Rabies
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| Rabies virus | ||||||||||
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| Rabies Classification and external resources | |
| ICD-10 | A82.- |
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| ICD-9 | 071 |
| DiseasesDB | 11148 |
| MedlinePlus | 001334 |
| eMedicine | med/1374 emerg/493 ped/1974 |
| MeSH | D011818 |
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US National Guidelines Clearinghouse on Rabies
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Related Key Words and Synonyms: Rabies virus infection
Overview
Rabies (Latin = rabies , "madness, rage, fury") is a viral zoonotic disease that causes acute encephalitis (inflammation of the brain) in mammals. In non-vaccinated humans, rabies is almost invariably fatal after neurological symptoms have developed, but prompt post-exposure vaccination may prevent the virus from progressing. There are only six known cases of a person surviving untreated rabies. [1]
Epidemiology and Demographics
The epidemiology of rabies addresses several questions: what animals have rabies and in what regions of the country, how many people get rabies and from what animals, and what are the best strategies for preventing rabies in people and animals. Epidemiologic information is often presented as statistical data (e.g., numbers or percentages in graphs and on maps). For example, in 2001, 7,437 cases of rabies were reported in the United States. Raccoons accounted for almost 40% of reported cases.
Rabies worldwide
Rabies is found on all continents except Antarctica. In certain areas of the world, canine rabies remains highly endemic, including (but not limited to) parts of Africa, Asia, and Central and South America (8,9). Table 4-14 lists countries that have reported no cases of rabies during the most recent period for which information is available (formerly referred to as “rabies-free countries”).
More than 99% of all human deaths from rabies occur in Africa, Asia, South America and India which report thirty thousand deaths annually.[1] One of the sources of recent flourishing of rabies in the East Asia is the pet boom. China introduced the "One-dog policy" in November 2006 to control the problem.[1]
The English Channel, dog licensing, killing of stray dogs, muzzling and other measures contributed to the eradication of rabies from the United Kingdom in the early 20th century. More recently, large-scale vaccination of cats, dogs and ferrets has been successful in combatting rabies in some developed countries.
The rabies virus survives in wide-spread, varied, rural fauna reservoirs. However, in Asia, parts of Latin America and large parts of Africa, dogs remain the principal host. Mandatory vaccination of animals is less effective in rural areas. Especially in developing countries, pets may not be privately kept and their destruction may be unacceptable. Oral vaccines can be safely distributed in baits, and this has successfully reduced rabies in rural areas of France, Ontario, Texas, Florida and elsewhere. Vaccination campaigns may be expensive, and a cost-benefit analysis can lead those responsible to opt for policies of containment rather than elimination of the disease.
Many territories, such as the United Kingdom, Ireland, Taiwan, Japan, Hawaii, Mauritius, Barbados and Guam, are free of rabies, although there may be a very low prevalence of rabies among bats in the UK; see below.
New Zealand and Australia have never had rabies.[3] However, in Australia, the Australian Bat Lyssavirus occurs normally in both insectivorous and fruit eating bats (flying foxes) from most mainland states. Scientists believe it is present in bat populations throughout the range of flying foxes in Australia.
Additional information can be obtained from the World Health Organization (http://www.who.int/rabies/rabnet/en/), the Pan American Health Organization (http://www.paho.org/english/ad/dpc/vp/rabia.htm), the Rabies Bulletin-Europe (http://www.rbe.fli.bund.de), the World Organization for Animal Health (http://www.oie.int/eng/en_index.htm), local health authorities of the country, the embassy, or the local consulate’s office in the United States. Lists are provided only as a guide, because up to date information may not be available, surveillance standards vary, and reporting status can change suddenly as a result of disease re-introduction or emergence.
Countries and political units reporting no indigenous cases of rabies during 2005:
Rabies in the United States
Rabies was once rare in the United States outside the Southern states, but raccoons in the mid-Atlantic and northeast United States have been suffering from a rabies epidemic since the 1970s, which is now moving westwards into Ohio.[1]
In the midwestern United States, skunks are the primary carriers of rabies, composing one hundred and thirty-four of the two hundred and thirty-seven documented non-human cases in 1996. The most widely distributed reservoir of rabies in the United States, however, and the source of most human cases in the U.S., are bats. Nineteen of the twenty-two human rabies cases documented in the United States between 1980 and 1997 have been identified genetically as bat rabies. In many cases, victims are not even aware of having been bitten by a bat, assuming that a small puncture wound found after the fact was the bite of an insect or spider; in some cases, no wound at all can be found, leading to the hypothesis that in some cases the virus can be contracted via inhaling airborne aerosols from the vicinity of bats. For instance, the Centers for Disease Control and Prevention warned on May 9, 1997, that a woman who died in October, 1996 in Cumberland County, Kentucky and a man who died in December, 1996 in Missoula County, Montana were both infected with a rabies strain found in silver-haired bats; although bats were found living in the chimney of the woman's home and near the man's place of employment, neither victim could remember having had any contact with them. This inability to recognize a potential infection, in contrast to a bite from a dog or raccoon, leads to a lack of proper prophylactic treatment, and is the cause of the high mortality rate for bat bites.
Rabies Prevalence in the United States
In this century, the number of human deaths in the United States attributed to rabies has declined from 100 or more each year to an average of 1 or 2 each year. Two programs have been responsible for this decline. First, animal control and vaccination programs begun in the 1940's have practically eliminated domestic dogs as reservoirs of rabies in the United States. Second, effective human rabies vaccines and immunolglobins have been developed . All human cases in the United States since 1990 are summarized in the Table of Human Rabies Cases from 1990- 2001.
- Virginia -1998
- California - 2000
- New York - 2000
- Georgia - 2000
- Minnesota - 2000
- Wisconsin - 2000
- California - 2001
- California - 2002
- Tennessee - 2002
- Iowa - 2002
- Virginia - 2003
United States Rabies Surveillance Data, 2001
Each year, scientists from the Centers for Disease Control and Prevention (CDC) collect information about cases of animal and human rabies from the state health departments and publish the information in a summary report. The most recent report, entitled "Rabies surveillance in the United States during 2001," contains the epidemiologic information on rabies during 2001. This report can be found in its entirety in Publications. Below is a brief summary of the surveillance information for 2000, including maps showing the distribution of rabies in the United States.
In 2001, 49 states, the District of Columbia, and Puerto Rico reported 7,437 cases of rabies in animals and no cases in humans to CDC (Hawaii is the only state that has never reported an indigenously acquired rabies case in humans or animals). The total number of reported cases increased by 0.92% from those reported in 2000 (7,369 cases).
Wild Animals
Wild animals accounted for 93% of reported cases of rabies in 2001. Raccoons continued to be the most frequently reported rabid wildlife species (37.2% of all animal cases during 2001), followed by skunks (30.7%), bats (17.2%), foxes (5.9%), and other wild animals, including rodents and lagomorphs (0.7%). Reported cases in raccoons and foxes decreased 0.4% and 3.5% respectively from the totals reported in 2000. Reported cases in skunks, and bats increased 2.6%, and 3.3% respectively from the totals reported in 2000.
Outbreaks of rabies infections in terrestrial mammals like raccoons, skunks, foxes, and coyotes are found in broad geographic regions across the United States. Geographic boundaries of currently recognized reservoirs for rabies in terrestrial mammals are shown on the map below.
Domestic Animals
Domestic species accounted for 6.8% of all rabid animals reported in the United States in 2001. The number of reported rabid domestic animals decreased 2.4% from the 509 cases reported in 2000 to 497 in 2001.
In 2001, cases of rabies in cats increased 8.4%, whereas those in dogs, cattle, horses, sheep and goats, and swine decreased 21.9%, 1.2%, 1.9% and 70.0% respectively compared with those reported in 2000. Rabies cases in cats continue to be more than twice as numerous as those in dogs or cattle. Pennsylvania reported the largest number of rabid domestic animals (46) for any state, followed by New York (43).
Successful vaccination programs that began in the 1940s caused a decline in dog rabies in this country. But, as the number of cases of rabies in dogs decreased, rabies in wild animals increased, as shown in the graph below.
Risk Factors
Risks for travelers:
Rabies vaccination is not a requirement for entry into any country. However, travelers to rabies-endemic countries should be warned about the risk of acquiring rabies and educated in animal bite prevention strategies (12-16). Travelers with extensive unprotected outdoor exposure such as might be experienced while bicycling, camping, hiking, or engaging in certain occupational activities, might be at higher risk even if their trip is brief. Also, children are considered at higher risk because of their tendencies to play with animals and to not report bites. Casual exposure to cave air is not a concern, but cavers should be warned not to handle bats (3).
Pathophysiology & Etiology
The rabies virus is a Lyssavirus. This genus of RNA viruses also includes the Aravan virus, Australian bat lyssavirus, Duvenhage virus, European bat lyssavirus 1, European bat lyssavirus 2, Irkut virus, Khujand virus, Lagos bat virus, Mokola virus and West Caucasian bat virus. Lyssaviruses have helical symmetry, so their infectious particles are approximately cylindrical in shape. This is typical of plant-infecting viruses; human-infecting viruses more commonly have cubic symmetry and take shapes approximating regular polyhedra. Negri bodies in the infected neurons are pathognomonic.
The virus has a bullet-like shape with a length of about 180 nm and a cross-sectional diameter of about 75 nm. One end is rounded or conical and the other end is planar or concave. The lipoprotein envelope carries knob-like spikes composed of Glycoprotein G. Spikes do not cover the planar end of the virion (virus particle). Beneath the envelope is the membrane or matrix (M) protein layer which may be invaginated at the planar end. The core of the virion consists of helically arranged ribonucleoprotein. The genome is unsegmented linear antisense RNA. Also present in the nucleocapsid are RNA dependent RNA transcriptase and some structural proteins.
Longitudinal and cross-sectional schematic view of rabies virus
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.
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 (see Figure, numbers 1 & 2), 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 (see Figure, number 3).
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 (see figure, number 4) 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 (see Figure, number 5). 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.
Natural History
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.
People have known about rabies for a long time, although the virus itself was not seen under the electron microscope until the 1960s. Rabies in animals was reported in early Babylonian, Greek, and Roman records. Rabies was likely brought to the Americas when settlers first came from Europe, bringing rabid animals with them.
A 9-year-old boy was the first person to have received an effective shot for rabies. In 1885, Joseph Meister was bitten by a rabid dog. His parents went to the famous French biologist Louis Pasteur. They begged him to help their son. Pasteur thought that if he injected a weak form of virus from one rabid animal into another, the second animal might be able to fight off the disease. He tried this hypothesis out on Joseph. The boy survived and lived a long life. That was how people starting giving shots for rabies.
After this success. other rabies vaccines were made. In the 1950s, people who had been bitten by a rabid animal got 23 shots along the abdomen. Today, the shots are more effective and less painful. They consist of a series of 6 shots given in the arm over a 1 month period. One shot is given around the bite and the rest are given in the arm.
Diagnosis
Several tests are necessary to diagnose rabies ante-mortem (before death) in humans; no single test is sufficient. Tests are performed on samples of saliva, serum, spinal fluid, and skin biopsies of hair follicles at the nape of the neck. Saliva can be tested by virus isolation or reverse transcription followed by polymerase chain reaction (RT-PCR). Serum and spinal fluid are tested for antibodies to rabies virus. Skin biopsy specimens are examined for rabies antigen in the cutaneous nerves at the base of hair follicles.
Histopathology: Brain, Rabies
Differential diagnosis
The differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis, particularly infection with viruses such as herpesviruses, enteroviruses, and arboviruses (e.g., West Nile virus). The most important viruses to rule out are herpes simplex virus type 1, varicella-zoster virus, and (less commonly) enteroviruses, including coxsackieviruses, echoviruses, polioviruses, and human enteroviruses 68 to 71. A specific diagnosis may be made by a variety of diagnostic techniques, including polymerase chain reaction (PCR) testing of cerebrospinal fluid, viral culture, and serology. In addition, consideration should be given to the local epidemiology of encephalitis caused by arboviruses belonging to several taxonomic groups, including eastern and western equine encephalitis viruses, St. Louis encephalitis virus, Powassan virus, the California encephalitis virus serogroup, and La Crosse virus.
New causes of viral encephalitis are also possible, as was evidenced by the recent outbreak in Malaysia of some 300 cases of encephalitis (mortality rate, 40%) caused by Nipah virus, a newly recognized paramyxovirus. Similarly, well-known viruses may be introduced into new locations, as is illustrated by the recent outbreak of encephalitis due to West Nile virus in the eastern United States. Epidemiologic factors (e.g., season, geographic location, and the patient’s age, travel history, and possible exposure to animal bites, rodents, and ticks) may help direct the diagnostic workup.
History and Symptoms
The virus is usually present in the nerves and saliva of a symptomatic rabid animal.[1][1] The route of infection is usually, but not necessarily, by a bite. In many cases the affected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behaviour[4]. Transmission may also occur via an aerosol through mucous membranes; transmission in this form may have happened in people exploring caves populated by rabid bats. Transmission between humans is extremely rare, although it can happen through transplant surgery (see below for recent cases), or, even more rarely, through bites or kisses.
After a typical human infection by bite, the virus directly or indirectly enters the peripheral nervous system. It then travels along the nerves towards the central nervous system. During this phase, the virus cannot be easily detected within the host, and vaccination may still confer cell-mediated immunity to prevent symptomatic rabies. Once the virus reaches the brain, it rapidly causes encephalitis and symptoms appear. It may also inflame the spinal cord producing myelitis.
The period between infection and the first flu-like symptoms is normally two to twelve weeks, but can be as long as two years. 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. The few humans who are known to have survived the disease were all left with severe brain damage, with the recent exception of Jeanna Giese (see below).
Treatment
Post-exposure prophylaxis
Treatment after exposure, known as post-exposure prophylaxis or "P.E.P.", is highly successful in preventing the disease if administered promptly, within fourteen days after infection. The first step is immediately washing the wound with soap and water, which is very effective at reducing the number of viral particles. In the United States, patients receive one dose of immunoglobulin and five doses of rabies vaccine over a twenty-eight day period. One-half the dose of immunoglobulin is injected in the region of the bite, if possible, with the remainder injected intramuscularly away from the bite. This is much less painful compared with administering immunoglobulin through the abdominal wall with a large needle, which is how it was done in the past. The first dose of rabies vaccine is given as soon as possible after exposure, with additional doses on days three, seven, fourteen, and twenty-eight after the first. Patients that have previously received pre-exposure vaccination do not receive the immunoglobulin, only the post-exposure vaccinations. Since the widespread vaccination of domestic dogs and cats and the development of effective human vaccines and immunoglobulin treatments, the number of recorded deaths in the U.S. from rabies has dropped from one hundred or more annually in the early twentieth century, to 1–2 per year, mostly caused by bat bites, which may go unnoticed by the victim and hence untreated.
P.E.P. is effective in treating rabies because the virus must travel from the site of infection through the peripheral nervous system (nerves in the body) before infecting the central nervous system (brain and spinal cord) and glands to cause lethal damage. This travel along the nerves is usually slow enough that vaccine and immunoglobulin can be administered to protect the brain and glands from infection. The amount of time this travel requires is dependent on how far the infected area is from the brain: if the victim is bitten in the face, for example, the time between initial infection and infection of the brain is very short and P.E.P. may not be successful.
Pre-exposure prophylaxis
Currently pre-exposure immunization has been used on domesticated and normal non-human populations. In many jurisdictions, domestic dogs, cats, and ferrets are required to be vaccinated. A pre-exposure vaccination is also available for humans, most commonly given to veterinarians and those traveling to regions where the disease is common, such as India. Most tourists do not need such a vaccination, just those doing substantial non-urban activities. However, should a vaccinated human be bitten by a carrier, failure to receive subsequent post-exposure treatment could be fatal, although post-exposure treatment for a vaccinated human is far less extensive than which would normally be required by one with no pre-exposure vaccination.
In 1984 researchers at the Wistar Institute developed a recombinant vaccine called V-RG by inserting the glycoprotein gene from rabies into a vaccinia virus.[1] The V-RG vaccine has since been commercialised by Merial under the trademark Raboral. It is harmless to humans and has been shown to be safe for various species of animals that might accidentally encounter it in the wild, including birds (gulls, hawks, and owls).[1]
V-RG has been successfully used in the field in Belgium, France, and the United States to prevent outbreaks of rabies in wildlife. The virus is stable under relatively high temperatures and can be delivered orally, making mass vaccination of wildlife possible by putting it in tasty baits. The plan for immunization of normal populations involves dropping bait containing food wrapped around a small dose of the live virus. The bait would be dropped by helicopter concentrating on areas that have not been infected yet. Just such a strategy of oral immunization of foxes in Europe has already achieved substantial reductions in the incidence of human rabies. A strategy of vaccinating "neighborhood dogs" in Jaipur, India, (combined with a sterilization program) has also resulted in a large reduction in the number of human cases.[1]
Induced coma treatment
In 2005, the case of Jeanna Giese, a girl of 15 who survived acute, unvaccinated rabies was reported, indicating the successful treatment of rabies through induction of a coma.[1] This treatment approach was based on the theory that rabies' detrimental effects were caused by temporary dysfunctions of the brain, and that the induction of a coma, by producing a temporary partial stop in brain function, would protect the brain from damage while the body built up an immune response to the virus. After thirty-one days of isolation and seventy-six days of hospitalisation, she was released from the hospital, having survived rabies. Later attempts to use the same treatment have failed.
The primary care physician in this case published in the April 2007 issue of Scientific American.[1] He notes that subsequent failures of what he calls the Milwaukee protocol did not use the cocktail of drugs used during the treatment. A point he makes for future research is the relationship of the virus to depletion of biopterin in the brain.
Prevention
There is no known cure for symptomatic rabies, but it can be prevented by vaccination, both in humans and other animals. Virtually every infection with rabies was a death sentence, until Louis Pasteur and Emile Roux developed the first rabies vaccination in 1885. This vaccine was first used on a human on July 6, 1885 – nine-year old boy Joseph Meister (1876–1940) had been mauled by a rabid dog.[5] [6]
Their vaccine consisted of a sample of the virus harvested from infected (and necessarily dead) rabbits, which was weakened by allowing it to dry. Similar nerve tissue-derived vaccines are still used now in some countries, and while they are much cheaper than modern cell culture vaccines, they are not as effective and carry a certain risk of neurological complications.
The human diploid cell rabies vaccine (H.D.C.V.) was started in 1967. Human diploid cell rabies vaccines are made using the attenuated Pitman-Moore L503 strain of the virus. Human diploid cell rabies vaccines have been given to more than 1.5 million humans as of 2006. Newer and less expensive purified chicken embryo cell vaccine, and purified Vero cell rabies vaccine are now available. The purified Vero cell rabies vaccine uses the attenuated Wistar strain of the rabies virus, and uses the Vero cell line as its host.
Primary Prevention
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 for 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.
Secondary Prevention
Prevention for travelers:
Pre-exposure vaccination with human diploid cell Rabies vaccine (HDCV), or purified chick embryo cell (PCEC) vaccine, may be recommended for international travelers based on the local incidence of rabies in the country to be visited, the availability of appropriate antirabies biologicals, and the intended activity and duration of stay of the traveler. Different schedules, alternative routes of administration, and other rabies vaccines besides HDCV and PCEC may be found abroad. Pre-exposure vaccination may be recommended for veterinarians, animal handlers, field biologists, spelunkers, missionaries, and certain laboratory workers. Pre-exposure vaccination does not eliminate the need for additional medical attention after a rabies exposure but simplifies postexposure prophylaxis in populations at risk by eliminating the need for rabies immune globulin (RIG) and by decreasing the number of doses of vaccine required. Pre-exposure vaccination is of particular importance for travelers at risk of exposure to rabies in countries where biologicals are in short supply and locally available rabies vaccines might carry a higher risk of adverse reactions. Pre-exposure vaccination may also provide some degree of protection when there is an unapparent or unrecognized exposure to rabies and when postexposure prophylaxis might be delayed. Planning is needed to ensure compliance in completion of the three pre-exposure vaccine doses, prior to commencing travel.
Travelers should be advised that any animal bite or scratch should receive prompt local treatment by thorough cleansing of the wound with copious amounts of soap and water (and povidone iodine, if available). This local treatment will substantially reduce the risk of rabies. Travelers who might have been exposed to rabies should be advised to always contact local health authorities immediately for advice about postexposure prophylaxis and should also contact their personal physician or state health department as soon as possible thereafter.
Equine rabies immune globulin (ERIG), or purified fractions of ERIG, has been used effectively in some developing countries where human rabies immune globulin (RIG) might not be available. If necessary, such heterologous products are preferable to no RIG administration in human rabies postexposure prophylaxis. The incidence of adverse reactions after the use of these products has been low (0.8%-6.0%), and most of those reactions were minor. However, such products are neither evaluated by U.S. standards nor regulated by the U.S. Food and Drug Administration, and their use cannot be unequivocally recommended at this time. In addition, unpurified antirabies serum of equine origin might still be used in some countries where neither human RIG nor ERIG is available. The use of this antirabies serum is associated with higher rates of serious adverse reactions, including anaphylaxis.
Adverse reactions
Travelers should be advised that they may experience local reactions after vaccination, such as pain, erythema, swelling, or itching at the injection site, or mild systemic reactions, such as headache, nausea, abdominal pain, muscle aches, and dizziness. Approximately 6% of persons receiving booster vaccinations with HDCV may experience an immune complex-like reaction characterized by urticaria, pruritus, and malaise. Once initiated, rabies postexposure prophylaxis should not be interrupted or discontinued because of local or mild systemic reactions to rabies vaccine.
Recently publicized cases
Transmission by bite
Several recently publicized cases have stemmed from bats, which are known to be a vector for rabies. See the Rabies and bats section below.
In October 2004 a female brown bear killed one human and injured several others near the city of Braşov in Central Romania. The bear was killed by human hunters and diagnosed with rabies. More than one hundred humans were vaccinated afterwards.
Transmission through organ transplants
Rabies is known to have been transmitted between humans by transplant surgery.
Infections by corneal transplant have been reported in Thailand (2 cases), India (2 cases), Iran (2 cases),[1] the United States (1 case), and France (1 case).[1] Details of two further cases of infection resulting from corneal transplants were described in 1996.
In June 2004, three organ recipients died in the United States from rabies transmitted in the transplanted kidneys and liver of an infected donor from Texarkana.[1] There were bats near the donor's home, and the donor had told others that he had been bitten.[1] The donor is now reported to have died of a cerebral hemorrhage, the culmination of an unidentified neurological disorder, although recipients are said to have been told the cause of death had been a car crash. Marijuana and cocaine were found in the donor's urine at the time of his death, according to a report in The New England Journal of Medicine.[1]
"[The surgeons] thought he had suffered a fatal crack-cocaine overdose, which can produce symptoms similar to those of rabies. 'We had an explanation for his condition,' says Dr. Goran Klintmalm, a surgeon who oversees transplantation at Baylor University Medical Center, where the transplants occurred. 'He'd recently smoked crack cocaine. He'd hemorrhaged around the brain. He'd died. That was all we needed to know'. Because of doctor-patient confidentiality rules, doctors involved with this case would not talk about it on the record, but a few did say that if no cocaine was found in the donor's blood, the E.R. doctors might have investigated his symptoms more aggressively instead of assuming he had overdosed. (Because no autopsy was done, doctors have not been able to establish whether the rabies or the drugs actually killed him.)"[1]
In February 2005, three German patients in Mainz and Heidelberg were diagnosed with rabies after receiving various organs and cornea transplants from a female donor. Two of the infected people died. Three other patients who received organs from the woman have not yet shown rabies symptoms. The 26 year old donor had died of heart failure in December 2004 after consuming cocaine and ecstasy. In October 2004, she had visited India, one of the countries worst affected by rabies worldwide. Dozens of medical staff were vaccinated against rabies in the two hospitals as a precautionary measure.
Associated Press reports that "Donated organs are never tested for rabies. The strain detected in the victims' bodies is one commonly found in bats, health officials said." According to CNN "Rabies tests are not routine donor screening tests, Virginia McBride, public health organ donation specialist with the Health Resources and Services Administration, said. The number of tests is limited because doctors have only about six hours from the time a patient is declared brain-dead until the transplantation must begin for the organs to maintain viability."
Transport of pet animals between countries
Rabies is endemic to many parts of the world, and one of the reasons given for quarantine periods in international animal transport has been to try to keep the disease out of uninfected regions. However, most developed countries, pioneered by Sweden, now allow unencumbered travel between their territories for pet animals that have demonstrated an adequate immune response to rabies vaccination.
Such countries may limit movement to animals from countries where rabies is considered to be under control in pet animals. There are various lists of such countries. The United Kingdom has developed a list, and France has a rather different list, said to be based on a list of the Office International des Epizooties (OIE). The European Union has a harmonised list. No list of rabies-free countries is readily available from OIE.
However, the recent spread of rabies in the northeastern United States and further may cause a restrengthening of precautions against movement of possibly rabid animals between countries.
Rabies and dogs
Rabies has a long history of association with dogs. The first written record of rabies is in the Codex of Eshnunna (ca. 1930 BC) (written prior to the Code of Hammurabi), which dictates that the owner of a dog showing symptoms of rabies should take preventative measure against bites. If a person is bitten by a rabid dog and later died, the owner was fined heavily.[1]
Three stages of rabies are recognized in dogs. The first stage is a one to three day period characterized by behavioral changes and is known as the prodromal stage. The second stage is the excitative stage, which lasts three to four days. It is this stage that is often known as furious rabies due to the tendency of the affected dog to be hyperreactive to external stimuli and bite at anything near. The third stage is the paralytic stage and is caused by damage to motor neurons. Incoordination is seen due to rear limb paralysis and drooling and difficulty swallowing is caused by paralysis of facial and throat muscles. Death is usually caused by respiratory arrest.[1]
Rabies and opossums
Experimental studies of rabies infection in the Virginia opossum have shown the importance of the mode of transmission. Opossums became infected when exposed to air-borne virus but were found to be fairly resistant to intramuscular inoculations [1][1][1].The aerosol transmission of rabies in opossum was investigated following the death from rabies of two men who had visited the Frio Caves, Texas, and did not remember any direct contact with bats.
The spatial and temporal distribution of opossum rabies
Rabies cases in the Virginia opossum are spillover cases from other wildlife species such as bats,skunks and the raccoon epizootic in the eastern United States. Cases have been reported across the United States from California to New York [1][1][1]. In New York state, the Wadsworth Center lists laboratory confirmed cases in opossums 5 years out of 10 from 1989 to 1998.
Rabies and domestic skunks in the United States
There is currently no USDA-approved vaccine for the strain of rabies that afflicts skunks. When cases are reported of pet skunks biting a human, the animals are frequently killed in order to be tested for rabies. or Humans exposed to the rabies virus must begin post-exposure prophylaxis before the disease can progress to the central nervous system. For this reason, it is necessary to determine whether the animal, in fact, has rabies as quickly as possible. Without a definitive quarantine period in place for skunks, quarantining the animals is not advised as there is no way of knowing how long it may take the animal to show symptoms. Destruction of the skunk is recommended and the brain is then tested for presence of rabies virus.
Skunk owners have recently organized to campaign for USDA approval of both a vaccine and an officially recommended quarantine period for skunks in the United States.
Rabies and bats
The problem of bat-transmitted rabies is found over most of North and South America but was first closely studied in Trinidad in the West Indies which had a dreadful reputation for bat rabies, which took a significant toll of livestock and humans alike. In the 10 years from 1925 and 1935, 89 people and thousands of livestock had died from it - "the highest human mortality from rabies-infected bats thus far recorded anywhere.".[1]
In early 1931, Dr. H. Metivier, a Veterinary surgeon, established the connection between the bites of bats and paralytic rabies. In September 1931, Dr. J. L. Pawan, a Government Bacteriologist found Negri bodies in the brain of a bat with unusual habits. In 1934 the Trinidad and Tobago Government began a program of vampire bat control, shooting, netting, trapping and poisoning, while encouraging the screening off of livestock buildings and free vaccination programs for exposed livestock.
After the opening of the Trinidad Regional Virus Laboratory in 1953, basic research on bats and rabies progressed rapidly under the able direction of Arthur Greenhall, who demonstrated that at least 8 species of bats in Trinidad had been infected with rabies - particularly the Common Vampire Bat, Desmodus rotundus (which "will attack any warm blooded creature"), the rare White-winged Vampire Bat, Diaemus youngi, (which "appears to have a special preference for birds and goats"), as well as two abundant species of Fruit Bats: the Seba's Short-tailed Bat or Short-tailed Fruit Bat, Carollia perspicillata, which commonly roosts with Vampires, and the Jamaican Fruit Bat, Artibeus jamaicensis.[1]
Non-bite transmission of rabies to susceptible animals placed in bat-proof cages in a cave with bat colonies was demonstrated by Constantine in Frio Cave, Texas, as early as 1960.[1] In 1967, rabies virus was isolated from the air in the same cave,[1] presumably passed by the bats urinating, potentially forming a source for infection of other susceptible animals, and presenting a hazard to researchers and spelunkers. While the risks may be low, they are deserving of further study and monitoring.[1]
The United Kingdom, which has stringent regulations on the importation of animals, had also been believed to be entirely free from rabies until 1996 when a single Daubenton's bat was found to be infected with a rabies-like virus usually found only in bats – European Bat Lyssavirus 2 (EBL2). There were no more known cases in the British Isles until September 2002 when another Daubenton's bat tested positive for EBL2 in Lancashire. A bat conservationist who was bitten by the infected bat received post-exposure treatment and did not develop rabies.
Then in November 2002 David McRae, a Scottish bat conservationist from Guthrie, Angus who was believed to have been bitten by a bat, became the first human to contract rabies in the United Kingdom since 1902. He died from the disease on November 24 2002.
In November 2004, Jeanna Giese, a fifteen-year old girl from Fond du Lac, Wisconsin, became one of only six humans known to have survived rabies after the onset of symptoms, and the first known instance of a human surviving rabies without vaccine treatment. Giese's disease was already too far progressed for the vaccine to help, and she was considered too weak to tolerate it. Doctors at the Children's Hospital of Wisconsin in Wauwatosa a suburb of Milwaukee, Wisconsin, achieved her survival with an experimental treatment that involved putting the girl into a drug-induced coma, and administering a cocktail of antiviral drugs. Giese had symptoms of full-blown rabies when she sought medical help, thirty-seven days after being bitten by a bat. Her family did not seek treatment at the time because the bat seemed healthy. Jeanna regained her weight, strength, and coordination while in the hospital. She was released from the Children's Hospital of Wisconsin on January 1, 2005.
On May 12, 2006 Harris County Texas. U.S.A. Health Department officials reported that a teenage boy, Zachary Jones of Humble, Texas, had died of rabies at Texas Children's Hospital in Houston, Texas. Zachary had contracted the disease after a bat flew in his bedroom and bit him in his sleep. He was unaware he had been bitten and was not hospitalized until he developed symptoms several weeks later. He died at Texas Children's Hospital after an attempt to cure the disease through a drug-induced coma, similar to that of Jeanna Giese.
On November 2, 2006 a 10 year old girl in Bourbon, Indiana, U.S.A. died of rabies. The Indianapolis Star reports that she was bitten by a bat in June 2006.
In August of 2006, a 73 year old rural resident located east of Edmonton, Alberta, Canada was bitten by a bat while he slept. He ignored the bite and became symptomatic in January 2007. Diagnosed with rabies in March of 2007, he was treated with the Milwaukee protocol, but died April 26, 2007.
On August 6, 2006, 950 Girl Scouts were urged to receive rabies shots by the Girl Scouts of America. The nine hundred and fifty girls had attended a camp in Virginia, U.S.A. in July, and had reported seeing bats in their cabins. Even though infections were relatively unlikely, the G.S.A. offered to pay for the shots, at a cost of nearly two million dollars. The Centers for Disease Control reports 27 cases of human rabies caused by the bat variant rabies virus in the United States from 1990 to 2002.[1]
See also
- Australian Bat Lyssavirus, a virus very similar to rabies that responds to rabies treatments.
- World Rabies Day
- Alliance for Rabies Control
Sources
Information on this page has been drawn from these CDC webpages:
- http://www.cdc.gov/ncidod/diseases/submenus/sub_rabies.htm
- http://www.cdc.gov/ncidod/dvrd/kidsrabies/
- http://www.cdc.gov/travel/diseases/rabies.htm
References
Further reading
- Waterman, James A. 1965. "The History of the Outbreak of Paralytic Rabies in Trinidad Transmitted by Bats to Human Beings and the Lower Animals from 1925." The Caribbean Medical Journal. 1954. Vol. XXVI, Nos. 1–4, pp. 164–169.
- Fleming, Theodore H. 2003. A Bat Man in the Tropics: Chasing El Duende. University of California Press. ISBN 0-520-23606-8.
Acknowledgements
The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.
External links
Sources
- Manbir Online
- CNN News report of CDC news release - July 1, 2004.
- Associated Press report: Families of rabies transplant victims react to deaths - July 3, 2004
- BBC News Europe Report: Romanian killer bear had rabies - 19 October, 2004.
- First Unvaccinated Rabies Survivor Goes Home - January 3, 2005
Other links
- Centers for Disease Control and Prevention
- World Health Organization factsheet on Rabies
- World Health Organization factsheet on Rabies vaccine
- Rules for importing pets to the United Kingdom
- A Rabies-Free World, Inc. - NPO dedicated to fighting rabies worldwide
- Kids4RabiesFreeWorld - RFW's site for kids & students
- Rules for importing pets to the European Union
- Rules for importing pets to the European Union Q&A
- Aspen Skunk Rabies Research
- "When Raccoons Attack" from Field & Stream Online
- "Only Known Unvaccinated Rabies Survivor Thrives" (USA Today) Progress report on the one known survivor of rabies
- "Filipino Child with Rabies" (metacafe.com) Disturbing video of a small child, exhibiting the advanced stages of rabies mentioned above