Rabies is a preventable viral disease of mammals that has been known since ancient times. The Greek word "lyssa" used for rabies means madness. The word rabies itself comes from the Latin "rabiere": to be violent, which in turn is derived from the old Sanskrit word "rabhas", to be violent. Rabies continues to be a completely incurable disease even today. This disease, which has practically disappeared in man in most developed countries, continues to be a major public health problem in many countries in Asia and Africa. Each year more than 55,000 deaths occur due to rabies. Vaccination against rabies is the sole method of effective prevention of the disease. It may be given either preventively or curatively in persons coming into contact with potentially rabid animals.
The name of Louis Pasteur remains closely connected with the victory over rabies. It was thanks to proliferation of the virus in live nervous tissue that Pasteur succeeded in 1881 in his experiments of propagation of rabies. In 1885, the concept of rabies vaccination became a reality following curative treatment of the young Joseph Meister. Not only did the boy not develop rabies, but he survived a high concentration of virulent virus contained in the final injections of vaccine.
Rabies is most often transmitted through the bite of a rabid animal. The vast majority of rabies cases reported to the Centers for Disease Control and Prevention (CDC) each year occur in wild animals like raccoons, skunks, bats, and foxes. Domestic animals account for less than 10% of the reported rabies cases, with cats, cattle, and dogs most often reported rabid.
Rabies infects the central nervous system, causing encephalopathy and ultimately death. Early symptoms of rabies in humans are nonspecific, consisting of fever, headache, and general malaise. As the disease progresses, neurological symptoms appear and may include insomnia, anxiety, confusion, slight or partial paralysis, excitation, hallucinations, agitation, hypersalivation, difficulty swallowing, and hydrophobia (fear of water). Death usually occurs within days of the onset of symptoms.
In individual cases of rabies, vaccination may be used both as a preventive measure, and as a prophylactic treatment measure in patients that may possibly have been contaminated. Vaccination to date constitutes the sole effective treatment against rabies. It allows neutralization of the virus before the latter reaches the brain, since once it has reached this stage the outcome of the disease is inevitably fatal.
Although once given exclusively to those exposed through their work (veterinary surgeons, laboratory personnel, stable hands, taxidermists, gamekeepers and foresters), protective vaccination against rabies now appears to be justified for travellers, including children aged over one year, visiting or staying for prolonged periods in endemic areas. Three injections are required for the initial vaccination, which nevertheless does not obviate the need for a booster (2 injections) in the event of suspect bites.
Public health importance of rabies
Over the last 100 years, rabies in the United States has changed dramatically. More than 90% of all animal cases reported annually to CDC now occur in wildlife; before 1960 the majority were in domestic animals. The principal rabies hosts today are wild carnivores and bats.. The number of rabies-related human deaths in the United States has declined from more than 100 annually at the turn of the century to one or two per year in the1990's. Modern day prophylaxis has proven nearly 100% successful. In the United States, human fatalities associated with rabies occur in people who fail to seek medical assistance, usually because they were unaware of their exposure.
Cost of rabies prevention
Although human rabies deaths are rare, the estimated public health costs associated with disease detection, prevention, and control have risen, exceeding $300 million annually. These costs include the vaccination of companion animals, animal control programs, maintenance of rabies laboratories, and medical costs, such as those incurred for rabies postexposure prophylaxis (PEP).
Accurate estimates of these expenditures are not available. Although the number of PEPs given in the United States each year is unknown, it is estimated to be about 40,000. When rabies becomes epizootic or enzootic in a region, the number of PEPs in that area increases. Although the cost varies, a course of rabies immune globulin and five doses of vaccine given over a 4-week period typically exceeds $1,000. The cost per human life saved from rabies ranges from approximately $10,000 to $100 million, depending on the nature of the exposure and the probability of rabies in a region.
Rabies virus causes an acute encephalitis in all warm-blooded hosts, including humans, and the outcome is almost always fatal. Although all species of mammals are susceptible to rabies virus infection, only a few species are important as reservoirs for the disease. In the United States, several distinct rabies virus variants have been identified in terrestrial mammals, including raccoons, skunks, foxes, and coyotes. In addition to these terrestrial reservoirs, several species of insectivorous bats are also reservoirs for rabies.
Transmission of rabies virus usually begins when infected saliva of a host is passed to an uninfected animal. Various routes of transmission have been documented and include contamination of mucous membranes (i.e., eyes, nose, mouth), aerosol transmission, and corneal transplantations. The most common mode of rabies virus transmission is through the bite and virus-containing saliva of an infected host.
Following primary infection the virus enters an eclipse phase in which it cannot be easily detected within the host. This phase may last for several days or months. Investigations have shown both direct entry of virus into peripheral nerves at the site of infection and indirect entry after viral replication in nonnervous tissue (i.e., muscle cells). During the eclipse phase, the host immune defenses may confer cell-mediated immunity against viral infection because rabies virus is a good antigen . The uptake of virus into peripheral nerves is important for progressive infection to occur.
After uptake into peripheral nerves, rabies virus is transported to the central nervous system (CNS) via retrograde axoplasmic flow. Typically this occurs via sensory and motor nerves at the initial site of infection. The incubation period is the time from exposure to onset of clinical signs of disease. The incubation period may vary from a few days to several years, but is typically 1 to 3 months. Dissemination of virus within the CNS is rapid, and includes early involvement of limbic system neurons. Active cerebral infection is followed by passive centrifugal spread of virus to peripheral nerves. The amplification of infection within the CNS occurs through cycles of viral replication and cell-to-cell transfer of progeny virus. Centrifugal spread of virus may lead to the invasion of highly innervated sites of various tissues, including the salivary glands. During this period of cerebral infection, the classic behavioral changes associated with rabies develop.
Signs and symptoms
The first symptoms of rabies may be nonspecific flu-like signs — malaise, fever, or headache, which may last for days. There may be discomfort or paresthesia at the site of exposure (bite), progressing within days to symptoms of cerebral dysfunction, anxiety, confusion, agitation, progressing to delirium, abnormal behavior, hallucinations, and insomnia. The acute period of disease typically ends after 2 to 10 days (6). Once clinical signs of rabies appear, the disease is nearly always fatal, and treatment is typically supportive. Disease prevention is entirely prophylactic and includes both passive antibody (immune globulin) and vaccine. Non-lethal exceptions are extremely rare. To date only six documented cases of human survival from clinical rabies have been reported and each included a history of either pre- or postexposure prophylaxis.
Pathology of rabies infection is typically defined by encephalitis and myelitis. Perivascular infiltration with lymphocytes, polymorphonuclear leukocytes, and plasma cells can occur throughout the entire CNS. Rabies infection frequently causes cytoplasmic eosinophilic inclusion bodies (Negri bodies) in neuronal cells, especially pyramidal cells of the hippocampus and Purkinje cells of the cerebellum. These inclusions have been identified as areas of active viral replication by the identification of rabies viral antigen.
Several factors may affect the outcome of rabies exposure. These include the virus variant, the dose of virus inoculum, the route and location of exposure,as well as individual host factors, such as age and host immune defenses.
Rabies vaccine and immune globulin
There is no treatment for rabies after symptoms of the disease appear. However, two decades ago scientists developed an extremely effective new rabies vaccine regimen that provides immunity to rabies when administered after an exposure (postexposure prophylaxis) or for protection before an exposure occurs (preexposure prophylaxis). Although rabies among humans is rare in the United States, every year an estimated 18,000 people receive rabies preexposure prophylaxis and an additional 40,000 receive postexposure prophylaxis.
Preexposure vaccination is recommended for persons in high-risk groups, such as veterinarians, animal handlers, and certain laboratory workers. Other persons whose activities bring them into frequent contact with rabies virus or potentially rabid bats, raccoons, skunks, cats, dogs, or other species at risk of having rabies should also be considered for preexposure prophylaxis. In addition, international travelers likely to come in contact with animals in areas of enzootic dog rabies which lack immediate access to appropriate medical care, including biologics, should be considered for preexposure prophylaxis. (For more information about preexposure prophylaxis, see Human Rabies Prevention - United States, 1999 Recommendations of the Immunization Practices Advisory Committee (ACIP).)
People who work with live rabies virus in research laboratories or vaccine production facilities are at the highest risk of inapparent exposures. Such persons should have a serum (blood) sample tested for antibody every 6 months and receive booster vaccine, when necessary. Routine preexposure prophylaxis for other situations may generally not be indicated.
Purpose of preexposure prophylaxis
Preexposure prophylaxis is given for several reasons. First, although preexposure vaccination does not eliminate the need for additional medical attention after a rabies exposure, it simplifies therapy by eliminating the need for human rabies immune globulin (HRIG) and decreasing the number of vaccine doses needed – a point of particular importance for persons at high risk of being exposed to rabies in areas where immunizing products may not be available, and it minimizes adverse reactions to multiple doses of vaccine. Second, it may enhance immunity in persons whose postexposure therapy might be delayed. Finally, it may provide protection to persons with inapparent exposures to rabies.
Preexposure prophylaxis regimen
Preexposure prophylaxis consists of three doses of rabies vaccine given on days 0, 7, and 21 or 28.
Postexposure prophylaxis (PEP) is indicated for persons possibly exposed to a rabid animal. Possible exposures include animal bites, or mucous membrane contamination with infectious tissue, such as saliva. PEP should begin as soon as possible after an exposure. There have been no vaccine failures in the United States (i.e. someone developed rabies) when PEP was given promptly and appropriately after an exposure.
Administration of rabies PEP is a medical urgency, not a medical emergency. Physicians should evaluate each possible exposure to rabies and as necessary consult with local or state public health officials regarding the need for rabies prophylaxis.
Postexposure prophylaxis regimen
In the United States, PEP consists of a regimen of one dose of immune globulin and five doses of rabies vaccine over a 28-day period. Rabies immune globulin and the first dose of rabies vaccine should be given as soon as possible after exposure. Additional doses of rabies vaccine should be given on days 3, 7, 14, and 28 after the first vaccination. Current vaccines are relatively painless and are given in your arm, like a flu or tetanus vaccine.
What to do after a possible exposure
If you are exposed to a potentially rabid animal, wash the wound thoroughly with soap and water, and seek medical attention immediately. A health care provider will care for the wound and will assess the risk for rabies exposure. The following information will help your health care provider assess your risk:
Steps taken by the health care practitioner will depend on the circumstances of the bite. Your health care practitioner should consult state or local health departments, veterinarians, or animal control officers to make an informed assessment of the incident and to request assistance. The important factor is that you seek care promptly after you are bitten by any animal.
- the geographic location of the incident • the type of animal that was involved • how the exposure occurred (provoked or unprovoked) • the vaccination status of animal • whether the animal can be safely captured and tested for rabies
What you can do to help prevent the spread of rabies
Be a responsible pet owner:
- Keep vaccinations up-to-date for all dogs, cats and ferrets. This requirement is important not only to keep your pets from getting rabies, but also to provide a barrier of protection to you, if your animal is bitten by a rabid wild animal. • Keep your pets under direct supervision so they do not come in contact with wild animals. If your pet is bitten by a wild animal, seek veterinary assistance for the animal immediately. • Call your local animal control agency to remove any stray animals from your neighborhood. They may be unvaccinated and could be infected by the disease. • Spay or neuter your pets to help reduce the number of unwanted pets that may not be properly cared for or regularly vaccinated.
Avoid direct contact with unfamiliar animals:
- Enjoy wild animals (raccoons, skunks, foxes) from afar. Do not handle, feed, or unintentionally attract wild animals with open garbage cans or litter. • Never adopt wild animals or bring them into your home. Do not try to nurse sick animals to health. Call animal control or an animal rescue agency for assistance. • Teach children never to handle unfamiliar animals, wild or domestic, even if they appear friendly. "Love your own, leave other animals alone" is a good principle for children to learn. • Prevent bats from entering living quarters or occupied spaces in homes, churches, schools, and other similar areas, where they might come in contact with people and pets. • When traveling abroad, avoid direct contact with wild animals and be especially careful around dogs in developing countries. Rabies is common in developing countries in Asia, Africa, and Latin America where dogs are the major reservoir of rabies. Tens of thousands of people die of rabies each year in these countries. Before traveling abroad, consult with a health care provider, travel clinic, or your health department about the risk of exposure to rabies, preexposure prophylaxis, and how you should handle an exposure, should it arise.
Questions and Answers about Rabies
1. Q: How can I protect my pet from rabies?
A: There are several things you can do to protect your pet from rabies. First, visit your veterinarian with your pet on a regular basis and keep rabies vaccinations up-to-date for all cats, ferrets, and dogs. Second, maintain control of your pets by keeping cats and ferrets indoors and keeping dogs under direct supervision. Third, spay or neuter your pets to help reduce the number of unwanted pets that may not be properly cared for or vaccinated regularly. Lastly, call animal control to remove all stray animals from your neighborhood since these animals may be unvaccinated or ill.
2. Q: Why does my pet need the rabies vaccine?
Although the majority of rabies cases occur in wildlife, most humans are given rabies vaccine as a result of exposure to domestic animals. This explains the tremendous cost of rabies prevention in domestic animals in the United States. While wildlife are more likely to be rabid than are domestic animals in the United States, the amount of human contact with domestic animals greatly exceeds the amount of contact with wildlife. Your pets and other domestic animals can be infected when they are bitten by rabid wild animals. When "spillover" rabies occurs in domestic animals, the risk to humans is increased. Pets are therefore vaccinated by your veterinarian to prevent them from acquiring the disease from wildlife, and thereby transmitting it to humans
3. Q: What happens if a neighborhood dog or cat bites me?
A: You should seek medical evaluation for any animal bite. However, rabies is uncommon in dogs, cats, and ferrets in the United States. Very few bites by these animals carry a risk of rabies. If the cat (or dog or ferret) appeared healthy at the time you were bitten, it can be confined by its owner for 10 days and observed. No anti-rabies prophylaxis is needed. No person in the United States has ever contracted rabies from a dog, cat or ferret held in quarantine for 10 days.
If a dog, cat, or ferret appeared ill at the time it bit you or becomes ill during the 10 day quarantine, it should be evaluated by a veterinarian for signs of rabies and you should seek medical advice about the need for anti-rabies prophylaxis.
The quarantine period is a precaution against the remote possibility that an animal may appear healthy, but actually be sick with rabies. To understand this statement, you have to understand a few things about the pathogenesis of rabies (the way the rabies virus affects the animal it infects). From numerous studies conducted on rabid dogs, cats, and ferrets, we know that rabies virus inoculated into a muscle travels from the site of the inoculation to the brain by moving within nerves. The animal does not appear ill during this time, which is called the incubation period and which may last for weeks to months. A bite by the animal during the incubation period does not carry a risk of rabies because the virus is not in saliva. Only late in the disease, after the virus has reached the brain and multiplied there to cause an encephalitis (or inflammation of the brain), does the virus move from the brain to the salivary glands and saliva. Also at this time, after the virus has multiplied in the brain, almost all animals begin to show the first signs of rabies. Most of these signs are obvious to even an untrained observer, but within a short period of time, usually within 3 to 5 days, the virus has caused enough damage to the brain that the animal begins to show unmistakable signs of rabies. As an added precaution, the quarantine period is lengthened to 10 days.
4. Q: What happens if my pet (cat, dog, ferret) is bitten by a wild animal?
A: Any animal bitten or scratched by either a wild, carnivorous mammal or a bat that is not available for testing should be regarded as having been exposed to rabies. Unvaccinated dogs, cats, and ferrets 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 and vaccinated 1 month before being released. Animals with expired vaccinations need to be evaluated on a case-by-case basis. Dogs and cats that are currently vaccinated are kept under observation for 45 days.
1. Q: How do people get rabies?
A: People usually get get rabies from the bite of a rabid animal. It is also possible, but quite rare, that people may get rabies if infectious material from a rabid animal, such as saliva, gets directly into their eyes, nose, mouth, or a wound.
2. Q: Can I get rabies in any way other than an animal bite?
A: Non-bite exposures to rabies are very rare. Scratches, abrasions, open wounds, or mucous membranes contaminated with saliva or other potentially infectious material (such as brain tissue) from a rabid animal constitute non-bite exposures. Occasionally reports of non-bite exposure are such that postexposure prophylaxis is given.
Inhalation of aerosolized rabies virus is also a potential non-bite route of exposure, but other than laboratory workers, most people are unlikely to encounter an aerosol of rabies virus.
Other contact, such as petting a rabid animal or contact with the blood, urine or feces (e.g., guano) of a rabid animal, does not constitute an exposure and is not an indication for prophylaxis.
3. Q: How soon after an exposure should I seek medical attention?
A: Medical assistance should be obtained as soon as possible after an exposure. There have been no vaccine failures in the United States (i.e., someone developed rabies) when postexposure prophylaxis (PEP) was given promptly and appropriately after an exposure.
4. Q: What medical attention do I need if I am exposed to rabies?
A: One of the most effective methods to decrease the chances for infection involves thorough washing of the wound with soap and water. Specific medical attention for someone exposed to rabies is called postexposure prophylaxis or PEP. In the United States, postexposure prophylaxis consists of a regimen of one dose of immune globulin and five doses of rabies vaccine over a 28-day period. Rabies immune globulin and the first dose of rabies vaccine should be given by your health care provider as soon as possible after exposure. Additional doses or rabies vaccine should be given on days 3, 7, 14, and 28 after the first vaccination. Current vaccines are relatively painless and are given in your arm, like a flu or tetanus vaccine.
5. Q: Will the rabies vaccine make me sick?
A: Adverse reactions to rabies vaccine and immune globulin are not common. Newer vaccines in use today cause fewer adverse reactions than previously available vaccines. Mild, local reactions to the rabies vaccine, such as pain, redness, swelling, or itching at the injection site, have been reported. Rarely, symptoms such as headache, nausea, abdominal pain, muscle aches, and dizziness have been reported. Local pain and low-grade fever may follow injection of rabies immune globulin.
6. Q: What if I cannot get rabies vaccine on the day I am supposed to get my next dose?
A: Consult with your doctor or state or local public health officials for recommended times if there is going to be a change in the recommended schedule of shots. Rabies prevention is a serious matter and changes should not be made in the schedule of doses.
7. Q: Can rabies be transmitted from one person to another?
A: The only well-documented documented cases of rabies caused by human-to-human transmission occurred among 8 recipients of transplanted corneas, and recently among three recipients of solid organs. Guidelines for acceptance of suitable cornea and organ donations, as well as the rarity of human rabies in the United States, reduce this risk. In addition to transmission from cornea and organ transplants, bite and non-bite exposures inflicted by infected humans could theoretically transmit rabies, but no such cases have been documented. Casual contact, such as touching a person with rabies or contact with non-infectious fluid or tissue (urine, blood, feces) does not constitute an exposure and does not require postexposure prophylaxis. In addition, contact with someone who is receiving rabies vaccination does not constitute rabies exposure and does not require postexposure prophylaxis.
1. Q: What animals get rabies?
A: Any mammal can get rabies. The most common wild reservoirs of rabies are raccoons, skunks, bats, foxes, and coyotes. Domestic mammals can also get rabies. Cats, cattle, and dogs are the most frequently reported rabid domestic animals in the United States.
2. Q: How can I find out what animals have rabies in my area?
A: Each state collects specific information about rabies, and is the best source for information on rabies in your area. In addition, the CDC publishes rabies surveillance data every year for the United States. The report, entitled Rabies Surveillance in the United States, contains information about the number of cases of rabies reported to CDC during the year, the animals reported rabid, maps showing where cases were reported for wild and domestic animals, and distribution maps showing outbreaks of rabies associated with specific animals. A summary of the report can be found in the Epidemiology section of this web site.
3. Q: What is the risk of rabies from squirrels, mice, rats, and other rodents?
A: Small rodents (such as squirrels, rats, mice, hamsters, guinea pigs, gerbils, and chipmunks, ) and lagomorphs (such as rabbits and hares) are almost never found to be infected with rabies and have not been known to cause rabies among humans in the United States. Bites by these animals are usually not considered a risk of rabies unless the animal was sick or behaving in any unusual manner and rabies is widespread in your area. However, from 1985 through 1994, woodchucks accounted for 86% of the 368 cases of rabies among rodents reported to CDC. Woodchucks or groundhogs (Marmota monax) are the only rodents that may be frequently submitted to state health department because of a suspicion of rabies. In all cases involving rodents, the state or local health department should be consulted before a decision is made to initiate postexposure prophylaxis (PEP).
Bats and Rabies
1. Q: Do bats get rabies?
A: Yes. Bats are mammals and are susceptible to rabies, but most do not have the disease. You cannot tell if a bat has rabies just by looking at it; rabies can be confirmed only by having the animal tested in a laboratory. To minimize the risk for rabies, it is best never to handle any bat.
2. Q: What should I do if I come in contact with a bat?
A: If you are bitten by a bat -- or if infectious material (such as saliva) from a bat gets into your eyes, nose, mouth, or a wound -- wash the affected area thoroughly and get medical attention immediately. Whenever possible, the bat should be captured and sent to a laboratory for rabies testing.
People usually know when they have been bitten by a bat. However, because bats have small teeth which may leave marks that are not easily seen, there are situations in which you should seek medical advice even in the absence of an obvious bite wound. For example, if you awaken and find a bat in your room, see a bat in the room of an unattended child, or see a bat near a mentally impaired or intoxicated person, seek medical advice and have the bat tested.
People cannot get rabies just from seeing a bat in an attic, in a cave, or at a distance. In addition, people cannot get rabies from having contact with bat guano (feces), blood, or urine, or from touching a bat on its fur (even though bats should never be handled!).
3. Q: What should I do if I find a bat in my home?
A: If you see a bat in your home and you are sure no human or pet exposure has occurred, confine the bat to a room by closing all doors and windows leading out of the room except those to the outside. The bat will probably leave soon. If not, it can be caught, as described below, and released outdoors away from people and pets.
However, if there is any question of exposure, leave the bat alone and call animal control or a wildlife conservation agency for assistance.
4. Q: How can I tell if a bat has rabies?
A: Rabies can be confirmed only in a laboratory. However, any bat that is active by day, is found in a place where bats are not usually seen (for example in rooms in your home or on the lawn), or is unable to fly, is far more likely than others to be rabid. Such bats are often the most easily approached. Therefore, it is best never to handle any bat.
1. Q: Should I be concerned about rabies when I travel outside the United States?
A: Yes. Rabies and the rabies-like viruses can occur in animals anywhere in the world. In most countries, the risk of rabies in an encounter with an animal and the precautions necessary to prevent rabies are the same as they are in the United States. When traveling, it is always prudent to avoid approaching any wild or domestic animal.
The developing countries in Africa, Asia, and Latin America have additional problems in that dog rabies is common there and preventive treatment for human rabies may be difficult to obtain. The importance of rabid dogs in these countries, where tens of thousands of people die of the disease each year, cannot be overstated. Unlike programs in developed countries, dog rabies vaccination programs in developing countries have not always been successful. Rates of postexposure prophylaxis in some developing countries are about 10 times higher than in the United States, and rates of human rabies are sometimes100 times higher. Before traveling abroad, consult a health care provider, travel clinic, or health department about your risk of exposure to rabies and how to handle an exposure should it arise.
2. Q: Should I receive rabies preexposure vaccination before traveling to other countries?
A: In most countries, the risk of rabies and the precautions for preventing rabies are the same as they are in the United States. However, in some developing countries in Africa, Asia, and Latin America, dog rabies may be common and preventive treatment for rabies may be difficult to obtain. If you are traveling to a rabies-endemic country, you should consult your health care provider about the possibility of receiving preexposure vaccination against rabies. Preexposure vaccination is suggested if:
1. Your planned activity will bring you into contact with wild or domestic animals (for example, biologists, veterinarians, or agriculture specialists working with animals). 2. You will be visiting remote areas where medical care is difficult to obtain or may be delayed (for example, hiking through remote villages where dogs are common). 3. Your stay is longer than 1 month in an area where dog rabies is common (the longer you stay, the greater the chance of an encounter with an animal).
3. Q: If I get preexposure vaccination before I travel, am I protected if I am bitten?
A: No. Preexposure prophylaxis is given for several reasons. First, although preexposure vaccination does not eliminate the need for additional therapy after a rabies exposure, it simplifies therapy by eliminating the need for human rabies immune globulin (HRIG) and decreasing the number of doses needed – a point of particular importance for persons at high risk of being exposed to rabies in areas where immunizing products may not be readily available. Second, it may protect persons whose postexposure therapy might be delayed. Finally, it may provide partial protection to persons with inapparent exposures to rabies.