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, and 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.
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.
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 diseaseproducing organism.
Zoonosis—Any disease of animals that can be transmitted to humans. Rabies is an example of a zoonosis.
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 ofMedical 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.
Janet Byron Anderson
Rebecca J. Frey, PhD
