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{{Rabies}}
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==Overview==
The [[symptoms]] of rabies depend upon the stage of the disease at the time of presentation. Rabies may present during [[incubation period]], prodromal period, acute neurologic period (clinical rabies), or [[coma]].  Patients are asymptomatic during the incubation period. Prodromal symptoms may include low-grade [[fever]], [[chills]], [[malaise]], [[myalgias]], [[weakness]], [[fatigue]], [[anorexia]], [[sore throat]], [[nausea]], [[vomiting]] and [[headache]].  Clinical rabies can present as encephalitic ("furious") rabies or paralytic ("dumb") rabies.  Encephalitic rabies is more common and presents as [[hydrophobia]], aerophobia, facial grimace, [[opisthotonos]], [[autonomic instability]], [[dysarthria]], [[dysphagia]], and [[diplopia]]. Rabies eventually results in progressive [[encephalopathy]], [[respiratory arrest]], [[coma]] and death within 10 days of the onset of [[symptoms]].
== History and Symptoms ==
== History and Symptoms ==
[[Image:Rabies Virus EM PHIL 1876.JPG|thumb|250px|Micrograph with numerous rabies [[virion]]s (small dark-grey rod-like particles) and [[Negri bodies]], larger [[pathognomonic]] cellular inclusions of rabies infection]]
=== History ===
The following aspects must be inquired about while taking a history from patients with suspected rabies:
*Details about the interaction with the animal
*Any unusual behavior by the animal
*Availability of the animal for testing
*[[Vaccination]] status of the animal<ref name="pmid15215738">{{cite journal |vauthors= |title=Compendium of animal rabies prevention and control, 2004: National Association of State Public Health Veterinarians, Inc. (NASPHV) |journal=MMWR Recomm Rep |volume=53 |issue=RR-9 |pages=1–8 |year=2004 |pmid=15215738 |doi= |url=}}</ref>
 
=== Symptoms ===
The symptoms of rabies depend upon the stage of the disease at the time of presentation. Rabies may present at any one of the following stages:
*[[Incubation period]]
*[[Prodromal symptoms|Prodromal]] period
*Acute [[Neurological|neurologic]] period (clinical rabies)
*[[Coma]]
 
== Incubation period ==
* During [[incubation period]], the patient is [[asymptomatic]] as the virus has not yet entered the [[central nervous system]] ([[CNS]]).
* [[Antibody]] response may not be observed during [[incubation period]] as the virus is still isolated from the [[immune system]].
* The duration of [[incubation period]] varies. The average duration is 20-90 days but can range from a few days to many years.<ref name="pmid15976877">{{cite journal |vauthors=Knobel DL, Cleaveland S, Coleman PG, Fèvre EM, Meltzer MI, Miranda ME, Shaw A, Zinsstag J, Meslin FX |title=Re-evaluating the burden of rabies in Africa and Asia |journal=Bull. World Health Organ. |volume=83 |issue=5 |pages=360–8 |year=2005 |pmid=15976877 |pmc=2626230 |doi=/S0042-96862005000500012 |url=}}</ref><ref name="pmid9634432">{{cite journal |vauthors=Noah DL, Drenzek CL, Smith JS, Krebs JW, Orciari L, Shaddock J, Sanderlin D, Whitfield S, Fekadu M, Olson JG, Rupprecht CE, Childs JE |title=Epidemiology of human rabies in the United States, 1980 to 1996 |journal=Ann. Intern. Med. |volume=128 |issue=11 |pages=922–30 |year=1998 |pmid=9634432 |doi= |url=}}</ref><ref name="pmid12144896">{{cite journal |vauthors=Rupprecht CE, Hanlon CA, Hemachudha T |title=Rabies re-examined |journal=Lancet Infect Dis |volume=2 |issue=6 |pages=327–43 |year=2002 |pmid=12144896 |doi= |url=}}</ref><ref name="pmid24038455">{{cite journal |vauthors=Boland TA, McGuone D, Jindal J, Rocha M, Cumming M, Rupprecht CE, Barbosa TF, de Novaes Oliveira R, Chu CJ, Cole AJ, Kotait I, Kuzmina NA, Yager PA, Kuzmin IV, Hedley-Whyte ET, Brown CM, Rosenthal ES |title=Phylogenetic and epidemiologic evidence of multiyear incubation in human rabies |journal=Ann. Neurol. |volume=75 |issue=1 |pages=155–60 |year=2014 |pmid=24038455 |pmc=4118733 |doi=10.1002/ana.24016 |url=}}</ref>
'''Factors associated with a shorter incubation period:'''
 
The following factors are associated with a shorter incubation period:
* Bite on head or face (richly [[innervated]] areas)
* Multiple bites transferring heavy [[inoculum]]
* Deep and large wounds
'''Factors associated with a longer incubation period:'''
 
The following factors are associated with a longer incubation period:
* Inadequate rabies [[prophylaxis]]  
* Unknown new exposure
** It is hypothesized that a latent viral infection and/or slow replication may be associated with it.<ref name="pmid1985241">{{cite journal |vauthors=Smith JS, Fishbein DB, Rupprecht CE, Clark K |title=Unexplained rabies in three immigrants in the United States. A virologic investigation |journal=N. Engl. J. Med. |volume=324 |issue=4 |pages=205–11 |year=1991 |pmid=1985241 |doi=10.1056/NEJM199101243240401 |url=}}</ref><ref name="pmid24038455">{{cite journal |vauthors=Boland TA, McGuone D, Jindal J, Rocha M, Cumming M, Rupprecht CE, Barbosa TF, de Novaes Oliveira R, Chu CJ, Cole AJ, Kotait I, Kuzmina NA, Yager PA, Kuzmin IV, Hedley-Whyte ET, Brown CM, Rosenthal ES |title=Phylogenetic and epidemiologic evidence of multiyear incubation in human rabies |journal=Ann. Neurol. |volume=75 |issue=1 |pages=155–60 |year=2014 |pmid=24038455 |pmc=4118733 |doi=10.1002/ana.24016 |url=}}</ref><ref name="pmid23602163">{{cite journal |vauthors=Hemachudha T, Ugolini G, Wacharapluesadee S, Sungkarat W, Shuangshoti S, Laothamatas J |title=Human rabies: neuropathogenesis, diagnosis, and management |journal=Lancet Neurol |volume=12 |issue=5 |pages=498–513 |year=2013 |pmid=23602163 |doi=10.1016/S1474-4422(13)70038-3 |url=}}</ref>
 
== Prodromal period ==
* In this stage, the patient presents with non-specific signs and symptoms and rabies usually remains unsuspected at this stage
* It usually lasts from a few days to a week (3-9days)<ref name="pmid12849514">{{cite journal |vauthors=Hemachudha T, Laothamatas J, Rupprecht CE |title=Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges |journal=Lancet Neurol |volume=1 |issue=2 |pages=101–9 |year=2002 |pmid=12849514 |doi= |url=}}</ref>
* Pathognomic presentation involves following [[symptoms]] at the [[inoculation]] site:<ref name="pmid22552206">{{cite journal |vauthors= |title=Imported human rabies in a U.S. Army soldier - New York, 2011 |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=61 |issue=17 |pages=302–5 |year=2012 |pmid=22552206 |doi= |url=}}</ref>
** [[Pain]]
** [[Paresthesia]]
** [[Itching]]
** [[Tingling]] or burning
** [[Numbness]]
 
==== Common symptoms include: ====
* [[Fever|Low-grade fever]]
* [[Chills]]
* [[Malaise]]
* [[Myalgias]]
* [[Weakness]]
* [[Fatigue]]
* [[Anorexia]]
* [[Sore throat]]
* [[Nausea]]
* [[Vomiting]]
* [[Headache]]
* [[Anxiety]]
* [[Agitation]]
* [[Insomnia]]
* [[Depression]]
'''Less common symptoms''':
* [[Photophobia]]
 
== Acute neurologic period (Clinical rabies) ==
* Clinical rabies has two forms, both of them evolving from prodromal symptoms
# [[Encephalitis|Encephalitic]] ("furious") rabies- more common (80% cases)
# [[Paralytic]] ("dumb") rabies
* Occasionally atypical cases with following features have been reported:<ref name="pmid12849514">{{cite journal |vauthors=Hemachudha T, Laothamatas J, Rupprecht CE |title=Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges |journal=Lancet Neurol |volume=1 |issue=2 |pages=101–9 |year=2002 |pmid=12849514 |doi= |url=}}</ref><ref name="pmid15614231">{{cite journal |vauthors= |title=Recovery of a patient from clinical rabies--Wisconsin, 2004 |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=53 |issue=50 |pages=1171–3 |year=2004 |pmid=15614231 |doi= |url=}}</ref>
** [[Sensory]] or [[Motor control|motor]] deficits
** Choreiform movements of the bitten limb (during the [[Prodromal symptoms|prodromal]] phase)
** Focal [[brainstem]] signs
** [[Cranial nerve palsies]]
** [[Myoclonus]]
** [[Seizure]]
 
* Following factors influence the course of disease:
** The depth and extent of bite
** Proximity to head
** Amount of secretions encountered at the site of bite
 
=== (a) Encephalitic ("furious") rabies: ===
This form usually involves short episodes (furious episodes) of hyperactivity, restlessness, and agitation lasting about 5 minutes, followed by calm and lucid intervals. Furious episodes may occur spontaneously or may be triggered by stimuli such as [[visual]], [[auditory]] or [[tactile]]. Common symptoms include:<ref name="pmid15132411">{{cite journal |vauthors=Hankins DG, Rosekrans JA |title=Overview, prevention, and treatment of rabies |journal=Mayo Clin. Proc. |volume=79 |issue=5 |pages=671–6 |year=2004 |pmid=15132411 |doi=10.1016/S0025-6196(11)62291-X |url=}}</ref><ref name="pmid12849514">{{cite journal |vauthors=Hemachudha T, Laothamatas J, Rupprecht CE |title=Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges |journal=Lancet Neurol |volume=1 |issue=2 |pages=101–9 |year=2002 |pmid=12849514 |doi= |url=}}</ref>
* [[Hydrophobia]]
* Aerophobia
* Facial grimace
* [[Opisthotonos]]
* [[Autonomic instability]]
** [[Lacrimation]]
** [[Hypersalivation]]
* [[Dysarthria]]
* [[Dysphagia]]
* [[Diplopia]]
* [[Vertigo]]
*[[Agitation]]
*Combativeness
Less common symptoms:
* [[Hallucinations]]
* [[Seizures]] (generalized)
 
=== (b) Paralytic ("dumb") rabies: ===
[[Prodromal symptoms]] may be followed by flaccid paralysis that may be symmetrical/asymmetrical and needs to be differentiated from  Guillain-Barré syndrome.
 
Common symptoms:
* [[Flaccid paralysis]] in the bitten limb followed by ascending paralysis and
** Dense [[paraplegia]]
** Loss of sphincter tone
** Subsequent [[paralysis]] of the muscles of [[deglutition]] and [[respiration]], leading to death.
* [[Headache]]
* Pain in the affected [[muscle]]
* Abnormal sensation in the affected [[muscle]]
Less common symptoms:
* [[Nuchal rigidity]]
* [[Cranial nerve palsies]]
* [[Hydrophobia]]


* The period between infection and the first [[flu]]-like symptoms is normally two to twelve weeks, but can be as long as two years.
== Coma ==
* The first symptoms of rabies may be nonspecific flu-like signs — malaise, [[fever]], or [[headache]], which may last for days.
*Rabies eventually results in progressive [[encephalopathy]], [[respiratory arrest]], [[coma]] and death within 10 days of the onset of [[symptoms]].<ref name="pmid23602163">{{cite journal |vauthors=Hemachudha T, Ugolini G, Wacharapluesadee S, Sungkarat W, Shuangshoti S, Laothamatas J |title=Human rabies: neuropathogenesis, diagnosis, and management |journal=Lancet Neurol |volume=12 |issue=5 |pages=498–513 |year=2013 |pmid=23602163 |doi=10.1016/S1474-4422(13)70038-3 |url=}}</ref><ref name="pmid5082226">{{cite journal |vauthors=Hattwick MA |title=Reactions to rabies |journal=N. Engl. J. Med. |volume=287 |issue=23 |pages=1204 |year=1972 |pmid=5082226 |doi= |url=}}</ref>
* There may be discomfort or paresthesia at the site of exposure (bite), progressing within days to symptoms of cerebral dysfunction, [[anxiety]], [[confusion]], agitation, progressing to [[delirium]], abnormal behavior, [[hallucination]]s, and [[insomnia]].
* The acute period of disease typically ends after 2 to 10 days (6).
* Once clinical signs of rabies appear, the disease is nearly always fatal, and treatment is typically supportive. Disease prevention is entirely prophylactic and includes both passive antibody (immune globulin) and vaccine.
* Non-lethal exceptions are extremely rare.
* To date only six documented cases of human survival from clinical rabies have been reported and each included a history of either pre- or postexposure prophylaxis.
* The few humans who are known to have survived the disease were all left with severe [[brain damage]], with the recent exception of [[Jeanna Giese]] (see [[Rabies#Induced coma treatment|below]]).


==References==
== References ==
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Latest revision as of 23:56, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Overview

The symptoms of rabies depend upon the stage of the disease at the time of presentation. Rabies may present during incubation period, prodromal period, acute neurologic period (clinical rabies), or coma. Patients are asymptomatic during the incubation period. Prodromal symptoms may include low-grade fever, chills, malaise, myalgias, weakness, fatigue, anorexia, sore throat, nausea, vomiting and headache. Clinical rabies can present as encephalitic ("furious") rabies or paralytic ("dumb") rabies. Encephalitic rabies is more common and presents as hydrophobia, aerophobia, facial grimace, opisthotonos, autonomic instability, dysarthria, dysphagia, and diplopia. Rabies eventually results in progressive encephalopathy, respiratory arrest, coma and death within 10 days of the onset of symptoms.

History and Symptoms

History

The following aspects must be inquired about while taking a history from patients with suspected rabies:

  • Details about the interaction with the animal
  • Any unusual behavior by the animal
  • Availability of the animal for testing
  • Vaccination status of the animal[1]

Symptoms

The symptoms of rabies depend upon the stage of the disease at the time of presentation. Rabies may present at any one of the following stages:

Incubation period

Factors associated with a shorter incubation period:

The following factors are associated with a shorter incubation period:

  • Bite on head or face (richly innervated areas)
  • Multiple bites transferring heavy inoculum
  • Deep and large wounds

Factors associated with a longer incubation period:

The following factors are associated with a longer incubation period:

  • Inadequate rabies prophylaxis
  • Unknown new exposure
    • It is hypothesized that a latent viral infection and/or slow replication may be associated with it.[6][5][7]

Prodromal period

  • In this stage, the patient presents with non-specific signs and symptoms and rabies usually remains unsuspected at this stage
  • It usually lasts from a few days to a week (3-9days)[8]
  • Pathognomic presentation involves following symptoms at the inoculation site:[9]

Common symptoms include:

Less common symptoms:

Acute neurologic period (Clinical rabies)

  • Clinical rabies has two forms, both of them evolving from prodromal symptoms
  1. Encephalitic ("furious") rabies- more common (80% cases)
  2. Paralytic ("dumb") rabies
  • Following factors influence the course of disease:
    • The depth and extent of bite
    • Proximity to head
    • Amount of secretions encountered at the site of bite

(a) Encephalitic ("furious") rabies:

This form usually involves short episodes (furious episodes) of hyperactivity, restlessness, and agitation lasting about 5 minutes, followed by calm and lucid intervals. Furious episodes may occur spontaneously or may be triggered by stimuli such as visual, auditory or tactile. Common symptoms include:[11][8]

Less common symptoms:

(b) Paralytic ("dumb") rabies:

Prodromal symptoms may be followed by flaccid paralysis that may be symmetrical/asymmetrical and needs to be differentiated from Guillain-Barré syndrome.

Common symptoms:

Less common symptoms:

Coma

References

  1. ↑ "Compendium of animal rabies prevention and control, 2004: National Association of State Public Health Veterinarians, Inc. (NASPHV)". MMWR Recomm Rep. 53 (RR-9): 1–8. 2004. PMID 15215738.
  2. ↑ Knobel DL, Cleaveland S, Coleman PG, Fèvre EM, Meltzer MI, Miranda ME, Shaw A, Zinsstag J, Meslin FX (2005). "Re-evaluating the burden of rabies in Africa and Asia". Bull. World Health Organ. 83 (5): 360–8. doi:/S0042-96862005000500012 Check |doi= value (help). PMC 2626230. PMID 15976877.
  3. ↑ Noah DL, Drenzek CL, Smith JS, Krebs JW, Orciari L, Shaddock J, Sanderlin D, Whitfield S, Fekadu M, Olson JG, Rupprecht CE, Childs JE (1998). "Epidemiology of human rabies in the United States, 1980 to 1996". Ann. Intern. Med. 128 (11): 922–30. PMID 9634432.
  4. ↑ Rupprecht CE, Hanlon CA, Hemachudha T (2002). "Rabies re-examined". Lancet Infect Dis. 2 (6): 327–43. PMID 12144896.
  5. ↑ 5.0 5.1 Boland TA, McGuone D, Jindal J, Rocha M, Cumming M, Rupprecht CE, Barbosa TF, de Novaes Oliveira R, Chu CJ, Cole AJ, Kotait I, Kuzmina NA, Yager PA, Kuzmin IV, Hedley-Whyte ET, Brown CM, Rosenthal ES (2014). "Phylogenetic and epidemiologic evidence of multiyear incubation in human rabies". Ann. Neurol. 75 (1): 155–60. doi:10.1002/ana.24016. PMC 4118733. PMID 24038455.
  6. ↑ Smith JS, Fishbein DB, Rupprecht CE, Clark K (1991). "Unexplained rabies in three immigrants in the United States. A virologic investigation". N. Engl. J. Med. 324 (4): 205–11. doi:10.1056/NEJM199101243240401. PMID 1985241.
  7. ↑ 7.0 7.1 Hemachudha T, Ugolini G, Wacharapluesadee S, Sungkarat W, Shuangshoti S, Laothamatas J (2013). "Human rabies: neuropathogenesis, diagnosis, and management". Lancet Neurol. 12 (5): 498–513. doi:10.1016/S1474-4422(13)70038-3. PMID 23602163.
  8. ↑ 8.0 8.1 8.2 Hemachudha T, Laothamatas J, Rupprecht CE (2002). "Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges". Lancet Neurol. 1 (2): 101–9. PMID 12849514.
  9. ↑ "Imported human rabies in a U.S. Army soldier - New York, 2011". MMWR Morb. Mortal. Wkly. Rep. 61 (17): 302–5. 2012. PMID 22552206.
  10. ↑ "Recovery of a patient from clinical rabies--Wisconsin, 2004". MMWR Morb. Mortal. Wkly. Rep. 53 (50): 1171–3. 2004. PMID 15614231.
  11. ↑ Hankins DG, Rosekrans JA (2004). "Overview, prevention, and treatment of rabies". Mayo Clin. Proc. 79 (5): 671–6. doi:10.1016/S0025-6196(11)62291-X. PMID 15132411.
  12. ↑ Hattwick MA (1972). "Reactions to rabies". N. Engl. J. Med. 287 (23): 1204. PMID 5082226.

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