View source for Medicine:Rabies

{{Short description|Deadly viral disease, transmitted through animals}}
{{Infobox medical condition (new)
| name          = Rabies
| image         = Manwithrabies4.png
| alt           = A man suffering from rabies tied to a hospital bed.
| caption       = A man with rabies, 1958
| field         = [[Medicine:Infectious disease (medical specialty)|Infectious disease]]
| symptoms      = [[Medicine:Fever|Fever]], extreme aversion to water, [[Medicine:Confusion|confusion]], excessive salivary secretion, [[Unsolved:Hallucination|hallucination]]s, [[Medicine:Insomnia|disrupted sleep]], [[Engineering:Paralysis|paralysis]], [[Medicine:Coma|coma]],<ref name=WHO2013/><ref>{{cite web |title=Rabies - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/rabies/symptoms-causes/syc-20351821 |website=Mayo Clinic |access-date=9 April 2018}}</ref> hyperactivity, [[Medicine:Headache|headache]], nausea, [[Medicine:Vomiting|vomiting]], [[Medicine:Anxiety|anxiety]]<ref>{{cite web  |title=Rabies |url=https://www.mayoclinic.org/diseases-conditions/rabies/symptoms-causes/syc-20351821#:~:text=Rabies%20is%20a%20deadly%20virus,%2C%20foxes%2C%20raccoons%20and%20skunks. |website=Mayo Clinic |access-date=5 October 2023}}</ref>
| complications = 
| onset         = 
| duration      = 
| causes        = Rabies virus, [[Biology:Australian bat lyssavirus|Australian bat lyssavirus]]<ref name=Au2014/>
| risks         = 
| diagnosis     = 
| differential  = 
| prevention    = [[Medicine:Rabies vaccine|Rabies vaccine]], animal control, [[Medicine:Rabies immunoglobulin|rabies immunoglobulin]]<ref name=WHO2013/>
| treatment     = Supportive care
| medication    = Incurable<ref>{{cite web|url= https://www.mayoclinic.org/diseases-conditions/rabies/diagnosis-treatment/drc-20351826#:~:text=Once%20a%20rabies%20infection%20is,the%20infection%20from%20taking%20hold. | title= Rabies diagnosis and treatment=27 June 2023|work=Mayo clinic}}</ref>
| prognosis     = >99% fatal after onset of symptoms<ref name=WHO2013/>
| frequency     = 
| deaths        = 59,000 per year worldwide<ref name="CDC01">{{cite web |title=Rabies |url=https://www.cdc.gov/rabies/location/world/index.html |website=CDC |date=29 July 2020 |access-date=31 January 2021 |language=en}}</ref>
}}
'''Rabies''' is a [[Medicine:Viral disease|viral disease]] that causes [[Medicine:Encephalitis|encephalitis]] in humans and other mammals.<ref name="WHO2013" /> It was historically referred to as '''hydrophobia''' ("fear of water") due to the symptom of panic when presented with liquids to drink. Early symptoms can include fever and abnormal sensations at the site of exposure.<ref name="WHO2013" /> 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.<ref name="WHO2013" /><ref>{{cite web |title=Rabies, Symptoms, Causes, Treatment |url=https://www.medicalnewstoday.com/articles/181980 |work=Medical News Today |date=15 November 2017}}</ref><ref>{{cite web |title=Rabies, Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/rabies/symptoms-causes/syc-20351821 |work=Mayo Clinic}}</ref><ref>{{cite web |title=Animal bites and rabies |url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/animal-bites-and-rabies |work=Johns Hopkins Medicine |date=27 February 2020}}</ref> Once symptoms appear, the result is virtually always death, regardless of treatment.<ref name="WHO2013" /> 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.<ref name="WHO2013" /> The time depends on the distance the virus must travel along [[Biology:Peripheral nervous system|peripheral nerves]] to reach the [[Biology:Central nervous system|central nervous system]].<ref name="Robbins">{{cite book |vauthors=Cotran RS, Kumar V, Fausto N |title=Robbins and Cotran Pathologic Basis of Disease |edition=7th |publisher=Elsevier/Saunders |year=2005 |page=1375 |isbn=978-0-7216-0187-8}}</ref>

Rabies is caused by [[Biology:Lyssavirus|lyssavirus]]es, including the rabies virus and [[Biology:Australian bat lyssavirus|Australian bat lyssavirus]].<ref name="Au2014">{{cite web |title=Rabies, Australian bat lyssavirus and other lyssaviruses |url=http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-rabies-consumer-info.htm |work=The Department of Health |access-date=1 March 2014 |date=Dec 2013 |url-status=live |archive-url=https://web.archive.org/web/20140304235230/http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-rabies-consumer-info.htm |archive-date=4 March 2014}}</ref> It is spread when an infected animal bites or scratches a human or other animals.<ref name="WHO2013" /> Saliva from an infected animal can also transmit rabies if the saliva comes into contact with the eyes, mouth, or nose.<ref name="WHO2013" /> Globally, dogs are the most common animal involved.<ref name="WHO2013" /> In countries where dogs commonly have the disease, more than 99% of rabies cases are the direct result of dog bites.<ref name="Tint2010">{{cite book | vauthors = Tintinalli JE |title=Emergency Medicine: A Comprehensive Study Guide (Emergency Medicine (Tintinalli)) |publisher=McGraw-Hill |year=2010 |pages=Chapter 152 |isbn=978-0-07-148480-0}}</ref> In the [[Earth:Americas|Americas]], [[Biology:Bat|bat]] bites are the most common source of rabies infections in humans, and less than 5% of cases are from dogs.<ref name="WHO2013" /><ref name="Tint2010" /> [[Biology:Rodent|Rodent]]s are very rarely infected with rabies.<ref name="Tint2010" /> The disease can be diagnosed only after the start of symptoms.<ref name="WHO2013" />

Animal control and vaccination programs have decreased the risk of rabies from dogs in a number of regions of the world.<ref name="WHO2013" /> 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.<ref name="WHO2013" /> In people who have been exposed to rabies, the [[Medicine:Rabies vaccine|rabies vaccine]] and sometimes [[Medicine:Rabies immunoglobulin|rabies immunoglobulin]] are effective in preventing the disease if the person receives the treatment before the start of rabies symptoms.<ref name="WHO2013" /> Washing bites and scratches for 15 minutes with soap and water, [[Chemistry:Povidone-iodine|povidone-iodine]], or detergent may reduce the number of viral particles and may be somewhat effective at preventing transmission.<ref name="WHO2013">{{cite web |title=Rabies Fact Sheet N°99 |url=https://www.who.int/mediacentre/factsheets/fs099/en/ |work=World Health Organization |access-date=28 February 2014 |date=July 2013 |url-status=live |archive-url=https://web.archive.org/web/20140401075427/http://www.who.int/mediacentre/factsheets/fs099/en/ |archive-date=1 April 2014}}</ref><ref>{{cite book | vauthors = Wunner WH |title=Rabies: Scientific Basis of the Disease and Its Management |date=2010 |publisher=Academic Press |isbn=9780080550091 |page=556 |url=https://books.google.com/books?id=C-U1LFK5zagC&pg=PA556}}</ref> {{As of|2016}}, only fourteen people were documented to have survived a rabies infection after showing symptoms.<ref name="ManojMukherjee2016">{{cite journal |vauthors=Manoj S, Mukherjee A, Johri S, Kumar KV |title=Recovery from rabies, a universally fatal disease |journal=Military Medical Research |volume=3 |issue=1 |pages=21 |year=2016 |pmid=27429788 |pmc=4947331 |doi=10.1186/s40779-016-0089-y |doi-access=free }}</ref><ref>{{cite journal | vauthors = Weyer J, Msimang-Dermaux V, Paweska JT, Blumberg LH, Le Roux K, Govender P, Coertse J, Markotter W, Nel LH | display-authors = 6 |title=A case of human survival of rabies, South Africa |journal=Southern African Journal of Infectious Diseases |date=9 June 2016 |volume=31 |issue=2 |pages=66–68 |doi=10.1080/23120053.2016.1128151 |language=en |issn=2312-0053|doi-access=free|hdl=2263/59121 |hdl-access=free }}</ref> However, research conducted in 2010 among a population of people in Peru with a self-reported history of one or more bites from [[Biology:Vampire bat|vampire bat]]s (commonly infected with rabies), found that out of 73 individuals reporting previous bat bites, seven people had rabies virus-neutralizing [[Biology:Antibodies|antibodies]] (rVNA).<ref>{{cite journal | vauthors = Gilbert AT, Petersen BW, Recuenco S, Niezgoda M, Gómez J, Laguna-Torres VA, Rupprecht C | title = Evidence of rabies virus exposure among humans in the Peruvian Amazon | journal = The American Journal of Tropical Medicine and Hygiene | volume = 87 | issue = 2 | pages = 206–215 | date = August 2012 | pmid = 22855749 | pmc = 3414554 | doi = 10.4269/ajtmh.2012.11-0689 }}</ref> Since only one member of this group reported prior vaccination for rabies, the findings of the research suggest previously undocumented cases of infection and viral replication followed by an abortive infection. This could indicate that people may have an exposure to the virus without treatment and develop natural antibodies as a result.

Rabies causes about 59,000 deaths worldwide per year,<ref name="CDC01"/> about 40% of which are in children under the age of 15.<ref>{{cite web |title=Rabies: The Facts |url=https://www.who.int/rabies/rabies_Infographic_updated_Global_International_meeting.pdf?ua=1 |website=World Health Organization |access-date=24 February 2017 |url-status=live |archive-url=https://web.archive.org/web/20170224220204/http://www.who.int/rabies/rabies_Infographic_updated_Global_International_meeting.pdf?ua=1 |archive-date=24 February 2017}}</ref> More than 95% of human deaths from rabies occur in Africa and Asia.<ref name="WHO2013" /> Rabies is present in more than 150 countries and on all continents but Antarctica.<ref name="WHO2013" /> More than 3&nbsp;billion people live in regions of the world where rabies occurs.<ref name="WHO2013" /> A number of countries, including Australia and Japan, as well as much of Western Europe, do not have rabies among dogs.<ref>{{cite book |title=WHO Expert Consultation on Rabies : second report. |date=2013 |publisher=WHO |location=Geneva |isbn=9789241209823 |page=3 |edition=2 |url=http://apps.who.int/iris/bitstream/10665/85346/1/9789240690943_eng.pdf |url-status=live |archive-url=https://web.archive.org/web/20141020024015/http://apps.who.int/iris/bitstream/10665/85346/1/9789240690943_eng.pdf |archive-date=20 October 2014}}</ref><ref name="CDCRFC">{{cite web |title=Rabies-Free Countries and Political Units |url=https://www.cdc.gov/animalimportation/rabies-free-countries.html |work=CDC |access-date=8 May 2019 |url-status=dead |archive-url=https://web.archive.org/web/20140305010256/http://www.cdc.gov/animalimportation/rabies-free-countries.html |archive-date=5 March 2014}}</ref> Many Pacific islands do not have rabies at all.<ref name="CDCRFC" /> It is classified as a neglected tropical disease.<ref name="NTD2017">{{cite web |title=Neglected Tropical Diseases |url=https://www.cdc.gov/globalhealth/ntd/diseases/index.html |website=cdc.gov |access-date=28 November 2014 |date=6 June 2011 |url-status=live |archive-url=https://web.archive.org/web/20141204084219/http://www.cdc.gov/globalhealth/ntd/diseases/index.html |archive-date=4 December 2014}}</ref>

==Etymology==
The name rabies is derived from the [[Social:Latin|Latin]] ''rabies'', "madness".<ref name="SimpsonDP1979">{{cite book |vauthors=Simpson DP |title=Cassell's Latin Dictionary |publisher=Cassell |year=1979 |edition=5 |location=London |page=883 |isbn=978-0-304-52257-6}}</ref> This, in turn, may be related to the Sanskrit ''rabhas'', "to rage".<ref>{{cite journal |vauthors=Dalfardi B, Esnaashary MH, Yarmohammadi H |title=Rabies in medieval Persian literature - the Canon of Avicenna (980-1037&nbsp;AD) |journal=Infectious Diseases of Poverty |volume=3 |issue=1 |pages=7 |date=February 2014 |pmid=24533686 |pmc=3933285 |doi=10.1186/2049-9957-3-7 |doi-access=free }}</ref> The Greeks derived the word ''lyssa'', from ''lud'' or "violent"; this root is used in the genus name of the rabies virus, ''Lyssavirus''.<ref name="Rotivel">{{cite journal | vauthors = Rotivel Y | veditors = Rupprecht CE, Smith JS, Fekadu M, Childs JE | title = Introduction: The ascension of wildlife rabies: a cause for public health concern or intervention? | journal = Emerging Infectious Diseases | volume = 1 | issue = 4 | pages = 107–14 | date = 1995 | pmid = 8903179 | pmc = 2626887 | doi = 10.3201/eid0104.950401 |url=https://fas.org/ahead/docs/rabies.htm |archive-url=https://web.archive.org/web/20090426031557/http://www.fas.org/ahead/docs/rabies.htm |archive-date=26 April 2009 }}</ref>

== Signs and symptoms ==
[[File:Dog with rabies.jpg|thumb|left|upright|Animals with "dumb" rabies appear depressed, lethargic, and uncoordinated]]

The [[Medicine:Incubation period|period]] between infection and the first [[Biology:Influenza-like illness|symptoms]] (incubation period) is typically one to three months in humans.<ref name="Giesen2015" /> 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.<ref name="Giesen2015" /> Initial symptoms of rabies are often nonspecific such as fever and headache.<ref name="Giesen2015">{{cite journal |vauthors=Giesen A, Gniel D, Malerczyk C |title=30 Years of rabies vaccination with Rabipur: a summary of clinical data and global experience |journal=Expert Review of Vaccines |volume=14 |issue=3 |pages=351–67 |date=March 2015 |pmid=25683583 |doi=10.1586/14760584.2015.1011134 |type=Review |doi-access=free}}</ref> As rabies progresses and causes inflammation of the brain and meninges, symptoms can include slight or partial [[Engineering:Paralysis|paralysis]], [[Medicine:Anxiety|anxiety]], [[Medicine:Insomnia|insomnia]], [[Medicine:Confusion|confusion]], [[Medicine:Psychomotor agitation|agitation]], abnormal behavior, [[Medicine:Paranoia|paranoia]], [[Philosophy:Fear|terror]], and [[Unsolved:Hallucination|hallucination]]s.<ref name="Robbins" /><ref name="Giesen2015" /> The person may also have fear of water.<ref name="WHO2013" />

The symptoms eventually progress to [[Medicine:Delirium|delirium]], and [[Medicine:Coma|coma]].<ref name="Robbins" /><ref name="Giesen2015" /> [[Biology:Death|Death]] usually occurs two to ten days after first symptoms. Survival is almost unknown once symptoms have presented, even with intensive care.<ref name="Giesen2015" /><ref name="Expert Review of Anti-infective Therapy">{{cite journal |vauthors=Rupprecht CE, Willoughby R, Slate D |title=Current and future trends in the prevention, treatment and control of rabies |journal=Expert Review of Anti-Infective Therapy |volume=4 |issue=6 |pages=1021–38 |date=December 2006 |pmid=17181418 |doi=10.1586/14787210.4.6.1021 |s2cid=36979186}}</ref>

[[File:Hydrophobia in rabies.webm|thumb|Man with rabies displaying hydrophobia]]

Rabies has also occasionally been referred to as hydrophobia ("fear of water") throughout its history.<ref>{{cite book | vauthors = Cliff AD, Haggett P, Smallman-Raynor M |title=World atlas of epidemic diseases |date=2004 |publisher=Arnold |location=London |isbn=9780340761717 |page=51 |url=https://books.google.com/books?id=yNVCiNnGVvsC&pg=PA51}}</ref> 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. 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 [[Medicine:Larynx|larynx]]. Since the infected individual cannot swallow saliva and water, the virus has a much higher chance of being transmitted, because it multiplies and accumulates in the salivary glands and is transmitted through biting.<ref>{{cite web |url=http://www.animalswecare.com/home_section/rabies/ |website=AnimalsWeCare.com |title=Rabies |url-status=dead |archive-url=https://web.archive.org/web/20140903193928/http://www.animalswecare.com/home_section/rabies/ |archive-date=3 September 2014}}</ref>

Hydrophobia is commonly associated with furious rabies, which affects 80% of rabies-infected people. This form of rabies causes irrational aggression in the host, which aids in the spreading of the virus through animal bites;<ref>{{cite web |title=How does rabies cause aggression? |url=https://www.medicalnewstoday.com/articles/319735#Virus-interacts-with-muscle-receptors |website=medicalnewstoday.com |date=14 October 2017 |publisher=Medical News Today |access-date=19 January 2023}}</ref>{{medical citation needed|date=December 2023}} a "foaming at the mouth" effect, caused by the accumulation of saliva, is also commonly associated with rabies in the public perception and in popular culture.<ref>{{cite book| vauthors = Wilson PJ, Rohde RE, Oertli EH, Willoughby Jr RE |date=2019 |title=Rabies: Clinical Considerations and Exposure Evaluations|url=https://books.google.com/books?id=vnWODwAAQBAJ&pg=PA28|edition=1st|publisher=[[Company:Elsevier|Elsevier]]|page=28|isbn=978-0323639798|access-date=May 10, 2023}}</ref><ref>{{cite web|url=https://www.cdc.gov/rabiesandkids/amy.html|title=How Do You Know if an Animal Has Rabies? {{!}} CDC Rabies and Kids|publisher=Centers for Disease Control and Prevention (CDC)|access-date=May 10, 2023}}</ref><ref>{{cite web|url=https://kidshealth.org/en/parents/rabies.html|title=Rabies (for Parents)|website=KidsHealth.org|publisher=Nemours KidsHealth|access-date=May 10, 2023}}</ref> The remaining 20% may experience a paralytic form of rabies that is marked by muscle [[Medicine:Muscle weakness|weakness]], loss of sensation, and [[Engineering:Paralysis|paralysis]]; this form of rabies does not usually cause fear of water.<ref name="NHS">{{cite web |title=Symptoms of rabies |url=http://www.nhs.uk/Conditions/Rabies/Pages/Symptoms.aspx |website=NHS.uk |access-date=3 September 2014 |date=12 June 2012 |url-status=live |archive-url=https://web.archive.org/web/20140914174652/http://www.nhs.uk/Conditions/Rabies/Pages/Symptoms.aspx |archive-date=14 September 2014}}</ref>

==Cause==
<gallery widths="200" heights="200">
File:Rabies Virus.jpg|Rendering of the rabies virus
File:Electron microscope image of rabies virus.jpg|An electron microscope image of the rabies virus
File:Rabies Virus EM PHIL 1876.JPG|[[Engineering:Transmission electron microscopy|TEM]] [[Micrograph|micrograph]] with numerous rabies virions (small, dark grey, rodlike particles) and [[Medicine:Negri bodies|Negri bodies]] (the larger [[Medicine:Pathognomonic|pathognomonic]] cellular inclusions of rabies infection)
File:Dr. Joseph Pawan.isolated rabies virus. Commemorative stamp.jpg|Commemorative stamp for [[Biography:Joseph Lennox Pawan|Joseph Lennox Pawan]], who isolated the rabies virus
</gallery>

Rabies is caused by a number of [[Biology:Lyssavirus|lyssavirus]]es including the rabies virus and [[Biology:Australian bat lyssavirus|Australian bat lyssavirus]].<ref name="Au2014" /> Duvenhage lyssavirus may cause a rabies-like infection.<ref name="Thiel2009">{{cite journal |vauthors=van Thiel PP, de Bie RM, Eftimov F, Tepaske R, Zaaijer HL, van Doornum GJ, Schutten M, Osterhaus AD, Majoie CB, Aronica E, Fehlner-Gardiner C, Wandeler AI, Kager PA |display-authors=6 |title=Fatal human rabies due to Duvenhage virus from a bat in Kenya: failure of treatment with coma-induction, ketamine, and antiviral drugs |journal=PLOS Neglected Tropical Diseases |volume=3 |issue=7 |pages=e428 |date=July 2009 |pmid=19636367 |pmc=2710506 |doi=10.1371/journal.pntd.0000428 |doi-access=free }}</ref>

The rabies virus is the [[Biology:Type species|type species]] of the ''[[Biology:Lyssavirus|Lyssavirus]]'' [[Biology:Genus|genus]], in the family'' [[Biology:Rhabdoviridae|Rhabdoviridae]]'', order ''[[Biology:Mononegavirales|Mononegavirales]]''. Lyssavirions have helical symmetry, with a length of about 180&nbsp;[[Nanometre|nm]] and a cross-section of about 75&nbsp;nm.<ref name="Sherris">{{cite book |vauthors=Drew WL |chapter=Chapter 41: Rabies | veditors = Ryan KJ, Ray CG |title=Sherris Medical Microbiology |edition=4th |pages=597–600 |publisher=McGraw Hill |year=2004 |isbn=978-0-8385-8529-0}}</ref> These virions are [[Biology:Viral envelope|enveloped]] and have a single-stranded [[Biology:RNA|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).<ref name="pmid15885837">{{cite journal |vauthors=Finke S, Conzelmann KK |title=Replication strategies of rabies virus |journal=Virus Research |volume=111 |issue=2 |pages=120–31 |date=August 2005 |pmid=15885837 |doi=10.1016/j.virusres.2005.04.004}}</ref>

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 [[Chemistry:Acetylcholine|acetylcholine]] receptor. The cellular membrane pinches in a procession known as [[Biology:Pinocytosis|pinocytosis]] and allows entry of the virus into the cell by way of an [[Biology:Endosome|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.<ref name="CDC_Rabies_PEP" />

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-translational modifications. For example, the G protein travels through the rough endoplasmic reticulum, where it undergoes further folding, and is then transported to the [[Biology:Golgi apparatus|Golgi apparatus]], where a sugar group is added to it ([[Biology:Glycosylation|glycosylation]]).<ref name="CDC_Rabies_PEP" />

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.<ref name="CDC_Rabies_PEP" />

From the point of entry, the virus is [[Biology:Neurotropic virus|neurotropic]], traveling along the neural pathways into the [[Biology:Central nervous system|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 [[Biology:Acetylcholine receptor|acetylcholine receptor]]s at the neuromuscular junction.<ref>{{cite journal |vauthors=Gluska S, Zahavi EE, Chein M, Gradus T, Bauer A, Finke S, Perlson E |title=Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery |journal=[[Biology:PLOS Pathogens|PLOS Pathogens]] |volume=10 |issue=8 |pages=e1004348 |date=August 2014 |pmid=25165859 |pmc=4148448 |doi=10.1371/journal.ppat.1004348 |doi-access=free }}</ref> The virus then travels through the nerve cell axon via [[Biology:Axonal transport#Retrograde transport|retrograde transport]], as its [[Biology:P protein|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 [[Biology:Central nervous system|central nervous system]] (CNS), replicating in motor neurons and eventually reaching the brain.<ref name="Robbins" /> 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.<ref name="Baer1991" />{{rp|317}}

== Transmission ==
All [[Biology:Warm-blooded|warm-blooded]] species, including humans, may become infected with the rabies virus and develop symptoms. [[Biology:Bird|Bird]]s were first artificially infected with rabies in 1884; however, infected birds are largely, if not wholly, asymptomatic, and recover.<ref name="serological">{{cite journal |vauthors=Shannon LM, Poulton JL, Emmons RW, Woodie JD, Fowler ME |title=Serological survey for rabies antibodies in raptors from California |journal=Journal of Wildlife Diseases |volume=24 |issue=2 |pages=264–7 |date=April 1988 |pmid=3286906 |doi=10.7589/0090-3558-24.2.264 |doi-access=free}}</ref> Other bird species have been known to develop rabies [[Biology:Antibody|antibodies]], a sign of infection, after feeding on rabies-infected mammals.<ref name="pmid16498885">{{cite journal |vauthors=Gough PM, Jorgenson RD |title=Rabies antibodies in sera of wild birds |journal=Journal of Wildlife Diseases |volume=12 |issue=3 |pages=392–5 |date=July 1976 |pmid=16498885 |doi=10.7589/0090-3558-12.3.392 |doi-access=free}}</ref><ref name="Owls">{{cite journal |vauthors=Jorgenson RD, Gough PM, Graham DL |title=Experimental rabies in a great horned owl |journal=Journal of Wildlife Diseases |volume=12 |issue=3 |pages=444–7 |date=July 1976 |pmid=16498892 |doi=10.7589/0090-3558-12.3.444 |s2cid=11374356 }}</ref>

The virus has also adapted to grow in cells of [[Biology:Poikilotherm|cold-blooded]] vertebrates.<ref>{{cite web|url=http://virology-online.com/viruses/Rhabdoviruses.htm |title=Rabies | vauthors = Wong D |publisher=Wong's Virology |access-date=19 March 2009 |url-status=live |archive-url=https://web.archive.org/web/20081203053955/http://virology-online.com/viruses/Rhabdoviruses.htm |archive-date=3 December 2008 }}</ref><ref>{{cite book|title=Developments in Veterinary Virology: Rabies| vauthors = Campbell JB, Charlton K |publisher=Springer|year=1988|page=48|isbn=978-0-89838-390-4}}</ref> 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.<ref>{{cite web|url=https://www.who.int/news-room/fact-sheets/detail/rabies| title=Rabies| website=World Health Organization| date=21 April 2020| access-date=3 May 2021}}</ref> Other sources of rabies in humans include [[Biology:Bat|bat]]s,<ref name="pmid13858519">{{cite journal | vauthors = Pawan JL | title = The transmission of paralytic rabies in Trinidad by the vampire bat (Desmodus rotundus murinus) Wagner | journal = Caribbean Medical Journal | volume = 21 | pages = 110–36 | year = 1959 | pmid = 13858519 }}</ref><ref name="pmid14431118">{{cite journal | vauthors = Pawan JL | title = Rabies in the vampire bat of Trinidad, with special reference to the clinical course and the latency of infection | journal = Caribbean Medical Journal | volume = 21 | pages = 137–56 | year = 1959 | pmid = 14431118 }}</ref> [[Biology:Monkey|monkey]]s, [[Biology:Raccoon|raccoon]]s, [[Biology:Fox|fox]]es, [[Biology:Skunk|skunk]]s, [[Biology:Cattle|cattle]], [[Biology:Wolf|wolves]], coyotes, [[Biology:Cat|cat]]s, and mongooses (normally either the small Asian mongoose or the yellow mongoose).<ref>{{cite journal | vauthors = Taylor PJ | title = A systematic and population genetic approach to the rabies problem in the yellow mongoose (Cynictis penicillata) | journal = The Onderstepoort Journal of Veterinary Research | volume = 60 | issue = 4 | pages = 379–87 | date = December 1993 | pmid = 7777324 }}</ref>

Rabies may also spread through exposure to infected bears, domestic farm animals, groundhogs, weasels, and other [[Biology:Carnivora|wild carnivorans]]. However, lagomorphs, such as [[Biology:Hare|hare]]s and [[Biology:Rabbit|rabbit]]s, and small [[Biology:Rodent|rodent]]s, such as [[Biology:Chipmunk|chipmunk]]s, [[Biology:Gerbillinae|gerbil]]s, [[Biology:Guinea pig|guinea pig]]s, [[Biology:Hamster|hamster]]s, mice, [[Biology:Rat|rat]]s, and squirrels, are almost never found to be infected with rabies and are not known to transmit rabies to humans.<ref>{{cite web|url=https://www.cdc.gov/rabies/exposure/animals/other.html |title=Rabies. Other Wild Animals: Terrestrial carnivores: raccoons, skunks and foxes. |access-date=2010-12-23 |publisher=Centers for Disease Control and Prevention(CDC) |url-status=live |archive-url=https://web.archive.org/web/20101220085305/http://www.cdc.gov/rabies/exposure/animals/other.html |archive-date=20 December 2010 }}</ref> 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.<ref>{{cite book| vauthors = Anderson J, Frey R | chapter = Rabies | veditors = Fundukian LJ | title = Gale Encyclopedia of Medicine|edition= 3rd |date= 2006}}</ref> The [[Biology:Virginia opossum|Virginia opossum]] (a marsupial, unlike the other mammals named in this paragraph, which are all eutherians/placental), has a lower internal body temperature than the rabies virus prefers and therefore is resistant but not immune to rabies.<ref>{{cite journal | vauthors = McRuer DL, Jones KD | title = Behavioral and nutritional aspects of the Virginian opossum (Didelphis virginiana) | journal = The Veterinary Clinics of North America. Exotic Animal Practice | volume = 12 | issue = 2 | pages = 217–36, viii | date = May 2009 | pmid = 19341950 | doi = 10.1016/j.cvex.2009.01.007 }}</ref> Marsupials, along with monotremes (platypuses and echidnas), typically have lower body temperatures than similarly sized eutherians.<ref>{{cite book| title=Abstract: Thermoregulation in marsupials and monotremes, chapter of Marsupials and monotremes: nature's enigmatic mammals| date=2015| vauthors = Gaughan JB, Hogan LA, Wallage A | publisher=Nova Science Publishers, Incorporated| url=https://espace.library.uq.edu.au/view/UQ:380292| isbn=9781634834872| accessdate=2022-04-20}}</ref>

The virus is usually present in the nerves and [[Biology:Saliva|saliva]] of a symptomatic rabid animal.<ref>{{cite book|title=The Merck Manual|edition= 11th |date=1983|page= 183}}</ref><ref>{{cite book |title=The Merck manual of Medical Information|edition= Second Home|date=2003|page= 484}}</ref> The route of [[Medicine:Infection|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.<ref>{{cite web| vauthors = Turton J |title=Rabies: a killer disease |publisher=National Department of Agriculture |year=2000 |url=http://www.nda.agric.za/docs/rabies/rabies.htm |url-status=live |archive-url=https://web.archive.org/web/20060923103559/http://www.nda.agric.za/docs/rabies/rabies.htm |archive-date=23 September 2006 }}</ref> 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 [[Biology:Peripheral nervous system|peripheral nervous system]]. It then travels retrograde along the [[Medicine:Efferent nerve fiber|efferent nerve]]s toward the [[Biology:Central nervous system|central nervous system]].<ref>{{cite book| vauthors = Jackson AC, Wunner WH |title=Rabies |url=https://books.google.com/books?id=p8rMezRaD4oC&pg=PA290 |year=2002 |publisher=Academic Press |isbn=978-0-12-379077-4 |page=290 |url-status=live |archive-url=https://web.archive.org/web/20140108014518/http://books.google.com/books?id=p8rMezRaD4oC&pg=PA290 |archive-date=8 January 2014 }}</ref> 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 [[Biology:Brain|brain]], it rapidly causes [[Medicine:Encephalitis|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 [[Biology:Spinal cord|spinal cord]], producing [[Medicine:Transverse myelitis|transverse myelitis]].<ref name="LynnNewton2012">{{cite book|vauthors=Lynn DJ, Newton HB, Rae-Grant AD|title=The 5-Minute Neurology Consult|url=https://books.google.com/books?id=kTzlC4UbFdcC&pg=PA414|year=2012|publisher=Lippincott Williams & Wilkins |isbn=978-1-4511-0012-9 |pages=414–}}</ref><ref>{{cite book| vauthors = Davis LE, King MK, Schultz JL  |title=Fundamentals of neurologic disease |url=https://books.google.com/books?id=moRp2jWZp0QC&pg=PA73 |date=15 June 2005 |publisher=Demos Medical Publishing |isbn=978-1-888799-84-2 |page=73 |url-status=live |archive-url=https://web.archive.org/web/20140108015452/http://books.google.com/books?id=moRp2jWZp0QC&pg=PA73 |archive-date=8 January 2014 }}</ref>

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, because 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.<ref>{{cite web | title = Rabies FAQs: Exposure, prevention and treatment | url = https://rabiesalliance.org/rabies/what-is-rabies-and-frequently-asked-questions/exposure-prevention-treatment | work = RabiesAlliance.org | archive-url = https://web.archive.org/web/20160924072630/https://rabiesalliance.org/rabies/what-is-rabies-and-frequently-asked-questions/exposure-prevention-treatment | archive-date = 24 September 2016 }}</ref> There are only a small number of recorded cases of human-to-human transmission of rabies, and all occurred through organ transplants, most frequently with corneal transplantation, from infected donors.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Transmission of rabies virus from an organ donor to four transplant recipients | journal = The New England Journal of Medicine | volume = 352 | issue = 11 | pages = 1103–11 | date = March 2005 | pmid = 15784663 | doi = 10.1056/NEJMoa043018 | doi-access = free }}</ref><ref>{{cite web | title=Human Rabies Prevention --- United States, 2008 Recommendations of the Advisory Committee on Immunization Practices | website=Centers for Disease Control and Prevention | date=2008-05-23 | url=https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5703a1.htm | access-date=2020-02-11}}</ref>

== Diagnosis ==
Rabies can be difficult to diagnose because, in the early stages, it is easily confused with other diseases or even with a simple aggressive temperament.<ref name="Merck">{{cite book|title=The Merck Veterinary Manual|year=2010|publisher=Courier Kendallville, Inc|location=Kendallville, Indiana|isbn=978-0-911910-93-3|page=1193|edition=10th| veditors = Kahn CM, Line S }}</ref> The [[Medicine:Gold standard (test)|reference method]] for diagnosing rabies is the fluorescent antibody test (FAT), an [[Biology:Immunohistochemistry|immunohistochemistry]] procedure, which is recommended by the [[Organization:World Health Organization|World Health Organization]] (WHO).<ref>{{cite book | vauthors = Dean DJ, Abelseth MK |chapter=Ch. 6: The fluorescent antibody test | veditors = Kaplan MM, Koprowski H |title=Laboratory techniques in rabies |publisher=World Health Organization |series=Monograph series |volume=23 |year=1973 |page=73 |isbn=9789241400237 |chapter-url=https://books.google.com/books?id=0jciAQAAIAAJ |edition=3rd}}</ref> 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.<ref name="Fooks AR 2009">{{cite journal | vauthors = Fooks AR, Johnson N, Freuling CM, Wakeley PR, Banyard AC, McElhinney LM, Marston DA, Dastjerdi A, Wright E, Weiss RA, Müller T | display-authors = 6 | title = Emerging technologies for the detection of rabies virus: challenges and hopes in the 21st century | journal = PLOS Neglected Tropical Diseases | volume = 3 | issue = 9 | pages = e530 | date = September 2009 | pmid = 19787037 | pmc = 2745658 | doi = 10.1371/journal.pntd.0000530 | doi-access = free }}</ref> The [[Biology:Reverse transcription polymerase chain reaction|RT PCR]] assays proved to be a sensitive and specific tool for routine diagnostic purposes,<ref>{{cite book | vauthors = Tordo N, Bourhy H, Sacramento D |chapter=Ch. 10: PCR technology for lyssavirus diagnosis | veditors = Clewley JP |title=The Polymerase Chain Reaction (PCR) for Human Viral Diagnosis |chapter-url=https://books.google.com/books?id=f4vTacTbViQC&pg=PA125 |year=1994 |publisher=CRC Press |isbn=978-0-8493-4833-4 |pages=125–145}}</ref> particularly in decomposed samples<ref name="pmid12034539">{{cite journal | vauthors = David D, Yakobson B, Rotenberg D, Dveres N, Davidson I, Stram Y | title = Rabies virus detection by RT-PCR in decomposed naturally infected brains | journal = Veterinary Microbiology | volume = 87 | issue = 2 | pages = 111–8 | date = June 2002 | pmid = 12034539 | doi = 10.1016/s0378-1135(02)00041-x }}</ref> or archival specimens.<ref name="pmid17881871">{{cite journal | vauthors = Biswal M, Ratho R, Mishra B | title = Usefulness of reverse transcriptase-polymerase chain reaction for detection of rabies RNA in archival samples | journal = Japanese Journal of Infectious Diseases | volume = 60 | issue = 5 | pages = 298–9 | date = September 2007 | pmid = 17881871 }}</ref> 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 [[Sensitivity and specificity|sensitive]] or reliable as brain samples.<ref name="Fooks AR 2009" /> Cerebral inclusion bodies called [[Medicine:Negri bodies|Negri bodies]] are 100% diagnostic for rabies infection but are found in only about 80% of cases.<ref name="Sherris" /> If possible, the animal from which the bite was received should also be examined for rabies.<ref name="Ly2009">{{cite journal | vauthors = Ly S, Buchy P, Heng NY, Ong S, Chhor N, Bourhy H, Vong S | title = Rabies situation in Cambodia | journal = PLOS Neglected Tropical Diseases | volume = 3 | issue = 9 | pages = e511 | date = September 2009 | pmid = 19907631 | pmc = 2731168 | doi = 10.1371/journal.pntd.0000511 | veditors = Carabin H | id = e511 | doi-access = free }}</ref>

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.<ref>{{cite journal | vauthors = Dürr S, Naïssengar S, Mindekem R, Diguimbye C, Niezgoda M, Kuzmin I, Rupprecht CE, Zinsstag J | display-authors = 6 | title = Rabies diagnosis for developing countries | journal = PLOS Neglected Tropical Diseases | volume = 2 | issue = 3 | pages = e206 | date = March 2008 | pmid = 18365035 | pmc = 2268742 | doi = 10.1371/journal.pntd.0000206 | veditors = Cleaveland S | id = e206 | doi-access = free }}</ref> 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.<ref name="CDC2018New" /> The test was developed by the Centers for Disease Control and Prevention (CDC) in 2018.<ref name="CDC2018New">{{cite web|title=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|access-date=23 May 2018|language=en-us|date=16 May 2018}}</ref>

The [[Medicine:Differential diagnosis|differential diagnosis]] in a case of suspected human rabies may initially include any cause of [[Medicine:Encephalitis|encephalitis]], in particular infection with viruses such as [[Biology:Herpesviridae|herpesviruses]], [[Biology:Enterovirus|enterovirus]]es, 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, [[Biology:Echovirus|echovirus]]es, [[Biology:Poliovirus|poliovirus]]es, and human enteroviruses 68 to 71.<ref>{{cite web|url=http://emedicine.medscape.com/article/220967-diagnosis |title=Rabies: Differential Diagnoses & Workup |work=eMedicine Infectious Diseases |date=3 October 2008 |access-date=2010-01-30 |url-status=live |archive-url=https://web.archive.org/web/20101128074240/http://emedicine.medscape.com/article/220967-diagnosis |archive-date=28 November 2010 }}</ref>

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 [[Biology:Nipah virus|Nipah virus]], a newly recognized [[Biology:Paramyxoviridae|paramyxovirus]].<ref name="refDiseasesOfSwine">{{cite book |vauthors=Taylor DH, Straw BE, Zimmerman JL, D'Allaire S |title=Diseases of swine |publisher=Blackwell |location=Oxford |year=2006 |pages=463–5 |isbn=978-0-8138-1703-3 |url=https://books.google.com/books?id=3o9l77HdZkgC&q=diseases%20of%20swine&pg=PA463 |access-date=2010-01-30}}</ref> 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.<ref>{{cite book |title=Inflammatory Disorders Of The Nervous System: Pathogenesis, Immunology, and Clinical Management | vauthors = Minagar A, Alexander JS |year=2005 |publisher=Humana Press |isbn=978-1-58829-424-1 }}</ref>

== Prevention ==

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.<ref>{{cite journal |vauthors=Geison GL |title=Pasteur's work on rabies: reexamining the ethical issues |journal=The Hastings Center Report |volume=8 |issue=2 |pages=26–33 |date=April 1978 |pmid=348641 |doi=10.2307/3560403 |jstor=3560403}}</ref> Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines.<ref name="pmid15069272">{{cite journal |vauthors=Srivastava AK, Sardana V, Prasad K, Behari M |title=Diagnostic dilemma in flaccid paralysis following anti-rabies vaccine |journal=Neurology India |volume=52 |issue=1 |pages=132–3 |date=March 2004 |pmid=15069272 |url=http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2004;volume=52;issue=1;spage=132;epage=133;aulast=Srivastava |url-status=live |archive-url=https://web.archive.org/web/20090802195908/http://www.neurologyindia.com/article.asp?issn=0028-3886%3Byear%3D2004%3Bvolume%3D52%3Bissue%3D1%3Bspage%3D132%3Bepage%3D133%3Baulast%3DSrivastava |archive-date=2 August 2009}}</ref>

The human diploid cell rabies vaccine was started in 1967. Less expensive purified chicken embryo cell vaccine and purified [[Biology:Vero cell|vero cell]] rabies vaccine are now available.<ref name="Ly2009" /> 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.<ref name="Reece_2006">{{cite journal |vauthors=Reece JF, Chawla SK |title=Control of rabies in Jaipur, India, by the sterilisation and vaccination of neighbourhood dogs |journal=The Veterinary Record |volume=159 |issue=12 |pages=379–83 |date=September 2006 |pmid=16980523 |doi=10.1136/vr.159.12.379 |s2cid=5959305 }}</ref> Immunization before exposure has been used in both human and nonhuman populations, where, as in many jurisdictions, domesticated animals are required to be vaccinated.<ref>{{cite web |title=Compendium of Animal Rabies Prevention and Control |date=31 December 2007 |access-date=2010-01-03 |publisher=National Association of State Public Health Veterinarians |url=http://www.nasphv.org/Documents/RabiesCompendium.pdf |url-status=dead |archive-url=https://web.archive.org/web/20100712235752/http://www.nasphv.org/Documents/RabiesCompendium.pdf |archive-date=12 July 2010 }}</ref>

[[File:Rabiesvaccination.png|thumb|A young girl about to receive PEP after being bitten by an animal thought to be rabid]]

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:<ref>{{cite report |date=2007 |title=2007 Annual Report |url=http://www.dhss.mo.gov/living/healthcondiseases/communicable/communicabledisease/annual07/Annual07.pdf |publisher=Bureau of Communicable Disease Control and Prevention |access-date=8 March 2011 |archive-date=11 May 2020 |archive-url=https://web.archive.org/web/20200511190553/https://health.mo.gov/living/healthcondiseases/communicable/communicabledisease/annual07/Annual07.pdf |url-status=dead }}</ref>

* 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.<ref>{{cite web|url=https://www.who.int/mediacentre/events/annual/world_rabies_day/en/ |title=World Rabies Day |publisher=World Health Organization (WHO) |url-status=live |archive-url=https://web.archive.org/web/20111231020108/http://www.who.int/mediacentre/events/annual/world_rabies_day/en/ |archive-date=31 December 2011}}</ref>

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 {{wipe|Canada}}, {{wipe|France}}, and the {{wipe|United States}}. In {{wipe|Montreal}}, Quebec, Canada, baits are successfully used on raccoons in the Mount-Royal Park area. Vaccination campaigns may be expensive, but cost-benefit analysis suggests baits may be a cost-effective method of control.<ref>{{cite journal |vauthors=Meltzer MI |title=Assessing the costs and benefits of an oral vaccine for raccoon rabies: a possible model |journal=Emerging Infectious Diseases |volume=2 |issue=4 |pages=343–9 |date=October–December 1996 |pmid=8969251 |pmc=2639934 |doi=10.3201/eid0204.960411}}</ref> In Ontario, a dramatic drop in rabies was recorded when an aerial bait-vaccination campaign was launched.<ref name=Grambo>{{cite book | vauthors = Grambo RL |title=The World of the Fox |year=1995 |publisher=Greystone Books |location=Vancouver |isbn=978-0-87156-377-4 |pages=[https://archive.org/details/worldoffox00gram/page/94 94–5] |url-access=registration |url=https://archive.org/details/worldoffox00gram/page/94}}</ref>

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.<ref name="CDC_Rabies_Epi">{{cite web |url=https://www.cdc.gov/rabies/location/usa/index.html |title=Rabies in the U.S. |publisher=Centers for Disease Control and Prevention (CDC) |date=22 April 2011 |access-date=31 December 2011 |url-status=live |archive-url=https://web.archive.org/web/20111231023841/http://www.cdc.gov/rabies/location/usa/index.html |archive-date=31 December 2011}}</ref>

==Treatment==
===After exposure===
Treatment after exposure can prevent the disease if given within 10 days. The rabies vaccine is 100% effective if given before symptoms of rabies appear.<ref name=Sherris/><ref name="CDC_Rabies_PEP"/><ref name="Lite2009">{{cite magazine|url=http://www.scientificamerican.com/article.cfm?id=jeanna-giese-rabies-survivor |title=Medical Mystery: Only One Person Has Survived Rabies without Vaccine—But How? |magazine=Scientific American | vauthors = Lite J |date=8 October 2008 |access-date=2010-01-30 |url-status=live |archive-url=https://web.archive.org/web/20091105091606/http://www.scientificamerican.com/article.cfm?id=jeanna-giese-rabies-survivor |archive-date=5 November 2009}}</ref> Every year, more than 15&nbsp;million people get vaccinated after potential exposure. While this works well, the cost is significant.<ref>{{Cite web|url=https://www.who.int/neglected_diseases/news/human_rabies_better_coordination_and_emerging_technology/en/ |title=Human rabies: better coordination and emerging technology to improve access to vaccines |publisher=World Health Organization |language=en-GB |access-date=2017-02-23 |url-status=dead |archive-url=https://web.archive.org/web/20170224131644/http://www.who.int/neglected_diseases/news/human_rabies_better_coordination_and_emerging_technology/en/ |archive-date=24 February 2017}}</ref> 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.<ref>{{cite web | url = https://www.cdc.gov/mmwr/pdf/rr/rr5902.pdf | title = Use of a Reduced (4-Dose) Vaccine Schedule for Postexposure Prophylaxis to Prevent Human Rabie | archive-url = https://web.archive.org/web/20110725112251/http://www.cdc.gov/mmwr/PDF/rr/rr5902.pdf | archive-date=25 July 2011 | work = Centers for Disease Control and Prevention (CDC) }}</ref> HRIG is expensive and makes up most of the cost of post-exposure treatment, ranging as high as several thousand dollars.<ref>{{cite web|url=https://www.cdc.gov/rabies/location/usa/cost.html |title=Cost of Rabies Prevention | work = U.S. Centers for Disease Control and Prevention |url-status=live |archive-url=https://web.archive.org/web/20160329143011/http://www.cdc.gov/rabies/location/usa/cost.html |archive-date=29 March 2016 |date=11 June 2019}}</ref> In the UK, one dose of HRIG costs the National Health Service £1,000,<ref>{{Cite web|url=https://bnf.nice.org.uk/medicinal-forms/rabies-immunoglobulin.html|title=BNF via NICE is only available in the UK | work = The National Institute for Health and Care Excellence | location = UK }}</ref> although this is not flagged as a "high-cost medication".<ref>{{Cite web|url=https://formularymk.nhs.uk/chaptersSubDetails.asp?FormularySectionID=14&SubSectionRef=14.05&SubSectionID=A100|title=Rabies immunoglobulin | work = Milton Keynes Formulary Formulary }}</ref> A full course of vaccine costs £120–180.<ref>{{Cite web|url=https://www.nhs.uk/conditions/rabies/vaccination/|title=Rabies - Vaccination|date=23 October 2017 | work = National Health Services (NHS) | location = UK }}</ref> 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.<ref name="CDC_Rabies_PEP">{{cite web |url=https://www.cdc.gov/rabies/exposure/postexposure.html |title=Rabies Post-Exposure Prophylaxis |publisher=Centers for Disease Control and Prevention (CDC) |date=23 December 2009 |access-date=2010-01-30 |url-status=dead |archive-url=https://web.archive.org/web/20100201085054/http://www.cdc.gov/rabies/exposure/postexposure.html |archive-date=1 February 2010}}</ref>

People who have previously been vaccinated against rabies do not need to receive the immunoglobulin—only the postexposure vaccinations on days 0 and 3.<ref>{{cite book |last1=Park K |title=Park's Textbook of Prentive and Social Medicine |date=2013 |publisher=Banarsidas Bhanot, Jabalpur |isbn=978-9382219026 |edition=22nd | page = 254 }}</ref> The side effects of modern [[Medicine:Cell-based vaccine|cell-based vaccine]]s 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.<ref name="Wilde1991">{{cite journal | vauthors = Hicks DJ, Fooks AR, Johnson N | title = Developments in rabies vaccines | journal = Clinical and Experimental Immunology | volume = 169 | issue = 3 | pages = 199–204 | date = September 2012 | pmid = 22861358 | pmc = 3444995 | doi = 10.1093/clinids/13.4.644 }}</ref> It is being phased out and replaced by affordable World Health Organization intradermal-vaccination regimens.<ref name="Ly2009" /> In children less than a year old, the lateral thigh is recommended.<ref>{{cite web|url=https://www.who.int/ith/vaccines/rabies/en/ |title=Rabies |publisher=[[Organization:World Health Organization|World Health Organization]] |access-date=1 February 2015 |url-status=live |archive-url=https://web.archive.org/web/20150215014809/http://www.who.int/ith/vaccines/rabies/en/ |archive-date=15 February 2015}}</ref> 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.<ref>{{cite web |url=http://www.health.vic.gov.au/ideas/bluebook/rabies_info |title=Rabies & Australian bat lyssavirus information sheet |publisher=Health.vic.gov.au |access-date=2012-01-30 |url-status=dead |archive-url=https://web.archive.org/web/20110818081218/http://www.health.vic.gov.au/ideas/bluebook/rabies_info |archive-date=18 August 2011}}</ref> [[Chemistry:Povidone-iodine|Povidone-iodine]] or alcohol is then recommended to reduce the virus further.<ref>{{cite web |author1=National Center for Disease Control |title=National Guidelines on Rabies Prophylaxis |url=http://nicd.nic.in/Rabies_guidelines2014.pdf |access-date=5 September 2014 |year=2014 |url-status=dead |archive-url=https://web.archive.org/web/20140905235321/http://nicd.nic.in/Rabies_guidelines2014.pdf |archive-date=5 September 2014}}</ref>

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 [[Medicine:Post-exposure prophylaxis|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|cost–benefit analysis]].<ref>{{cite journal |vauthors=De Serres G, Skowronski DM, Mimault P, Ouakki M, Maranda-Aubut R, Duval B |title=Bats in the bedroom, bats in the belfry: reanalysis of the rationale for rabies postexposure prophylaxis |journal=Clinical Infectious Diseases |volume=48 |issue=11 |pages=1493–1499 |date=June 2009 |pmid=19400689 |doi=10.1086/598998 |doi-access=free}}</ref> However, a 2002 study has supported the protocol of precautionary administration 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.<ref>{{cite journal |vauthors=Despond O, Tucci M, Decaluwe H, Grégoire MC, S Teitelbaum J, Turgeon N |title=Rabies in a nine-year-old child: The myth of the bite |journal=The Canadian Journal of Infectious Diseases |volume=13 |issue=2 |pages=121–125 |date=March 2002 |pmid=18159381 |pmc=2094861 |doi=10.1155/2002/475909 |doi-access=free}}</ref>

{{anchor|Jeanna Giese}}

===After onset===

Once rabies develops, death almost certainly follows. Palliative care in a hospital setting is recommended with administration of large doses of pain medication, and sedatives in preference to physical restraint. Ice fragments can be given by mouth for thirst, but there is no good evidence intravenous hydration is of benefit.<ref name=pall>{{cite book |title=Rabies &nbsp;&ndash; Scientific Basis of the Disease and Its Management |publisher=Elsevier Science |veditors=Jackson AC, Fooks AR |isbn=9780128187050 |page=561 |chapter=Chapter 17: Therapy of human rabies |doi=10.1016/B978-0-12-818705-0.00017-0 |year=2020 |vauthors=Jackson AC |s2cid=240895449 |edition=4th}}</ref>

A treatment known as the Milwaukee protocol, which involves putting a person into a [[Medicine:Induced coma|chemically induced coma]] and using antiviral medications, has been proposed but subsequently found not to be useful.<ref name=Jack2016>{{cite journal |vauthors=Jackson AC |title=Human Rabies: a 2016 Update |journal=Curr Infect Dis Rep |volume=18 |issue=11 |pages=38 |year=2016 |pmid=27730539 |doi=10.1007/s11908-016-0540-y |s2cid=25702043 |type=Review}}</ref> It initially came into use in 2003, following Jeanna Giese, a teenage girl from Wisconsin, becoming the first person known to have survived rabies without preventive treatments before symptom onset.<ref>{{cite news | url=https://www.scientificamerican.com/article/jeanna-giese-rabies-survivor/ | title=Medical Mystery: Only One Person Has Survived Rabies without Vaccine--But How? | work = Scientific American | author = Jordan Lite | date = 8 October 2008 | accessdate = 2008-10-16 }}</ref><ref name="SciAmApr07">Rodney E. Willoughby Jr., [http://www.scientificamerican.com/article.cfm?id=a-cure-for-rabies online "A Cure for Rabies?"] ''Scientific American'', V. 256, No. 4, April 2007, p. 95.</ref> While this treatment has been tried multiple times since, there have been no further cases of survival.<ref name=Jack2016/> The protocol has since been assessed as an ineffective treatment with concerns related to the costs and ethics of its use.<ref name=Jack2016/><ref name=zeiler>{{cite journal |vauthors=Zeiler FA, Jackson AC |title=Critical Appraisal of the Milwaukee Protocol for Rabies: This Failed Approach Should Be Abandoned |journal=Can J Neurol Sci |volume=43 |issue=1 |pages=44–51 |year=2016 |pmid=26639059 |doi=10.1017/cjn.2015.331 |type=Review|doi-access=free }}</ref>

==Prognosis==
[[Biology:Vaccination|Vaccination]] after exposure, PEP, is highly successful in preventing rabies.<ref name="Lite2009"/> In unvaccinated humans, rabies is almost certainly fatal after neurological symptoms have developed.<ref name="WHO factsheet">{{cite web|url=https://www.who.int/mediacentre/factsheets/fs099/en/ |title=Rabies |date=September 2011 |publisher=World Health Organization (WHO) |access-date=31 December 2011 |url-status=live |archive-url=https://web.archive.org/web/20111231021303/http://www.who.int/mediacentre/factsheets/fs099/en/ |archive-date=31 December 2011 }}</ref>

==Epidemiology==
{{Main|Medicine:Prevalence of rabies}}
[[File:Rabies world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.5|Deaths from rabies per million persons in 2012 {{Div col|small=yes|colwidth=10em}}{{legend|#ffff20|0}}{{legend|#ff9a20|1}}{{legend|#f08015|2–4}}{{legend|#e06815|5–9}}{{legend|#d85010|10–17}}{{legend|#d02010|18–69}}{{div col end}}]]
[[File:Rabies Free Countries and Territories.svg|thumb|upright=1.5|Map of rabies-free countries and territories]]

In 2010, an estimated 26,000 people died from rabies, down from 54,000 in 1990.<ref name=Loz2012>{{cite journal | vauthors = Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, etal | title = 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 | journal = Lancet | volume = 380 | issue = 9859 | pages = 2095–128 | date = December 2012 | pmid = 23245604 | doi = 10.1016/S0140-6736(12)61728-0 | pmc = 10790329 | hdl = 10536/DRO/DU:30050819 | s2cid = 1541253 | url = https://zenodo.org/record/2557786 | hdl-access = free }}</ref> The majority of the deaths occurred in Asia and Africa.<ref name="WHO factsheet" /> {{As of|2015}}, India (approximately 20,847), followed by China (approximately 6,000) and the Democratic Republic of the Congo (5,600), had the most cases.<ref>{{cite journal | vauthors = Hampson K, Coudeville L, Lembo T, Sambo M, Kieffer A, Attlan M, Barrat J, Blanton JD, Briggs DJ, Cleaveland S, Costa P, Freuling CM, Hiby E, Knopf L, Leanes F, Meslin FX, Metlin A, Miranda ME, Müller T, Nel LH, Recuenco S, Rupprecht CE, Schumacher C, Taylor L, Vigilato MA, Zinsstag J, Dushoff J | display-authors = 6 | title = Estimating the global burden of endemic canine rabies | journal = PLOS Neglected Tropical Diseases | volume = 9 | issue = 4 | pages = e0003709 | date = April 2015 | pmid = 25881058 | pmc = 4400070 | doi = 10.1371/journal.pntd.0003709 | doi-access = free }}</ref> 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.<ref>{{Cite web|url=https://www.who.int/mediacentre/factsheets/fs099/en/ |title=Rabies |website=World Health Organization |language=en-GB |access-date=2017-02-23 |url-status=live |archive-url=https://web.archive.org/web/20170215062245/http://www.who.int/mediacentre/factsheets/fs099/en/ |archive-date=15 February 2017 }}</ref>

===India===
{{wipe|India}} has the highest rate of human rabies in the world, primarily because of stray dogs,<ref>{{cite news |url=https://www.independent.co.uk/news/science/dead-as-a-dodo-why-scientists-fear-for-the-future-of-of-the-asian-vulture-818059.html |title=Dead as a dodo? Why scientists fear for the future of the Asian vulture |access-date=2008-10-11 | vauthors = Dugan E |date=30 April 2008 |newspaper=The Independent |quote=India now has the highest rate of human rabies in the world. |location=London |url-status=dead |archive-url=https://web.archive.org/web/20080517100919/http://www.independent.co.uk/news/science/dead-as-a-dodo-why-scientists-fear-for-the-future-of-of-the-asian-vulture-818059.html |archive-date=17 May 2008}}</ref> whose number has greatly increased since a 2001 law forbade the killing of dogs.<ref name="harris">{{cite news|url=https://www.nytimes.com/2012/08/07/world/asia/india-stray-dogs-are-a-menace.html |title=Where Streets Are Thronged With Strays Baring Fangs |newspaper=New York Times | vauthors = Harris G |date=6 August 2012 |access-date=6 August 2012 |url-status=live |archive-url=https://web.archive.org/web/20120808125223/http://www.nytimes.com//2012/08/07/world/asia/india-stray-dogs-are-a-menace.html |archive-date=8 August 2012 }}</ref> Effective control and treatment of rabies in India is hindered by a form of mass hysteria known as [[Social:Puppy pregnancy syndrome|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.<ref>{{cite web | url = http://www.dw.de/medicine-challenges-indian-superstition/a-16489334 | title = Medicine challenges Indian superstition | work = DW.DE | date = 31 December 2012 | archive-url = https://web.archive.org/web/20130131194746/http://www.dw.de/medicine-challenges-indian-superstition/a-16489334 | archive-date=31 January 2013 }}</ref> An estimated 20,000 people die every year from rabies in India, more than a third of the global total.<ref name="harris"/>

===Australia===
Australia has an official rabies-free status,<ref>{{cite web | url = https://www.who.int/rabies/rabies_maps/en/index.html | title = Essential rabies maps | archive-url = https://web.archive.org/web/20100217210150/http://www.who.int/rabies/rabies_maps/en/index.html | archive-date = 17 February 2010 | work = World Health Organization (WHO) }}</ref> although [[Biology:Australian bat lyssavirus|Australian bat lyssavirus]] (ABLV), discovered in 1996, is a rabies-causing virus related to the rabies virus prevalent in Australian native bat populations.

===United States===
[[File:Mm6823e1-F1.gif|thumb|upright=1.5|Rabies cases in humans and domestic animals — United States, 1938–2018]]

Canine-specific rabies has been eradicated in the United States, but rabies is common among wild animals, and an average of 100 dogs become infected from other wildlife each year.<ref>{{cite web|title=CDC – Rabies Surveillance in the U.S.: Human Rabies – Rabies |url=https://www.cdc.gov/rabies/location/usa/surveillance/human_rabies.html |website=www.cdc.gov |access-date=10 April 2017 |language=en-us |url-status=live |archive-url=https://web.archive.org/web/20170118072742/https://www.cdc.gov/rabies/location/usa/surveillance/human_rabies.html |archive-date=18 January 2017 }}</ref><ref>{{cite news|url=https://www.reuters.com/article/us-rabies-usa-idUSN0741162020070907 |title=U.S. free of canine rabies virus | vauthors = Fox M |date=7 September 2007 |newspaper={{wipe|Reuters}} |access-date=11 April 2017 |quote="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. |url-status=live |archive-url=https://web.archive.org/web/20170517072630/https://www.reuters.com/article/us-rabies-usa-idUSN0741162020070907 |archive-date=17 May 2017 }}</ref>

Due to 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.<ref name=MMWR2019/> Among the 89 infections acquired in the United States, 62 (70%) were attributed to bats.<ref name=MMWR2019>{{cite journal | vauthors = Pieracci EG, Pearson CM, Wallace RM, Blanton JD, Whitehouse ER, Ma X, Stauffer K, Chipman RB, Olson V | display-authors = 6 | title = Vital Signs: Trends in Human Rabies Deaths and Exposures - United States, 1938-2018 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 68 | issue = 23 | pages = 524–528 | date = June 2019 | pmid = 31194721 | pmc = 6613553 | doi = 10.15585/mmwr.mm6823e1 }}</ref> The most recent rabies death in the United States was in November 2021, where a Texas child was bitten by a bat in late August 2021 but his parents failed to get him treatment. He died less than three months later.<ref>{{Cite journal |last=Blackburn |first=Dawn |date=2022 |title=Human Rabies — Texas, 2021 |journal=MMWR. Morbidity and Mortality Weekly Report |language=en-us |volume=71 |issue=49 |pages=1547–1549 |doi=10.15585/mmwr.mm7149a2 |pmid=36480462 |pmc=9762899 |issn=0149-2195|doi-access=free }}</ref>

===Europe===
Either no or very few cases of rabies are reported each year in Europe; cases are contracted both during travel and in Europe.<ref>{{cite web|url=http://ecdc.europa.eu/sites/portal/files/documents/AER_for_2015-rabies.pdf|title= Surveillance Report - Annual Epidemiological Report for 2015 - Rabies  | publisher = European Centre for Disease Prevention and Control (ECDC) | access-date=30 August 2018}}</ref>

In Switzerland the disease was virtually eliminated after scientists placed chicken heads laced with live [[Medicine:Attenuated vaccine|attenuated vaccine]] in the Swiss Alps.<ref name="Grambo"/> Foxes, proven to be the main source of rabies in the country, ate the chicken heads and became immunized.<ref name="Grambo"/><ref name="thefactsource.com">{{cite web |url=https://thefactsource.com/switzerland-rabies-epidemic-air-dropping-chicken-heads/ |title=Switzerland ended rabies epidemic by air dropping vaccinated chicken heads from helicopters | work = thefactsource.com |access-date=2019-12-10|date=20 November 2019 }}</ref>

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 [[Place:Balkans|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.<ref>{{cite web|url=http://www.izsvenezie.com/rabies-in-africa-the-resolab-network/ |title=Rabies in Africa: The RESOLAB network |date=29 June 2015 |access-date=2016-04-18 |url-status=live |archive-url=https://web.archive.org/web/20160803081821/http://www.izsvenezie.com/rabies-in-africa-the-resolab-network/ |archive-date=3 August 2016 }}</ref><ref>{{cite web|url=http://www.quotidianosanita.it/governo-e-parlamento/articolo.php?articolo_id=13650 |title=Ministero della Salute: "Italia è indenne dalla rabbia". l'Ultimo caso nel 2011 - Quotidiano Sanità |access-date=2016-04-18 |url-status=live |archive-url=https://web.archive.org/web/20160603183359/http://www.quotidianosanita.it/governo-e-parlamento/articolo.php?articolo_id=13650 |archive-date=3 June 2016 }}</ref>

The United Kingdom has been free of rabies since the early 20th century except for a [[Biology:European bat 2 lyssavirus|rabies-like virus (EBLV-2)]] in a few Daubenton's bats. There has been one fatal case of EBLV-2 transmission to a human.<ref>{{Cite news | url=http://news.bbc.co.uk/1/hi/scotland/2509375.stm | title=Man dies from rabies after bat bite| date=2002-11-24 | work = BBC News }}</ref> 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.<ref>{{cite web |url=https://www.nhs.uk/conditions/rabies/ |title=Rabies|website=NHS |date=23 February 2017 |access-date= 30 August 2018}}</ref><ref>{{cite news |url=https://www.bbc.co.uk/news/health-18188682 |title=Q&A: Rabies|website=BBC News |date=17 April 2015 |access-date= 30 August 2018}}</ref>

Sweden and mainland Norway have been free of rabies since 1886.<ref>{{cite journal | vauthors = Mehnert E |title=Rabies och bekämpningsåtgärder i 1800-talets Sverige |journal=Svensk veterinärtidning | trans-journal = Swedish veterinary magazine |date=1988 |volume=1988/40 |pages=277–88 |trans-title=Rabies and remedies in 19th century Sweden |publisher=Sveriges veterinärförbund |language=Swedish}}</ref> Bat rabies antibodies (but not the virus) have been found in bats.<ref>{{cite web |title=Fladdermusrabies | trans-title = Bat rabies |url=https://www.sva.se/amnesomraden/djursjukdomar-a-o/fladdermusrabies/ | work = Statens Veterinärmedicinska Anstalt | trans-work = State Veterinary Medical Institution |access-date=2022-10-28 |language=Swedish}}</ref> On Svalbard, animals can cross the arctic ice from Greenland or Russia.

=== Mexico ===
Mexico was certified by the [[Organization:World Health Organization|World Health Organization]] as being free of dog-transmitted rabies in 2019 because no case of dog-human transmission had been recorded in two years.<ref>{{cite web|url=https://www.bbc.com/mundo/noticias-50390407|title=Cómo México se convirtió en el primer país del mundo libre de rabia transmitida por perros | trans-title = How Mexico became the first country in the world free of rabies transmitted by dogs | language = Spanish |website =BBC News|date=12 November 2019|access-date=12 November 2019}}</ref>

==History==
Rabies has been known since around 2000 BC.<ref>{{cite journal | vauthors = Adamson PB | title = The spread of rabies into Europe and the probable origin of this disease in antiquity | journal = Journal of the Royal Asiatic Society of Great Britain & Ireland. Royal Asiatic Society of Great Britain and Ireland | volume = 109 | issue = 2 | pages = 140–4 | year = 1977 | pmid = 11632333 | doi = 10.1017/S0035869X00133829 | jstor = 25210880 | s2cid = 27354751 }}</ref> The first written record of rabies is in the [[Place:Mesopotamia|Mesopotamia]]n Codex of Eshnunna ({{circa|1930 BC}}), which dictates that the owner of a dog showing symptoms of rabies should take preventive measures against bites. If another person were<!--subjunctive--> bitten by a rabid dog and later died, the owner was heavily fined.<ref>{{cite book | vauthors = Dunlop RH, Williams DJ | title = Veterinary Medicine: An Illustrated History | publisher = Mosby | year= 1996 | isbn=978-0-8016-3209-9 }}</ref>

In Ancient Greece, rabies was supposed to be caused by Lyssa, the spirit of mad rage.<ref>{{Cite web|title=Rabies: an ancient disease|url=https://www.gob.mx/salud/articulos/56248 | work = Gobierno de México }}</ref>

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.<ref>{{cite book| vauthors = Barrett AD, Stanberry LR |title=Vaccines for Biodefense and Emerging and Neglected Diseases |publisher=[[Company:Academic Press|Academic Press]] |date=2009 |page=612 |language=en |url=https://books.google.com/books?id=6Nu058ZNa1MC |isbn=9780080919027 |access-date=2016-01-08 |url-status=live |archive-url=https://web.archive.org/web/20160428020308/https://books.google.com/books?id=6Nu058ZNa1MC |archive-date=28 April 2016 }}</ref>

Rabies appears to have originated in the Old World, the first [[Biology:Epizootic|epizootic]] in the New World occurring in Boston in 1768.<ref>{{cite book | vauthors = Baer GM | title = The Natural History of Rabies | edition = 2nd | publisher = CRC Press | date = 1991 | isbn = 978-0-8493-6760-1 | url =  https://books.google.com/books?id=dw8qW6jcfWUC&q=history+of+rabies&pg=PA1 | quote = 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 }}</ref>

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 [[Philosophy:Magical thinking|magical thinking]], dogs were branded with the key in hopes of protecting them from rabies.

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.<ref name="Rotivel"/>

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.<ref name="Baer1991">{{cite book| vauthors = Baer G |title=The Natural History of Rabies|url=https://books.google.com/books?id=dw8qW6jcfWUC&q=rabies+history&pg=PA1|publisher=CRC Press|access-date=31 October 2011|isbn=9780849367601|year=1991}}</ref> Louis Pasteur's 1885 nerve tissue vaccine was successful, and was progressively improved to reduce often severe side-effects.<ref name=Giesen2015/>

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 [[Social:Zombie|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.<ref>{{cite web| vauthors = Than K |title='Zombie Virus' Possible via Rabies-Flu Hybrid? |url=http://news.nationalgeographic.com/news/2010/10/1001027-rabies-influenza-zombie-virus-science/ |website=National Geographic |access-date=13 September 2015 |url-status=dead |archive-url=https://web.archive.org/web/20150913232030/http://news.nationalgeographic.com/news/2010/10/1001027-rabies-influenza-zombie-virus-science/ |archive-date=13 September 2015 |date=27 October 2010 }}</ref>

<gallery widths="200" heights="200">
File:Cantigas de Santa Maria-275-5.jpg|Miniature of the ''Cantiga'' #275 depicting two monks hospitaller with rabies being carried before St. Mary of Terena.<ref>{{Cite book|pages=172–173|year=2002|title=La asistencia a los enfermos en Castilla en la Baja Edad Media| vauthors = Santo Tomás Pérez M |isbn=84-688-3906-X|url=http://www.cervantesvirtual.com/descargaPdf/la-asistencia-a-los-enfermos-en-castilla-en-la-baja-edad-media--0/|publisher=[[Organization:University of Valladolid|Universidad de Valladolid]]|via=[[Biblioteca Virtual Miguel de Cervantes]]}}</ref>
File:Middle Ages rabid dog.jpg|A woodcut from the [[History:Middle Ages|Middle Ages]] showing a rabid dog
File:Sauvages de la Croix, François Boissier de – Dissertation sur la nature et la cause de la Rage, 1777 – BEIC 3001126.jpg|François Boissier de Sauvages de Lacroix, ''Della natura e causa della rabbia'' (''Dissertation sur la nature et la cause de la Rage''), 1777
File:Medieval rabies folio.jpg|alt=An ancient folio from the medieval times depicting a rabid dog biting a man. circa 1224|An Arabic [[Folio|folio]] from the [[History:Middle Ages|medieval]] times depicting a rabid [[Biology:Dog|dog]] biting a man. circa 1224
</gallery>

==Other animals==
[[File:PHIL 2184.png|thumb|Two dogs with the paralytic, or dumb, form of rabies]]

Rabies is infectious to [[Biology:Mammal|mammal]]s; three stages of central nervous system infection are recognized. The clinical course is often shorter in animals than in humans, but result in similar symptoms and almost always death. 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 or attack anything near. In some cases, animals skip the excitative stage and develop paralysis, as in the third phase; the paralytic phase. This stage develops due to damage to motor neurons. Incoordination is seen, owing to rear limb [[Engineering:Paralysis|paralysis]], and drooling and difficulty swallowing is caused by paralysis of facial and throat muscles. Death is usually caused by [[Medicine:Respiratory arrest|respiratory arrest]].<ref name=Ettinger_1995>{{cite book| vauthors = Ettinger SJ, Feldman EC |title=Textbook of Veterinary Internal Medicine|edition=4th|publisher=W.B. Saunders Company|year=1995|isbn=978-0-7216-6795-9}}</ref>

== See also ==
* [[Biology:Eradication of infectious diseases|Eradication of infectious diseases]]
* Madstone (folklore)
* [[Medicine:Rabies in Haiti|Rabies in Haiti]]

== References ==
{{Reflist}}

==Further reading==
*Pankhurst, Richard. "The history and traditional treatment of rabies in Ethiopia." ''Medical History'' 14, no. 4 (1970): 378–389.

== External links ==
{{offline|med}}
{{EB1911 poster|Hydrophobia}}
<!--------------------
DEFAULT SHORT: ALPHA WEBPAGE TITLE, WEBSITE TITLE
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* {{Curlie|Health/Conditions_and_Diseases/Infectious_Diseases/Viral/Rabies/}}
* {{cite web|title=Rabies|url=https://www.cdc.gov/rabies/index.html|publisher=Centers for Disease Control and Prevention|access-date=12 August 2012}}
* {{cite web | url = https://www.viprbrc.org/brc/search_landing.spg?decorator=rhabdo | work = Virus Pathogen Database and Analysis Resource (ViPR) | title = Rhabdoviridae }}
* {{cite web | url = http://www.oie.int/en/animal-health-in-the-world/rabies-portal/ | title = OIE's Rabies Portal | archive-url = https://web.archive.org/web/20200813050639/https://www.oie.int/en/animal-health-in-the-world/rabies-portal/ | archive-date = 13 August 2020 }}
* {{cite web | vauthors = Karuturi S | date = 20 June 2009 | url = http://www.doctorshangout.com/forum/topics/videos-of-aerophobia-and | title = Videos of Aerophobia and Hydrophobia in a suspected Rabies case | work =  Doctors Hangout | archive-url = https://web.archive.org/web/20160402053228/http://www.doctorshangout.com/forum/topics/videos-of-aerophobia-and | archive-date = 2 April 2016 }}
* {{cite web |title=''Rabies virus'' |work=NCBI Taxonomy Browser |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11292 |id=11292}}

{{Medical condition classification and resources
| DiseasesDB = 11148
| ICD10 = {{ICD10|A|82||a|82}}
| ICD9 = {{ICD9|071}}
| ICDO =
| OMIM =
| MedlinePlus = 001334
| eMedicineSubj = med
| eMedicineTopic = 1374
| eMedicine_mult = {{eMedicine2|eerg|493}} {{eMedicine2|ped|1974}}
| MeshID = D011818
|Orphanet=770
}}
{{Viral diseases}}
{{Zoonotic viral diseases}}

[[Category:Neurological disorders]]
[[Category:Tropical diseases]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Zoonoses]]
[[Category:Infectious diseases]]

{{Sourceattribution|Rabies}}