Rabies

Definition

Rabies is an acute viral disease of the central nervous system that affects humans and other mammals but is most common in carnivores (flesh-eaters). It is sometimes referred to as a zoonosis, or disease of animals that can be communicated to humans. Rabies is almost exclusively transmitted through saliva from the bite of an infected animal. Another name for the disease is hydrophobia, which literally means "fear of water," a symptom shared by half of all people infected with rabies. Other symptoms include fever, depression, confusion, painful muscle spasms, sensitivity to touch, loud noise, and light, extreme thirst, painful swallowing, excessive salivation, and loss of muscle tone. If rabies is not prevented by immunization, it is almost always fatal.

Description

Cases of rabies in humans are very infrequent in the United States and Canada, averaging one or two a year (down from over 100 cases annually in 1900), but the worldwide incidence is estimated to be between 30,000 and 50,000 cases each year. These figures are based on data collected by the World Health Organization (WHO) in 1997 and updated in 2002. Rabies is most common in developing countries in Africa, Latin America, and Asia, particularly India. Dog bites are the major origin of infection for humans in developing countries, but other important host animals may include the wolf, mongoose, raccoon, jackal, and bat. A group of researchers in India found that monkeys as well as dogs were frequent vectors of rabies. The team also reported that the male:female ratio of rabies patients in India is 4:1.

Most deaths from rabies in the United States and Canada result from bat bites; the most recent fatality was a 66-year-old man in California who died in September 2003. The death of a nine-year-old girl in Quebec in the fall of 2000 was the first case of human rabies in Canada since 1985. Public health officials eventually determined that the girl had been bitten while she was sleeping by a silver-haired bat that had gotten into the family's home.

On October 18, 2004, a Wisconsin teenager was diagnosed with full-blown rabies after suffering from a minor bat bite on September 12, 2004. Miraculously, she was cured of rabies after doctors induced coma and administered four antiviral drugs to her. Since the therapy was only given and successful for one case, its curative properties needs to be corroborated by other cases before it will be considered a viable treatment option. The case and the physicians' findings will be published in a medical journal.

People whose work frequently brings them in contact with animals are considered to be at higher risk than the general population. This would include those in the fields of veterinary medicine, animal control, wildlife work, and laboratory work involving live rabies virus. People in these occupations and residents of or travelers to areas where rabies is a widespread problem should consider being immunized.

In late 2002, rabies re-emerged as an important public health issue. Dr. Charles E. Rupprecht, director of the World Health Organization (WHO) Collaborating Center for Rabies Reference and Research, has listed several factors responsible for the increase in the number of rabies cases worldwide:

• Rapid evolution of the rabies virus. Bats in the United States have developed a particularly infectious form of the virus.
• Increased diversity of animal hosts for the disease.

• Changes in the environment that are bringing people and domestic pets into closer contact with infected wildlife.
• Increased movement of people and animals across international borders. In one recent case, a man who had contracted rabies in the Philippines was not diagnosed until he began to feel ill in the United Kingdom.
• Lack of advocacy about rabies.

Causes and symptoms

Rabies is caused by a rod- or bullet-shaped virus that belongs to the family Rhabdoviridae. The rabies virus is a member of a genus of viruses called lyssaviruses, which include several related viruses that infect insects as well as mammals. The rabies virus is usually transmitted via an animal bite, however, cases have also been reported in which the virus penetrated the body through infected saliva, moist tissues such as the eyes or lips, a scratch on the skin, or the transplantation of infected tissues. Inhalation of the virus in the air, as might occur in a highly populated bat cave, is also thought to occur.

From the bite or other area of penetration, the virus multiplies as it spreads along nerves that travel away from the spinal cord and brain (efferent nerves) and into the salivary glands. The rabies virus may lie dormant in the body for several weeks or months, but rarely much longer, before symptoms appear. Initially, the area around the bite may burn and be painful. Early symptoms may also include a sore throat, low-grade fever, headache, loss of appetite, nausea and vomiting, and diarrhea. Painful spasms develop in the muscles that control breathing and swallowing. The individual may begin to drool thick saliva and may have dilated or irregular pupils, increased tears and perspiration, and low blood pressure.

Later, as the disease progresses, the patient becomes agitated and combative and may exhibit increased mental confusion. The affected person usually becomes sensitive to touch, loud noises, and bright lights. The victim also becomes extremely thirsty, but is unable to drink because swallowing is painful. Some patients begin to dread water because of the painful spasms that occur. Other severe symptoms during the later stage of the disease include excessive salivation, dehydration, and loss of muscle tone. Death usually occurs three to 20 days after symptoms have developed. Unfortunately, recovery is very rare.

Diagnosis

After the onset of symptoms, blood tests and cerebrospinal fluid (CSF) analysis tests will be conducted. CSF will be collected during a procedure called a lumbar puncture in which a needle is used to withdraw a sample of CSF from the area around the spinal cord. The CSF tests do not confirm diagnosis but are useful in ruling out other potential causes for the patient's altered mental state.

The two most common diagnostic tests are the fluorescent antibody test and isolation of the rabies virus from an individual's saliva or throat culture. The fluorescent antibody test involves taking a small sample of skin (biopsy) from the back of the neck of the patient. If specific proteins, called antibodies, that are produced only in response to the rabies virus are present, they will bind with the fluorescent dye and become visible. Another diagnostic procedure involves taking a corneal impression in which a swab or slide is pressed lightly against the cornea of the eye to determine whether viral material is present.

Treatment

Until the most recent successful cure of a late-term rabies case can be validated with further success and validation from the medical community, the historic treatment options for rabies prevention immediately following a bite remains the most viable treatment. Because of the extremely serious nature of a rabies infection, the need for rabies immunizations will be carefully considered for anyone who has been bitten by an animal, based on a personal history and results of diagnostic tests.

If necessary, treatment includes the following:

• The wound is washed thoroughly with medicinal soap and water. Deep puncture wounds should be flushed with a catheter and soapy water. Unless absolutely necessary, a wound should not be sutured.
• Tetanus toxoid and antibiotics will usually be administered.
• Rabies vaccination may or not be given, based on the available information. If the individual was bitten by a domestic animal and the animal was captured, the animal will be placed under observation in quarantine for ten days. If the animal does not develop rabies within four to seven days, then no immunizations are required. If the animal is suspected of being rabid, it is killed, and the brain is examined for evidence of rabies infection. In cases involving bites from domestic animals where the animal is not available for examination, the decision for vaccination is made based on the prevalence of rabies within the region where the bite occurred. If the bite was from a wild animal and the animal was captured, it is generally killed because the incubation period of rabies is unknown in most wild animals.
• If necessary, the patient is vaccinated immediately, generally through the administration of human rabies immune globulin (HRIG) for passive immunization, followed by human diploid cell vaccine (HDCV) or rabies vaccine adsorbed (RVA) for active immunization. Passive immunization is designed to provide the individual with antibodies from an already immunized individual, while active immunization involves stimulating the individual's own immune system to produce antibodies against the rabies virus. Both rabies vaccines are equally effective and carry a lower risk of side effects than some earlier treatments. Unfortunately, however, in underdeveloped countries, these newer vaccines are usually not available. Antibodies are administered to the patient in a process called passive immunization. To do this, the HRIG vaccine is administered once, at the beginning of treatment. Half of the dose is given around the bite area, and the rest is given in the muscle. Inactivated viral material (antigenic) is then given to stimulate the patient's own immune system to produce antibodies against rabies. For active immunization, either the HDCV or RVA vaccine is given in a series of five injections. Immunizations are typically given on days one, three, seven, 14, and 28.

In those rare instances in which rabies has progressed beyond the point where immunization would be effective, the groundbreaking treatment involving a drug-induced coma and the administration of four different antiviral drugs will most likely be a radical treatment option. The traditional approach prior to October 2004 was to provide as much relief from pain and suffering as possible through medical intervention while waiting to see if survival was possible. The patient would be given medication to prevent seizures, relieve some of the anxiety, and relieve painful muscle spasms. Pain relievers would also be given. In the later stages, aggressive supportive care would be provided to maintain breathing and heart function. Survival via the traditional treatment is rare but can occur.

Prognosis

If preventative treatment is sought promptly, rabies need not be fatal. Immunization is almost always effective if started within two days of the bite. Chance of effectiveness declines, however, the longer vaccination is put off. It is, however, important to start immunizations, even if it has been weeks or months following a suspected rabid animal bite, because the vaccine can be effective even in these cases. If immunizations do not prove effective or are not received, rabies is nearly always fatal with a few days of the onset of symptoms.

KEY TERMS

Active immunization— Treatment that provides immunity by challenging an individual's own immune system to produce antibody against a particular organism, in this case the rabies virus.

Antibody— A specific protein produced by the immune system in response to a specific foreign protein or particle called an antigen.

Biopsy— The removal of a small sample of tissue for diagnostic purposes.

Efferent nerves— Nerves that convey impulses away from the central nervous system to the periphery.

Fluorescent antibody test (FA test)— A test in which a fluorescent dye is linked to an antibody for diagnostic purposes.

Lumbar puncture— A procedure that involves withdrawing a small sample of cerebrospinal fluid from the back around the spinal cord.

Lyssavirus— A genus of viruses that includes the rabies virus and related viruses that infect insects as well as mammals.

Passive immunization— Treatment that provides immunity through the transfer of antibodies obtained from an immune individual.

Rhabdovirus— A type of virus named for its rod- or bullet-like shape. The rabies virus belongs to a family of viruses called Rhabdoviridae.

Vector— An animal or insect that carries a disease-producing organism.

Zoonosis— Any disease of animals that can be transmitted to humans. Rabies is an example of a zoonosis.

As of October 2004, the medical community awaits the publication of findings by the doctors that administered a life-saving treatment that cured a Wisconsin teenager of full-blown rabies. Further test cases will prove whether or not this treatment option will be a historic development in the search for a cure for rabies.

Prevention

One promising preventive strategy that has been used since the early 2000s is the distribution of wildlife baits containing an oral vaccine against rabies. This strategy has been used in Germany to vaccinate wild foxes, which are frequent carriers of the disease in Europe. In the United States, veterinary researchers at Kansas State University have developed an oral vaccine for fruit bats; early trials of the vaccine have given promising results.

The following precautions should be observed in environments where humans and animals may likely come into contact.

• Domesticated animals, including household pets, should be vaccinated against rabies. If a pet is bitten by an animal suspected to have rabies, its owner should contact a veterinarian immediately and notify the local animal control authorities. Domestic pets with current vaccinations should be revaccinated immediately; unvaccinated dogs, cats, or ferrets are usually euthanized (put to sleep). Further information about domestic pets and rabies is available on the American Veterinary Medical Association (AVMA) web site.
• Wild animals should not be touched or petted, no matter how friendly they may appear. It is also important not to touch an animal that appears ill or passive, or whose behavior seems odd, such as failing to show the normal fear of humans. These are all possible signs of rabies. Many animals, such as raccoons and skunks, are nocturnal and their activity during the day should be regarded as suspicious.
• People should not interfere in fights between animals.
• Because rabies is transmitted through saliva, a person should wear rubber gloves when handling a pet that has had an encounter with a wild animal.
• Garbage or pet food should not be left outside the house or camp site because it may attract wild or stray animals.
• Windows and doors should be screened. Some victims of rabies have been attacked by infected animals, particularly bats, that entered through unprotected openings.
• State or county health departments should be consulted for information about the prevalence of rabies in an area. Some areas, such as New York City, have been rabies-free, only to have the disease reintroduced at a later time.
• Preventative vaccination against rabies should be considered if one's occupation involves frequent contact with wild animals or non-immunized domestic animals.
• Bites from mice, rats, or squirrels rarely require rabies prevention because these rodents are typically killed by any encounter with a larger, rabid animal, and would, therefore, not be carriers.
• Travelers should ask about the prevalence of the disease in countries they plan to visit.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Central Nervous System Viral Diseases: Rabies (Hydrophobia)." Section 13, Chapter 162 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

PERIODICALS

Chhabra, M., R. L. Ichhpujani, K. N. Tewari, and S. Lal. "Human Rabies in Delhi." Indian Journal of Pediatrics 71 (March 2004): 217-220.

Deshaies, D., P. A. Pilon, L. Valiquette, and J. Carsley. "A Public Health Intervention at the Time of a Case of Rabies in Quebec." [in French] Canadian Journal of Public Health 95 (March-April 2004): 138-141.

Fooks, A. R., N. Johnson, S. M. Brookes, et al. "Risk Factors Associated with Travel to Rabies Endemic Countries." Journal of Applied Microbiology 94, Supplement (2003): 31S-36S.

"Human Death Associated with Bat Rabies—California, 2003." Morbidity and Mortality Weekly Report 53 (January 23, 2004): 33-35.

Messenger, S. L., J. S. Smith, L. A. Orciari, et al. "Emerging Pattern of Rabies Deaths and Increased Viral Infectivity." Emerging Infectious Diseases 9 (February 2003): 151-154.

Peters, C., R. Isaza, D. J. Heard, et al. "Vaccination of Egyptian Fruit Bats (Rousettus aegyptiacus ) with Monovalent Inactivated Rabies Vaccine." Journal of Zoo and Wildlife Medicine 35 (March 2004): 55-59.

Rosenthal, Elisabeth. "Girl is first to survive rabies without a shot." The New York Times November 25, 2004: A28.

Smith, J., L. McElhinney, G. Parsons, et al. "Case Report: Rapid Ante-Mortem Diagnosis of a Human Case of Rabies Imported Into the UK from the Philippines." Journal of Medical Virology 69 (January 2003): 150-155.

Stringer, C. "Post-Exposure Rabies Vaccination." Nursing Standard 17 (February 5-11, 2003): 41-42.

Thulke, H. H., T. Selhorst, T. Muller, et al. "Assessing Anti-Rabies Baiting—What Happens on the Ground?" BMC Infectious Diseases 4 (March 9, 2004): 9.

Weiss, R. A. "Cross-Species Infections." Current Topics in Microbiology and Immunology 278 (2003): 47-71.

ORGANIZATIONS

American Veterinary Medical Association (AVMA). 1931 North Meacham Road, Suite 100, Schaumburg, IL 60173-4360. 〈http://www.avma.org〉.

Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311. 〈http://www.cdc.gov〉.

Institut Pasteur. 25-28, rue du Dr. Roux, 75015 Paris, France. +33 (0) 1 45 68 80 00. 〈http://www.pasteur.fr/haut_ext.html〉.

OTHER

CDC. "Epidemiology of Rabies." 〈http://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm〉.

National Association of State Public Health Veterinarians, Inc. "Compendium of Animal Rabies Prevention and Control, 2003." Morbidity and Mortality Weekly Report Recommendations and Reports 52 (March 21, 2003) (RR-5): 1-6.

Rabies

Definition

Rabies is a viral illness that can affect any mammal but is most common in carnivores (flesh-eaters). It is sometimes referred to as a zoonosis, or disease of animals that can be communicated to humans. Rabies is usually transmitted in the saliva through a bite wound. The virus attacks the central nervous system, and is fatal once symptoms begin, with very rare exceptions.

Description

Rabies, also known as hydrophobia, belongs to the rhabdovirus family. Fewer than 10% of animal cases reported in the United States in 1998 were in domestic animals. Raccoons accounted for the largest number of cases in wild animals. Cases of rabies in humans are very infrequent in the United States, averaging one or two a year (down from over 100 cases annually in 1900), but the worldwide incidence is estimated to be between 30,000 and 50,000 cases each year. These figures are based on data collected by the World Health Organization (WHO) in 1997 and updated in 2002. Rabies is most common in developing countries in Africa, Latin America, and Asia, particularly India. Dog bites are the major origin of infection for humans in developing countries, but other important host animals may include the wolf, mongoose, and bat. Most deaths from rabies in the United States result from bat bites; the most recent victim was a man in Iowa who died in September 2002.

People whose work frequently brings them in contact with animals are considered to be at higher risk than the general population. This would include those in the fields of veterinary medicine, animal control, wildlife work, and laboratory work involving live rabies virus. People in these occupations and residents of or travelers to areas where rabies is a widespread problem should consider being immunized.

In late 2002, rabies re-emerged as an important public health issue. Dr. Charles E. Rupprecht, director of the World Health Organization (WHO) Collaborating Center for Rabies Reference and Research, has listed several factors responsible for the increase in the number of rabies cases worldwide:

• Rapid evolution of the rabies virus. Bats in the United States have developed a particularly infectious form of the virus.
• Increased diversity of animal hosts for the disease.
• Changes in the environment that are bringing people and domestic pets into closer contact with infected wildlife.
• Increased movement of people and animals across international borders. In one recent case, a man who had contracted rabies in the Philippines was not diagnosed until he began to feel ill in the United Kingdom.
• Lack of advocacy about rabies.

Causes & symptoms

The most common way to contract rabies is from the bite of an infected animal. Although bats are the most frequent source of human infection in the United States, dogs are the primary vector of rabies in most parts of the world. The disease may also be transmitted by tissues and body fluids other than saliva. Rare cases have occurred as a result of infection through corneal transplantation.

Rabies travels from the site of the bite along the peripheral nerves to the brain. The average incubation period in humans is 30–50 days, although it varies from 10 days to over a year. The initial symptoms are flu-like and nonspecific. They may include fever, headache , muscle pain, sore throat, fatigue, nausea , and vomiting . Altered sensation and muscle twitching in the area of the bite are signs that are more suspicious of rabies. When the virus reaches the brain, signs related to encephalitis (local or general inflammation of brain tissue) appear. This typically involves agitation, progressing to confusion,

combativeness, seizures, and localized areas of paralysis. There may also be hypersensitivity to light, sound, and touch. The patient may be coherent at times, but less so as the disease progresses. Many viruses causing encephalitis may produce similar signs. The next stage is dysfunction of the brainstem. The well-known phenomenon of foaming at the mouth is caused by excessive saliva production combined with difficulty swallowing. Many patients will refuse liquids at this point due to the painful muscle contractions caused by swallowing. This is how rabies came to be known as hydrophobia, which means "fear of water." Coma ensues soon after brainstem involvement, and death occurs when the respiratory center is affected. The course of the disease is four to 20 days after symptoms appear, unless life support is used.

Diagnosis

Early in its course, and without a known history of an animal bite, rabies can be difficult to diagnose. Symptoms of the early encephalitic (brain tissue inflammation) phase are similar to those of most viral types of encephalitis. When signs of brainstem dysfunction appear shortly after this time, rabies becomes a more likely possibility. Several tests are available for rabies diagnosis, but none are extremely reliable in the living patient. Part of the challenge is that rabies is so limited to nerve tissue until the late phases of the disease. The examination of brain tissue reveals a characteristic known as a Negri body, which is diagnostic. Direct fluorescent antibody (dFA) staining of saliva, skin biopsy, and corneal impressions may also yield a diagnosis.

Treatment

Local wound cleansing is important. Anyone who has experienced an animal bite should wash it thoroughly with soap and water. Rabies is a fatal illness, so a bite that breaks the skin warrants a call to a health care provider for evaluation of whether post-exposure prophylaxis (PEP) is necessary. Alternative treatments are recommended as a complementary therapy to conventional treatment in the case of rabies. Observation of the animal for signs of rabies is recommended whenever possible.

Allopathic treatment

If a person is bitten by a domestic animal and the owner is known, vaccination status should be checked. People bitten by healthy, immunized animals are unlikely to need post-exposure prophylaxis (PEP). The animal can be confined for 10 days. If it is healthy at the end of that time, it is presumed not to have been capable of transmitting rabies at the time of the bite, so PEP for the person bitten is not necessary.

Wild animals that have bitten can be captured, destroyed, and tested for rabies. Postexposure vaccine and specific immune globulin can be given if deemed necessary. In the United States, if the person who was bitten has not had prophylactic immunization and has a high-risk bite, generally five rabies vaccinations and one injection of human rabies immune globulin are given. There have been no cases in this country of people contracting rabies after receiving correctly administered PEP.

Bites from mice, rats, or squirrels rarely require rabies prevention because these rodents are typically killed by any encounter with a larger, rabid animal, and would therefore be less likely to be carriers. Bites from raccoons, bats, or unvaccinated dogs or cats are more suspect. Anyone bitten by a bat in the United States should receive PEP unless the bat is captured and proven not to be rabid.

If a pet is bitten by an animal suspected to have rabies, its owner should contact a veterinarian immediately and notify the local animal control authorities. Domestic pets with current vaccinations should be revaccinated immediately; unvaccinated dogs, cats, or ferrets are usually euthanized (put to sleep). Further information about domestic pets and rabies is available on the American Veterinary Medical Association (AVMA) web site.

Expected results

Survival of rabies after the appearance of symptoms is exceedingly rare.

Prevention

The following precautions should be observed in environments where humans and animals may likely come into contact. Domesticated animals, including household pets, should be vaccinated against rabies. Booster shots, given according to the manufacturer's recommendations, are required to maintain immunity. Wild animals should not be touched or petted, no matter how friendly an animal may appear. It is also important not to touch an animal that appears ill or passive, or whose behavior seems odd, such as failing to show the normal fear of humans. These are all possible signs of rabies. Many animals, such as raccoons and skunks, are nocturnal and their activity during the day should be regarded as suspicious. People should not interfere with fights between animals. Because rabies is transmitted through saliva, a person should wear rubber gloves when handling a pet that has had an encounter with a wild animal. Windows and doors should be screened. Some victims of rabies have been attacked by infected animals, particularly bats, that entered through unprotected openings. Finally, garbage or pet food should not be left outside because it may attract wild or stray animals.

Members of the high-risk occupations mentioned above should consider prophylactic immunization. Those who receive this pre-exposure vaccine still require PEP in the event of a potentially infective episode, but they have several advantages. One is that they require fewer post-exposure vaccines. A second advantage is that the timing of the PEP may be less critical for people who are in remote areas, or don't have ready access to vaccine for other reasons. Last, some people may be exposed without being aware of it, and the prophylactic vaccine might protect them.

Resources

BOOKS

"Central Nervous System Viral Diseases: Rabies (Hydrophobia)." Section 13, Chapter 162 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Corey, Lawrence. "Rabies Virus and Other Rhabdoviruses." Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci et al., 14th ed.; New York: McGraw-Hill, 1998.

PERIODICALS

Fooks, A. R., N. Johnson, S. M. Brookes, et al. "Risk Factors Associated with Travel to Rabies Endemic Countries." Journal of Applied Microbiology 94 (2003) (Supplement): 31S–36S.

"Human Rabies—Iowa, 2002." Morbidity and Mortality Weekly Report 52 (January 24, 2003): 47–48.

Messenger, S. L., J. S. Smith, L. A. Orciari, et al. "Emerging Pattern of Rabies Deaths and Increased Viral Infectivity." Emerging Infectious Diseases 9 (February 2003): 151–154.

Smith, J., L. McElhinney, G. Parsons, et al. "Case Report: Rapid Ante-Mortem Diagnosis of a Human Case of Rabies Imported Into the UK from the Philippines." Journal of Medical Virology 69 (January 2003): 150–155.

Stringer, C. "Post-Exposure Rabies Vaccination." Nursing Standard 17 (February 5-11, 2003): 41–42.

Weiss, R. A. "Cross-Species Infections." Current Topics in Microbiology and Immunology 278 (2003): 47–71.

ORGANIZATIONS

American Veterinary Medical Association (AVMA). 1931 North Meacham Road, Suite 100, Schaumburg, IL 60173-4360. <http://www.avma.org>.

Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311. <http://www.cdc.gov>.

Institut Pasteur. 25-28, rue du Dr. Roux, 75015 Paris, France. +33 (0) 1 45 68 80 00. <http://www.pasteur.fr/haut_ext.html>.

OTHER

CDC. "Epidemiology of Rabies." http://www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm.

National Association of State Public Health Veterinarians, Inc. "Compendium of Animal Rabies Prevention and Control, 2003." Morbidity and Mortality Weekly Report Recommendations and Reports 52 (March 21, 2003) (RR-5): 1–6.

Judith Turner

Rebecca J. Frey, PhD

Rabies

Definition

Rabies is an acute viral disease of the central nervous system that is transmitted through saliva from the bite of an infected animal.

Description

Rabies affects humans and other mammals but is most common in carnivores (flesh eaters). It is sometimes referred to as a zoonosis, or disease of animals that can be communicated to humans. Rabies is almost exclusively transmitted through saliva from the bite of an infected animal. Another name for the disease is hydrophobia, which literally means fear of water, a symptom shared by half of all people infected with rabies. Other symptoms include fever , depression, confusion, painful muscle spasms , sensitivity to touch, loud noise, and light, extreme thirst, painful swallowing, excessive salivation, and loss of muscle tone. If rabies is not prevented by immunization, it is almost always fatal.

In late 2002, rabies re-emerged as an important public health issue. Charles E. Rupprecht, director of the World Health Organization (WHO) Collaborating Center for Rabies Reference and Research, listed several factors responsible for the increase in the number of rabies cases worldwide:

• Rapid evolution of the rabies virus. Bats in the United States have developed a particularly infectious form of the virus.
• Increased diversity of animal hosts for the disease.
• Changes in the environment that are bringing people and domestic pets into closer contact with infected wildlife.
• Increased movement of people and animals across international borders. In one case, a man who had contracted rabies in the Philippines was not diagnosed until he began to feel ill in the United Kingdom.
• Lack of advocacy about rabies.

Demographics

Cases of rabies in humans are very infrequent in the United States, averaging one or two a year (down from over 100 cases annually in 1900), but the worldwide incidence is estimated to be between 30,000 and 50,000 cases each year. These figures are based on data collected by the World Health Organization (WHO) in 1997 and updated in 2002. Rabies is most common in developing countries in Africa, Latin America, and Asia, particularly India. Dog bites are the major origin of infection for humans in developing countries, but other important host animals are the wolf, mongoose, and bat. Worldwide, the highest risk groups for contracting rabies are boys under the age of fifteen. Most deaths from rabies in the United States result from bat bites.

People whose work frequently brings them in contact with animals are also considered to be at higher risk than the general population. This group includes those in the fields of veterinary medicine, animal control, wildlife work, and laboratory work involving live rabies virus. People in these occupations and residents of or travelers to areas where rabies is a widespread problem should consider being immunized.

Causes and symptoms

Rabies is caused by a rod- or bullet-shaped virus that belongs to the family Rhabdoviridae. The virus is usually transmitted via an animal bite; however, cases have also been reported in which the virus penetrated the body through infected saliva, moist tissues such as the eyes or lips, a scratch on the skin, or the transplantation of infected tissues. Inhalation of the virus from the air, as might occur in a highly populated bat cave, is also thought to occur.

From the bite or other area of penetration, the virus multiplies as it spreads along nerves that travel away from the spinal cord and brain (efferent nerves) and into the salivary glands. The rabies virus may lie dormant in the body for several weeks or months, but rarely much longer, before symptoms appear. Initially, the area around the bite may burn and be painful. Early symptoms may also include a sore throat , low-grade fever, headaches, loss of appetite, nausea and vomiting , and diarrhea . Painful spasms develop in the muscles that control breathing and swallowing. The individual may begin to drool thick saliva and may have dilated or irregular pupils, increased tears and perspiration, and low blood pressure.

As the disease progresses, the patient becomes agitated and combative and may exhibit increased mental confusion. The affected person usually becomes sensitive to touch, loud noises, and bright lights. The victim also becomes extremely thirsty but is unable to drink because swallowing is painful. Some patients begin to dread water because of the painful spasms that occur. Other severe symptoms during the later stage of the disease are excessive salivation, dehydration , and loss of muscle tone. Death usually occurs three to 20 days after symptoms have developed. Recovery is very rare.

Diagnosis

After the onset of symptoms, blood tests and cerebrospinal fluid (CSF) analysis tests will be conducted. CSF will be collected during a procedure called a lumbar puncture in which a needle is used to withdraw a sample of CSF from the area around the spinal cord. The CSF tests do not confirm diagnosis but are useful in ruling out other potential causes for the patient's altered mental state.

The two most common diagnostic tests are the fluorescent antibody test and isolation of the rabies virus from an individual's saliva or throat culture . The fluorescent antibody test involves taking a small sample of skin (biopsy) from the back of the neck of the patient. If specific proteins, called antibodies, that are produced only in response to the rabies virus are present, they will bind with the fluorescent dye and become visible. Another diagnostic procedure involves taking a corneal impression in which a swab or slide is pressed lightly against the cornea of the eye to determine whether viral material is present.

Treatment

Because of the extremely serious nature of a rabies infection, the need for rabies immunizations should be carefully considered for anyone who has been bitten by an animal, based on a personal history and results of diagnostic tests.

If necessary, treatment includes the following:

• The wound is washed thoroughly with medicinal soap and water. Deep puncture wounds should be flushed with a catheter and soapy water. Unless absolutely necessary, a wound should not be sutured.
• Tetanus toxoid and antibiotics will usually be administered.
• Rabies vaccination may or not be given, based on the available information. If the individual was bitten by a domestic animal and the animal was captured, the animal will be placed under observation in quarantine for ten days. If the animal does not develop rabies within four to seven days, then no immunizations are required. If the animal is suspected of being rabid, it is killed, and the brain is examined for evidence of rabies infection. In cases involving bites from domestic animals in which the animal is not available for examination, the decision for vaccination is made based on the prevalence of rabies within the region where the bite occurred. If the bite was from a wild animal and the animal was captured, it is generally killed because the incubation period of rabies is unknown in most wild animals.
• If necessary, the patient is vaccinated immediately, generally through the administration of human rabies immune globulin (HRIG) for passive immunization, followed by human diploid cell vaccine (HDCV) or rabies vaccine adsorbed (RVA) for active immunization. Passive immunization is designed to provide the individual with antibodies from an already immunized individual, while active immunization involves stimulating the individual's own immune system to produce antibodies against the rabies virus. These rabies vaccines are equally effective and carry a lower risk of side effects than some earlier treatments. Unfortunately, however, in underdeveloped countries, these vaccines are usually not available. Antibodies are administered to the patient in a process called passive immunization. To do so, the HRIG vaccine is administered once, at the beginning of treatment. Half of the dose is given around the bite area, and the rest is given in the muscle. Inactivated viral material (antigenic) is then given to stimulate the patient's own immune system to produce antibodies against rabies. For active immunization, either the HDCV or RVA vaccine is given in a series of five injections. Immunizations are typically given on days 1, 3, 7, 14, and 28.

In those rare instances in which rabies has progressed beyond the point where immunization would be effective, the patient is given medication to prevent seizures, relieve some of the anxiety , and relieve painful muscle spasms. Pain relievers are also given. In the later stages, aggressive supportive care will be provided to maintain breathing and heart function. Survival is rare but can occur.

Prognosis

If preventative treatment is sought promptly, rabies need not be fatal. Immunization is almost always effective if started within two days of the bite. Chance of effectiveness declines, however, the longer vaccination is put off. It is, however, important to start immunizations, even if it has been weeks or months following a suspected rabid animal bite, because the vaccine can be effective even in these cases. If immunizations do not prove effective or are not received, rabies is nearly always fatal within a few days of the onset of symptoms.

Prevention

The following precautions should be observed in environments where humans and animals are likely to come into contact:

KEY TERMS

Active immunization —Treatment that provides immunity by challenging an individual's own immune system to produce antibody against a particular organism.

Antibody —A special protein made by the body's immune system as a defense against foreign material (bacteria, viruses, etc.) that enters the body. It is uniquely designed to attack and neutralize the specific antigen that triggered the immune response.

Biopsy —The surgical removal and microscopic examination of living tissue for diagnostic purposes or to follow the course of a disease. Most commonly the term refers to the collection and analysis of tissue from a suspected tumor to establish malignancy.

Efferent nerves —Peripheral nerves that carry signals away from the brain and spinal cord.

Fluorescent antibody test —A test in which a fluorescent dye is linked to an antibody for diagnostic purposes.

Lumbar puncture —A procedure in which the doctor inserts a small needle into the spinal cavity in the lower back to withdraw spinal fluid for testing. Also known as a spinal tap.

Passive immunization —Treatment that provides immunity through the transfer of antibodies obtained from an immune individual.

Rhabdovirus —A family of viruses named for their rod- or bullet-like shapes. The rabies virus is a rhabdovirus.

Vector —A carrier organism (such as a fly or mosquito) which serves to deliver a virus (or other agent of infection) to a host. Also refers to a retrovirus that had been modified and is used to introduce specific genes into the genome of an organism.

Zoonosis —Any disease of animals that can be transmitted to humans. Rabies is an example of a zoonosis.

• Domesticated animals, including household pets, should be vaccinated against rabies. If a pet is bitten by an animal suspected to have rabies, its owner should contact a veterinarian immediately and notify the local animal control authorities. Domestic pets with current vaccinations should be revaccinated immediately; unvaccinated dogs, cats, or ferrets are usually euthanized (killed).
• Wild animals should not be touched or petted, no matter how friendly they may appear. It is also important not to touch an animal that appears ill or passive or whose behavior seems odd, such as failing to show the normal fear of humans. These are all possible signs of rabies. Many animals, such as raccoons and skunks, are nocturnal and their activity during the day should be regarded as suspicious.
• People should not interfere in fights between animals.
• Because rabies is transmitted through saliva, a person should wear rubber gloves when handling a pet that has had an encounter with a wild animal.
• Garbage or pet food should not be left outside the house or camp site because it may attract wild or stray animals.
• Windows and doors should be screened. Some victims of rabies have been attacked by infected animals, particularly bats, that entered through unprotected openings.
• State or county health departments should be consulted for information about the prevalence of rabies in an area. Some areas, such as New York City, have been rabies-free, only to have the disease reintroduced at a later time.
• Preventative vaccination against rabies should be considered if one's occupation involves frequent contact with wild animals or non-immunized domestic animals.
• Bites from mice, rats, or squirrels rarely require rabies prevention because these rodents are typically killed by any encounter with a larger, rabid animal, and would, therefore, not be carriers.
• Travelers should ask about the prevalence of the disease in countries they plan to visit.

Parental concerns

Parents should speak with their children about the importance of avoiding contact with wild animals and reporting strange behavior in any animal, even a pet.

Resources

BOOKS

Adams, William G. "Rabies." In Nelson Textbook of Pediatrics. Edited by Richard E. Behrman et al. Philadelphia: Saunders, 2004.

Plotkin, Stanley A. "Rabies Virus." In Principles and Practice of Pediatric Infectious Diseases, 2nd ed. Edited by Sarah S. Long et al. St. Louis, MO: Elsevier, 2003.

PERIODICALS

Fooks, A. R., et al. "Risk Factors Associated with Travel to Rabies Endemic Countries." Journal of Applied Microbiology 94 Suppl. (2003): 31S–6S.

"Human Rabies—Iowa, 2002." Morbidity and Mortality Weekly Report 52 (January 24, 2003): 47–8.

Messenger, S. L., et al. "Emerging Pattern of Rabies Deaths and Increased Viral Infectivity." Emerging Infectious Diseases 9 (February 2003): 151–4.

National Association of State Public Health Veterinarians Inc. "Compendium of Animal Rabies Prevention and Control, 2003." Morbidity and Mortality Weekly Report Recommendations and Reports 52 (March 21, 2003): 1–6.

Smith, J., et al. "Case Report: Rapid Ante-Mortem Diagnosis of a Human Case of Rabies Imported into the UK from the Philippines." Journal of Medical Virology 69 (January 2003): 150–5.

Stringer, C. "Post-Exposure Rabies Vaccination." Nursing Standard 17 (February 5–11, 2003): 41–2.

Weiss, R. A. "Cross-Species Infections." Current Topics in Microbiology and Immunology 278 (2003): 47–71.

ORGANIZATIONS

American Veterinary Medical Association (AVMA). 1931 North Meacham Road, Suite 100, Schaumburg, IL 60173–4360. Web site: <www.avma.org>.

Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. Web site: <www.cdc.gov>.

WEB SITES

"Epidemiology [of rabies]." National Center for Infectious Diseases. Available online at <www.cdc.gov/ncidod/dvrd/rabies/Epidemiology/Epidemiology.htm> (accessed January 9, 2005).

Janet Byron Anderson Rebecca J. Frey, PhD Rosalyn Carson-DeWitt, MD

Rabies

From animal to man

Dogs, cats, raccoons, and bats

Rabies in humans

Resources

Rabies is a viral disease that is almost always fatal in humans and animals. The disease, which typically spreads to humans from animals through a scratch or a bite, causes inflammation of the brain. The disease is also called hydrophobia (meaning fear of water) because it causes painful muscle spasms in the throat that prevent swallowing. In fact, this is often what leads to fatalities in untreated cases: victims become dehydrated and die. Carriers of rabies include dogs, cats, bats, skunks, raccoons, and foxes; rodents are not likely to be infected. About 70% of rabies cases develop from wild animal bites that break the skin. Though a vaccine used first in 1885 is widely used, fatalities still occur due to rabies. Most fatalities take place in Africa and Asia, but some also occur in the United States. The cost of efforts to prevent rabies in the United States may be as high as $1 billion per year.

From animal to man

While many animal diseases cannot be passed from animal to man, rabies has long been known as an easy traveler from one species to the next. The disease was known among ancient people. The very name rabies, Latin for “rage” or “madness,” suggests the fear with which early men and women must have viewed the disease.

Rabies is described in medical writings dating from 300 BC, but the method of transmission or contagion was not recognized until 1804. In 1884, the French bacteriologist Louis Pasteur developed a preventive vaccine against rabies, and modifications of Pasteur’s methods are still used in rabies therapy today. The Pasteur program, or variations of it, has greatly reduced the fatalities in humans from rabies. Modern treatment (known as post-exposure prophylaxis, or PEP) following a bite by a rabid or presumed rabid animal consists of immediate and thorough cleansing of the wound and injection into the wound and elsewhere of immunoglobulin, along with five doses of rabies vaccine over a twenty-eight day period. With the widespread use of vaccine, rabies cases in the United States declined to fewer than five per year.

The transmission of rabies is almost invariably through the bite of an infected animal. The fact that the virus is eliminated in the saliva is of great significance, and unless saliva is introduced beneath the skin, the disease is seldom transmitted. The virus has been demonstrated in the saliva of dogs from three to eight days before the onset of symptoms. However, it has also been reported that only about 50–60% of the infected dogs shed the virus in the saliva. Rare cases of rabies have been reported where only clawing and scratching occurred, or where the skin was contaminated with saliva. The virus is most concentrated in the central nervous system and saliva, but it has also been demonstrated in various organs of the body and milk from infected animals.

In humans, the rabies virus, in addition to entering the body by the usual route through skin broken by a bite or scratch, can enter the body through intact mucous membranes, can be inhaled as an aerosol (rarely, this occurred in a bat cave) and can be transplanted in infected donor organs. Vertical transmission from mother to fetus and from lactating mother to suckling young has been described in nonhuman mammals.

The incubation period in natural cases of rabies is variable. In general, the greater the quantity of virus introduced into the wound is correlated with the length of incubation before symptoms occur. In dogs, the minimum period is ten days, the average is from 21 to 60 days, but may be as long as six months.

In humans, the incubation period is usually one to three months, with a minimum of ten days.

Rabies is caused by a number of different viruses that vary depending on geographic area and species. While the viruses are different, the disease they cause is singular in its course. The bullet-shaped virus is spread when it breaks through skin or has contact with a mucous membrane. The virus begins to reproduce itself initially in muscle cells near the place of first contact. At this point, within the first five days or so, treatment by vaccination has a high rate of success.

Once the rabies virus passes to the nervous system, immunization is no longer effective. The virus passes to the central nervous system, where it replicates itself in the system and moves to other tissues such as the heart, the lung, the liver, and the salivary glands. Symptoms appear when the virus reaches the spinal cord.

A bite from a rabid animal does not guarantee that one will get rabies; only about 50% of people who are bitten and do not receive treatment ever develop the disease. But it is best not to take any chances.

If one is bitten by or has had any exposure to an animal that may have rabies, medical intervention should be sought immediately. Any delay could diminish the treatment’s effectiveness.

In humans and in animals, rabies may be manifest in one of two forms: the furious (agitated) type or the paralytic (dumb) type. Furious rabies in animals, especially in the dog, is characterized by altered behavior such as restlessness, hiding, depraved appetite, excitement, unprovoked biting, aimless wandering, excessive salivation, altered voice, pharyngeal paralysis, staggering, general paralysis, and finally death. Death usually occurs within three to four days after the onset of symptoms. Animals with the paralytic form of rabies usually show a short period of excitement followed by uncoordination, ataxia, paralysis, dehydration, and death.

In humans, “furious” rabies patients typically show bizarre behavior, ranging from episodes of severe agitation to periods of depression. Confusion becomes more and more extreme as the disease progresses, and the patient can become very aggressive. Hydrophobia is always seen with this type of disease, until the patient becomes comatose. Inspiratory spasms also occur. This type of rabies is also characterized by hypersalivation, from 1 to 1.6 qt (1 to 1.5 l) of saliva in 24 hours, and excessive sweating.

The paralytic form of rabies in humans is often indistinguishable from that of most viral encephalitis, except for the fact that a patient suffering from rabies often remains conscious during most of the course of the disease. Paralysis usually begins at the extremity exposed to the bite and gradually involves other extremities finally affecting the pharyngeal and respiratory muscles.

Dogs, cats, raccoons, and bats

The dog is an important animal as a disseminator of rabies virus, not only to man but also to other animals. Wild carnivores may also be infected and transmit the disease. In the United States, foxes, skunks, bats, and raccoons are the most commonly involved. These animals are sometimes responsible for infecting domestic farm animals.

The disease in wildlife has become more prevalent in recent years, accounting for approximately 85% of all reported cases of animal rabies every year since 1976. Wildlife now constitute the most important potential source of infection for both human and domestic animals in the United States. Rabies among animals is present throughout the United States with the exception of Hawaii, which has remained consistently rabies-free. The likelihood of different animals contracting rabies varies from one location to the next. Dogs are a good example. In areas where public health efforts to control rabies have been aggressive, dogs make up less than 5% of rabies cases in animals. These areas include the United States, most European countries, and Canada.

However, dogs are the most common source of rabies in many countries. They make up at least 90% of reported cases of rabies in most developing countries of Africa and Asia (especially India) and many parts of Latin America. In these countries, public health efforts to control rabies have not been as aggressive. Other key carriers of rabies include the fox in Europe and Canada, the jackal in Africa, and the vampire bat in Latin America.

In the United States, 7,369 cases of rabies were reported in animals in 2000 and five cases were reported in humans. Over one third of all wildlife cases in 2000 were among raccoons. The high number of cases in raccoons reflects an animal epidemic, or, more properly, an epizootic. The epizootic began when diseased raccoons were carried from further south to Virginia and West Virginia. Since then, rabies in raccoons has spread up the eastern seaboard of the United States. Concentrations of animals with rabies include coyotes in southern Texas (although oral vaccines in bait have recently reduced the coyote disease rate), skunks in California and in Southern and North Central states, and gray foxes in southeastern Arizona. Bats throughout the United States also develop rabies. When rabies first enters a species, large numbers of animals die. When it has been around for a long time, the species adapts, and smaller numbers of animals die.

Rabies in humans

There are few deaths from rabies in the United States. Between 1980 and the middle of 1994, a total of 19 people in the United States died of rabies, far fewer than the 200 Americans killed by lightning, to give one example. Eight of these cases were acquired outside the United States. Eight of the 11 cases contracted in the United States stemmed from bat-transmitted strains of rabies.

Medical history was made in 2004, when 15-year-old Jeanna Giese from Fon-du-Lac, Wisconsin, became the first known human to survive rabies without receiving the vaccine treatment. Giese contracted rabies after she was bitten on the finger by a bat and did not seek PEP. When she developed tremors and trouble walking a little more than one month after the bat bite, physicians diagnosed rabies. After her condition quickly deteriorated, her parents consented to an experimental treatment involving administering antiviral drugs while she was put into a drug-induced coma. Giese survived, and with extensive rehabilitation, resumed her normal activities within a year. The experimental treatment protocol was later attempted in four other persons with rabies, but without success.

Internationally, more than 33,000 people die annually from rabies, according to the World Health Association. A great majority of cases internationally stem from dog bites. Different countries employ different strategies in the fight against rabies. The United States depends primarily on vaccination of domestic animals and on immunization following exposure to possibly rabid animals. Other countries employ a lengthy quarantine for all domestic animals entering the country.

Continental Europe, which has a long history of rabies, developed an aggressive program in the 1990s of airdropping a new vaccine for wild animals. The vaccine is mixed with pellets of food for red foxes, the

KEY TERMS

Central nervous system— The brain and spinal cord components of the nervous system that control the activities of internal organs, movements, perceptions, thoughts, and emotions.

Epizootic— The abnormally high occurrence of a specific disease in animals in a particular area, similar to a human epidemic.

Vaccine— A substance given to ward off an infection. Usually made of attenuated (weakened) or killed viruses or bacteria, the vaccine causes the body to produce antibodies against the disease.

Virus— Agent of infection which does not have its own metabolism and reproduces only in the living cells of other hosts. Viruses can live on bacteria, animals, or plants, and range in appearance from rod-shaped to tadpole-shaped, among other forms.

primary carrier there. Public health officials have announced that fox rabies was greatly reduced from Western Europe by the year 2000. In fact, Belgium, France, Luxembourg, and Switzerland are now considered free of rabies. The World Health Organization is also planning to use the vaccine in parts of Africa.

Though the United States has been largely successful in controlling rabies in humans, the disease remains present in the animal population, a constant reminder of the serious threat rabies could become without continuing successful prevention efforts.

Resources

BOOKS

Corey, Lawrence. “Rabies, Rhabdoviruses, and Marburg-Like Agents.” In Harrison’s Principles of Internal Medicine, vol. 1, edited by Dennis L. Kasper, et al. 16th ed. New York: McGraw-Hill Inc., 2004.

Jackson, Alan C. Rabies. New York: Academic Press, 2002.

PERIODICALS

Cross, M.L., et al. “The Potential for Oral Vaccines for Disease Control in Wildlife Species.” The Veterinary Journal. 172 (2006).

OTHER

National Association of State Public Health Veterinarians. “Compendium of Animal Rabies Prevention and Control, 2005.” MMWR 54 (March 18, 2005):1-8. <http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5403a1.htm> (accessed November 17, 2006).

Patricia Braus

Rabies

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

BIBLIOGRAPHY

Introduction

Rabies, from the Latin word rabies for mad, has long been one of the most-feared of diseases. It was described by the Greek philosopher Aristotle (384–322 BC) who realized that humans could contract rabies through being bitten by infected dogs, which is still the most common way the disease is transmitted. Rabies claims the lives of around 55,000 people around the world each year, mainly in rural parts of Africa and Asia.

Rabies is an acute viral illness which affects the brain and nervous system. Left untreated, it is invariably fatal. The symptoms are dramatic, including seizures, hallucinations, foaming at the mouth, and violent throat spasms. Rabies is a zoonosis—a disease of animals which can affect humans. Wild mammals are the reservoir of the rabies virus and they can, in turn, affect domestic animals like cats and dogs. Humans usually become infected through a bite from a wild or domestic animal with rabies. Fortunately, an effective vaccine against rabies is available and this can be used either before or after exposure to the virus.

Disease History, Characteristics, and Transmission

The rabies virus belongs to the rhabdovirus group and is a bullet-shaped enveloped RNA virus (that is, its genetic material is RNA, rather than DNA). The incubation period of the virus is between ten days and as long as one year. Early symptoms are vague and may resemble flu—and include fatigue, headache and nausea.

Once the rabies virus reaches the brain and nervous system, dramatic neurological symptoms set in. These include hallucinations, agitation, muscle spasm, paralysis, and seizures. Foaming at the mouth is a classic symptom of rabies and is a combination of increased salivation and difficulty in swallowing. The latter produces another classic symptom—hydrophobia, or fear of water, where extreme throat spasms may be induced by even the sight of water. Sometimes rabies dominated by agitation is known as furious rabies, while that dominated by paralysis is called dumb rabies.

Within days of the onset of symptoms, a person with rabies will enter a coma and death is usually by paralysis of the respiratory muscles. Survival is extremely rare— there have been only six documented cases and all of these individuals had been protected to some extent by vaccination before or after exposure to the rabies virus.

The rabies virus eventually passes through the nervous system to the salivary glands and it is the saliva of an infected animal which transmits the disease to other animals and to humans. Exposure to the rabies virus usually occurs from a bite by an infected animal, although the virus might also sometimes be transmitted through a scratch or lick from the animal. Infections have also occurred through inhaling aerosols from the droppings of infected bats.

Wild carnivorous mammals, including skunks, foxes, wolves, jackals, raccoons and coyotes, act as a reservoir for rabies virus. The infection may be passed to domestic animals—that is, dogs and cats. Humans can be infected by direct contact with either wild or domestic mammals. The former is sometimes known as sylvatic rabies, the latter as urban rabies. An animal with rabies virus will not be infectious all the time—only when the virus is in their saliva which can happen late on in the incubation period, because it has to pass from the muscle, where infection occurs, through the nervous system to the salivary glands.

Insectivorous and vampire bats can also transmit rabies. Rodents, such as rats, mice, and hamsters, and lagomorphs, such as rabbits and hares, hardly ever get infected with rabies and have never been shown to transmit it to humans. However, woodchucks and groundhogs were responsible for 86 per cent of 368 cases of rabies among rodents reported to the Centers for Disease Control and Prevention (CDC) between 1985 and 1994. Other herbivorous mammals including cattle, horses, and deer can become infected with rabies but very rarely infect humans.

Human to human transmission of rabies is rare, but not unknown. There have been eight cases recorded among recipients of transplanted corneas and three in recipients of solid transplanted organs. In theory, bites could also transmit rabies from one person to another, although no such cases are known. Casual contact, such as touching or contact with non-infectious fluids, does not carry a risk of infection with rabies virus.

Scope and Distribution

Rabies is a global problem which has been recognized for at least 3,000 years. At the turn of the twentieth century, there were over one hundred cases of rabies in the United States each year. Now that number is fewer than five. The disease is notifiable to the CDC and states also collect data on cases. According to a survey carried out by the World Health Organization (WHO) in 2004, there are around 55,000 deaths from rabies each year worldwide, most of them in rural Africa and Asia. Around half of all cases of rabies from dog bites occur among children under the age of 15.

WORDS TO KNOW

INCUBATION PERIOD: Incubation period refers to the time between exposure to disease causing virus or bacteria and the appearance of symptoms of the infection. Depending on the microorganism, the incubation time can range from a few hours (an example is food poisoning due to Salmonella) to a decade or more (an example is acquired immunodeficiency syndrome, or AIDS).

NOTIFIABLE: By law, occurrences of some diseases must be reported to government authorities when observed by health-care professionals. Such diseases are called notifiable diseases or reportable diseases. Cholera and yellow fever are examples of notifiable diseases.

RESERVOIR: The animal or organism in which the virus or parasite normally resides.

SYLVATIC: Sylvatic means pertaining to the woods and refers to diseases such as plague that are spread by animals such as ground squirrels and other wild rodents.

ZOONOSES: Zoonoses are diseases of microbiological origin that can be transmitted from animals to people. The causes of the diseases can be bacteria, viruses, parasites, and fungi.

There is marked geographical variation in the mammal species that pose a threat of rabies. In the United States, sylvatic rabies accounts for most cases and urban rabies is rare; the reverse is true in developing countries. Bats are the most common reservoirs of the disease in Latin America and the wolf in Eastern Europe.

Treatment and Prevention

There is no specific treatment for rabies once the symptoms have begun. A rabies vaccine was first developed by Louis Pasteur in the late 1880s. This was a crude preparation made from the dried spinal cord of infected rabbit. Similar vaccines are still in use in some countries, although WHO does not recommend them. Rabies vaccines made in cell culture are preferred for safety reasons.

Rabies vaccine can be given either before or after exposure to the virus. Pre-exposure vaccine should be given where a person's occupation brings them into contact with wild animals or with the virus itself—for instance, veterinarians, animal handlers, and certain laboratory workers. Travelers to regions where rabies is common and children living in these countries should also be vaccinated.

Post-exposure vaccination is needed if someone has been potentially exposed to rabies virus through an animal bite or other contact. Each year, over one million Americans receive an animal bite and these must always be taken seriously. But only a few of these will pose any risk of rabies infection, so each case must be carefully evaluated. An important part of this is having an expert examine the animal involved for symptoms and signs of rabies.

Vaccination of domestic animals against rabies plays an important role in keeping the disease at bay. Some European countries, such as France, Switzerland, and Belgium, have eliminated rabies in their wildlife through vaccination campaigns, and this is being tried in places where the disease is more common such as India and South Africa.

Impacts and Issues

In 2004, WHO was informed of a case of rabies in a dog owned by a resident of the city of Bordeaux, in France. Many people had handled this dog over a five-week period when the animal was potentially infectious. WHO had to put out a call for these individual to come forward for assessment and possible post-exposure vaccination. The dog had been imported illegally from Morocco and had not been vaccinated against rabies.

This incident shows the importance of taking animal import and quarantine regulations seriously. By flouting these on entry to France, the dog's owner put many people's lives at risk. Responsible owners get their pets vaccinated against rabies. And, when it comes to wildlife, it is best to admire from afar and never to handle or touch an animal that you do not know.

Wisconsin teenager Jeanna Giese became the first person known to have survived symptomatic rabies without vaccination. In September 2004, Giese contracted rabies after being bitten on the finger by a bat. One month after the bite, she was admitted to the hospital. Rabies was considered always fatal in unvaccinated patients, but physicians and Giese's family chose an experimental treatment. Physicians put Giese into a drug-induced coma for a week, at the same time giving her several strong antiviral drugs (amantadine and ribavirin). Giese's immune system fought the infection. She returned to school the following academic year after several months of recovery and intense physical therapy. Physicians and medical researchers continue to debate whether Giese survived because of the experimental treatment, or whether other factors, such as a stronger-than-average immune system or a weaker-thanaverage strain of rabies, played a larger role.

Following the Geise case, there was an increased focus on bats as potentials vectors of disease. Though bats are beneficial in controlling mosquito and insect populations, researchers estimate that 1% of bats in the United States carry rabies. Bats rarely bite humans and cause only minor injury at the location of the bite. It is possible for bites on sleeping victims to go undetected. In August 2006, over 1,000 young girls were advised to obtain rabies vaccinations after attending a Girl Scout camp where bats were present in sleeping quarters. Not all of families opted for vaccination, but none of the girls have developed rabies.

Cases of rabies are increasing, even in developed urban environment. In 2006, the Chinese government passed a law that forbid dogs in many in public places and limited dog ownership to one animal per household. Rabies is endemic in China, and is one of the nation's leading causes of death from infectious disease. However, officials cited the popularization of pet ownership and the failure of many pet owners to vaccinate dogs as primary causes for the resurgence of rabies, especially in the nation's cities.

LOUIS PASTEUR AND THE RABIES VACCINE

By 1880 French scientist Louis Pasteur (1822–1895) had shown that vaccination against anthrax worked in animals. He used a weakened, or attenuated, form of a culture of the anthrax bacterium as the vaccine and found it protected animals against the disease, compared to control animals that had not been vaccinated. In 1880, he decided to turn his attention to rabies a feared disease with a high mortality rate. Pasteur showed that a vaccine made from an attenuated form of the rabies virus could protect dogs that had been bitten by rabid animals. He hesitated, however, before trying his vaccine on humans.

Pasteur's first human patient was a young boy called Joseph Meister who was brought to him from Alsace on July 6, 1885. Joseph had been bitten fourteen times by a rabid dog on his hands, legs, and thighs. Clearly, his life was in danger and Pasteur administered the first dose of vaccine the next day. He used the dried-out spinal cord from a rabid rabbit as the source of vaccine. The drying process allowed the virus to lose much of its virulent character and helped allay safety fears. The boy was given increasingly strong doses of vaccine over the next twelve days and was soon able to return to Alsace in good health, having developed no symptoms of rabies, nor any ill effects from the vaccination.

The development of an effective rabies vaccine was the final, and most dramatic, success of Pasteur's long and distinguished career in medicine, chemistry, and microbiology. Pasteur's work on rabies led to the establishment of the now world-famous Pasteur Institute in Paris. The Institute was funded through public contributions and was initially devoted to rabies vaccination. Since its launch in 1888, the Institute has been home to many distinguished scientists, including several Nobel Prize winners.

See AlsoAnimal Importation; Zoonoses.

BIBLIOGRAPHY

Books

Wilson, Walter R. and Merle A. Sande. Current Diagnosis & Treatment in Infectious Diseases. New York: McGraw Hill, 2001.

Web Sites

Center for Diseases Control and Prevention (CDC) National Center for Infectious Diseases. “Rabies.” January 7, 2005 <http://www.cdc.gov/ncidod/dvrd/rabies> (accessed Apr 19, 2007).

World Health Organization. “Rabies.” <http://www.who.int/mediacentre/factsheets/fs099/en> (accessed April 19, 2007).

Susan Aldridge