Rabies: Symptoms, Treatments, Medications and Prevention

by topschoolsintheusa · Published September 15, 2024 · Updated September 16, 2024

Rabies is a viral disease that primarily affects the central nervous system (CNS), causing severe brain inflammation and nearly always resulting in death if not treated in time. Transmitted most commonly through the bite of a rabid animal, the virus has a long incubation period, and early symptoms can mimic other illnesses, making it difficult to diagnose until it is too late. Despite its near-total fatality rate after symptoms appear, rabies is a preventable disease, thanks to effective vaccines and post-exposure treatments.

What is Rabies?

Rabies

Rabies is caused by a virus of the Rabies lyssavirus genus, which is a member of the Rhabdoviridae family. This virus infects the CNS of mammals, causing progressive and ultimately fatal inflammation of the brain. The virus is transmitted to humans primarily through the saliva of infected animals, typically via bites, but it can also spread through scratches, open wounds, or mucous membranes if they come into contact with the saliva of a rabid animal.

Rabies exists in two primary clinical forms:

Furious (encephalitic) rabies: The most recognized form, associated with agitation, aggression, hyperactivity, hydrophobia (fear of water), and a general state of confusion and restlessness.
Paralytic (dumb) rabies: A less common form that primarily affects the muscles, leading to progressive paralysis without the violent symptoms seen in furious rabies. This form can be harder to diagnose and is often mistaken for other neurological conditions.

Both forms are almost universally fatal once clinical symptoms manifest, making rabies one of the deadliest infectious diseases known to humankind.

The Transmission Cycle

Rabies is typically transmitted through a bite from an infected animal, as the virus is shed in the saliva. After the bite occurs, the virus travels through the peripheral nerves toward the central nervous system, where it replicates and causes progressive inflammation in the brain. This process can take weeks to months depending on the location of the bite, the amount of virus introduced, and the species of animal involved.

Once symptoms appear, rabies rapidly progresses to death within a matter of days, making early intervention critical to survival.

Who is at Risk of Rabies?

While rabies can infect any mammal, certain populations are at higher risk based on geography, occupation, and lifestyle. Rabies remains a significant public health threat, particularly in developing regions where access to post-exposure treatment is limited and domestic animals are not routinely vaccinated.

1. Geographic Risk Factors

Rabies is endemic in many parts of the world, especially in regions with high populations of unvaccinated domestic animals. The areas most affected include:

Asia: This region has the highest number of rabies cases globally, with India alone accounting for nearly 36% of human rabies deaths worldwide. Southeast Asian countries also face high rabies incidence due to unvaccinated dogs and limited access to medical resources in rural areas.
Africa: Rabies is a major concern in Sub-Saharan Africa, where dog populations are large, and veterinary public health infrastructure is often inadequate. Many African countries face challenges in controlling the spread of the disease among domestic and wild animals.
South America: Rabies is still reported in parts of Central and South America, though vaccination campaigns have reduced its spread. However, rural and remote areas continue to experience outbreaks.
Eastern Europe: Although much of Western Europe has successfully controlled rabies through vaccination, parts of Eastern Europe, particularly in rural areas, still report human and animal cases of rabies.
North America: In the United States and Canada, rabies is relatively rare due to widespread vaccination of domestic animals. However, certain wildlife species, such as bats, raccoons, and foxes, continue to serve as reservoirs for the virus. In recent years, bats have become the leading cause of human rabies infections in these regions.

2. Occupational and Lifestyle Risk Factors

Certain groups of people are more likely to come into contact with potentially rabid animals due to their jobs or lifestyles. These individuals are considered at higher risk of contracting rabies:

Veterinarians and Animal Handlers: Professionals who work closely with animals, such as veterinarians, animal control officers, and wildlife rehabilitators, are at increased risk of being exposed to rabid animals.
Outdoor Enthusiasts: People who spend a lot of time outdoors, such as hunters, hikers, and campers, are more likely to encounter wild animals that could carry the rabies virus.
Children: Children are particularly at risk of rabies exposure because they are more likely to approach animals, particularly stray dogs and cats, without understanding the potential danger. Additionally, children may not report minor bites or scratches to adults, delaying medical intervention.
Travelers: Individuals traveling to countries where rabies is endemic, particularly in Asia and Africa, may be at increased risk. Tourists engaging in outdoor activities or visiting rural areas where stray dogs are common may be exposed to rabid animals.

3. Animal Risk Factors

Rabies can affect any mammal, but certain species are known to be significant carriers of the virus:

Dogs: In most parts of the world, domestic dogs are the primary reservoir of rabies, responsible for the vast majority of human cases. This is especially true in areas where canine rabies vaccination is not widespread.
Bats: In North and South America, bats have become a leading source of human rabies infections. People may be bitten by bats while sleeping or handling them without realizing the risk.
Foxes, Raccoons, and Skunks: These wild animals are common rabies reservoirs in parts of North America and Europe, where they can transmit the virus to humans and domestic animals.
Monkeys: In regions like Southeast Asia, monkeys are becoming an increasing source of rabies transmission due to frequent human-monkey interactions in tourist areas.

Symptoms of Rabies

Rabies progresses through distinct stages, each with its own set of symptoms. Early-stage symptoms can often mimic other illnesses, making it challenging to diagnose the disease until it has progressed.

1. Incubation Period

The incubation period for rabies is typically between 1 and 3 months, but it can range from a few days to over a year. The length of this period depends on factors such as the location of the bite (bites closer to the head or CNS shorten the incubation period), the amount of virus introduced, and the species of the biting animal.

During the incubation period, the virus travels through the peripheral nerves to the central nervous system. The individual is asymptomatic during this time, meaning there are no clinical signs of the disease. The length of this phase offers a critical window of opportunity for post-exposure prophylaxis (PEP), which can prevent the onset of symptoms.

2. Prodromal Stage (Early Symptoms)

Once the virus reaches the brain, the prodromal stage begins, typically lasting 2 to 10 days. Symptoms at this stage are often non-specific and resemble common viral infections, which can make early diagnosis difficult. Early symptoms include:

Fever
Headache
Malaise (a general feeling of discomfort)
Loss of appetite
Nausea and vomiting
Sore throat
Pain, itching, or tingling at the site of the bite (paresthesia), which occurs in about 50% of cases

At this point, the virus has started to affect the nervous system, but it has not yet caused the severe neurological symptoms associated with later stages.

3. Acute Neurological Stage

As the virus continues to spread through the CNS, more severe and characteristic symptoms begin to appear. This stage can present as either furious rabies or paralytic rabies, depending on how the virus affects the brain.

Furious Rabies (Encephalitic Rabies)

Furious rabies is the most recognizable form of the disease, accounting for about 70-80% of human rabies cases. Symptoms include:

Hyperactivity: The individual may become agitated, restless, and aggressive.
Hydrophobia: One of the hallmark symptoms of rabies, hydrophobia is an extreme fear of water. Attempting to drink water may cause painful spasms in the throat and larynx, leading to difficulty swallowing and fear of water.
Aerophobia: Fear of air or drafts, triggered by even slight air movement, is another hallmark symptom.
Excessive Salivation: As swallowing becomes difficult, patients may drool excessively.
Seizures: Seizures and muscle spasms are common as the brain becomes increasingly inflamed.
Hallucinations and Delirium: Mental confusion, hallucinations, and delirium are often present.
Aggression: In some cases, patients may become extremely aggressive and lash out violently.

Furious rabies progresses rapidly, and most patients enter a coma within a few days. Without intervention, death occurs within a week of the onset of symptoms, usually due to respiratory failure.

Paralytic Rabies (Dumb Rabies)

Paralytic rabies is less common, accounting for about 20-30% of cases. It is characterized by gradual muscle weakness and paralysis rather than the hyperactivity seen in furious rabies. Symptoms include:

Weakness and Paralysis: Paralysis often begins at the site of the bite and spreads to the rest of the body.
Loss of Reflexes: Reflexes gradually diminish as the virus affects motor neurons.
Coma: The patient may eventually lapse into a coma.

Although paralytic rabies is less dramatic than furious rabies, it is just as deadly, leading to death within days to weeks of symptom onset.

4. Terminal Stage

In the final stages of rabies, patients experience widespread paralysis, organ failure, and coma. Death is inevitable once the disease reaches this point, typically occurring due to cardiac or respiratory failure.

Diagnosis of Rabies

Diagnosing rabies in humans can be challenging, especially in the early stages when symptoms mimic other viral illnesses. Because rabies is almost always fatal once symptoms appear, early and accurate diagnosis is critical for effective treatment.

1. Medical History

The first step in diagnosing rabies is to obtain a detailed medical history, including any recent animal bites, scratches, or contact with potentially rabid animals. Doctors will ask about:

The type of animal involved in the bite or exposure
The geographic location of the exposure (to assess rabies risk)
The vaccination status of the animal (if known)
Whether the person has received any rabies vaccinations in the past

A history of animal exposure in a high-risk area can provide strong evidence for rabies, but further laboratory testing is usually required to confirm the diagnosis.

2. Laboratory Tests

Several diagnostic tests are available to detect rabies infection, but no single test is sufficient on its own. Diagnosis typically involves a combination of methods:

RT-PCR (Reverse Transcription Polymerase Chain Reaction): This test detects rabies virus RNA in samples of saliva, cerebrospinal fluid (CSF), or skin biopsies. RT-PCR is one of the most reliable diagnostic tools for rabies.
Antibody Testing: Blood tests may be used to detect rabies antibodies in the serum or CSF. The presence of antibodies indicates that the immune system is responding to the virus.
Direct Fluorescent Antibody (DFA) Test: In post-mortem cases, this test is used to confirm rabies by detecting viral antigens in brain tissue samples.
Skin Biopsy: A skin biopsy taken from the base of hair follicles at the nape of the neck can sometimes show rabies virus antigens in nerve cells. This test is less invasive and can be done while the patient is still alive.
Saliva and Nerve Biopsies: Saliva and nerve tissue may also be tested to confirm the presence of the rabies virus, though these tests are less commonly used.

While rabies is challenging to diagnose in its early stages, laboratory tests and clinical history are essential for confirming the disease. Once symptoms appear, however, treatment options become extremely limited.

Treatment of Rabies

Rabies is one of the few diseases that is almost universally fatal once clinical symptoms appear. However, if treatment is administered before the onset of symptoms, rabies is entirely preventable. The key to effective rabies treatment is prompt wound care and the administration of post-exposure prophylaxis (PEP).

1. Immediate Wound Care

The first step after a potential rabies exposure is to thoroughly clean the wound. Immediate and effective wound care can significantly reduce the risk of infection.

Washing the Wound: The bite or scratch should be washed thoroughly with soap and water for at least 15 minutes to remove as much virus as possible from the wound.
Disinfecting: After washing, the wound should be disinfected with an alcohol or iodine solution to kill any remaining virus.
Seek Medical Attention: Even if the wound appears minor, it is crucial to seek medical attention immediately. A doctor can assess the risk of rabies and determine whether post-exposure prophylaxis is necessary.

2. Post-Exposure Prophylaxis (PEP)

PEP is the standard treatment for rabies following exposure to the virus. It involves a combination of rabies vaccinations and, in some cases, rabies immune globulin (RIG). PEP must be administered as soon as possible after exposure to be effective.

Rabies Vaccine: The rabies vaccine is given in a series of injections over the course of several weeks. The typical vaccination schedule includes doses on days 0, 3, 7, and 14. The vaccine helps the immune system develop a response to the virus, preventing it from spreading to the CNS.
Rabies Immune Globulin (RIG): If the person has never been vaccinated against rabies before, rabies immune globulin is administered at the same time as the first vaccine dose. RIG provides immediate passive immunity by delivering antibodies that neutralize the virus. It is injected directly into the wound site and surrounding tissue to stop the virus from traveling further.

When administered promptly after exposure, PEP is almost 100% effective in preventing rabies. Delaying PEP treatment, however, increases the risk of the virus reaching the CNS, where it becomes nearly impossible to treat.

3. Treatment After Symptom Onset

Unfortunately, once symptoms of rabies appear, the disease is almost always fatal, and there is no universally accepted treatment that can reverse its progression. Some experimental treatments have been attempted, but none have shown consistent success.

The Milwaukee Protocol

One of the most well-known experimental treatments for rabies is the Milwaukee Protocol, which involves inducing a coma in the patient to give the body time to fight the virus while administering antiviral medications. The protocol was first used in 2004 on a young girl who survived rabies after developing symptoms. However, subsequent attempts to use the protocol have had limited success, and it remains controversial.

In the overwhelming majority of cases, once clinical rabies symptoms appear, the outcome is fatal within a few days to weeks.

Common Medications for Rabies

Rabies treatment focuses primarily on preventing the disease after exposure through the use of vaccines and immune globulin. Once symptoms develop, medications play a limited role in managing the disease, as rabies progresses too quickly for antiviral drugs to be effective.

1. Rabies Vaccine

The rabies vaccine is the cornerstone of both post-exposure and pre-exposure prophylaxis for rabies. It is an inactivated virus vaccine, meaning it contains killed virus particles that stimulate the immune system to produce antibodies against the rabies virus without causing the disease.

Post-exposure prophylaxis (PEP): After exposure, individuals receive four doses of the rabies vaccine, typically on days 0, 3, 7, and 14. In some cases, a fifth dose may be given to immunocompromised individuals.
Pre-exposure prophylaxis (PrEP): For people at high risk of rabies exposure (such as veterinarians or travelers to endemic areas), a series of three rabies vaccine doses may be administered before exposure to provide long-term immunity.

The rabies vaccine is highly effective at preventing rabies, especially when combined with immediate wound care and rabies immune globulin.

2. Rabies Immune Globulin (RIG)

Rabies immune globulin (RIG) is a crucial component of PEP for individuals who have not been previously vaccinated against rabies. It contains pre-formed antibodies that provide immediate passive immunity to neutralize the rabies virus.

Administration: RIG is injected directly into the wound site to stop the virus from spreading to the CNS. If there is insufficient tissue at the bite site to accommodate the full dose, the remaining amount may be injected into nearby muscles.
Limited Use in Previously Vaccinated Individuals: People who have already received a full course of rabies vaccination do not require RIG, as their immune system has already been primed to produce rabies antibodies.

RIG is typically given at the same time as the first dose of the rabies vaccine. While the vaccine takes time to stimulate an immune response, RIG provides immediate protection against the virus.

3. Antiviral Medications (Experimental)

Several antiviral drugs, including ribavirin and amantadine, have been used experimentally in the treatment of symptomatic rabies. These drugs aim to reduce viral replication and give the immune system more time to respond to the infection. However, none of these treatments have proven consistently effective, and the use of antiviral medications remains largely experimental.

Where is Rabies Most Prevalent?

Rabies is a global health issue, but it disproportionately affects certain regions, particularly in low- and middle-income countries where vaccination programs and access to post-exposure treatment are limited. Understanding where rabies is most prevalent is essential for directing prevention efforts and improving outcomes for at-risk populations.

1. Asia

Asia accounts for the majority of rabies cases worldwide, with India being the country most affected. In India, rabies is endemic due to the large population of stray dogs, many of which are unvaccinated. Southeast Asia also faces significant challenges in controlling rabies, particularly in rural areas where healthcare access is limited.

In addition to dogs, wild animals such as bats, monkeys, and feral cats are also common sources of rabies in some parts of Asia.

2. Africa

Rabies remains a significant public health problem in Sub-Saharan Africa, where dog bites are the leading cause of human rabies infections. In many African countries, veterinary public health infrastructure is underdeveloped, making it difficult to vaccinate domestic animals and control the spread of the virus.

Limited access to healthcare and rabies vaccines in rural areas exacerbates the problem, leading to a high rate of rabies fatalities.

3. Latin America

Rabies has been largely controlled in much of Latin America due to successful vaccination campaigns targeting both dogs and wild animals. However, some countries in Central and South America still report cases, particularly in remote or rural areas where access to vaccines and PEP may be limited.

Bats are the primary reservoirs of rabies in Latin America, with vampire bats posing a particular risk to livestock and humans.

4. Eastern Europe

In Eastern Europe, rabies is still reported in some rural areas, though vaccination and control measures have reduced its prevalence compared to the past. Foxes, raccoons, and stray dogs are the primary reservoirs of the virus in this region.

5. North America

In North America, rabies is relatively rare in humans due to widespread vaccination of domestic animals. However, rabies remains endemic in certain wildlife populations, particularly bats, raccoons, foxes, and skunks. Human rabies cases in the United States and Canada are extremely rare, but they do occur, primarily due to exposure to bats.

Prevention of Rabies

Rabies is a preventable disease, and preventing exposure to the virus is the best way to protect both humans and animals. Prevention efforts focus on vaccination, responsible animal management, public education, and early medical intervention following potential exposure.

1. Vaccination

Vaccination is the most effective way to prevent rabies in both animals and humans. A coordinated vaccination effort can significantly reduce the transmission of rabies and prevent human fatalities.

Vaccination of Domestic Animals

Ensuring that pets, particularly dogs and cats, are regularly vaccinated against rabies is a critical component of rabies prevention. In many countries, rabies vaccination is required by law for domestic animals. Vaccinating pets not only protects them but also creates a barrier between wild rabies reservoirs and humans.

Pre-exposure Vaccination for High-Risk Individuals

Pre-exposure prophylaxis (PrEP) is recommended for individuals at high risk of rabies exposure, such as:

Veterinarians and animal control workers
Wildlife handlers and biologists
Travelers to countries where rabies is endemic
Laboratory workers who handle rabies virus

Pre-exposure vaccination involves a series of three rabies vaccine doses administered over several weeks. In the event of rabies exposure, these individuals will still need post-exposure prophylaxis but can skip the rabies immune globulin (RIG) and receive only two booster doses of the vaccine.

Wildlife Vaccination

In some regions, particularly in Europe and North America, wildlife vaccination programs have been implemented to control rabies in wild animal populations. These programs typically involve distributing oral rabies vaccines to wild animals, such as foxes, raccoons, and coyotes, in bait form. Wildlife vaccination helps reduce the risk of rabies transmission to humans and domestic animals.

2. Animal Control and Population Management

Controlling the population of stray animals, particularly dogs, is another key strategy for rabies prevention. Stray dogs are the leading cause of human rabies infections in many parts of the world. Effective animal control programs should focus on:

Spaying and Neutering: Sterilization programs help control the population of stray dogs and reduce the overall number of unvaccinated animals that could serve as rabies reservoirs.
Capture and Vaccination: In some regions, animal control officers capture stray animals and vaccinate them against rabies before releasing them back into the environment. This approach is particularly effective in areas where culling (the killing of stray animals) is not culturally or ethically acceptable.
Quarantine and Monitoring: In regions where rabies is endemic, animals suspected of being infected should be quarantined and monitored for signs of the disease. Infected animals should be euthanized to prevent the spread of the virus to other animals or humans.

3. Public Education and Awareness

Educating the public about rabies and how to prevent it is a critical component of any rabies control program. Public awareness campaigns should focus on:

Avoiding Contact with Wild Animals: People should be taught to avoid handling wild animals, especially bats, raccoons, foxes, and skunks. Even if an animal appears healthy, it may carry the rabies virus.
Reporting Animal Bites: Education should emphasize the importance of reporting animal bites and seeking immediate medical attention. Many people are unaware of the seriousness of rabies and may delay treatment, increasing their risk of developing symptoms.
Vaccinating Pets: Pet owners should be educated about the importance of vaccinating their animals against rabies and ensuring that their vaccinations are kept up to date.
Avoiding Stray Animals: In areas where stray dogs and cats are common, children and adults should be taught to avoid contact with unfamiliar animals, particularly those that appear aggressive or unwell.

4. Traveler’s Precautions

Travelers to countries where rabies is endemic should take specific precautions to protect themselves from rabies exposure:

Avoid Contact with Stray Animals: Travelers should avoid petting or handling stray dogs, cats, or wildlife, even if the animals seem friendly. Rabies is often transmitted by animals that appear healthy but are infected.
Get Vaccinated Before Traveling: Pre-exposure vaccination is recommended for travelers planning to spend extended periods in countries where rabies is common, especially in rural areas where access to medical care is limited.
Seek Medical Care After Animal Bites: If a traveler is bitten or scratched by an animal while abroad, they should seek medical attention immediately, even if they have been vaccinated. Post-exposure prophylaxis may still be required to prevent the virus from spreading.