Rabies in dogs and cats… an update

Introduction

Rabies virus is a lyssavirus, a type of enveloped RNA virus that infects mammals, causing almost invariably fatal disease. Predominantly transmitted by bites, rabies has profound impacts on humans and animals internationally, with an estimated 50,000 human deaths annually and an unknown but substantial number of animal deaths. Despite this, it is highly preventable through vaccination and post-exposure prophylaxis; sadly, access to and uptake of these highly effective measures is often inadequate. This article offers an update on our current knowledge of the disease.

Epidemiology of rabies 

Hosts and reservoirs

Rabies virus is maintained in mammalian reservoirs, with different virus variants that are adapted to different species. These host-adapted variants are maintained and spread effectively within their species, but can spill over into other species. Sustained transmission is not expected within non-reservoir species, but there is always the potential for sporadic transmission. For example, raccoon rabies is widespread in raccoons in some parts of the United States. It is maintained through circulation in the raccoon population, but occasional infections occur in other species, such as cats (Figure 1). This results in fatal infection in cats, and the potential for transmission to other individuals, but sustained transmission of raccoon rabies virus variant in cats does not occur. Common reservoir hosts with their own virus variants include dogs, raccoons, skunks, foxes and mongooses. In addition to terrestrial mammals, rabies virus is widespread in bats internationally and bats are a leading source of spillover into domestic animals and humans in areas where canine rabies is not dominant.

While understanding of host adapted variants and reservoirs is important, it is critical to be aware that dogs and cats can be infected with other rabies virus variants. Therefore, a risk of rabies remains in dogs in countries that have no canine rabies virus variant but that have other rabies virus variants. This is an important distinction, so that people do not consider “canine rabies has been eradicated here” to mean “there is no risk of rabies to or from a dog”. Similarly, while there is no feline rabies virus variant, cats are among the most commonly affected domestic species in areas where canine rabies is not endemic.

Figure 1. Raccoon-variant rabies virus is widespread in some parts of the United States, and occasionally the virus can cross the species barrier, for example if a cat is bitten by an infected animal. 
© Shutterstock

Canine rabies

Canine variant rabies is well established in many regions, accounting for the vast majority of human rabies deaths every year. It is most common in India and sub-Saharan Africa, but is present throughout Asia and Africa, and in parts of eastern Europe, South America and the Caribbean. It has been eradicated from many countries through various approaches, but with a focus on vaccination. Some island nations (e.g., United Kingdom, Australia, New Zealand) have been, and remain rabies free, as the virus has not been introduced. These countries often have strict controls for importation of mammals to reduce the risk of introduction of the virus and establishment of endemic rabies.

Pathophysiology and transmission

Rabies virus must enter the body through broken skin (e.g., bite, wound) or mucous membranes (e.g., eye, nose, mouth). Once there, the virus may replicate in muscle tissue or directly enter peripheral nerves. It takes time to infect peripheral nerves, but once it does, it can rapidly spread to the central nervous system and enter the brain, where it multiplies and causes substantial inflammation and damage. The virus then migrates out of the brain through nerves, including to the salivary glands, where it is secreted in saliva. Once rabies virus is present in saliva, the animal poses a risk to other animals and people for a short period of time until its death. 

The incubation period is variable and can be prolonged, but is commonly 3-8 weeks, although incubation of greater than 6 months has been identified in dogs. In humans, disease more often occurs within weeks of exposure, but in some cases the incubation period can be many years (1-3). The severity of the bite (which influences the amount of virus deposited in the wound) and location of the bite (which influences the distance the virus must travel to infect the central nervous system) can influence the incubation period. 

Clinical signs

Rabies can be highly variable and mimic many different diseases of almost any body system. Classically, it is differentiated into “furious” and “paralytic” (dumb) forms, but these may not be present, may overlap, or may not be seen until late in disease. 

Typically, there is an initial period of a few days of non-specific signs, such as changes in behavior, fever or pruritus. The furious stage usually follows, characterized by significant and unpredictable behavior changes and aggression (Figure 2). Neurological abnormalities such as muscle tremors, hyperesthesia and seizures may be noted. In the paralytic phase, animals have more overt signs of brain disease, with excessive salivation (from difficulty swallowing), weakness, changes in vocalization, difficulty eating and difficulty breathing. Coma and death from respiratory failure most often develop quickly once this phase is entered. However, there can be variable presentations, with differences in neurological deficits within each stage, or without recognition of one or more of these stages. Classically, though, a combination of aggression, weakness, paralysis/paresis, seizures and hypersalivation are present, with rapid progression to death.

Figure 2. A dog infected with the rabies virus will typically have a few days of non-specific signs before the “furious” stage develops, characterized by aggression and significant unpredictable behavior changes.
© Shutterstock

 

Diagnosis and treatment

Diagnosis of rabies requires testing of the brain, with samples collected after death or euthanasia of the animal. Other options can potentially be used, such as virus testing in saliva or cerebrospinal fluid by PCR (4,5), but these are not generally accepted as routine tests because they are not as validated and definitive as testing of brain tissue. Given the seriousness of rabies and the implications of the test result on management of people and animals that might have been exposed, a definitive result is needed. 

In humans, a small number of individuals have been successfully treated, but the vast majority of infected individuals die despite intensive care. Previously, much attention was paid to the “Milwaukee protocol”, a treatment regime that was used successfully in a girl with rabies; this included putting her in a coma and treating with antiviral drugs, along with intensive supportive care (6). However, despite initial optimism, success has not been repeatable (7). Aggressive supportive care may be the main factor in the rare survivors, keeping the person alive and limiting neurological impacts while allowing the body to develop an effective immune response against the virus. Even with aggressive supportive care, survival remains very rare, and survival without serious long-term neurological damage is even rarer.

There are no treatment options for dogs and cats; rabies is invariably fatal. Theoretically, aggressive supportive care, as in humans, could result in rare survival, but given the exceptionally poor prognosis and the human risks involved in treating an infected animal, this is not recommended.

What constitutes rabies exposure?

Dogs and cats

Determining rabies exposure can be challenging; it can have major implications on an animal’s life, given the potential for long-term isolation or euthanasia in some situations, and dictates whether people need to undergo post-exposure prophylaxis. There are two main components in assessing potential rabies exposure; the likelihood the animal was infected and the likelihood that there was virus exposure from the animal. 

Determination of potential risk from the suspected “aggressor” animal is clear when it is known to have been rabid based on testing of the brain. This is not often an option. Monitoring the animal is sometimes possible, when the animal is available for confinement and observation. Once the virus has reached the brain and spread down nerves into the salivary glands, death will occur quickly, so for some species, such as dogs and cats, a 10-day observation period is widely accepted (8). If the animal is alive and neurologically unchanged after 10 days, it could not have been shedding rabies virus at the time of the encounter. The same timeframe is not usually applied to rabies reservoir species (e.g., raccoons) because of uncertainly around the timing of disease in these situations. 

When testing and observation are not possible, a risk assessment is required. This considers the species involved, the rabies epidemiology in the area, the nature of the encounter, and the behavior of the animal. For example, an indoor-outdoor cat seen fighting a stray cat in the yard, where both were acting normally and aggressive behavior was explained by normal cat behavior, would not often be considered potential exposure (Figure 3). Similarly, two dogs playing at an off-leash park where one was nipped during boisterous play or in response to overly aggressive behavior would be low risk in an area where canine rabies was not endemic. A dog that was bitten by a raccoon that it chased and cornered would also not necessarily be considered potential exposure, but the presence and abundance of raccoon rabies in the area would be an important consideration. In contrast, a raccoon that attacked a dog in an open area in the middle of the day would be considered high risk because of the raccoon’s abnormal behavior. The approach to potential exposure is highly variable across regions based on the degree of risk aversion, the expertise and experience of individuals making the assessment, and local rabies epidemiology. Any potential exposure of a pet dog or cat with a mammal (wild or domestic) should be investigated, but it is important that critical assessment be performed so to avoid over-reaction in situations with negligible risk. 

Figure 3. Risk assessment; an indoor-outdoor cat fighting a stray cat, where the aggressive signs could be explained by normal feline behavior, would often not be considered as a potential exposure to rabies virus.
© Shutterstock

 

Risk of exposure relates to whether contaminated saliva was inoculated into the body. Rabies virus does not penetrate intact skin, so bites are the main concern. Contact of saliva with open wounds and mucous membranes (e.g., eyes, nose, mouth) also constitutes exposure. Scratches are low risk and can be difficult to assess. The scratch itself poses no direct risk, since rabies virus is not harbored on the claws. However, there is potential risk if saliva was deposited on the skin and then driven into the body via a scratch. This is challenging, as it is often hard to rule out the potential for such an exposure in situations where the encounter was unobserved or is not a simple, isolated scratch (e.g., if handling a fractious cat that might have spat or otherwise spread saliva).

Indirect exposure from the environment and objects pose negligible risk, as rabies virus is readily inactivated outside the body. For there to be any risk, virus would have to be almost immediately transferred from an animal’s saliva (or brain) onto a surface and then into a wound or mucous membrane, so while not impossible, indirect exposure is not considered a realistic concern. 

People

This is similar to what is described above for animals. If a person is bitten by a dog or cat, the typical response is to observe the biting animal for 10 days. If it is alive and neurologically unchanged at that point, it could not have been shedding virus at the time of the bite, and rabies exposure can be dismissed. If the animal cannot be kept alive because of health or welfare reasons, or if keeping it under observation creates undue risk to people (e.g., a very aggressive dog destined for euthanasia), testing of the brain is required after euthanasia. Whenever possible, observation is to be preferred, both to prevent unnecessary euthanasia, and because observation provides a definitive answer (as there is a very small (but non-zero) risk of an equivocal test or even loss of the brain during transit). 

Vaccination 

Dogs and cats

Vaccination is the foundation of rabies control, with safe and effective vaccines available for dogs and cats. These are recommended as core vaccines (and are often required by law) for all dogs and cats in areas where rabies is present in wildlife and where canine rabies variant is present (9,10). Rabies vaccines are typically given starting at 12 weeks of age. When risk of exposure is ongoing, booster vaccination is indicated, as per the specific manufacturer’s label, often one year after the primary dose and 1-3 years later, depending on the vaccine. If risk of exposure is time-limited, such as when vaccination is because of travel requirements and the risk of exposure is short term, a single dose may be adequate.

Humans

Rabies vaccines are available for humans, usually as a 2-dose series (11), although some countries may still use a 3-dose regime. Veterinarians in many regions will be vaccinated routinely, and is also recommended for people living in or traveling to areas where canine rabies is endemic (if there is any potential for dog contact), as well as for people that work with wildlife rabies reservoirs in endemic areas (e.g., raccoon rehabilitators in areas with raccoon rabies). Vaccination of the general public is not recommended, including dog and cat owners in areas where rabies is present in wildlife reservoirs. 

Traditionally, biannual rechecking of rabies titers in vaccinated individuals that maintain a risk of rabies exposure was recommended, but this has recently been revisited, and titers are not as widely recommended for moderate risk groups (including most veterinarians). Rabies titers are still endorsed for people at high risk of exposure, such as those that frequently handle bats, regularly perform necropsies, or work with rabies virus in a laboratory setting. For typical veterinary personnel, the US Advisory Committee on Immunization Practices (ACIP) now recommends either a one-time titer evaluation between 1-3 years after vaccination with a 2-dose regime, or administration of a 3^rd vaccine dose 3 weeks to 3 years after the 2^nd dose, with no evaluation of titers (11). 

Response to potential rabies exposure 

Dogs and cats 

The response to potential rabies exposure varies between regions, and local rules need to be followed. In general, if a dog or cat is exposed to rabies, it is subject to some form of observation or isolation period to check for development of the disease and to limit its contacts should it develop rabies. The duration and intensity are influenced by whether the animal is vaccinated against rabies, whether vaccination is up-to-date, and whether a booster vaccine was given within 7 days of exposure (as a means of boosting the animal’s immune response). This may result in responses ranging from a 45-day observation period – where the pet is kept with the owners but always under control and away from other individuals (if properly vaccinated and having received a rabies vaccine booster), to a 6 month strict isolation period or euthanasia (if unvaccinated or significantly lapsed vaccination, and no vaccine is given after exposure). Where rabies vaccination is out-of-date, the default may be to consider the animal as unvaccinated, properly vaccinated or with a modified (intermediate strictness) response, depending on the circumstances and decision-makers. 

The potential animal health and welfare of prolonged strict isolation can be profound, and euthanasia is sometimes elected because of these concerns or owner challenges in implementing the required measures. This highlights the importance of rabies vaccination and ensuring that vaccination remains up to date. In situations where there is unwillingness to vaccinate, or to provide required booster vaccines, because of health concerns or vaccine hesitancy, people sometimes evaluate rabies antibody titers. There are standard cutoffs for titer results, but these are mainly for proof of prior vaccination, not a guarantee of protection. Most jurisdictions will not consider titer results during risk assessment following rabies exposure; if a pet is overdue vaccination and is exposed to rabies, the vaccine history will guide the required response, with no consideration of rabies titers. Therefore, if titers are being used in lieu of re-vaccination, people should be aware that their animal may be at risk of substantial control measures should they be exposed to rabies. 

People

Post-exposure prophylaxis (PEP) is highly effective at preventing rabies, if provided exposure is identified and care is sought. There may be different approaches in different areas, and appropriate public health authorities must be involved. However, the general approach to potential rabies exposure involves good wound care, trying to remove as much contaminated saliva as possible, and PEP. In people that have not previously been vaccinated, this involves a dose of rabies immunoglobulin (antibody against rabies virus) and a series of 4 rabies vaccines. People that have been vaccinated against rabies do not receive immunoglobulin, since they should already have antibodies in circulation from vaccination, and will typically receive two rabies vaccines.

Rabies exposure is considered a medical urgency, but not an emergency. Care should be sought as soon as possible, but there is time to get appropriate care. Time is of the greatest concern for large exposures closer to the brain, such as serious bites to the head and face, where large amounts of rabies virus could have been deposited within a short distance of travel to the brain. Ocular exposure could be considered an emergency because of the very short distance to the brain. 

Rabies PEP is highly effective even when given well after exposure, provided clinical signs are not present. Most apparent PEP failures are from inadequate treatment regimens, use of questionable quality vaccine (a concern in some resource-limited settings), or in immunocompromised individuals that may not have responded well to the vaccine series (12). 

Canine rabies:  challenges and implications

Countries with endemic rabies

In areas where canine rabies is endemic, there is typically a large pool of feral and semi-feral dogs that maintain the virus. Canine vaccination and sterilization campaigns aim to reduce the susceptible population to a minimum, to curtail transmission between dogs, and from dogs to humans (Figure 4). The World Health Organization has set a vaccination target of 70% of dogs in endemic areas if eradication is to be attempted (13). While eradication is possible based on the high efficacy of vaccination, the large number of dogs, sporadic nature of vaccination campaigns, and high reproduction rate of dogs mean that hitting and maintaining the 70% target is challenging. Extensive efforts to vaccinate dogs and improve access to post-exposure care have resulted in substantial drops in rabies in both humans and animals. For example, in China, human rabies numbers dropped from 3,300 cases in 2007 to 120 in 2024 (14). However, eradication remains a challenge even with substantial efforts. 

Depopulation (culling of feral and unhomed dogs) has been used in some jurisdictions as a control measure, but it has never been shown to be an effective tool, because in the absence of parallel sterilization and vaccination the natural replacement rate means that there is little long-term impact on the number of susceptible and infected dogs in the population.

Figure 4. Vaccination campaigns in areas where canine rabies is endemic aim to reduce the susceptible canine population to a minimum.
© Shutterstock

 

Rabies and dog importation

Importation of dogs from areas with canine variant rabies poses a risk of movement of infected animals (15-18). Because animals can be infected, but clinically normal for weeks to months prior to the onset of disease, assessment of health status at the time of exportation or importation is not a fully effective control measure. Requiring imported dogs to be vaccinated is an important factor, but is not a guarantee because of variable vaccine quality in different regions, as well as concerns about veracity of vaccine documentation (19,20). Further, rabies has developed in purportedly vaccinated imported dogs; here vaccination likely occurred after the dog had already been infected. For these reasons, countries often have strict importation controls for dogs from areas where canine rabies is endemic. This can include total bans on importation, bans on importing certain types of dogs (e.g., if not an individual’s own pet), vaccination requirements, rabies titer requirements, documentation about the origin of the animal, and health status verification.

Conclusion

Rabies remains an important disease of humans and other mammals across much of the world, and awareness is required even in non-endemic areas because of the risk of exposure while travelling or from imported animals. Vaccination remains a cornerstone for rabies control and for eradication measures. Veterinarians and pet owners should be aware of local risks from rabies, ensure proper vaccination of dogs and cats, properly report and manage potential rabies exposure of humans and domestic animals, and take measures to reduce bites. Rabies control is multimodal, but is based on a series of practical measures that can greatly reduce the human and animal health risks.

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