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rabies
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{{other uses|Rabies (disambiguation)}}{{redirect|Rabid}}{{pp-semi|small=yes}}{{Use dmy dates|date=March 2019}}







factoids
| complications =| onset =| duration =| causes = Rabies virus and Australian bat lyssavirus| risks =| diagnosis =| differential =| prevention = Rabies vaccine, animal control, rabies immunoglobulin| treatment =| medication =| prognosis = Nearly always death| frequency =| deaths = 17,400 (2015)}}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.BOOK, Cotran RS, Robbins and Cotran Pathologic Basis of Disease, 7th, Elsevier/Saunders, 2005, 1375, 978-0-7216-0187-8, vanc, Kumar V, Fausto N, Rabies is caused by lyssaviruses, including the rabies virus and Australian bat lyssavirus.WEB, Rabies, Australian bat lyssavirus and other lyssaviruses,weblink The Department of Health, 1 March 2014, Dec 2013, live,weblink" title="web.archive.org/web/20140304235230weblink">weblink 4 March 2014, 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. In countries where dogs commonly have the disease, more than 99% of rabies cases are the direct result of dog bites.BOOK, Tintinalli, Judith E., Emergency Medicine: A Comprehensive Study Guide (Emergency Medicine (Tintinalli)), McGraw-Hill, 2010, Chapter 152, 978-0-07-148480-0, 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.WEB, Rabies Fact Sheet N°99,weblink World Health Organization, 28 February 2014, July 2013, live,weblink" title="web.archive.org/web/20140401075427weblink">weblink 1 April 2014, BOOK, William H. Wunner, Rabies: Scientific Basis of the Disease and Its Management, 2010, Academic Press, 9780080550091, 556,weblink {{As of|2016}}, only fourteen people had survived a rabies infection after showing symptoms.JOURNAL, Hemachudha T, Ugolini G, Wacharapluesadee S, Sungkarat W, Shuangshoti S, Laothamatas J, Human rabies: neuropathogenesis, diagnosis, and management., Lancet Neurology, 12, 5, 498–513, May 2013, 23602163, 10.1016/s1474-4422(13)70038-3, WEB, UC Davis Children's Hospital patient becomes third person in U.S. to survive rabies,weblink UC Davis Medical Center, 3 May 2012, live,weblink" title="web.archive.org/web/20120521165713weblink">weblink 21 May 2012, JOURNAL, Manoj, S., Mukherjee, A., Johri, S., Kumar, K. V. S. Hari, Recovery from rabies, a universally fatal disease, Military Medical Research, 3, 1, 21, 2016, 2054-9369, 10.1186/s40779-016-0089-y, 27429788, 4947331, Rabies caused about 17,400 human deaths worldwide in 2015.JOURNAL, GBD 2015 Mortality and Causes of Death, Collaborators., Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015., Lancet, 8 October 2016, 388, 10053, 1459–1544, 27733281, 10.1016/s0140-6736(16)31012-1, 5388903, 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.WEB, Rabies: The Facts,weblink World Health Organization, 24 February 2017, live,weblink" title="web.archive.org/web/20170224220204weblink">weblink 24 February 2017, 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.BOOK, WHO Expert Consultation on Rabies : second report., 2013, WHO, Geneva, 9789241209823, 3, 2,weblink live,weblink" title="web.archive.org/web/20141020024015weblink">weblink 20 October 2014, WEB, Rabies-Free Countries and Political Units,weblink CDC, 8 May 2019, live,weblink" title="web.archive.org/web/20140305010256weblink">weblink 5 March 2014, Many Pacific islands do not have rabies at all. It is classified as a neglected tropical disease.WEB, Neglected Tropical Diseases,weblink cdc.gov, 28 November 2014, 6 June 2011, live,weblink" title="web.archive.org/web/20141204084219weblink">weblink 4 December 2014,

Signs and symptoms

(File:Rabies patient.jpg|right|thumb|A man with rabies, 1959)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.JOURNAL, Giesen, A, Gniel, D, Malerczyk, C, 30 Years of rabies vaccination with Rabipur: a summary of clinical data and global experience, Expert Review of Vaccines, 14, 3, 351–67, March 2015, 25683583, 10.1586/14760584.2015.1011134, Review, free, 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.JOURNAL, Rupprecht CE, Willoughby R, Slate D, Current and future trends in the prevention, treatment and control of rabies, Expert Review of Anti-infective Therapy, 4, 6, 1021–38, 2006, 17181418, 10.1586/14787210.4.6.1021,

Fear of water

missing image!
- Rabid dog.jpg -
A rabid dog
Hydrophobia ("fear of water") is the historic name for rabies.BOOK, Smallman-Raynor, Andrew Cliff, Peter Haggett, Matthew, World atlas of epidemic diseases, 2004, Arnold, London, 9780340761717, 51,weblink 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.WEB,weblink AnimalsWeCare.com, Rabies, dead,weblink" title="web.archive.org/web/20140903193928weblink">weblink 3 September 2014, 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.WEB, Symptoms of rabies,weblink NHS.uk, 3 September 2014, 12 June 2012, live,weblink" title="web.archive.org/web/20140914174652weblink">weblink 14 September 2014,

Cause

(File:Rabies Virus.jpg|thumb|Drawing of the rabies virus.)File:Rabies Virus EM PHIL 1876.JPG|thumb|TEM micrograph with numerous rabies virions (small, dark grey, rodlike particles) and Negri bodies (the larger pathognomonicpathognomonicRabies is caused by a number of lyssaviruses including the rabies virus and Australian bat lyssavirus.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.BOOK, Drew WL, Chapter 41: Rabies, Ryan KJ, Ray CG, Sherris Medical Microbiology, 4th, 597–600, McGraw Hill, 2004, 978-0-8385-8529-0, 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).JOURNAL, Finke S, Conzelmann KK, Replication strategies of rabies virus, Virus Res., 111, 2, 120–31, August 2005, 15885837, 10.1016/j.virusres.2005.04.004, 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).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.JOURNAL, Gluska, Shani, Zahavi, Eitan Erez, Chein, Michael, Gradus, Tal, Bauer, Anja, Finke, Stefan, Perlson, Eran, Schnell, Matthias Johannes, Rabies virus hijacks and accelerates the p75NTR retrograde axonal transport machinery, PLoS Pathogens, 28 August 2014, 10, 8, e1004348, 10.1371/journal.ppat.1004348, 25165859, 4148448, 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.{{rp|317}}

Transmission

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.JOURNAL, Shannon LM, Poulton JL, Emmons RW, Woodie JD, Fowler ME, Serological survey for rabies antibodies in raptors from California, J. Wildl. Dis., 24, 2, 264–7, April 1988, 3286906, 10.7589/0090-3558-24.2.264, free, Other bird species have been known to develop rabies antibodies, a sign of infection, after feeding on rabies-infected mammals.JOURNAL, Gough PM, Jorgenson RD, Rabies antibodies in sera of wild birds, Journal of Wildlife Diseases, 12, 3, 392–5, 1976, 16498885, 10.7589/0090-3558-12.3.392, free, JOURNAL, Jorgenson RD, Gough PM, Experimental rabies in a great horned owl, J. Wildl. Dis., 12, 3, 444–7, July 1976, 10.7589/0090-3558-12.3.444, 16498892, The virus has also adapted to grow in cells of cold-blooded vertebrates.WEB,weblink Rabies, Wong, Derek, Wong's Virology, 19 March 2009, live,weblink" title="web.archive.org/web/20081203053955weblink">weblink 3 December 2008, BOOK, Developments in Veterinary Virology: Rabies, Campbell, James B., Charlton, K.M., Springer, 1988, 48, 978-0-89838-390-4, Most animals can be infected by the virus and can transmit the disease to humans. Infected bats,JOURNAL, Pawan JL, The transmission of paralytic rabies in Trinidad by the vampire bat (Desmodus rotundus murinus Wagner), Caribbean Medical Journal, 21, 110–36, 1959, 13858519, JOURNAL, Pawan JL, 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, 1959, 14431118, monkeys, raccoons, foxes, skunks, cattle, wolves, coyotes, dogs, cats, and mongooses (normally either the small Asian mongoose or the yellow mongoose)JOURNAL, Taylor PJ, 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, December 1993, 7777324, 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.WEB,weblink Rabies. Other Wild Animals: Terrestrial carnivores: raccoons, skunks and foxes., 2010-12-23, Centers for Disease Control and Prevention(CDC), live,weblink" title="web.archive.org/web/20101220085305weblink">weblink 20 December 2010, 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.NEWS, Anderson, Janet & Frey, Rebecca, Rabies, Gale Encyclopedia of Medicine, 3rd, 2006, The Virginia opossum is resistant but not immune to rabies.JOURNAL, McRuer DL, Jones KD, Behavioral and nutritional aspects of the Virginian opossum (Didelphis virginiana), The Veterinary Clinics of North America. Exotic Animal Practice, 12, 2, 217–36, viii, May 2009, 19341950, 10.1016/j.cvex.2009.01.007, The virus is usually present in the nerves and saliva of a symptomatic rabid animal.BOOK, The Merck Manual, 11th, 1983, 183, BOOK, The Merck manual of Medical Information, Second Home, 2003, 484, 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.WEB, Turton, Jenny, Rabies: a killer disease, National Department of Agriculture, 2000,weblink live,weblink" title="web.archive.org/web/20060923103559weblink">weblink 23 September 2006, 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.JOURNAL, Srinivasan A, Burton EC, Kuehnert MJ, Rupprecht C, Sutker WL, Ksiazek TG, Paddock CD, Guarner J, Shieh WJ, Goldsmith C, Hanlon CA, Zoretic J, Fischbach B, Niezgoda M, El-Feky WH, Orciari L, Sanchez EQ, Likos A, Klintmalm GB, Cardo D, LeDuc J, Chamberland ME, Jernigan DB, Zaki SR, Transmission of rabies virus from an organ donor to four transplant recipients, New England Journal of Medicine, N Engl J Med, 352, 11, 1103–11, March 2005, 15784663, 10.1056/NEJMoa043018, 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.WEB,weblink Exposure to the Virus, live,weblink" title="web.archive.org/web/20160908222542weblink">weblink 8 September 2016, 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.RabiesAlliance.org {{webarchive|url=https://web.archive.org/web/20160924072630weblink |date=24 September 2016 }}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.BOOK, Jackson, Alan C., Wunner, William H., Rabies,weblink 2002, Academic Press, 978-0-12-379077-4, 290, live,weblink" title="web.archive.org/web/20140108014518weblink">weblink 8 January 2014, 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.BOOK, Lynn DJ, Newton HB, Rae-Grant AD, The 5-Minute Neurology Consult,weblink 2012, Lippincott Williams & Wilkins, 978-1-4511-0012-9, 414–, BOOK, Davis, Larry Ernest, King, Molly K., Schultz, Jessica L., Fundamentals of neurologic disease,weblink 15 June 2005, Demos Medical Publishing, 978-1-888799-84-2, 73, live,weblink" title="web.archive.org/web/20140108015452weblink">weblink 8 January 2014,

Diagnosis

Rabies can be difficult to diagnose because, in the early stages, it is easily confused with other diseases or with aggressiveness.BOOK, The Merck Veterinary Manual, 2010, Courier Kendallville, Inc, Kendallville, Indiana, 978-0-911910-93-3, 1193, 10th, Cynthia M., Kahn, BA, The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an immunohistochemistry procedure, which is recommended by the World Health Organization (WHO).BOOK, Dean, D.J., M.K., Abelseth, Ch. 6: The fluorescent antibody test, M.M., Kaplan, H., Koprowski, Laboratory techniques in rabies, World Health Organization, Monograph series, 23, 1973, 73,weblink 3rd, 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.JOURNAL, Fooks AR, Johnson N, Freuling CM, Wakeley PR, Banyard AC, McElhinney LM, Marston DA, Dastjerdi A, Wright E, Weiss RA, Müller T, Emerging technologies for the detection of rabies virus: challenges and hopes in the 21st century, PLoS Neglected Tropical Diseases, 3, 9, e530, 2009, 19787037, 2745658, 10.1371/journal.pntd.0000530, The RT PCR assays proved to be a sensitive and specific tool for routine diagnostic purposes,BOOK, Tordo, N, Bourhy, H, Sacramento, D, Ch. 10: PCR technology for lyssavirus diagnosis, J.P., Clewley, The Polymerase Chain Reaction (PCR) for Human Viral Diagnosis,weblink 1994, CRC Press, 978-0-8493-4833-4, 125–145, particularly in decomposed samplesJOURNAL, David D, Yakobson B, Rotenberg D, Dveres N, Davidson I, Stram Y, Rabies virus detection by RT-PCR in decomposed naturally infected brains, Veterinary Microbiology, 87, 2, 111–8, 2002, 12034539, 10.1016/s0378-1135(02)00041-x, or archival specimens.JOURNAL, Biswal M, Ratho R, Mishra B, Usefulness of reverse transcriptase-polymerase chain reaction for detection of rabies RNA in archival samples, Japanese Journal of Infectious Diseases, 60, 5, 298–9, September 2007, 17881871, 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.JOURNAL, Ly S, Buchy P, Heng NY, Ong S, Chhor N, Bourhy H, Vong S, Rabies situation in Cambodia, PLoS Neglected Tropical Diseases, 3, 9, e511, 2009, 19907631, 2731168, 10.1371/journal.pntd.0000511, Carabin, Hélène, e511, 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.JOURNAL, Dürr S, Naïssengar S, Mindekem R, Diguimbye C, Niezgoda M, Kuzmin I, Rupprecht CE, Zinsstag J, Rabies diagnosis for developing countries, PLoS Neglected Tropical Diseases, 2, 3, e206, 2008, 18365035, 2268742, 10.1371/journal.pntd.0000206, Cleaveland, Sarah, e206, 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.WEB, New Rapid Rabies Test Could Revolutionize Testing and Treatment {{!, CDC Online Newsroom {{!}} CDC|url=https://www.cdc.gov/media/releases/2018/p0516-rapid-rabies-test.html|website=www.cdc.gov|accessdate=23 May 2018|language=en-us|date=16 May 2018}}

Differential diagnosis

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.WEB,weblink Rabies: Differential Diagnoses & Workup, eMedicine Infectious Diseases, 3 October 2008, 2010-01-30, live,weblink" title="web.archive.org/web/20101128074240weblink">weblink 28 November 2010, 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.BOOK, Taylor DH, Straw BE, Zimmerman JL, D'Allaire S, Diseases of swine, Blackwell, Oxford, 2006, 463–5, 978-0-8138-1703-3,weblink 2010-01-30, 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.BOOK, Inflammatory Disorders Of The Nervous System: Pathogenesis, Immunology, and Clinical Management, Minagar, Alireza, J. Steven Alexander, 2005, Humana Press, 978-1-58829-424-1, 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.

Prevention

{{See|Dog bite prevention}}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.JOURNAL, Geison GL, Pasteur's work on rabies: Reexamining the ethical issues, Hastings Center Report, 8, 2, 26–33, April 1978, 348641, 10.2307/3560403, 3560403, Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines.JOURNAL, Srivastava AK, Sardana V, Prasad K, Behari M, Diagnostic dilemma in flaccid paralysis following anti-rabies vaccine, Neurol India, 52, 1, 132–3, March 2004, 15069272,weblink live,weblink" title="web.archive.org/web/20090802195908weblink">weblink 2 August 2009, 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.JOURNAL, Reece JF, Chawla SK, Control of rabies in Jaipur, India, by the sterilisation and vaccination of neighbourhood dogs, Vet Rec, 159, 12, 379–83, 2006, 16980523, 10.1136/vr.159.12.379, Immunization before exposure has been used in both human and nonhuman populations, where, as in many jurisdictions, domesticated animals are required to be vaccinated.WEB, Compendium of Animal Rabies Prevention and Control, 31 December 2007, 2010-01-03, National Association of State Public Health Veterinarians,weblink dead,weblink" title="web.archive.org/web/20100712235752weblink">weblink 12 July 2010, 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:REPORT, 2007, 2007 Annual Report,weblink Bureau of Communicable Disease Control and Prevention,
  • 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
28 September is World Rabies Day, which promotes the information, prevention, and elimination of the disease.WEB,weblink World Rabies Day, World Health Organization (WHO), live,weblink" title="web.archive.org/web/20111231020108weblink">weblink 31 December 2011,

Vaccinating other animals

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.JOURNAL, Meltzer MI, Assessing the costs and benefits of an oral vaccine for raccoon rabies: a possible model, Emerg Infect Dis, 2, 4, 343–9, October–December 1996, 8969251, 2639934, 10.3201/eid0204.960411, In Ontario, a dramatic drop in rabies was recorded when an aerial bait-vaccination campaign was launched.BOOK, Grambo, Rebecca L, The World of the Fox, 1995, Greystone Books, Vancouver, 978-0-87156-377-4, 94–5, registration,weblink 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.WEB,weblink Rabies in the U.S., Centers for Disease Control and Prevention (CDC), 22 April 2011, 31 December 2011, live,weblink" title="web.archive.org/web/20111231023841weblink">weblink 31 December 2011,

Treatment

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.WEB,weblink Rabies & Australian bat lyssavirus information sheet, Health.vic.gov.au, 2012-01-30, dead,weblink" title="web.archive.org/web/20110818081218weblink">weblink 18 August 2011, Povidone-iodine or alcohol is then recommended to reduce the virus further.WEB, National Center for Disease Control, National Guidelines on Rabies Prophylaxis,weblink 5 September 2014, 2014, dead,weblink" title="web.archive.org/web/20140905235321weblink">weblink 5 September 2014, 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."Use of a Reduced (4-Dose) Vaccine Schedule for Postexposure Prophylaxis to Prevent Human Rabies" {{webarchive|url=https://web.archive.org/web/20110725112251weblink |date=25 July 2011 }}. Centers for Disease Control and Prevention (CDC). 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.WEB,weblink Cost of Rabies Prevention, live,weblink" title="web.archive.org/web/20160329143011weblink">weblink 29 March 2016, 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.WEB,weblink Rabies Post-Exposure Prophylaxis, Centers for Disease Control and Prevention (CDC), 23 December 2009, 2010-01-30, dead,weblink" title="web.archive.org/web/20100201085054weblink">weblink 1 February 2010, 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.Park's textbook of Community medicine, 22nd edition, 2013, p 254.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.WEB,weblink Rabies, www.who.int, World Health Organization, 1 February 2015, live,weblink" title="web.archive.org/web/20150215014809weblink">weblink 15 February 2015, 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.JOURNAL, De Serres G, Skowronski DM, Mimault P, Ouakki M, Maranda-Aubut R, Duval B, Bats in the bedroom, bats in the belfry: Reanalysis of the rationale for rabies post-exposure prophylaxis, Clin Infect Dis, 48, 11, 1493–9, 2009, 19400689, 10.1086/598998, free, 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.JOURNAL, Despond O, Tucci M, Decaluwe H, Grégoire MC, S Teitelbaum J, Turgeon N, Rabies in a nine-year-old child: The myth of the bite, Can J Infect Dis, 13, 2, 121–5, March 2002, 18159381, 2094861, 10.1155/2002/475909, 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.WEB,weblink Human rabies: better coordination and emerging technology to improve access to vaccines, World Health Organization, en-GB, 2017-02-23, live,weblink" title="web.archive.org/web/20170224131644weblink">weblink 24 February 2017,

Milwaukee protocol

The Milwaukee protocol, sometimes referred to as the Wisconsin protocol,WEB,weblink Rabies Rescue Protocol Fails in New Cases, 20 April 2007, WEB,weblink Human Rabies --- Indiana and California, 2006, www.cdc.gov, 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,MAGAZINE,weblink Medical Mystery: Only One Person Has Survived Rabies without Vaccine—But How?, Scientific American, Jordan Lite, 8 October 2008, 2010-01-30, live,weblink" title="web.archive.org/web/20091105091606weblink">weblink 5 November 2009, 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%.JOURNAL, 10.2217/fvl.09.52, Willoughby RE, Are we getting closer to the treatment of rabies?: medical benchmarks, 2009,weblink Future Virology, 4, 6, 563–70, live,weblink" title="web.archive.org/web/20110313063137weblink">weblink 13 March 2011, The protocol is not an effective treatment for rabies and its use is not recommended.JOURNAL, Jackson AC, Human Rabies: a 2016 Update, Curr Infect Dis Rep, 18, 11, 38, 2016, 27730539, 10.1007/s11908-016-0540-y, Review,

Prognosis

In unvaccinated humans, rabies is almost always fatal after neurological symptoms have developed.WEB,weblink Rabies, September 2011, World Health Organization (WHO), 31 December 2011, live,weblink" title="web.archive.org/web/20111231021303weblink">weblink 31 December 2011, Vaccination after exposure, PEP, is highly successful in preventing the disease if administered promptly, in general within six 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.

Epidemiology

(File:Rabies world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.3|Deaths from rabies per million persons in 2012 {{legend|#ffff20|0}}{{legend|#ff9a20|1}}{{legend|#f08015|2–4}}{{legend|#e06815|5–9}}{{legend|#d85010|10–17}}{{legend|#d02010|18–69}})(File:Rabies Free Countries Sourced 2010.svg|thumb|upright=1.3|Rabies-free countries (in green) {{As of|2010|lc=on}}.{{Farbindex|30b762|always rabies-free}}{{Farbindex|3CE67B|rabies eliminated before 1990}}{{Farbindex|97F3B8|rabies eliminated in or after 1990}}{{Farbindex|CAF9DB|year of rabies elimination unknown}})In 2010, an estimated 26,000 people died from rabies, down from 54,000 in 1990.JOURNAL, Lozano, R, Naghavi, M, Foreman, K, Lim, S, Shibuya, K, Aboyans, V, Abraham, J, Adair, T, Aggarwal, R, 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, 15 December 2012, 23245604, 10.1016/S0140-6736(12)61728-0, etal, 10536/DRO/DU:30050819, 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.JOURNAL, 10.1371/journal.pntd.0003709, 25881058, Estimating the Global Burden of Endemic Canine Rabies, PLOS Neglected Tropical Diseases, 9, 4, e0003709, 2015, Hampson, Katie, Coudeville, Laurent, Lembo, Tiziana, Sambo, Maganga, Kieffer, Alexia, Attlan, Michaël, Barrat, Jacques, Blanton, Jesse D., Briggs, Deborah J., Cleaveland, Sarah, Costa, Peter, Freuling, Conrad M., Hiby, Elly, Knopf, Lea, Leanes, Fernando, Meslin, François-Xavier, Metlin, Artem, Miranda, Mary Elizabeth, Müller, Thomas, Nel, Louis H., Recuenco, Sergio, Rupprecht, Charles E., Schumacher, Carolin, Taylor, Louise, Vigilato, Marco Antonio Natal, Zinsstag, Jakob, Dushoff, Jonathan, 4400070, 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.WEB,weblink Rabies, World Health Organization, en-GB, 2017-02-23, live,weblink" title="web.archive.org/web/20170215062245weblink">weblink 15 February 2017,

India

India has the highest rate of human rabies in the world, primarily because of stray dogs,NEWS,weblink Dead as a dodo? Why scientists fear for the future of the Asian vulture, 2008-10-11, Dugan, Emily, 30 April 2008, The Independent, India now has the highest rate of human rabies in the world., London, live,weblink" title="web.archive.org/web/20080517100919weblink">weblink 17 May 2008, whose number has greatly increased since a 2001 law forbade the killing of dogs.NEWS,weblink Where Streets Are Thronged With Strays Baring Fangs, New York Times, Harris, Gardiner, 6 August 2012, 6 August 2012, live,weblink" title="web.archive.org/web/20120808125223weblink">weblink2012/08/07/world/asia/india-stray-dogs-are-a-menace.html, 8 August 2012, 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.[http:www.dw.de/medicine-challenges-indian-superstition/a-16489334 Medicine challenges Indian superstition | Asia | DW.DE | 31.12.2012] {{webarchive|url=https://web.archive.org/web/20130131194746weblink |date=31 January 2013 }} An estimated 20,000 people die every year from rabies in India, more than a third of the global total.

Australia

The rabies virus survives in widespread, varied, rural animal reservoirs. Despite Australia's official rabies-free status,"Essential rabies maps" {{webarchive|url=https://web.archive.org/web/20100217210150weblink |date=17 February 2010 }}. World Health Organization (WHO). 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.

United States

{{More citations needed section|date=June 2019}}(File:Mm6823e1-F1.gif|thumb|upright=1.5|Rabies cases in humans and domestic animals — United States, 1938–2018)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.JOURNAL, Pieracci, Emily G., Pearson, Christine M., Wallace, Ryan M., Blanton, Jesse D., Whitehouse, Erin R., Ma, Xiaoyue, Stauffer, Kendra, Chipman, Richard B., Olson, Victoria, Trends in Human Rabies Deaths and Exposures — United States, 1938–2018, MMWR. Morbidity and Mortality Weekly Report, 14 June 2019, 68, 23, 524–528, 10.15585/mmwr.mm6823e1, 31194721, 6613553, While canine-specific rabies does not circulate among dogs, about a hundred dogs become infected from other wildlife per year in the US.WEB, CDC – Rabies Surveillance in the U.S.: Human Rabies – Rabies,weblink www.cdc.gov, 10 April 2017, en-us, live,weblink 18 January 2017, NEWS,weblink U.S. free of canine rabies virus, Fox, Maggie, 7 September 2007, Reuters, 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., live,weblink 17 May 2017, 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.WEB,weblink Rabies Surveillance Data in the United States, Centers for Disease Control and Prevention, live,weblink" title="web.archive.org/web/20111008193211weblink">weblink 8 October 2011, 12 July 2017,

Europe

Either no or very few cases of rabies are reported each year in Europe; cases are contracted both during travel and in Europe.WEB,weblink SURVEILLANCE REPORT - Annual Epidemiological Report for 2015 - Rabies, ECDC (European Centre for Disease Prevention and Control), 30 August 2018, 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.WEB,weblink Rabies in Africa: The RESOLAB network, 2016-04-18, live,weblink" title="web.archive.org/web/20160803081821weblink">weblink 3 August 2016, WEB,weblink Ministero della Salute: "Italia è indenne dalla rabbia". l'Ultimo caso nel 2011 - Quotidiano Sanità, 2016-04-18, live,weblink" title="web.archive.org/web/20160603183359weblink">weblink 3 June 2016, 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.WEB,weblink Rabies, NHS, 23 February 2017, 30 August 2018, NEWS,weblink Q&A: Rabies, BBC News, 17 April 2015, 30 August 2018, Unlike the other countries of Europe it is protected by being an island, and by strict quarantine procedures.

History

File:Middle Ages rabid dog.jpg|thumb|250px|A woodcut from the Middle AgesMiddle AgesFile:Sauvages de la Croix, François Boissier de – Dissertation sur la nature et la cause de la Rage, 1777 – BEIC 3001126.jpg|thumb|François Boissier de Sauvages de LacroixFrançois Boissier de Sauvages de LacroixRabies has been known since around 2000 BC.JOURNAL, Adamson PB, The spread of rabies into Europe and the probable origin of this disease in antiquity, The Journal of the Royal Asiatic Society of Great Britain and Ireland, 109, 2, 140–4, 1977, 11632333, 10.1017/S0035869X00133829, 25210880, 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.BOOK, Dunlop, Robert H, Williams, David J, Veterinary Medicine: An Illustrated History, Mosby, 1996, 978-0-8016-3209-9, 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.BOOK, Barrett, Alan D.T., Stanberry, Lawrence R., Vaccines for Biodefense and Emerging and Neglected Diseases, Academic Press, 2009, 612, English,weblink 9780080919027, 2016-01-08, live,weblink 28 April 2016, Rabies appears to have originated in the Old World, the first epizootic in the New World occurring in Boston in 1768.The Natural History of Rabies {{webarchive|url=https://web.archive.org/web/20160302162818weblink |date=2 March 2016 }}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 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.BOOK, Baer, George, The Natural History of Rabies,weblink CRC Press, 31 October 2011, 9780849367601, 1991, 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.WEB, Than, Ker, "Zombie Virus" Possible via Rabies-Flu Hybrid?,weblink National Geographic, National Geographic, 13 September 2015, live,weblink" title="web.archive.org/web/20150913232030weblink">weblink 13 September 2015, 27 October 2010,

Milwaukee protocol

The Milwaukee protocol was developed and named by Rodney Willoughby Jr., following its use in the treatment of Jeanna Giese.Rodney E. Willoughby Jr., online "A Cure for Rabies?" Scientific American, V. 256, No. 4, April 2007, p. 95. Giese, a teenager from Wisconsin, became the first patient known to have survived rabies without receiving the rabies vaccine.NEWS,weblink Medical Mystery: Only One Person Has Survived Rabies without Vaccine--But How?, Scientific American, Jordan Lite, 8 October 2008, 2008-10-16, 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.JOURNAL, Zeiler FA, Jackson AC, Critical Appraisal of the Milwaukee Protocol for Rabies: This Failed Approach Should Be Abandoned, Can J Neurol Sci, 43, 1, 44–51, 2016, 26639059, 10.1017/cjn.2015.331, Review, free,

Etymology

The term is derived from the Latin rabies, "madness".BOOK, Simpson DP, Cassell's Latin Dictionary, Cassell, 1979, 5, London, 883, 978-0-304-52257-6, This, in turn, may be related to the Sanskrit rabhas, "to rage".JOURNAL, Dalfardi, Behnam, Esnaashary, Mohammad Hosein, Yarmohammadi, Hassan, 17 February 2014, Rabies in medieval Persian literature – the Canon of Avicenna (980–1037 AD), 3933285, Infectious Diseases of Poverty, 3, 1, 7, 10.1186/2049-9957-3-7, 2049-9957, 24533686, The Greeks derived the word lyssa, from lud or "violent"; this root is used in the genus name of the rabies virus, Lyssavirus.WEB, Yolande, Rotivel, Introduction,weblink Federation of American Scientists, 2009-04-25, dead,weblink" title="web.archive.org/web/20090426031557weblink">weblink 26 April 2009,

Other animals

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.BOOK, Ettinger, Stephen J, Feldman, Edward C, Textbook of Veterinary Internal Medicine, 4th, W.B. Saunders Company, 1995, 978-0-7216-6795-9,

Research

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.JOURNAL, Carpentier DC, Vevis K, Trabalza A, Georgiadis C, Ellison SM, Asfahani RI, Mazarakis ND, Enhanced pseudotyping efficiency of HIV-1 lentiviral vectors by a rabies/vesicular stomatitis virus chimeric envelope glycoprotein, Gene Therapy, 19, 7, 761–74, 8 September 2011, 21900965, 10.1038/gt.2011.124, free, Evidence indicates artificially increasing the permeability of the blood–brain barrier, which normally does not allow most immune cells across, promotes viral clearance.JOURNAL, Roy A, Hooper DC, Lethal silver-haired bat rabies virus infection can be prevented by opening the blood–brain barrier, J. Virol., 81, 15, 7993–8, 2007, 17507463, 1951307, 10.1128/JVI.00710-07, JOURNAL, Roy A, Phares TW, Koprowski H, Hooper DC, 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, J. Virol., 81, 3, 1110–8, 2007, 17108029, 1797506, 10.1128/JVI.01964-06,

See also

References

{{Reflist}}

External links

{{Medical condition classification and resources| DiseasesDB = 11148A82}}071}}| ICDO =| OMIM =| MedlinePlus = 001334| eMedicineSubj = med| eMedicineTopic = 1374eergped|1974}}| MeshID = D011818|Orphanet=770}}{{offline|med}}{{Commons category|Rabies}}{{Wiktionary}} {{Viral diseases}}{{Zoonotic viral diseases}}{{Domestic cat}}{{Domestic dog}}{{Authority control}}

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