From Wikipedia the free encyclopedia
|A man with rabies, 1958|
|Symptoms||Fever, fear of water, confusion, excessive salivation, hallucinations, trouble sleeping, paralysis, coma|
|Causes||Rabies virus, Australian bat lyssavirus|
|Prevention||Rabies vaccine, animal control, rabies immunoglobulin|
|Prognosis||Nearly always death after onset of symptoms|
|Deaths||56,000 per year|
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: nausea, vomiting, 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 bites or scratches a human or other animal. 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. In countries where dogs commonly have the disease, more than 99% of rabies cases 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 be diagnosed only 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[update], only fourteen people had survived a rabies infection after showing symptoms.
Rabies causes about 56,000 deaths worldwide per year. 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 in the Asia-Pacific such as Australia, Japan and Singapore, as well as much of Western Europe, do not have rabies among dogs. Many Pacific islands do not have rabies at all. It is classified as a neglected tropical disease.
Signs and symptoms
The period between infection and the first symptoms (incubation period) is typically 1–3 months in humans. This period may be as short as four days or longer than six years, depending on the location and severity of the wound and the amount of virus introduced. Initial symptoms of rabies are often nonspecific such as fever and headache. As rabies progresses and causes inflammation of the brain and meninges, symptoms can include slight or partial paralysis, anxiety, insomnia, confusion, agitation, abnormal behavior, paranoia, terror, and hallucinations. The person may also have fear of water.
The symptoms eventually progress to delirium, and coma. Death usually occurs 2 to 10 days after first symptoms. Survival is almost unknown once symptoms have presented, even with intensive care.
Rabies has also occasionally been referred to as hydrophobia ("fear of water") throughout its history. 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. Since the infected individual cannot swallow saliva and water, the virus has a much higher chance of being transmitted, since it multiplies and accumulates in the salivary glands and is transmitted through biting. 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).
To enter cells, 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.
Once within a muscle or nerve cell, the virus undergoes replication. 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).
When there are enough viral 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 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. Worldwide, about 99% of human rabies cases come from domestic dogs. Other sources of rabies in humans include bats, monkeys, raccoons, foxes, skunks, cattle, wolves, coyotes, cats, and mongooses (normally either the small Asian mongoose or the yellow mongoose).
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 has a lower internal body temperature than the rabies virus prefers and therefore 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. After a typical human infection by bite, the virus enters the peripheral nervous system. It then travels retrograde along the efferent 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.
Although it is theoretically possible for rabies-infected humans to transmit it to others by biting or otherwise, no such cases have ever 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. But as the virus is present in sperm and vaginal secretions, it might be possible for rabies to spread through sex. There are only a handful of recorded cases of human-to-human transmission of rabies, and all occurred through organ transplants from infected donors.
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 or 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 exposure to rabies was 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:
- Vaccinating dogs, cats, and ferrets against rabies
- Keeping pets under supervision
- Not handling wild animals or strays
- Contacting an animal control officer upon observing a wild animal or a stray, especially if the animal is acting strangely
- If bitten by an animal, washing the wound with soap and water for 10 to 15 minutes and contacting a healthcare provider to determine if post-exposure prophylaxis is required
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 given within 10 days. The rabies vaccine is 100% effective if given early, and still has a chance of success if delivery is delayed. Every year, more than 15 million people get vaccinated after potential exposure. While this works well, the cost is significant. In the US it is recommended people receive one dose of human rabies immunoglobulin (HRIG) and four doses of rabies vaccine over a 14-day period. HRIG is expensive and makes up most of the cost of post exposure treatment, ranging as high as several thousand dollars.. In the UK, one dose of HRIG costs the National Health Service £1000 , although this is not flagged as a "high-cost medication". A full course of vaccine costs £120-£180 . As much as possible of HRIG should be injected around the bites, with the remainder being given by deep intramuscular injection at a site distant from the vaccination site.
People who have previously been vaccinated against rabies do not need to receive the immunoglobulin, only the postexposure vaccinations on days 0 and 3. The side effects of modern cell-based vaccines are similar to the side effects of flu shots. The old nerve-tissue-based vaccination required multiple injections into the abdomen with a large needle but is inexpensive. It is 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 children less than a year old, the lateral thigh is recommended. 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.
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 with the victim being unaware.
At least two treatment schemes have been proposed to treat rabies after the onset of disease, namely the Milwaukee Protocol and the Recife Protocol. The Milwaukee Protocol initially came into use in 2003, when it was tested on Jeanna Giese. Subsequently, the teenager from Wisconsin, USA became the first person known to have survived rabies without preventive treatments before symptom onset. The basic idea is to put a person into a chemically induced coma and to use antiviral medications to prevent fatal dysautonomia. However, the overall protocol is complex. The sixth version of the protocol last updated in 2018 consists of 17 pages with 22 steps of treatment, detailed monitoring and a timeline of expected complications. The Recife Protocol follows the same principle but differs in details like termination of sedation and supplementary medication. Some experts assessed the Milwaukee Protocol as an ineffective treatment with concerns related to the costs and ethics. Yet a study published in 2020 found 38 case reports for the Milwaukee Protocol and only one for the Recife Protocol with a total of 11 known survivors with varying sequelae.
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[update], 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.
Singapore has been completely rabies free for decades, with its last reported case in 1953. This has been attributed to strict quarantine laws including stringent checks on dogs, cats and wild animals imported into the country, as well as intensive control of feral animal populations. Such measures are regulated by the Agri-Food and Veterinary Authority of Singapore, a government statutory board.
Canine-specific rabies has been eradicated in the United States. But rabies is common among wild animals in the United States, and an average of 100 dogs become infected from other wildlife each year. 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 in the United States. From 1960 to 2018, a total of 125 human rabies cases were reported in the United States; 36 (28%) were attributed to dog bites during international travel. Among the 89 infections acquired in the United States, 62 (70%) were attributed to bats. No Americans have died from rabies since 2018, when a 55-year-old Utah man who had "extensive contact with bats" died from the disease.
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.
The United Kingdom has been free of rabies since the early 20th 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 bites, since 2000. The last infection in the UK occurred in 1922, and the last death from indigenous rabies was in 1902. Unlike many of the other countries of Europe it is protected by being an island, and by strict quarantine procedures.
Rabies has been known since around 2000 BC. 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 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.
- "Rabies Fact Sheet N°99". World Health Organization. July 2013. Archived from the original on 1 April 2014. Retrieved 28 February 2014.
- "Rabies - Symptoms and causes". Mayo Clinic. Retrieved 9 April 2018.
- "Rabies, Australian bat lyssavirus and other lyssaviruses". The Department of Health. December 2013. Archived from the original on 4 March 2014. Retrieved 1 March 2014.
- "Rabies". CDC. 29 July 2020. Retrieved 31 January 2021.
- "Rabies, Symptoms, Causes, Treatment". Medical News Today. 15 November 2017.
- "Rabies, Symptoms and causes". Mayo Clinic.
- "Animal bites and rabies". Johns Hopkins Medicine.
- Cotran RS, Kumar V, Fausto N (2005). Robbins and Cotran Pathologic Basis of Disease (7th ed.). Elsevier/Saunders. p. 1375. ISBN 978-0-7216-0187-8.
- Tintinalli JE (2010). Emergency Medicine: A Comprehensive Study Guide (Emergency Medicine (Tintinalli)). McGraw-Hill. pp. Chapter 152. ISBN 978-0-07-148480-0.
- Wunner WH (2010). Rabies: Scientific Basis of the Disease and Its Management. Academic Press. p. 556. ISBN 9780080550091.
- Hemachudha T, Ugolini G, Wacharapluesadee S, Sungkarat W, Shuangshoti S, Laothamatas J (May 2013). "Human rabies: neuropathogenesis, diagnosis, and management". The Lancet. Neurology. 12 (5): 498–513. doi:10.1016/s1474-4422(13)70038-3. PMID 23602163. S2CID 1798889.
- "UC Davis Children's Hospital patient becomes third person in U.S. to survive rabies". UC Davis Medical Center. Archived from the original on 21 May 2012. Retrieved 3 May 2012.
- Manoj S, Mukherjee A, Johri S, Kumar KV (2016). "Recovery from rabies, a universally fatal disease". Military Medical Research. 3 (1): 21. doi:10.1186/s40779-016-0089-y. PMC 4947331. PMID 27429788.
- "Rabies: The Facts" (PDF). World Health Organization. Archived (PDF) from the original on 24 February 2017. Retrieved 24 February 2017.
- WHO Expert Consultation on Rabies : second report (PDF) (2 ed.). Geneva: WHO. 2013. p. 3. ISBN 9789241209823. Archived (PDF) from the original on 20 October 2014.
- "Rabies-Free Countries and Political Units". CDC. Archived from the original on 5 March 2014. Retrieved 8 May 2019.
- "Neglected Tropical Diseases". cdc.gov. 6 June 2011. Archived from the original on 4 December 2014. Retrieved 28 November 2014.
- Giesen A, Gniel D, Malerczyk C (March 2015). "30 Years of rabies vaccination with Rabipur: a summary of clinical data and global experience". Expert Review of Vaccines (Review). 14 (3): 351–67. doi:10.1586/14760584.2015.1011134. PMID 25683583.
- Rupprecht CE, Willoughby R, Slate D (December 2006). "Current and future trends in the prevention, treatment and control of rabies". Expert Review of Anti-Infective Therapy. 4 (6): 1021–38. doi:10.1586/14787220.127.116.111. PMID 17181418. S2CID 36979186.
- Cliff AD, Haggett P, Smallman-Raynor M (2004). World atlas of epidemic diseases. London: Arnold. p. 51. ISBN 9780340761717.
- "Symptoms of rabies". NHS.uk. 12 June 2012. Archived from the original on 14 September 2014. Retrieved 3 September 2014.
- "Rabies". AnimalsWeCare.com. Archived from the original on 3 September 2014.
- van Thiel PP, de Bie RM, Eftimov F, Tepaske R, Zaaijer HL, van Doornum GJ, et al. (July 2009). "Fatal human rabies due to Duvenhage virus from a bat in Kenya: failure of treatment with coma-induction, ketamine, and antiviral drugs". PLOS Neglected Tropical Diseases. 3 (7): e428. doi:10.1371/journal.pntd.0000428. PMC 2710506. PMID 19636367.
- Drew WL (2004). "Chapter 41: Rabies". In Ryan KJ, Ray CG (eds.). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 597–600. ISBN 978-0-8385-8529-0.
- Finke S, Conzelmann KK (August 2005). "Replication strategies of rabies virus". Virus Research. 111 (2): 120–31. doi:10.1016/j.virusres.2005.04.004. PMID 15885837.
- "Rabies Post-Exposure Prophylaxis". Centers for Disease Control and Prevention (CDC). 23 December 2009. Archived from the original on 1 February 2010. Retrieved 30 January 2010.
- Gluska S, Zahavi EE, Chein M, Gradus T, Bauer A, Finke S, Perlson E (August 2014). "Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery". PLOS Pathogens. 10 (8): e1004348. doi:10.1371/journal.ppat.1004348. PMC 4148448. PMID 25165859.
- Baer G (1991). The Natural History of Rabies. CRC Press. ISBN 9780849367601. Retrieved 31 October 2011.
- Shannon LM, Poulton JL, Emmons RW, Woodie JD, Fowler ME (April 1988). "Serological survey for rabies antibodies in raptors from California". Journal of Wildlife Diseases. 24 (2): 264–7. doi:10.7589/0090-3558-24.2.264. PMID 3286906.
- Gough PM, Jorgenson RD (July 1976). "Rabies antibodies in sera of wild birds". Journal of Wildlife Diseases. 12 (3): 392–5. doi:10.7589/0090-3558-12.3.392. PMID 16498885.
- Jorgenson RD, Gough PM, Graham DL (July 1976). "Experimental rabies in a great horned owl". Journal of Wildlife Diseases. 12 (3): 444–7. doi:10.7589/0090-3558-12.3.444. PMID 16498892. S2CID 11374356.
- Wong D. "Rabies". Wong's Virology. Archived from the original on 3 December 2008. Retrieved 19 March 2009.
- Campbell JB, Charlton K (1988). Developments in Veterinary Virology: Rabies. Springer. p. 48. ISBN 978-0-89838-390-4.
- "Rabies". World Health Organization. 21 April 2020. Retrieved 3 May 2021.
- Pawan JL (1959). "The transmission of paralytic rabies in Trinidad by the vampire bat (Desmodus rotundus murinus Wagner". Caribbean Medical Journal. 21: 110–36. PMID 13858519.
- Pawan JL (1959). "Rabies in the vampire bat of Trinidad, with special reference to the clinical course and the latency of infection". Caribbean Medical Journal. 21: 137–56. PMID 14431118.
- Taylor PJ (December 1993). "A systematic and population genetic approach to the rabies problem in the yellow mongoose (Cynictis penicillata)". The Onderstepoort Journal of Veterinary Research. 60 (4): 379–87. PMID 7777324.
- "Rabies. Other Wild Animals: Terrestrial carnivores: raccoons, skunks and foxes". Centers for Disease Control and Prevention(CDC). Archived from the original on 20 December 2010. Retrieved 23 December 2010.
- Anderson J, Frey R (2006). "Rabies". In Fundukian LJ (ed.). Gale Encyclopedia of Medicine (3rd ed.).
- McRuer DL, Jones KD (May 2009). "Behavioral and nutritional aspects of the Virginian opossum (Didelphis virginiana)". The Veterinary Clinics of North America. Exotic Animal Practice. 12 (2): 217–36, viii. doi:10.1016/j.cvex.2009.01.007. PMID 19341950.
- The Merck Manual (11th ed.). 1983. p. 183.
- The Merck manual of Medical Information (Second Home ed.). 2003. p. 484.
- Turton J (2000). "Rabies: a killer disease". National Department of Agriculture. Archived from the original on 23 September 2006.
- Jackson AC, Wunner WH (2002). Rabies. Academic Press. p. 290. ISBN 978-0-12-379077-4. Archived from the original on 8 January 2014.
- Lynn DJ, Newton HB, Rae-Grant AD (2012). The 5-Minute Neurology Consult. Lippincott Williams & Wilkins. pp. 414–. ISBN 978-1-4511-0012-9.
- Davis LE, King MK, Schultz JL (15 June 2005). Fundamentals of neurologic disease. Demos Medical Publishing. p. 73. ISBN 978-1-888799-84-2. Archived from the original on 8 January 2014.
- RabiesAlliance.org Archived 24 September 2016 at the Wayback Machine
- Srinivasan A, Burton EC, Kuehnert MJ, Rupprecht C, Sutker WL, Ksiazek TG, et al. (March 2005). "Transmission of rabies virus from an organ donor to four transplant recipients". The New England Journal of Medicine. 352 (11): 1103–11. doi:10.1056/NEJMoa043018. PMID 15784663.
- "Human Rabies Prevention --- United States, 2008 Recommendations of the Advisory Committee on Immunization Practices". Centers for Disease Control and Prevention. 23 May 2008. Retrieved 11 February 2020.
- Kahn CM, Line S, eds. (2010). The Merck Veterinary Manual (10th ed.). Kendallville, Indiana: Courier Kendallville, Inc. p. 1193. ISBN 978-0-911910-93-3.
- Dean DJ, Abelseth MK (1973). "Ch. 6: The fluorescent antibody test". In Kaplan MM, Koprowski H (eds.). Laboratory techniques in rabies. Monograph series. 23 (3rd ed.). World Health Organization. p. 73. ISBN 9789241400237.
- Fooks AR, Johnson N, Freuling CM, Wakeley PR, Banyard AC, McElhinney LM, et al. (September 2009). "Emerging technologies for the detection of rabies virus: challenges and hopes in the 21st century". PLOS Neglected Tropical Diseases. 3 (9): e530. doi:10.1371/journal.pntd.0000530. PMC 2745658. PMID 19787037.
- Tordo N, Bourhy H, Sacramento D (1994). "Ch. 10: PCR technology for lyssavirus diagnosis". In Clewley JP (ed.). The Polymerase Chain Reaction (PCR) for Human Viral Diagnosis. CRC Press. pp. 125–145. ISBN 978-0-8493-4833-4.
- David D, Yakobson B, Rotenberg D, Dveres N, Davidson I, Stram Y (June 2002). "Rabies virus detection by RT-PCR in decomposed naturally infected brains". Veterinary Microbiology. 87 (2): 111–8. doi:10.1016/s0378-1135(02)00041-x. PMID 12034539.
- Biswal M, Ratho R, Mishra B (September 2007). "Usefulness of reverse transcriptase-polymerase chain reaction for detection of rabies RNA in archival samples". Japanese Journal of Infectious Diseases. 60 (5): 298–9. PMID 17881871.
- Ly S, Buchy P, Heng NY, Ong S, Chhor N, Bourhy H, Vong S (September 2009). Carabin H (ed.). "Rabies situation in Cambodia". PLOS Neglected Tropical Diseases. 3 (9): e511. doi:10.1371/journal.pntd.0000511. PMC 2731168. PMID 19907631. e511.
- Dürr S, Naïssengar S, Mindekem R, Diguimbye C, Niezgoda M, Kuzmin I, et al. (March 2008). Cleaveland S (ed.). "Rabies diagnosis for developing countries". PLOS Neglected Tropical Diseases. 2 (3): e206. doi:10.1371/journal.pntd.0000206. PMC 2268742. PMID 18365035. e206.
- "New Rapid Rabies Test Could Revolutionize Testing and Treatment | CDC Online Newsroom | CDC". www.cdc.gov. 16 May 2018. Retrieved 23 May 2018.
- "Rabies: Differential Diagnoses & Workup". eMedicine Infectious Diseases. 3 October 2008. Archived from the original on 28 November 2010. Retrieved 30 January 2010.
- Taylor DH, Straw BE, Zimmerman JL, D'Allaire S (2006). Diseases of swine. Oxford: Blackwell. pp. 463–5. ISBN 978-0-8138-1703-3. Retrieved 30 January 2010.
- Minagar A, Alexander JS (2005). Inflammatory Disorders Of The Nervous System: Pathogenesis, Immunology, and Clinical Management. Humana Press. ISBN 978-1-58829-424-1.
- Geison GL (April 1978). "Pasteur's work on rabies: reexamining the ethical issues". The Hastings Center Report. 8 (2): 26–33. doi:10.2307/3560403. JSTOR 3560403. PMID 348641.
- Srivastava AK, Sardana V, Prasad K, Behari M (March 2004). "Diagnostic dilemma in flaccid paralysis following anti-rabies vaccine". Neurology India. 52 (1): 132–3. PMID 15069272. Archived from the original on 2 August 2009.
- Reece JF, Chawla SK (September 2006). "Control of rabies in Jaipur, India, by the sterilisation and vaccination of neighbourhood dogs". The Veterinary Record. 159 (12): 379–83. doi:10.1136/vr.159.12.379. PMID 16980523. S2CID 5959305.
- "Compendium of Animal Rabies Prevention and Control" (PDF). National Association of State Public Health Veterinarians. 31 December 2007. Archived from the original (PDF) on 12 July 2010. Retrieved 3 January 2010.
- 2007 Annual Report (PDF) (Report). Bureau of Communicable Disease Control and Prevention. 2007.
- "World Rabies Day". World Health Organization (WHO). Archived from the original on 31 December 2011.
- Meltzer MI (October–December 1996). "Assessing the costs and benefits of an oral vaccine for raccoon rabies: a possible model". Emerging Infectious Diseases. 2 (4): 343–9. doi:10.3201/eid0204.960411. PMC 2639934. PMID 8969251.
- Grambo RL (1995). The World of the Fox. Vancouver: Greystone Books. pp. 94–5. ISBN 978-0-87156-377-4.
- "Rabies in the U.S." Centers for Disease Control and Prevention (CDC). 22 April 2011. Archived from the original on 31 December 2011. Retrieved 31 December 2011.
- Lite J (8 October 2008). "Medical Mystery: Only One Person Has Survived Rabies without Vaccine—But How?". Scientific American. Archived from the original on 5 November 2009. Retrieved 30 January 2010.
- "Human rabies: better coordination and emerging technology to improve access to vaccines". World Health Organization. Archived from the original on 24 February 2017. Retrieved 23 February 2017.
- "Use of a Reduced (4-Dose) Vaccine Schedule for Postexposure Prophylaxis to Prevent Human Rabies" Archived 25 July 2011 at the Wayback Machine. Centers for Disease Control and Prevention (CDC).
- "Cost of Rabies Prevention". 11 June 2019. Archived from the original on 29 March 2016.
- Park's textbook of Community medicine, 22nd edition, 2013, p 254.
- "Rabies". www.who.int. World Health Organization. Archived from the original on 15 February 2015. Retrieved 1 February 2015.
- "Rabies & Australian bat lyssavirus information sheet". Health.vic.gov.au. Archived from the original on 18 August 2011. Retrieved 30 January 2012.
- National Center for Disease Control (2014). "National Guidelines on Rabies Prophylaxis" (PDF). Archived from the original (PDF) on 5 September 2014. Retrieved 5 September 2014.
- De Serres G, Skowronski DM, Mimault P, Ouakki M, Maranda-Aubut R, Duval B (June 2009). "Bats in the bedroom, bats in the belfry: reanalysis of the rationale for rabies postexposure prophylaxis". Clinical Infectious Diseases. 48 (11): 1493–9. doi:10.1086/598998. PMID 19400689.
- Despond O, Tucci M, Decaluwe H, Grégoire MC, S Teitelbaum J, Turgeon N (March 2002). "Rabies in a nine-year-old child: The myth of the bite". The Canadian Journal of Infectious Diseases. 13 (2): 121–5. doi:10.1155/2002/475909. PMC 2094861. PMID 18159381.
- "Milwaukee Protocol, version 6 (updated November 2018)" (PDF).
- Ledesma, L. A.; Lemos, E. R.; Horta, M. A. (2020). "Comparing clinical protocols for the treatment of human rabies: the Milwaukee protocol and the Brazilian protocol (Recife)". Revista da Sociedade Brasileira de Medicina Tropical. 53: e20200352. doi:10.1590/0037-8682-0352-2020. PMC 7670764. PMID 33174958.
- "Rabies". World Health Organization (WHO). September 2011. Archived from the original on 31 December 2011. Retrieved 31 December 2011.
- Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. (December 2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. hdl:10536/DRO/DU:30050819. PMID 23245604. S2CID 1541253.
- Hampson K, Coudeville L, Lembo T, Sambo M, Kieffer A, Attlan M, et al. (April 2015). "Estimating the global burden of endemic canine rabies". PLOS Neglected Tropical Diseases. 9 (4): e0003709. doi:10.1371/journal.pntd.0003709. PMC 4400070. PMID 25881058.
- "Rabies". World Health Organization. Archived from the original on 15 February 2017. Retrieved 23 February 2017.
- Dugan E (30 April 2008). "Dead as a dodo? Why scientists fear for the future of the Asian vulture". The Independent. London. Archived from the original on 17 May 2008. Retrieved 11 October 2008.
India now has the highest rate of human rabies in the world.
- Harris G (6 August 2012). "Where Streets Are Thronged With Strays Baring Fangs". New York Times. Archived from the original on 8 August 2012. Retrieved 6 August 2012.
- Medicine challenges Indian superstition | Asia | DW.DE | 31.12.2012 Archived 31 January 2013 at the Wayback Machine
- "Essential rabies maps" Archived 17 February 2010 at the Wayback Machine. World Health Organization (WHO).
- "Rabies - National Centre for Infectious Diseases". www.ncid.sg. Retrieved 11 May 2021.
- "Rabies". www.nparks.gov.sg. Retrieved 11 May 2021.
- "CDC – Rabies Surveillance in the U.S.: Human Rabies – Rabies". www.cdc.gov. Archived from the original on 18 January 2017. Retrieved 10 April 2017.
- Fox M (7 September 2007). "U.S. free of canine rabies virus". Reuters. Archived from the original on 17 May 2017. Retrieved 11 April 2017.
"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.
- Pieracci EG, Pearson CM, Wallace RM, Blanton JD, Whitehouse ER, Ma X, et al. (June 2019). "Vital Signs: Trends in Human Rabies Deaths and Exposures - United States, 1938-2018". MMWR. Morbidity and Mortality Weekly Report. 68 (23): 524–528. doi:10.15585/mmwr.mm6823e1. PMC 6613553. PMID 31194721.
- Lorenz, Jonna. "Human Rabies Case in Utah Underscores Importance of Public Health Efforts". ContagionLive. Retrieved 11 August 2020.
- "SURVEILLANCE REPORT - Annual Epidemiological Report for 2015 - Rabies, ECDC (European Centre for Disease Prevention and Control)" (PDF). Retrieved 30 August 2018.
- "Switzerland ended rabies epidemic by air dropping vaccinated chicken heads from helicopters / thefactsource.com". 20 November 2019. Retrieved 10 December 2019.
- "Rabies in Africa: The RESOLAB network". 29 June 2015. Archived from the original on 3 August 2016. Retrieved 18 April 2016.
- "Ministero della Salute: "Italia è indenne dalla rabbia". l'Ultimo caso nel 2011 - Quotidiano Sanità". Archived from the original on 3 June 2016. Retrieved 18 April 2016.
- "Rabies". NHS. 23 February 2017. Retrieved 30 August 2018.
- "Q&A: Rabies". BBC News. 17 April 2015. Retrieved 30 August 2018.
- "Cómo México se convirtió en el primer país del mundo libre de rabia transmitida por perros". BBC News. 12 November 2019. Retrieved 12 November 2019.
- Santo Tomás Pérez, Magdalena (2002). La asistencia a los enfermos en Castilla en la Baja Edad Media. Universidad de Valladolid. pp. 172–173. ISBN 84-688-3906-X – via Biblioteca Virtual Miguel de Cervantes.
- Adamson PB (1977). "The spread of rabies into Europe and the probable origin of this disease in antiquity". Journal of the Royal Asiatic Society of Great Britain & Ireland. Royal Asiatic Society of Great Britain and Ireland. 109 (2): 140–4. doi:10.1017/S0035869X00133829. JSTOR 25210880. PMID 11632333.
- Dunlop RH, Williams DJ (1996). Veterinary Medicine: An Illustrated History. Mosby. ISBN 978-0-8016-3209-9.
- "Rabies: an ancient disease".
- Barrett AD, Stanberry LR (2009). Vaccines for Biodefense and Emerging and Neglected Diseases. Academic Press. p. 612. ISBN 9780080919027. Archived from the original on 28 April 2016. Retrieved 8 January 2016.
- The Natural History of Rabies Archived 2 March 2016 at the Wayback Machine
The first major epizootic in North America was reported in 1768, continuing until 1771 when foxes and dogs carried the disease to swine and domestic animals. The malady was so unusual that it was reported as a new disease
- Rotivel Y. "Introduction". Federation of American Scientists. Archived from the original on 26 April 2009. Retrieved 25 April 2009.
- Than K (27 October 2010). ""Zombie Virus" Possible via Rabies-Flu Hybrid?". National Geographic. National Geographic. Archived from the original on 13 September 2015. Retrieved 13 September 2015.
- Simpson DP (1979). Cassell's Latin Dictionary (5 ed.). London: Cassell. p. 883. ISBN 978-0-304-52257-6.
- Dalfardi B, Esnaashary MH, Yarmohammadi H (February 2014). "Rabies in medieval Persian literature - the Canon of Avicenna (980-1037 AD)". Infectious Diseases of Poverty. 3 (1): 7. doi:10.1186/2049-9957-3-7. PMC 3933285. PMID 24533686.
- Ettinger SJ, Feldman EC (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 978-0-7216-6795-9.
- Carpentier DC, Vevis K, Trabalza A, Georgiadis C, Ellison SM, Asfahani RI, Mazarakis ND (July 2012). "Enhanced pseudotyping efficiency of HIV-1 lentiviral vectors by a rabies/vesicular stomatitis virus chimeric envelope glycoprotein". Gene Therapy. 19 (7): 761–74. doi:10.1038/gt.2011.124. PMID 21900965.
- Roy A, Hooper DC (August 2007). "Lethal silver-haired bat rabies virus infection can be prevented by opening the blood-brain barrier". Journal of Virology. 81 (15): 7993–8. doi:10.1128/JVI.00710-07. PMC 1951307. PMID 17507463.
- Roy A, Phares TW, Koprowski H, Hooper DC (February 2007). "Failure to open the blood-brain barrier and deliver immune effectors to central nervous system tissues leads to the lethal outcome of silver-haired bat rabies virus infection". Journal of Virology. 81 (3): 1110–8. doi:10.1128/JVI.01964-06. PMC 1797506. PMID 17108029.
|Wikimedia Commons has media related to Rabies.|
|Look up rabies in Wiktionary, the free dictionary.|
- Rabies at Curlie
- "Rabies". Centers for Disease Control and Prevention. Retrieved 12 August 2012.
- Virus Pathogen Database and Analysis Resource (ViPR): Rhabdoviridae
- OIE's Rabies Portal
- Aerophobia and Hydrophobia in Rabies Videos
- "Rabies virus". NCBI Taxonomy Browser. 11292.