Rabies is a viral disease that causes inflammation of the brain in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness. Once symptoms appear, the result is nearly always death. The time period between contracting the disease and the start of symptoms is usually one to three months, but can vary from less than one week to more than one year. The time depends on the distance the virus must travel along peripheral nerves to reach the central nervous system.
Rabies is caused by lyssaviruses, including the rabies virus and Australian bat lyssavirus. It is spread when an infected animal scratches or bites another animal or human. Saliva from an infected animal can also transmit rabies if the saliva comes into contact with the eyes, mouth, or nose. Globally, dogs are the most common animal involved. More than 99% of rabies cases in countries where dogs commonly have the disease are the direct result of dog bites. In the Americas, bat bites are the most common source of rabies infections in humans, and less than 5% of cases are from dogs. Rodents are very rarely infected with rabies. The disease can only be diagnosed after the start of symptoms.
Animal control and vaccination programs have decreased the risk of rabies from dogs in a number of regions of the world. Immunizing people before they are exposed is recommended for those at high risk, including those who work with bats or who spend prolonged periods in areas of the world where rabies is common. In people who have been exposed to rabies, the rabies vaccine and sometimes rabies immunoglobulin are effective in preventing the disease if the person receives the treatment before the start of rabies symptoms. Washing bites and scratches for 15 minutes with soap and water, povidone iodine, or detergent may reduce the number of viral particles and may be somewhat effective at preventing transmission. As of 2016, only fourteen people had survived a rabies infection after showing symptoms.
Rabies caused about 17,400 deaths worldwide in 2015. More than 95% of human deaths from rabies occur in Africa and Asia. About 40% of deaths occur in children under the age of 15. Rabies is present in more than 150 countries and on all continents but Antarctica. More than 3 billion people live in regions of the world where rabies occurs. A number of countries, including Australia and Japan, as well as much of Western Europe, do not have rabies among dogs. Many islands do not have rabies at all. It is classified as a neglected tropical disease.
|A dog with rabies in the paralytic (post-furious) stage|
|Symptoms||Fever, fear of water, confusion, excessive salivation, hallucinations, trouble sleeping, paralysis, coma|
|Causes||Rabies virus and Australian bat lyssavirus|
|Prevention||Rabies vaccine, animal control, rabies immunoglobulin|
|Prognosis||Nearly always death|
The period between infection and the first symptoms (incubation period) is typically 1–3 months in humans. Incubation periods as short as four days and longer than six years have been documented, depending on the location and severity of the contaminated wound and the amount of virus introduced. Initial signs and symptoms of rabies are often nonspecific such as fever and headache. As rabies progresses and causes inflammation of the brain and/or meninges, signs and symptoms can include slight or partial paralysis, anxiety, insomnia, confusion, agitation, abnormal behavior, paranoia, terror, and hallucinations, progressing to delirium, and coma. The person may also have hydrophobia. Death usually occurs 2 to 10 days after first symptoms. Survival is almost unknown once symptoms have presented, even with the administration of proper and intensive care.
Hydrophobia ("fear of water") is the historic name for rabies. It refers to a set of symptoms in the later stages of an infection in which the person has difficulty swallowing, shows panic when presented with liquids to drink, and cannot quench their thirst. Any mammal infected with the virus may demonstrate hydrophobia.
Saliva production is greatly increased, and attempts to drink, or even the intention or suggestion of drinking, may cause excruciatingly painful spasms of the muscles in the throat and larynx. This can be attributed to the fact that the virus multiplies and assimilates in the salivary glands of the infected animal with the effect of further transmission through biting. The ability to transmit the virus would decrease significantly if the infected individual could swallow saliva and water.
Hydrophobia is commonly associated with furious rabies, which affects 80% of rabies-infected people. The remaining 20% may experience a paralytic form of rabies that is marked by muscle weakness, loss of sensation, and paralysis; this form of rabies does not usually cause fear of water.
The rabies virus is the type species of the Lyssavirus genus, in the family Rhabdoviridae, order Mononegavirales. Lyssavirions have helical symmetry, with a length of about 180 nm and a cross-section of about 75 nm. These virions are enveloped and have a single-stranded RNA genome with negative sense. The genetic information is packed as a ribonucleoprotein complex in which RNA is tightly bound by the viral nucleoprotein. The RNA genome of the virus encodes five genes whose order is highly conserved: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and the viral RNA polymerase (L).
Once within a muscle or nerve cell, the virus undergoes replication. The trimeric spikes on the exterior of the membrane of the virus interact with a specific cell receptor, the most likely one being the acetylcholine receptor. The cellular membrane pinches in a procession known as pinocytosis and allows entry of the virus into the cell by way of an endosome. The virus then uses the acidic environment, which is necessary, of that endosome and binds to its membrane simultaneously, releasing its five proteins and single strand RNA into the cytoplasm.
The L protein then transcribes five mRNA strands and a positive strand of RNA all from the original negative strand RNA using free nucleotides in the cytoplasm. These five mRNA strands are then translated into their corresponding proteins (P, L, N, G and M proteins) at free ribosomes in the cytoplasm. Some proteins require post-translative modifications. For example, the G protein travels through the rough endoplasmic reticulum, where it undergoes further folding, and is then transported to the Golgi apparatus, where a sugar group is added to it (glycosylation).
Where there are enough proteins, the viral polymerase will begin to synthesize new negative strands of RNA from the template of the positive strand RNA. These negative strands will then form complexes with the N, P, L and M proteins and then travel to the inner membrane of the cell, where a G protein has embedded itself in the membrane. The G protein then coils around the N-P-L-M complex of proteins taking some of the host cell membrane with it, which will form the new outer envelope of the virus particle. The virus then buds from the cell.
From the point of entry, the virus is neurotropic, traveling along the neural pathways into the central nervous system. The virus usually first infects muscle cells close to the site of infection, where they are able to replicate without being 'noticed' by the host's immune system. Once enough virus has been replicated, they begin to bind to acetylcholine receptors (p75NR) at the neuromuscular junction. The virus then travels through the nerve cell axon via retrograde transport, as its P protein interacts with dynein, a protein present in the cytoplasm of nerve cells. Once the virus reaches the cell body it travels rapidly to the central nervous system (CNS), replicating in motor neurons and eventually reaching the brain. After the brain is infected, the virus travels centrifugally to the peripheral and autonomic nervous systems, eventually migrating to the salivary glands, where it is ready to be transmitted to the next host.:317
All warm-blooded species, including humans, may become infected with the rabies virus and develop symptoms. Birds were first artificially infected with rabies in 1884; however, infected birds are largely, if not wholly, asymptomatic, and recover. Other bird species have been known to develop rabies antibodies, a sign of infection, after feeding on rabies-infected mammals.
The virus has also adapted to grow in cells of cold-blooded vertebrates. Most animals can be infected by the virus and can transmit the disease to humans. Infected bats, monkeys, raccoons, foxes, skunks, cattle, wolves, coyotes, dogs, mongooses (normally either the small Asian mongoose or the yellow mongoose) and cats present the greatest risk to humans.
Rabies may also spread through exposure to infected bears, domestic farm animals, groundhogs, weasels, and other wild carnivorans. However, lagomorphs, such as hares and rabbits, and small rodents such as chipmunks, gerbils, guinea pigs, hamsters, mice, rats, and squirrels, are almost never found to be infected with rabies and are not known to transmit rabies to humans. 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. The Virginia opossum is resistant but not immune to rabies.
The virus is usually present in the nerves and saliva of a symptomatic rabid animal. The route of infection is usually, but not always, by a bite. In many cases, the infected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behavior. This is an example of a viral pathogen modifying the behavior of its host to facilitate its transmission to other hosts.
Transmission between humans is extremely rare. A few cases have been recorded through transplant surgery. The only well-documented cases of rabies caused by human-to-human transmission occurred among eight recipients of transplanted corneas and among three recipients of solid organs. In addition to transmission from cornea and organ transplants, bite and non-bite exposures inflicted by infected humans could theoretically transmit rabies, but no such cases have been documented, since infected humans are usually hospitalized and necessary precautions taken. Casual contact, such as touching a person with rabies or contact with non-infectious fluid or tissue (urine, blood, feces) does not constitute an exposure and does not require post-exposure prophylaxis. Additionally, as the virus is present in sperm or vaginal secretions, spread through sex may be possible.
After a typical human infection by bite, the virus enters the peripheral nervous system. It then travels along the afferent nerves toward 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. When the virus reaches the brain, it rapidly causes encephalitis, the prodromal phase, which is the beginning of the symptoms. Once the patient becomes symptomatic, treatment is almost never effective and mortality is over 99%. Rabies may also inflame the spinal cord, producing transverse myelitis.
Rabies can be difficult to diagnose, because, in the early stages, it is easily confused with other diseases or with aggressiveness. The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an immunohistochemistry procedure, which is recommended by the World Health Organization (WHO). The FAT relies on the ability of a detector molecule (usually fluorescein isothiocyanate) coupled with a rabies-specific antibody, forming a conjugate, to bind to and allow the visualisation of rabies antigen using fluorescent microscopy techniques. Microscopic analysis of samples is the only direct method that allows for the identification of rabies virus-specific antigen in a short time and at a reduced cost, irrespective of geographical origin and status of the host. It has to be regarded as the first step in diagnostic procedures for all laboratories. Autolysed samples can, however, reduce the sensitivity and specificity of the FAT. The RT PCR assays proved to be a sensitive and specific tool for routine diagnostic purposes, particularly in decomposed samples or archival specimens. The diagnosis can be reliably made from brain samples taken after death. The diagnosis can also be made from saliva, urine, and cerebrospinal fluid samples, but this is not as sensitive and reliable as brain samples. Cerebral inclusion bodies called Negri bodies are 100% diagnostic for rabies infection but are found in only about 80% of cases. If possible, the animal from which the bite was received should also be examined for rabies.
Some light microscopy techniques may also be used to diagnose rabies at a tenth of the cost of traditional fluorescence microscopy techniques, allowing identification of the disease in less-developed countries. A test for rabies, known as LN34, is easier to run on a dead animal's brain and might help determine who does and does not need post-exposure prevention. The test was developed by the CDC in 2018.
The differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis, in particular infection with viruses such as herpesviruses, enteroviruses, and arboviruses such as West Nile virus. The most important viruses to rule out are herpes simplex virus type one, varicella zoster virus, and (less commonly) enteroviruses, including coxsackieviruses, echoviruses, polioviruses, and human enteroviruses 68 to 71.
New causes of viral encephalitis are also possible, as was evidenced by the 1999 outbreak in Malaysia of 300 cases of encephalitis with a mortality rate of 40% caused by Nipah virus, a newly recognized paramyxovirus. Likewise, well-known viruses may be introduced into new locales, as is illustrated by the outbreak of encephalitis due to West Nile virus in the eastern United States. Epidemiologic factors, such as season, geographic location, and the patient's age, travel history, and possible exposure to bites, rodents, and ticks, may help direct the diagnosis.
Almost all human cases of rabies were fatal until a vaccine was developed in 1885 by Louis Pasteur and Émile Roux. Their original vaccine was harvested from infected rabbits, from which the virus in the nerve tissue was weakened by allowing it to dry for five to ten days. Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines.
The human diploid cell rabies vaccine was started in 1967. Less expensive purified chicken embryo cell vaccine and purified vero cell rabies vaccine are now available. A recombinant vaccine called V-RG has been used in Belgium, France, Germany, and the United States to prevent outbreaks of rabies in undomesticated animals. Immunization before exposure has been used in both human and nonhuman populations, where, as in many jurisdictions, domesticated animals are required to be vaccinated.
The Missouri Department of Health and Senior Services Communicable Disease Surveillance 2007 Annual Report states the following can help reduce the risk of contracting rabies:
In Asia and in parts of the Americas and 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, a practice that has successfully reduced rabies in rural areas of Canada, France, and the United States. In Montreal, Quebec, Canada, baits are successfully used on raccoons in the Mount-Royal Park area. Vaccination campaigns may be expensive, and cost-benefit analysis suggests baits may be a cost-effective method of control. In Ontario, a dramatic drop in rabies was recorded when an aerial bait-vaccination campaign was launched.
The number of recorded human deaths from rabies in the United States has dropped from 100 or more annually in the early 20th century to one or two per year due to widespread vaccination of domestic dogs and cats and the development of human vaccines and immunoglobulin treatments. Most deaths now result from bat bites, which may go unnoticed by the victim and hence untreated.
Treatment after exposure can prevent the disease if administered promptly, generally within 10 days of infection. Thoroughly washing the wound as soon as possible with soap and water for approximately five minutes is effective in reducing the number of viral particles. Povidone-iodine or alcohol is then recommended to reduce the virus further.
In the US, the Centers for Disease Control and Prevention recommends people receive one dose of human rabies immunoglobulin (HRIG) and four doses of rabies vaccine over a 14-day period. The immunoglobulin dose should not exceed 20 units per kilogram body weight. HRIG is expensive and constitutes most of the cost of post exposure treatment, ranging as high as several thousand dollars. As much as possible of this dose should be injected around the bites, with the remainder being given by deep intramuscular injection at a site distant from the vaccination site.
The first dose of rabies vaccine is given as soon as possible after exposure, with additional doses on days 3, 7 and 14 after the first. Patients who have previously received pre-exposure vaccination do not receive the immunoglobulin, only the postexposure vaccinations on days 0 and 3.
The pain and side effects of modern cell-based vaccines are similar to flu shots. The old nerve-tissue-based vaccinations that require multiple painful injections into the abdomen with a large needle are inexpensive, but are being phased out and replaced by affordable World Health Organization intradermal-vaccination regimens.
Intramuscular vaccination should be given into the deltoid, not the gluteal area, which has been associated with vaccination failure due to injection into fat rather than muscle. In infants, the lateral thigh is recommended.
Awakening to find a bat in the room, or finding a bat in the room of a previously unattended child or mentally disabled or intoxicated person, is an indication for post-exposure prophylaxis (PEP). The recommendation for the precautionary use of PEP in bat encounters where no contact is recognized has been questioned in the medical literature, based on a cost–benefit analysis. However, a 2002 study has supported the protocol of precautionary administering of PEP where a child or mentally compromised individual has been alone with a bat, especially in sleep areas, where a bite or exposure may occur without the victim being aware. Begun with little or no delay, PEP is 100% effective against rabies. In the case in which there has been a significant delay in administering PEP, the treatment should be administered regardless, as it may still be effective. Every year, more than 15 million people get vaccination after potential exposure. While this works well, the cost is significant.
The Milwaukee protocol, sometimes referred to as the Wisconsin protocol, is a method of attempted treatment of rabies infection in a human being. The treatment involves putting the person into a chemically induced coma and giving antiviral drugs. Jeanna Giese, who in 2004 was the first patient treated with the Milwaukee protocol, became the first person ever recorded to have survived rabies without receiving successful post-exposure prophylaxis. An intention-to-treat analysis has since found this protocol has a survival rate of about 8%. The protocol is not an effective treatment for rabies and its use is not recommended.
Vaccination after exposure, PEP, is highly successful in preventing the disease if administered promptly, in general within 6 days of infection. Begun with little or no delay, PEP is 100% effective against rabies. In the case of significant delay in administering PEP, the treatment still has a chance of success.
In 2010, an estimated 26,000 people died from rabies, down from 54,000 in 1990. The majority of the deaths occurred in Asia and Africa. As of 2015, India, followed by China (approximately 6,000), and the Democratic Republic of the Congo (5,600) had the most cases. A 2015 collaboration between the World Health Organization, World Organization of Animal Health (OIE), Food and Agriculture Organization of the United Nation (FAO), and Global Alliance for Rabies Control has a goal of eliminating deaths from rabies by 2030.
India has the highest rate of human rabies in the world, primarily because of stray dogs, whose number has greatly increased since a 2001 law forbade the killing of dogs. Effective control and treatment of rabies in India is hindered by a form of mass hysteria known as puppy pregnancy syndrome (PPS). Dog bite victims with PPS, male as well as female, become convinced that puppies are growing inside them, and often seek help from faith healers rather than medical services. An estimated 20,000 people die every year from rabies in India, more than a third of the global total.
The rabies virus survives in widespread, varied, rural animal reservoirs. Despite Australia's official rabies-free status, Australian bat lyssavirus (ABLV), discovered in 1996, is a strain of rabies prevalent in native bat populations. There have been three human cases of ABLV in Australia, all of them fatal.
While canine-specific rabies does not circulate among dogs, about a hundred dogs become infected from other wildlife per year in the US. Rabies is common among wild animals in the United States. Bats, raccoons, skunks and foxes account for almost all reported cases (98% in 2009). Rabid bats are found in all 48 contiguous states. Other reservoirs are more limited geographically; for example, the raccoon rabies virus variant is only found in a relatively narrow band along the East Coast. Due to a high public awareness of the virus, efforts at vaccination of domestic animals and curtailment of feral populations, and availability of postexposure prophylaxis, incidence of rabies in humans is very rare. A total of 49 cases of the disease was reported in the country between 1995 and 2011; of these, 11 are thought to have been acquired abroad. Almost all domestically acquired cases are attributed to bat bites.
Either no or very few cases of rabies are reported each year in Europe; cases are contracted both during travel and in Europe.
In Switzerland the disease was virtually eliminated after scientists placed chicken heads laced with live attenuated vaccine in the Swiss Alps. The foxes of Switzerland, proven to be the main source of rabies in the country, ate the chicken heads and immunized themselves.
Italy, after being declared rabies-free from 1997 to 2008, has witnessed a reemergence of the disease in wild animals in the Triveneto regions (Trentino-Alto Adige/Südtirol, Veneto and Friuli-Venezia Giulia), due to the spreading of an epidemic in the Balkans that also affected Austria. An extensive wild animal vaccination campaign eliminated the virus from Italy again, and it regained the rabies-free country status in 2013, the last reported case of rabies being reported in a red fox in early 2011.
Great Britain has been free of rabies since the beginning of the twentieth century except for a rabies-like virus in a few Daubenton's bats; there has been one, fatal, case of transmission to a human. There have been four deaths from rabies, transmitted abroad by dog bite, since 2000. The last infection in the UK occurred in 1922, and the last death from indigenous rabies was in 1902. Unlike the other countries of Europe it is protected by being an island, and by strict quarantine procedures.
Rabies has been known since around 2000 B.C. The first written record of rabies is in the Mesopotamian Codex of Eshnunna (circa 1930 BC), which dictates that the owner of a dog showing symptoms of rabies should take preventive measure against bites. If another person were bitten by a rabid dog and later died, the owner was heavily fined.
Ineffective folk remedies abounded in the medical literature of the ancient world. The physician Scribonius Largus prescribed a poultice of cloth and hyena skin; Antaeus recommended a preparation made from the skull of a hanged man.
Rabies appears to have originated in the Old World, the first epizootic in the New World occurring in Boston in 1768. It spread from there, over the next few years, to various other states, as well as to the French West Indies, eventually becoming common all across North America.
Rabies was considered a scourge for its prevalence in the 19th century. In France and Belgium, where Saint Hubert was venerated, the "St Hubert's Key" was heated and applied to cauterize the wound. By an application of magical thinking, dogs were branded with the key in hopes of protecting them from rabies. The fear of rabies was almost irrational, due to the number of vectors (mostly rabid dogs) and the absence of any efficacious treatment. It was not uncommon for a person bitten by a dog merely suspected of being rabid to commit suicide or to be killed by others.
In ancient times the attachment of the tongue (the lingual frenulum, a mucous membrane) was cut and removed as this was where rabies was thought to originate. This practice ceased with the discovery of the actual cause of rabies. Louis Pasteur's 1885 nerve tissue vaccine was successful, and was progressively improved to reduce often severe side-effects.
In modern times, the fear of rabies has not diminished, and the disease and its symptoms, particularly agitation, have served as an inspiration for several works of zombie or similarly-themed fiction, often portraying rabies as having mutated into a stronger virus which fills humans with murderous rage or incurable illness, bringing about a devastating, widespread pandemic.
The Milwaukee protocol was developed and named by Rodney Willoughby, Jr., following its use in the treatment of Jeanna Giese. Giese, a teenager from Wisconsin, became the first patient known to have survived rabies without receiving the rabies vaccine. It is unclear precisely why Giese survived, but her case led to sustained and heavy advocacy for the Milwaukee protocol. Subsequent medical research determined that the Milwaukee protocol is not an effective treatment for rabies infection, and its use is not recommended.
The term is derived from the Latin rabies, "madness". This, in turn, may be related to the Sanskrit rabhas, "to rage". The Greeks derived the word lyssa, from lud or "violent"; this root is used in the genus name of the rabies virus, Lyssavirus.
Rabies is infectious to mammals; three stages of central nervous system infection are recognized. The first stage is a one- to three-day period characterized by behavioral changes and is known as the prodromal stage. The second is the excitative stage, which lasts three to four days. This stage is often known as "furious rabies" for the tendency of the affected animal to be hyper-reactive to external stimuli and bite at anything near. The third is the paralytic stage and is caused by damage to motor neurons. Incoordination is seen, owing 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.
The outer shell of the rabies virus, stripped of its RNA contents and thus unable to cause disease, may be used as a vector for the delivery of unrelated genetic material in a research setting. It has the advantage over other pseudotyping methods for gene delivery that the cell targeting (tissue tropism) is more specific for the central nervous system, a difficult-to-reach site, obviating the need for invasive delivery methods. It is also capable of infecting neighboring "upstream" cells, moving from one cell to axons of the next at synapses, and is thus used for retrograde tracing in neuronal circuits.
India now has the highest rate of human rabies in the world.
"We don't want to misconstrue that rabies has been eliminated – dog rabies virus has been," CDC rabies expert Dr. Charles Rupprecht told Reuters in a telephone interview.
Australian bat lyssavirus (ABLV) (initially named pteropid lyssavirus PLV) is a zoonotic virus closely related to the rabies virus. It was first identified in a 5-month-old juvenile black flying fox (Pteropus alecto) collected near Ballina in northern New South Wales, Australia in January 1995 during a national surveillance program for the recently identified Hendra virus. ABLV is the seventh member of the genus Lyssavirus (which includes rabies virus) and the only Lyssavirus member present in Australia.Cujo
Cujo () is a 1981 psychological horror novel by American writer Stephen King, about a rabid dog. The novel won the British Fantasy Award in 1982, and was made into a film in 1983.Duvenhage lyssavirus
Duvenhage virus (DUVV) is a member of the genus Lyssavirus, which also contains the rabies virus. The virus was discovered in 1970, when a South African farmer (after whom the virus is named) died of a rabies-like encephalitic illness, after being bitten by a bat. In 2006, Duvenhage virus claimed a second victim, when a man was scratched by a bat in North West Province, South Africa, 80 km from the 1970 infection. He developed a rabies-like illness 27 days after the bat encounter, and died 14 days after the onset of illness. A 34-year-old woman who died in Amsterdam on December 8, 2007 was the third recorded fatality. She had been scratched on the nose by a small bat while travelling through Kenya in October 2007, and was admitted to hospital four weeks later with rabies-like symptoms.Microbats are believed to be the natural reservoir of Duvenhage virus. It has been isolated twice from insectivorous bats, in 1981 from Miniopterus schreibersi, and in 1986 from Nycteris thebaica, and the virus is closely related to another bat-associated lyssavirus endemic to Africa, Lagos bat virus.Free-ranging dog
A free-ranging dog is a dog that is not confined to a yard or house. Free-ranging dogs include street dogs, village dogs, stray dogs, and feral dogs. The global dog population is estimated to be 900 million, of which 83% are unrestrained.Fun Run
"Fun Run" is the first and second episode of the fourth season of the American comedy television series The Office, and the show's fifty-fourth and fifty-fifth episode overall. Written and directed by executive producer and showrunner Greg Daniels, the episode first aired on NBC in the United States on September 27, 2007.In the episode, Michael Scott (Steve Carell) believes the office is cursed after he accidentally hits Meredith Palmer (Kate Flannery) with his car. After being taken to the hospital, Meredith is found to have rabies. In an attempt to make amends with Meredith, Michael sponsors a fun run for rabies. Meanwhile, it is revealed that Jim Halpert (John Krasinski) and Pam Beesly (Jenna Fischer) are dating, while Angela Martin (Angela Kinsey) is mad at Dwight Schrute (Rainn Wilson) for killing her cat Sprinkles.
The episode received mixed reviews from the varying critics, while most praised the episode for Jim and Pam's relationship. However, critics had differing opinions when it came to how Michael behaved throughout the episode.Lagos bat lyssavirus
Lagos bat lyssavirus, formerly Lagos bat virus (LBV) is a Lyssavirus of southern and central Africa that causes a rabies-like illness in mammals. It was first isolated from a fruit bat (Eidolon helvum) from Lagos Island, Nigeria in 1956. Brain samples from the bat showed poor cross-reactivity to rabies antibodies but the virus was found to be closely related to the rabies virus. This was the first discovery of a rabies-related virus. Until this time, rabies was thought to have a single causal agent.
Lagos bat lyssavirus has been isolated from wild and domestic mammals in southern Africa including bats, cats and one dog. One isolate was detected in France in 1999 when a fruit bat (Rousettus egypticus), which had been displaying signs of aggression, died. The bat had been imported from Africa.No human cases of Lagos bat lyssavirus infection have been documented.Louis Pasteur
Louis Pasteur (, French: [lwi pastœʁ]; December 27, 1822 – September 28, 1895) was a French biologist, microbiologist and chemist renowned for his discoveries of the principles of vaccination, microbial fermentation and pasteurization. He is remembered for his remarkable breakthroughs in the causes and prevention of diseases, and his discoveries have saved many lives ever since. He reduced mortality from puerperal fever, and created the first vaccines for rabies and anthrax.
His medical discoveries provided direct support for the germ theory of disease and its application in clinical medicine. He is best known to the general public for his invention of the technique of treating milk and wine to stop bacterial contamination, a process now called pasteurization. He is regarded as one of the three main founders of bacteriology, together with Ferdinand Cohn and Robert Koch, and is popularly known as the "father of microbiology".Pasteur was responsible for disproving the doctrine of spontaneous generation. He performed experiments that showed that without contamination, microorganisms could not develop. Under the auspices of the French Academy of Sciences, he demonstrated that in sterilized and sealed flasks nothing ever developed, and in sterilized but open flasks microorganisms could grow. Although Pasteur was not the first to propose the germ theory, his experiments indicated its correctness and convinced most of Europe that it was true.
Today, he is often regarded as one of the fathers of germ theory. Pasteur made significant discoveries in chemistry, most notably on the molecular basis for the asymmetry of certain crystals and racemization. Early in his career, his investigation of tartaric acid resulted in the first resolution of what is now called optical isomers. His work led the way to the current understanding of a fundamental principle in the structure of organic compounds.
He was the director of the Pasteur Institute, established in 1887, until his death, and his body was interred in a vault beneath the institute. Although Pasteur made groundbreaking experiments, his reputation became associated with various controversies. Historical reassessment of his notebook revealed that he practiced deception to overcome his rivals.Lyssa
In Greek mythology, Lyssa (; Ancient Greek: Λύσσα Lússā), called Lytta (; Λύττα Lúttā) by the Athenians, was the spirit of mad rage, frenzy, and rabies in animals. She was closely related to the Maniae, the spirits of madness and insanity. Her Roman equivalent was variously named Ira, Furor, or Rabies. Sometimes she was multiplied into a host of Irae and Furores.Mokola lyssavirus
Mokola virus (MOKV) is a RNA virus related to rabies virus that has been sporadically isolated from mammals across sub-Saharan Africa. The majority of isolates have come from domestic cats exhibiting symptoms characteristically associated to rabies virus infection.There have been two reported cases of humans being infected with Mokola virus.Pet passport
The Pet Travel Scheme ("PETS") is a system which allows animals to travel easily between member countries without undergoing quarantine. A pet passport is a document that officially records information related to a specific animal, as part of that procedure. The effect is to drastically speed up and simplify travel with and transport of animals between member countries, compared to previous procedures, if the regulations are followed.Prevalence of rabies
Almost all human deaths caused by rabies occur in Asia and Africa. There are an estimated 55,000 human deaths annually from rabies worldwide.Dog licensing, euthanasia of stray dogs, muzzling, and other measures contributed to the elimination 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 combating rabies in many developed countries.
Rabies is a zoonotic disease, caused by the rabies virus. The rabies virus, a member of the Lyssavirus genus of the Rhabdoviridae family, survives in a diverse variety of animal species, including bats, monkeys, raccoons, foxes, skunks, wolves, coyotes, dogs, mongoose, weasels, cats, cattle, domestic farm animals, groundhogs, bears, and wild carnivores. However, dogs are the principal host in Asia, parts of America, and large parts of Africa. Mandatory vaccination of animals is less effective in rural areas, especially in developing countries where pets may be community property and their destruction unacceptable. Oral vaccines can be safely administered to wild animals through bait, a method initiated on a large scale in Belgium that has successfully reduced rabies in rural areas of Canada, France, the United States, and elsewhere. For example, in Montreal baits are successfully ingested by raccoons in the Mount Royal park area.Rabies (1958 film)
Rabies is a 1958 Swedish television drama film directed by Ingmar Bergman.Rabies in animals
Rabies is a viral zoonotic neuroinvasive disease which causes inflammation in the brain and is usually fatal. Rabies, caused by the rabies virus, primarily infects mammals. In the laboratory it has been found that birds can be infected, as well as cell cultures from birds, reptiles and insects. Animals with rabies suffer deterioration of the brain and tend to behave bizarrely and often aggressively, increasing the chances that they will bite another animal or a person and transmit the disease. Most cases of humans contracting the disease from infected animals are in developing nations. In 2010, an estimated 26,000 people died from rabies, down from 54,000 in 1990.Rabies vaccine
Rabies vaccine is a vaccine used to prevent rabies. There are a number of vaccines available that are both safe and effective. They can be used to prevent rabies before and for a period of time after exposure to the virus such as by a dog or bat bite. The immunity that develops is long lasting after a full course. Doses are usually given by injection into the skin or muscle. After exposure vaccination is typically used along with rabies immunoglobulin. It is recommended that those who are at high risk of exposure be vaccinated before potential exposure. Vaccines are effective in humans and other animals. Vaccinating dogs is very effective in preventing the spread of rabies to humans.Rabies vaccines may be safely used in all age groups. About 35 to 45 percent of people develop a brief period of redness and pain at the injection site. About 5 to 15 percent of people may have fever, headaches, or nausea. After exposure to rabies there is no contraindication to its use. Most vaccines do not contain thimerosal. Vaccines made from nerve tissue are used in a few countries, mainly in Asia and Latin America, but are less effective and have greater side effects. Their use is thus not recommended by the World Health Organization.The first rabies vaccine was introduced in 1885, and was followed by an improved version in 1908. Millions of people globally have been vaccinated and it is estimated that this saves more than 250,000 people a year. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is between 44 and 78 USD for a course of treatment as of 2014. In the United States a course of rabies vaccine is more than 750 USD.Rabies virus
Rabies lyssavirus, formerly Rabies virus, is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. Rabies lyssavirus, like many rhabdoviruses, has an extremely wide host range. In the wild it has been found infecting many mammalian species, while in the laboratory it has been found that birds can be infected, as well as cell cultures from mammals, birds, reptiles and insects.Rabies lyssavirus has a cylindrical morphology and is the type species of the Lyssavirus genus of the Rhabdoviridae family. These viruses are enveloped and have a single stranded RNA genome with negative-sense. The genetic information is packaged as a ribonucleoprotein complex in which RNA is tightly bound by the viral nucleoprotein. The RNA genome of the virus encodes five genes whose order is highly conserved. These genes code for nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and the viral RNA polymerase (L). The complete genome sequences range from 11,615 to 11,966 nt in length.All transcription and replication events take place in the cytoplasm inside a specialized “virus factory”, the Negri body (named after Adelchi Negri). These are 2–10 µm in diameter and are typical for a rabies infection and thus have been used as definite histological proof of such infection.Rhabdoviridae
The Rhabdoviridae are a family of viruses in the order Mononegavirales. Vertebrates (including mammals and humans), invertebrates, and plants serve as natural hosts. Currently, 18 genera are recognised. Diseases associated with viruses of this family include rabies encephalitis caused by rabies virus, and vesicular diseases and encephalitis flu-like symptoms in humans caused by vesiculoviruses. The name is derived from the Greek rhabdos, meaning rod, referring to the shape of the viral particles.Silver-haired bat
The silver-haired bat (Lasionycteris noctivagans) is a solitary migratory species of vesper bat in the family Vespertilionidae and the only member of the genus Lasionycteris.Vaccination of dogs
Programs supporting regular vaccination of dogs have contributed both to the health of dogs and to the public health. In countries where routine rabies vaccination of dogs is practiced, for example, rabies in humans is reduced to a very rare event.
Currently, there are geographically defined core vaccines and individually chosen non-core vaccine recommendations for dogs. A number of controversies surrounding adverse reactions to vaccines have resulted in authoritative bodies revising their guidelines as to the type, frequency, and methods/locations for dog vaccination.Zoonosis
Zoonoses (also known as zoonotic diseases) are infectious diseases caused by bacteria, viruses and parasites that spread between animals (usually vertebrates) and humans.Major modern diseases such as Ebola virus disease and salmonellosis are zoonoses. HIV was a zoonotic disease transmitted to humans in the early part of the 20th century, though it has now mutated to a separate human-only disease. Most strains of influenza that infect humans are human diseases, although many strains of swine and bird flu are zoonoses; these viruses occasionally recombine with human strains of the flu and can cause pandemics such as the 1918 Spanish flu or the 2009 swine flu. Taenia solium infection is one of the neglected tropical diseases with public health and veterinary concern in endemic regions. Zoonoses can be caused by a range of disease pathogens such as viruses, bacteria, fungi and parasites; of 1,415 pathogens known to infect humans, 61% were zoonotic. Most human diseases originated in animals; however, only diseases that routinely involve animal to human transmission, like rabies, are considered direct zoonosis.Zoonoses have different modes of transmission. In direct zoonosis the disease is directly transmitted from animals to humans through media such as air (influenza) or through bites and saliva (rabies). In contrast, transmission can also occur via an intermediate species (referred to as a vector), which carry the disease pathogen without getting infected. When humans infect animals, it is called reverse zoonosis or anthroponosis. The term is from Greek: ζῷον zoon "animal" and νόσος nosos "sickness".
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