. As such, control through immunization is paramount to protecting dogs.

Rabies is a deadly zoonotic disease of mammals. It is now rarely reported in dogs in the United States owing to widespre...
05/10/2022

Rabies is a deadly zoonotic disease of mammals. It is now rarely reported in dogs in the United States owing to widespread vaccination programs effectively eliminating the canine variant. However, education of the public regarding the need to vaccinate dogs and the continued diligent practice of rabies vaccination in dogs will help to prevent re-emergence of this fatal zoonotic infection.
Public Health Significance Of Rabies
Rabies is responsible for tens of thousands of human deaths annually, with infection usually following a bite or scratch from a rabies-infected animal. According to the World Health Organization, rabies-infected dogs serve as the main source of human rabies transmission globally, contributing up to 99% of all rabies cases in humans, while in the Americas, bats are the most common source of human infections.1 In the U.S., the dog rabies variant, once endemic in small animals, has now been nearly eradicated.2 However, wildlife species, which carry their own rabies variants, present a constant danger of reintroduction of rabies to dogs.
Rabies Disease
Rabies is caused by viruses in the genus Lyssavirus. Virtually all mammals are susceptible to rabies infection, including domestic animals (e.g., dogs, cats, cattle, horses) as well as wild mammalian reservoir populations (e.g., raccoons, skunks, foxes, bats) where multiple rabies virus variants are maintained.3,4 Regardless of the species affected, rabies causes an acute, progressive encephalitis.
Pathogenesis of Rabies
Transmission most commonly occurs through a bite or scratch from an infected animal. The incubation period is highly variable and depends on the age of the individual bitten, the degree of innervation of the bite site, the distance from the point of inoculation to the spinal cord or brain, and the variant and amount of virus introduced, as well as other factors.5 In domestic animals, the incubation period is generally 3 to 12 weeks, but can range from several days to months, rarely exceeding 6 months.3 Once the virus is introduced in the body, it enters peripheral nerves and subsequently gains entry into the central nervous system (CNS). After replication within the CNS, the virus moves outward to other body tissues via the peripheral, sensory, and motor nerves

Vaccination RequirementsAll dogs vaccinated against rabies for the first time must be vaccinated at least 4 weeks (28 da...
05/10/2022

Vaccination Requirements
All dogs vaccinated against rabies for the first time must be vaccinated at least 4 weeks (28 days) before traveling.
Puppies must NOT be vaccinated against rabies before they are 3-months (12 weeks or 84 days) old. The rabies certificate must include the puppy’s age or date of birth.
Adult dogs (15 months or older) must show a history of previous rabies vaccination with at least one vaccine given after they were 3-months old and one current booster rabies vaccination. With this record, adult dogs don’t need to wait 4 weeks before traveling.

16/08/2022

Rabies is a viral disease that is transmitted through the saliva or nervous system tissues of an infected mammal to another mammal. The rabies virus infects the central nervous system and causes severely distressing neurological symptoms, disease in the brain, and, ultimately, death.
Rabies is a zoonotic disease, which means that it can pass from other animals to humans. Rabies is the deadliest disease on earth with a 99.9% fatality rate.
How is Rabies transmitted?
Infection usually occurs following a bite or scratch from an infected animal, and the rabies virus is transmitted through the saliva of the host animal. Most often, the virus is passed to human populations through dogs (95% of worldwide cases), but the other species have been identified as important reservoirs of the rabies virus, including bats, raccoons, skunks, foxes, and coyotes.
While not as prevalent, transmission can also occur when saliva comes into direct contact with mucous membranes (i.e., eyes, nose, mouth), and very rarely through inhalation of aerosolized saliva, and through corneal and internal organ transplantation.
There have been cases where butchering raw meat from rabid animals has transmitted the infection, presumably through infectious neural tissue coming into contact with open wounds in the skin.
Where does Rabies occur?
Rabies is found on every continent except Antarctica. In Africa, the Middle East, and Asia, canine rabies is a wide-spread problem and contributes to over 90% of rabies cases world-wide. In developed nations and island nations, rabies is either well-controlled amongst domesticated animals, or it is non-existent.
Today, over 90% of rabies deaths are in Africa, Asia and the Middle East where canine rabies is widespread.
How big is the problem in the world?
Rabies kills people, domestic animals (such as dogs and cattle) and causes financial hardship when people have to pay for vaccination after bite wounds. It is estimated that more than 5.5 billion people live at daily risk of rabies.
How many people die each year from Rabies?
Estimates suggest that over 5.5 billion people live with the daily risk of rabies, with 59,000 deaths every year. Over 95% of these deaths are in Africa and Asia, with the majority occurring from rabid dog bites. Around half of the people who die are children.
In western nations, deaths are rare (1-3 deaths per year in the United States), with cases of clinical rabies occurring typically in people who did not realize that they had been exposed.
Is Rabies always fatal?
Yes, there is no effective treatment once clinical symptoms appear. Rabies has the highest case-fatality rate of any infectious disease known to man, because there is no proven cure or treatment available once there are signs of an infection.
However, if proper medical treatment (post-exposure prophylaxis, PEP) is received immediately after exposure to the bite or scratch of a rabid animal, rabies infection can be halted before symptoms of the disease are present, and the disease can be prevented.

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