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==Overview==
==Overview==
Rabies is a [[virus (biology)|viral]] [[zoonotic]] disease that causes acute [[encephalitis]] (inflammation of the brain) in [[mammal]]s. In non-vaccinated humans, rabies is almost invariably fatal after [[neurological]] symptoms have developed, but prompt post-exposure [[vaccination]] may prevent the virus from progressing. There are only six known cases of a person surviving untreated rabies. <ref>[http://pathmicro.med.sc.edu/virol/rabies.htm VIROLOGY - CHAPTER  TWENTY RABIES] pathmicro.med.sc.edu</ref>
Rabies is a [[virus (biology)|viral]] [[zoonotic]] disease that causes acute [[encephalitis]] (inflammation of the brain) in [[mammal]]s. In non-vaccinated humans, rabies is almost invariably fatal after [[neurological]] symptoms have developed, but prompt post-exposure [[vaccination]] may prevent the virus from progressing. The ''[[rabies virus]]'' is categorized as a [[Lyssavirus]]. The [[molecular biology]] of rabies consists of bullet shaped [[virus]] with helical symmetry that has a length of approximately 180 nm. Rabies typically has its greatest effect on the [[brain]]. Rabies is typically defined by [[encephalitis]] and [[myelitis]]. Various carnivorous animal species have been identified as the source of ''[[rabies virus]]'' (RV). In Africa and Asia, domestic dogs are the main reservoirs of ''[[rabies virus]] [[infection]].'' Whereas, in the United States, racoons, foxes, skunks, coyotes, possums and bats are understood to be responsible for the spread of [[rabies virus]]. RV infects [[Neuron|neurons]] and leads to the degeneration of the [[neuronal]] processes by disrupting [[Cytoskeleton|cytoskeletal]] integrity. The differential diagnosis for rabies deals with eliminating diseases with similar [[symptoms]] from the diagnosis. There are many [[viruses]] that can appear similar to rabies such as [[encephalitis]] and the [[herpes simplex virus]]. According to the [[World Health Organization]] ([[World Health Organization|WHO]]), human rabies is present in 150 countries and territories and on all continents, except for Antarctica. India has been known to have the highest [[incidence]] of rabies. A bite from an [[Infection (disambiguation)|infected]] animal is the biggest [[risk factor]]. Rabies is a [[clinical]] diagnosis that includes a thorough medical history and a high degree of suspicion. 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. Rabies eventually results in progressive [[encephalopathy]], [[respiratory arrest]], [[coma]] and death within 10 days of the onset of [[symptoms]]. Common physical examination findings of rabies include [[hyperpyrexia]] alternating with [[hypothermia]], [[tachycardia]], [[respiratory]] collapse, [[hypersalivation]], [[lacrimation]], [[sweating]], [[Pupillary dilation|dilatation of the pupils]] and [[bradycardia]]. Skin findings may include percussion myoedema, bite marks and [[bruises]]. [[Lumbar puncture|Lumbar]] <nowiki/>[[Lumbar puncture|puncture]] may show [[lymphocytic]] [[pleocytosis]], [[CSF]] [[protein]]-elevation and normal [[glucose]] concentration. Patients with suspected exposure to rabies or asymptomatic patients can benefit from thorough wound cleaning followed by a combined rabies [[Vaccinations|vaccination]] and [[immune globulin]] administration, these patients have a good [[prognosis]]. Human diploid cell rabies vaccines are made using the attenuated Pitman-Moore L503 strain of the [[virus]]. Human diploid cell [[Rabies vaccine|rabies vaccines]] have been given to more than 1.5 million humans as of 2006. Treatment after exposure, known as [[post-exposure prophylaxis]] or "P.E.P.", is highly successful in preventing the disease if administered promptly, within fourteen days after infection. The first step is immediately washing the wound with soap and water, which is very effective at reducing the number of viral particles. In the United States, patients receive one dose of [[immunoglobulin]] and five doses of rabies vaccine over a twenty-eight day period. One-half the dose of immunoglobulin is injected in the region of the bite, if possible, with the remainder injected [[Intramuscular injection|intramuscularly]] away from the bite.  


==Historical Perspective==
==Historical Perspective==
Rabies is a disease that has been classically associated with infected animals, mainly dogs. The first written record was from approximately 1930 BC when the owner of a dog with Rabies [[rabies history and symptoms|symptoms]] was told to take preventative measures against bites. If a person died from being bitten by a rabid dog, the owner was fined heavily. Although dogs are viewed as the main culprit of rabies, rabies is also associated with animals such as possums, skunks, and more importantly, bats.
Rabies is a [[disease]] that has been classically associated with [[Infection (disambiguation)|infected]] animals, mainly dogs.The first written record of rabies is in the Codex of Eshnunna (ca. 1930 BC - written prior to the Code of Hammurabi), which demonstrates that the owner of a dog showing symptoms of rabies should take [[Prevention (medical)|preventive]] measure against bites. Although dogs are viewed as the main culprit of rabies, rabies is also associated with animals such as possums, skunks, and more importantly, bats. In 1885, 9-year-old boy named Joseph Meister was the first person to have received an effective shot for rabies after being bitten by a rabid dog. Louis Pasteur treated the first case of rabies by a weak form of [[virus]] (which later became the basis of [[active immunization]] for rabies). In the 1950s, people who had been bitten by a rabid animal got 23 shots along the [[abdomen]]. Today, the shots are more effective and less painful. They consist of a series of 6 shots given in the arm over a 1 month period. One shot is given around the bite and the rest are given in the arm.


==Pathophysiology==
==Pathophysiology==
The rabies virus is categorized as a [[Lyssavirus]]. The molecular biology of rabies consists of bullet shaped virus with helical symmetry that has a length of approximately 180 nm. Rabies typically has its greatest effect on the brain. It is typically defined by [[encephalitis]] and [[myelitis]]. It is very important to avoid being bitten by a rabid animal because the virus is typically transmitted through the saliva of an infected organism.
The ''[[rabies virus]]'' is categorized as [[Lyssavirus]]. The [[molecular biology]] of rabies consists of bullet shaped [[virus]] with helical symmetry that has a length of approximately 180 nm. Rabies typically has its greatest effect on the [[brain]]. Rabies is typically defined by [[encephalitis]] and [[myelitis]]. Various carnivorous animal species have been identified as the source of ''[[rabies virus]]'' (RV). In Africa and Asia, domestic dogs are the main reservoirs of ''[[rabies virus]] [[infection]].'' Whereas, in the United States, racoons, foxes, skunks, coyotes, possums and bats are understood to be responsible for the spread of [[rabies virus]].The [[neuromuscular junction]] is the major site of entry into [[neurons]]. RV infects [[peripheral nerves]]<nowiki/>and then reaches the [[CNS|central nervous system (CNS)]] via retrograde [[axonal]] transport''.'' The primary mechanism involved in the neuroinvasion of RV is trans-synaptic [[neuronal]]<nowiki/>spread. RV infects [[Neuron|neurons]] and leads to the degeneration of the [[neuronal]] processes by disrupting [[Cytoskeleton|cytoskeletal]] integrity. [[Histopathologic]] evidence of rabies [[encephalomyelitis]]([[inflammation]]) in [[brain]] [[Tissue (biology)|tissue]] and [[meninges]] includes, [[Mononuclear cells|mononuclear]] infiltration, [[Perivascular cell|perivascular]] cuffing of [[lymphocytes]] or [[polymorphonuclear cells]], [[lymphocytic]] foci, Babes nodules consisting of [[glial cells]] and [[Negri bodies]].
 
== Causes ==
The [[Rabies virus]] is the cause of rabies.


==Differentiating Rabies from other Diseases==
==Differentiating Rabies from other Diseases==
The differential diagnosis for rabies deals with eliminating diseases with similar symptoms from the diagnosis. There are many viruses that can appear similar to rabies such as encephalitis and the herpes simplex virus. It is very important to rule out certain diseases such as echovirus and poliovirus. Rabies is a serious disease that needs to be treated quickly if someone is suspected to be infected with the virus.
The differential diagnosis for rabies deals with eliminating diseases with similar [[symptoms]] from the diagnosis. There are many [[viruses]] that can appear similar to rabies such as [[encephalitis]] and the [[herpes simplex virus]]. It is very important to rule out certain diseases such as [[echovirus]] and [[poliovirus]]. Rabies is a serious disease that needs to be treated quickly if someone is suspected to be infected with the virus.


==Epidemiology and Demographics==
==Epidemiology and Demographics==
The epidemiology of rabies addresses several questions: what animals have rabies and in what regions of the country, how many people get rabies and from what animals, and what are the best strategies for preventing rabies in people and animals. Epidemiologic information is often presented as statistical data (e.g., numbers or percentages in graphs and on maps). For example, in 2001, 7,437 cases of rabies were reported in the United States. Raccoons accounted for almost 40% of reported cases.
According to the [[World Health Organization]] ([[World Health Organization|WHO]]), human rabies is present in 150 countries and territories and on all continents, except for Antarctica. India has been known to have the highest [[incidence]] of rabies. Twenty-three cases of human rabies have been reported in the United States in the past decade (2008-2017). Many territories, such as the United Kingdom, Ireland, Taiwan, Japan, Hawaii, Mauritius, Barbados and Guam, are free of rabies. Worldwide, 55,000 human deaths occur annually from rabies, with 56 % of deaths estimated to occur in Asia and 44 % in Africa.


==Risk Factors==
==Risk Factors==
A bite from an infected animal is the biggest risk factor. People that live in an area, or travel to an area that has a large incidence for rabies, are at a high risk for acquiring rabies from a rabid animal. Handling certain wild animals such as bats or raccoons will put a person at a higher risk.
A bite from an [[Infection (disambiguation)|infected]] animal is the biggest [[risk factor]]. People that live in an area, or travel to an area that has a large [[incidence]] for rabies, are at a high risk for acquiring rabies from a rabid animal. Handling certain wild animals such as bats or raccoons will put a person at a higher risk.
 
== Screening ==
There is insufficient evidence to recommend routine [[Screening (medicine)|screening]] for rabies. [[Enzyme linked immunosorbent assay (ELISA)|Enzyme immunoassay]] (EIA) is currently under investigation as a convenient test for [[Screening (medicine)|screening]] [[hybridoma]] supernatants because nanogram amounts of [[antibody]] can be detected and up to 100 samples can be tested at the same time.
 
== Natural history, complications and prognosis ==
If left untreated, rabies runs its course very rapidly. Once [[symptoms]] begin to appear, the disease is almost always [[fatal]]. The acute period of disease typically ends after 2 to 10 days. Common complications of rabies include, [[psychosis]], [[seizures]], [[aphasia]], [[muscular]] twitching, [[delirium]] and death. Treatment after exposure (receiving the [[vaccines]]), known as post-exposure [[prophylaxis]] (PEP), is highly successful in [[Prevention (medical)|preventing]] the disease if administered promptly, in general within ten days of [[infection]].


==Diagnosis==
==Diagnosis==
===Symptoms===
When a person contracts rabies, they do not show symptoms immediately. The disease take a period of time to manifest in the body which is know as its period of [[incubation]]. Once symptoms arise, the patients condition deteriorates rapidly. There is not a great deal of time available to perform a routine physical examination. A patient will most likely present with some severe symptoms that may be misdiagnosed as diseases such as [[Guillain-Barre syndrome]].


===Laboratory Findings===
=== Diagnostic criteria ===
Several tests are necessary to diagnose rabies ante-mortem (before death) in humans; no single test is sufficient. Tests are performed on samples of saliva, serum, spinal fluid, and [[skin]] biopsies of hair follicles at the nape of the neck. Saliva can be tested by virus isolation or reverse transcription followed by polymerase chain reaction (RT-PCR). Serum and [[cerebrospinal fluid]] are tested for [[antibodies]] to rabies virus. Skin biopsy specimens are examined for rabies antigen in the cutaneous nerves at the base of hair follicles.
Rabies is a [[clinical]] diagnosis that includes a thorough medical history and a high degree of suspicion. Laboratory findings that help with the diagnosis of rabies include skin [[biopsy]] specimens showing [[virus]]-specific [[immunofluorescent]] [[staining]], [[Isolation (health care)|isolation]] of [[virus]] from the samples of [[saliva]] and detection of anti-rabies [[antibodies]] in [[serum]] or [[Cerebrospinal fluid|cerebrospinal fluid (CSF)]].
 
===History and symptoms===
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.
 
=== Physical examination ===
Common physical examination findings of rabies include [[hyperpyrexia]] alternating with [[hypothermia]], [[tachycardia]], [[respiratory]] collapse, [[hypersalivation]], [[lacrimation]], [[sweating]], [[Pupillary dilation|dilatation of the pupils]] and [[bradycardia]]. Skin findings may include percussion myoedema, bite marks and [[bruises]]. 
 
===Laboratory findings===
Routine lab findings are non-specific and may include peripheral [[leukocytosis]], [[respiratory alkalosis]] followed by [[respiratory acidosis]], [[albuminuria]] and [[pyuria]]. [[Lumbar puncture]]<nowiki/>may show [[lymphocytic]] [[pleocytosis]], [[CSF]] [[protein]]-elevation and normal [[glucose]] concentration. [[Serology]] is useful in assessing the serostatus in [[Immunization|immunized]] humans and animals as it is difficult to document the neutralizing [[antibody]] response via [[immunofluorescence]] because mostly death occurs prior to mounting a response. [[Serological testing|Serologic]] tests include [[Reverse transcription polymerase chain reaction|reverse transcriptase polymerase chain reaction]] ([[Reverse transcription polymerase chain reaction|RT-PCR]]), [[viral culture]], [[immunofluorescence]] staining, indirect [[immunofluorescence]], [[Direct fluorescent antibody|direct fluorescent antibody test]] (dFA) and [[virus]] [[neutralization]] assays.
 
=== Electrocardiogram ===
[[EKG]] findings may show [[supraventricular arrhythmias]], [[atrioventricular block]], [[sinus bradycardia]], [[sinus arrest]] with non-specific [[ST segments|ST segment]] and [[T-wave]] changes.
 
=== Chest X-ray ===
[[Chest X-ray|CXR]] may show infiltrates secondary to [[aspiration]], [[pneumonia]], [[acute respiratory distress syndrome]] and [[congestive heart failure]].


===CT===
===CT===
With a disease that progresses so quickly, imaging is often very difficult to do and it is not used very often<ref name="pmid11290477">{{cite journal |author=Awasthi M, Parmar H, Patankar T, Castillo M |title=Imaging findings in rabies encephalitis |journal=[[AJNR. American Journal of Neuroradiology]] |volume=22 |issue=4 |pages=677–80 |year=2001 |month=April |pmid=11290477 |doi= |url=http://www.ajnr.org/cgi/pmidlookup?view=long&pmid=11290477 |accessdate=2012-02-10}}</ref>. Although it is not done very often, there are certain manifestations with a CT scan that can be seen in rabies patients.
[[Computed tomography|CT]] is usually normal. Late findings may include [[cerebral edema]] and decreased [[attenuation]] in the [[hippocampus]], [[brain stem]], [[basal ganglia]], and periventricular [[white matter]].
 
=== MRI ===
Findings on [[Magnetic resonance imaging|MRI]] suggestive of rabies include areas of increased [[Magnetic resonance imaging|T2]] intensity (flare) may be seen in [[hippocampus]], [[hypothalamus]], and [[brainstem]].
 
== Treatment ==
 
=== Medical therapy ===
Two presentations must be considered in the treatment of rabies. [[Symptomatic]] patients with delayed presentation in the emergency department, associated with a low survival rate and treated with "Milwaukee protocol" (which is still being studied) and patients with a suspected exposure to [[rabies virus]] or early diagnosed asymptomatic rabies patients. Patients with suspected exposure to rabies or asymptomatic patients can benefit from thorough wound cleaning followed by a combined rabies [[Vaccinations|vaccination]] and [[immune globulin]] administration, these patients have a good [[prognosis]].
 
=== Surgery ===
Immediate gentle irrigation with water or a dilute water [[Povidone-iodine|povidone-iodine solution]] has been shown to markedly decrease the risk of [[bacterial infection]]. [[Wound]] cleansing is especially important in rabies prevention.
 
=== Primary prevention ===
There is no known cure for symptomatic rabies, but it can be prevented by [[vaccination]], both in [[humans]] and other animals. Virtually every [[infection]] with [[Rabies virus|rabies]] was a death sentence, until Louis Pasteur and [[Emile Roux]] developed the first [[Rabies vaccine|rabies vaccination]] in 1885. This [[vaccine]] was first used on a human on July 6, 1885 – nine-year old boy Joseph Meister (1876–1940) had been mauled by a rabid dog.Their vaccine consisted of a sample of the [[Rabies virus|virus]] harvested from [[infected]] (and necessarily dead) rabbits, which was weakened by allowing it to dry. Similar nerve tissue-derived [[vaccines]] are still used now in some countries, and while they are much cheaper than modern cell culture vaccines, they are not as effective and carry a certain risk of [[neurological]] complications.The human [[diploid]] cell [[rabies vaccine]] (H.D.C.V.) was started in 1967. Human diploid cell rabies vaccines are made using the attenuated Pitman-Moore L503 strain of the [[virus]]. Human diploid cell [[Rabies vaccine|rabies vaccines]] have been given to more than 1.5 million humans as of 2006. Newer and less expensive purified chicken embryo cell vaccine, and purified [[Vero cell]] rabies vaccine are now available. The purified Vero cell rabies vaccine uses the attenuated Wistar strain of the [[rabies virus]], and uses the Vero cell line as its host.
 
=== Secondary prevention ===
Treatment after exposure, known as [[post-exposure prophylaxis]] or "P.E.P.", is highly successful in preventing the disease if administered promptly, within fourteen days after infection. The first step is immediately washing the wound with soap and water, which is very effective at reducing the number of viral particles. In the United States, patients receive one dose of [[immunoglobulin]] and five doses of rabies vaccine over a twenty-eight day period. One-half the dose of immunoglobulin is injected in the region of the bite, if possible, with the remainder injected [[Intramuscular injection|intramuscularly]] away from the bite. Pre-exposure [[vaccination]] with human [[diploid cell]] [[Rabies vaccine]] (HDCV), or purified chick embryo cell (PCEC) vaccine, may be recommended for international travelers based on the local incidence of rabies in the country to be visited, the availability of appropriate [[antirabies biologicals]], and the intended activity and duration of stay of the traveler. 


==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: Mahshid Mir, M.D. [2]

Overview

Rabies is a viral zoonotic disease that causes acute encephalitis (inflammation of the brain) in mammals. In non-vaccinated humans, rabies is almost invariably fatal after neurological symptoms have developed, but prompt post-exposure vaccination may prevent the virus from progressing. The rabies virus is categorized as a Lyssavirus. The molecular biology of rabies consists of bullet shaped virus with helical symmetry that has a length of approximately 180 nm. Rabies typically has its greatest effect on the brain. Rabies is typically defined by encephalitis and myelitis. Various carnivorous animal species have been identified as the source of rabies virus (RV). In Africa and Asia, domestic dogs are the main reservoirs of rabies virus infection. Whereas, in the United States, racoons, foxes, skunks, coyotes, possums and bats are understood to be responsible for the spread of rabies virus. RV infects neurons and leads to the degeneration of the neuronal processes by disrupting cytoskeletal integrity. The differential diagnosis for rabies deals with eliminating diseases with similar symptoms from the diagnosis. There are many viruses that can appear similar to rabies such as encephalitis and the herpes simplex virus. According to the World Health Organization (WHO), human rabies is present in 150 countries and territories and on all continents, except for Antarctica. India has been known to have the highest incidence of rabies. A bite from an infected animal is the biggest risk factor. Rabies is a clinical diagnosis that includes a thorough medical history and a high degree of suspicion. Patients are asymptomatic during the incubation period. Prodromal symptoms may include low-grade feverchillsmalaisemyalgiasweaknessfatigueanorexiasore throatnauseavomiting and headache. Clinical rabies can present as encephalitic ("furious") rabies or paralytic ("dumb") rabies. Rabies eventually results in progressive encephalopathy, respiratory arrest, coma and death within 10 days of the onset of symptoms. Common physical examination findings of rabies include hyperpyrexia alternating with hypothermia, tachycardia, respiratory collapse, hypersalivation, lacrimation, sweating, dilatation of the pupils and bradycardia. Skin findings may include percussion myoedema, bite marks and bruises. Lumbar puncture may show lymphocytic pleocytosisCSF protein-elevation and normal glucose concentration. Patients with suspected exposure to rabies or asymptomatic patients can benefit from thorough wound cleaning followed by a combined rabies vaccination and immune globulin administration, these patients have a good prognosis. Human diploid cell rabies vaccines are made using the attenuated Pitman-Moore L503 strain of the virus. Human diploid cell rabies vaccines have been given to more than 1.5 million humans as of 2006. Treatment after exposure, known as post-exposure prophylaxis or "P.E.P.", is highly successful in preventing the disease if administered promptly, within fourteen days after infection. The first step is immediately washing the wound with soap and water, which is very effective at reducing the number of viral particles. In the United States, patients receive one dose of immunoglobulin and five doses of rabies vaccine over a twenty-eight day period. One-half the dose of immunoglobulin is injected in the region of the bite, if possible, with the remainder injected intramuscularly away from the bite.

Historical Perspective

Rabies is a disease that has been classically associated with infected animals, mainly dogs.The first written record of rabies is in the Codex of Eshnunna (ca. 1930 BC - written prior to the Code of Hammurabi), which demonstrates that the owner of a dog showing symptoms of rabies should take preventive measure against bites. Although dogs are viewed as the main culprit of rabies, rabies is also associated with animals such as possums, skunks, and more importantly, bats. In 1885, 9-year-old boy named Joseph Meister was the first person to have received an effective shot for rabies after being bitten by a rabid dog. Louis Pasteur treated the first case of rabies by a weak form of virus (which later became the basis of active immunization for rabies). In the 1950s, people who had been bitten by a rabid animal got 23 shots along the abdomen. Today, the shots are more effective and less painful. They consist of a series of 6 shots given in the arm over a 1 month period. One shot is given around the bite and the rest are given in the arm.

Pathophysiology

The rabies virus is categorized as a Lyssavirus. The molecular biology of rabies consists of bullet shaped virus with helical symmetry that has a length of approximately 180 nm. Rabies typically has its greatest effect on the brain. Rabies is typically defined by encephalitis and myelitis. Various carnivorous animal species have been identified as the source of rabies virus (RV). In Africa and Asia, domestic dogs are the main reservoirs of rabies virus infection. Whereas, in the United States, racoons, foxes, skunks, coyotes, possums and bats are understood to be responsible for the spread of rabies virus.The neuromuscular junction is the major site of entry into neurons. RV infects peripheral nervesand then reaches the central nervous system (CNS) via retrograde axonal transport. The primary mechanism involved in the neuroinvasion of RV is trans-synaptic neuronalspread. RV infects neurons and leads to the degeneration of the neuronal processes by disrupting cytoskeletal integrity. Histopathologic evidence of rabies encephalomyelitis(inflammation) in brain tissue and meninges includes, mononuclear infiltration, perivascular cuffing of lymphocytes or polymorphonuclear cellslymphocytic foci, Babes nodules consisting of glial cells and Negri bodies.

Causes

The Rabies virus is the cause of rabies.

Differentiating Rabies from other Diseases

The differential diagnosis for rabies deals with eliminating diseases with similar symptoms from the diagnosis. There are many viruses that can appear similar to rabies such as encephalitis and the herpes simplex virus. It is very important to rule out certain diseases such as echovirus and poliovirus. Rabies is a serious disease that needs to be treated quickly if someone is suspected to be infected with the virus.

Epidemiology and Demographics

According to the World Health Organization (WHO), human rabies is present in 150 countries and territories and on all continents, except for Antarctica. India has been known to have the highest incidence of rabies. Twenty-three cases of human rabies have been reported in the United States in the past decade (2008-2017). Many territories, such as the United Kingdom, Ireland, Taiwan, Japan, Hawaii, Mauritius, Barbados and Guam, are free of rabies. Worldwide, 55,000 human deaths occur annually from rabies, with 56 % of deaths estimated to occur in Asia and 44 % in Africa.

Risk Factors

A bite from an infected animal is the biggest risk factor. People that live in an area, or travel to an area that has a large incidence for rabies, are at a high risk for acquiring rabies from a rabid animal. Handling certain wild animals such as bats or raccoons will put a person at a higher risk.

Screening

There is insufficient evidence to recommend routine screening for rabies. Enzyme immunoassay (EIA) is currently under investigation as a convenient test for screening hybridoma supernatants because nanogram amounts of antibody can be detected and up to 100 samples can be tested at the same time.

Natural history, complications and prognosis

If left untreated, rabies runs its course very rapidly. Once symptoms begin to appear, the disease is almost always fatal. The acute period of disease typically ends after 2 to 10 days. Common complications of rabies include, psychosisseizuresaphasiamuscular twitching, delirium and death. Treatment after exposure (receiving the vaccines), known as post-exposure prophylaxis (PEP), is highly successful in preventing the disease if administered promptly, in general within ten days of infection.

Diagnosis

Diagnostic criteria

Rabies is a clinical diagnosis that includes a thorough medical history and a high degree of suspicion. Laboratory findings that help with the diagnosis of rabies include skin biopsy specimens showing virus-specific immunofluorescent stainingisolation of virus from the samples of saliva and detection of anti-rabies antibodies in serum or cerebrospinal fluid (CSF).

History and symptoms

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 feverchillsmalaisemyalgiasweaknessfatigueanorexiasore throatnauseavomiting 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, opisthotonosautonomic instabilitydysarthriadysphagia, and diplopia. Rabies eventually results in progressive encephalopathyrespiratory arrestcoma and death within 10 days of the onset of symptoms.

Physical examination

Common physical examination findings of rabies include hyperpyrexia alternating with hypothermia, tachycardia, respiratory collapse, hypersalivation, lacrimation, sweating, dilatation of the pupils and bradycardia. Skin findings may include percussion myoedema, bite marks and bruises

Laboratory findings

Routine lab findings are non-specific and may include peripheral leukocytosisrespiratory alkalosis followed by respiratory acidosisalbuminuria and pyuriaLumbar puncturemay show lymphocytic pleocytosisCSF protein-elevation and normal glucose concentration. Serology is useful in assessing the serostatus in immunized humans and animals as it is difficult to document the neutralizing antibody response via immunofluorescence because mostly death occurs prior to mounting a response. Serologic tests include reverse transcriptase polymerase chain reaction (RT-PCR), viral cultureimmunofluorescence staining, indirect immunofluorescencedirect fluorescent antibody test (dFA) and virus neutralization assays.

Electrocardiogram

EKG findings may show supraventricular arrhythmias, atrioventricular block, sinus bradycardia, sinus arrest with non-specific ST segment and T-wave changes.

Chest X-ray

CXR may show infiltrates secondary to aspirationpneumoniaacute respiratory distress syndrome and congestive heart failure.

CT

CT is usually normal. Late findings may include cerebral edema and decreased attenuation in the hippocampusbrain stembasal ganglia, and periventricular white matter.

MRI

Findings on MRI suggestive of rabies include areas of increased T2 intensity (flare) may be seen in hippocampushypothalamus, and brainstem.

Treatment

Medical therapy

Two presentations must be considered in the treatment of rabies. Symptomatic patients with delayed presentation in the emergency department, associated with a low survival rate and treated with "Milwaukee protocol" (which is still being studied) and patients with a suspected exposure to rabies virus or early diagnosed asymptomatic rabies patients. Patients with suspected exposure to rabies or asymptomatic patients can benefit from thorough wound cleaning followed by a combined rabies vaccination and immune globulin administration, these patients have a good prognosis.

Surgery

Immediate gentle irrigation with water or a dilute water povidone-iodine solution has been shown to markedly decrease the risk of bacterial infectionWound cleansing is especially important in rabies prevention.

Primary prevention

There is no known cure for symptomatic rabies, but it can be prevented by vaccination, both in humans and other animals. Virtually every infection with rabies was a death sentence, until Louis Pasteur and Emile Roux developed the first rabies vaccination in 1885. This vaccine was first used on a human on July 6, 1885 – nine-year old boy Joseph Meister (1876–1940) had been mauled by a rabid dog.Their vaccine consisted of a sample of the virus harvested from infected (and necessarily dead) rabbits, which was weakened by allowing it to dry. Similar nerve tissue-derived vaccines are still used now in some countries, and while they are much cheaper than modern cell culture vaccines, they are not as effective and carry a certain risk of neurological complications.The human diploid cell rabies vaccine (H.D.C.V.) was started in 1967. Human diploid cell rabies vaccines are made using the attenuated Pitman-Moore L503 strain of the virus. Human diploid cell rabies vaccines have been given to more than 1.5 million humans as of 2006. Newer and less expensive purified chicken embryo cell vaccine, and purified Vero cell rabies vaccine are now available. The purified Vero cell rabies vaccine uses the attenuated Wistar strain of the rabies virus, and uses the Vero cell line as its host.

Secondary prevention

Treatment after exposure, known as post-exposure prophylaxis or "P.E.P.", is highly successful in preventing the disease if administered promptly, within fourteen days after infection. The first step is immediately washing the wound with soap and water, which is very effective at reducing the number of viral particles. In the United States, patients receive one dose of immunoglobulin and five doses of rabies vaccine over a twenty-eight day period. One-half the dose of immunoglobulin is injected in the region of the bite, if possible, with the remainder injected intramuscularly away from the bite. Pre-exposure vaccination with human diploid cell Rabies vaccine (HDCV), or purified chick embryo cell (PCEC) vaccine, may be recommended for international travelers based on the local incidence of rabies in the country to be visited, the availability of appropriate antirabies biologicals, and the intended activity and duration of stay of the traveler. 

References

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