Editing Rabies (section)

== Diagnosis ==

Rabies can be difficult to diagnose because, in the early stages, it is easily confused with other diseases or with aggressiveness.<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  [[Gold standard (test)|reference method]] for diagnosing rabies is the fluorescent antibody test (FAT),  an [[immunohistochemistry]] procedure, which is recommended by the [[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 }}</ref> The [[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 [[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 | editor1-last = Carabin | id = e511 | editor1-first = Hélène }}</ref>

Some [[Light microscopy#Optical microscopy|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 | editor1-last = Cleaveland | id = e206 | editor1-first = Sarah }}</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 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 [[differential diagnosis]] in a case of suspected human rabies may initially include any cause of [[encephalitis]], in particular infection with viruses such as [[herpesviridae|herpesviruses]], [[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 [[coxsackie virus|coxsackievirus]]es, [[echovirus]]es, [[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 [[Nipah virus]], a newly recognized [[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 |last1=Minagar |first1=Alireza | first2 = J. Steven | last2 = Alexander | name-list-style = vanc  |year=2005 |publisher=Humana Press |isbn=978-1-58829-424-1 }}</ref> 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.{{cn|date=May 2021}}