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Rabies

Rabies

Overview
Rabies (ˈreɪbiːz. From , "madness") is a viral
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

 disease that causes acute encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...

 (inflammation of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

) in warm-blooded animals. It is zoonotic (i.e., transmitted by animals), most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis
Post-exposure prophylaxis
Post-exposure prophylaxis is any prophylactic treatment started immediately after exposure to a pathogen , in order to prevent infection by the pathogen and the development of disease.-Rabies:...

 is not administered prior to the onset of severe symptoms. The rabies virus infects the central nervous system, ultimately causing disease in the brain and death.

The rabies virus
Rabies virus
The rabies virus is neurotropic virus that causes fatal disease in human and animals. Rabies transmission can occur through the saliva of animals....

 travels to the brain by following the peripheral nerves
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...

.
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Encyclopedia
Rabies (ˈreɪbiːz. From , "madness") is a viral
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

 disease that causes acute encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...

 (inflammation of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

) in warm-blooded animals. It is zoonotic (i.e., transmitted by animals), most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis
Post-exposure prophylaxis
Post-exposure prophylaxis is any prophylactic treatment started immediately after exposure to a pathogen , in order to prevent infection by the pathogen and the development of disease.-Rabies:...

 is not administered prior to the onset of severe symptoms. The rabies virus infects the central nervous system, ultimately causing disease in the brain and death.

The rabies virus
Rabies virus
The rabies virus is neurotropic virus that causes fatal disease in human and animals. Rabies transmission can occur through the saliva of animals....

 travels to the brain by following the peripheral nerves
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...

. The incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...

 of the disease is usually a few months in humans, depending on the distance the virus must travel to reach the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

. Once the rabies virus reaches the central nervous system and symptoms begin to show, the infection is effectively untreatable and usually fatal within days.

Early-stage symptoms of rabies are malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...

, headache and fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, progressing to acute pain, violent movements, uncontrolled excitement, depression, and hydrophobia
Hydrophobia
Hydrophobia or hydrophobe may refer to:* Rabies, especially a set of symptoms of the later stages of an infection, in which the victim has difficulty swallowing, shows panic when presented with liquids to drink, and cannot quench his or her thirst....

. Finally, the patient may experience periods of mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...

 and lethargy, eventually leading to coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...

. The primary cause of death is usually respiratory insufficiency. Worldwide, roughly 97% of rabies cases come from dog bites. In the United States, however, animal control and vaccination programs have effectively eliminated domestic dogs as reservoirs of rabies. In several countries, including Australia, Japan, and the United Kingdom, rabies carried by animals that live on the ground has been eradicated entirely. Concerns exist about airborne and mixed-habitat animals including bats. A small number of bats of three species in the UK and in some other countries have been found to have European Bat Lyssavirus
Lyssavirus
Lyssavirus is a genus of viruses belonging to the family Rhabdoviridae, in the order Mononegavirales. This group of RNA viruses includes the Rabies virus traditionally associated with the disease.-Structure:Viruses typically have either helical or cubic symmetry...

 1 and European Bat Lyssavirus 2. The symptoms of these viruses are similar to those of rabies and so the viruses are both known as bat rabies.

The economic impact is also substantial, as rabies is a significant cause of death of livestock in some countries.

Signs and symptoms



The period between infection and the first flu-like symptoms is normally two to twelve weeks, but can be as long as two years. Soon after, the symptoms expand to slight or partial paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...

, cerebral dysfunction, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

, confusion
ConFusion
ConFusion is an annual science fiction convention organized by the Stilyagi Air Corps and its parent organization, the Ann Arbor Science Fiction Association. Commonly, it is held the third weekend of January. It is the oldest science fiction convention in Michigan, a regional, general SF con...

, agitation, abnormal behavior, paranoia
Paranoia
Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...

, terror, hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

s, progressing to delirium
Delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...

. The production of large quantities of saliva and tears coupled with an inability to speak or swallow are typical during the later stages of the disease; this can result in hydrophobia, in which the patient has difficulty swallowing because the throat and jaw become slowly paralyzed, shows panic when presented with liquids to drink, and cannot quench his or her thirst.

Death almost invariably results two to ten days after first symptoms. In 2005, the first patient was treated with the Milwaukee protocol, and Jeanna Giese became the first person ever recorded to survive rabies without receiving successful post-exposure prophylaxis. An intention to treat analysis
Intention to treat analysis
In epidemiology, an intention to treat analysis is an analysis based on the initial treatment intent, not on the treatment eventually administered. ITT analysis is intended to avoid various misleading artifacts that can arise in intervention research...

 has since found that this protocol has a survival rate of about 8%. The results of this study are, however, under serious contention and clinical rabies should still be regarded as incurable at present.

Virology



The rabies virus is the type species
Type species
In biological nomenclature, a type species is both a concept and a practical system which is used in the classification and nomenclature of animals and plants. The value of a "type species" lies in the fact that it makes clear what is meant by a particular genus name. A type species is the species...

 of the Lyssavirus
Lyssavirus
Lyssavirus is a genus of viruses belonging to the family Rhabdoviridae, in the order Mononegavirales. This group of RNA viruses includes the Rabies virus traditionally associated with the disease.-Structure:Viruses typically have either helical or cubic symmetry...

genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...

, in the family Rhabdoviridae
Rhabdoviridae
Rhabdoviruses are viruses belonging to the family Rhabdoviridae, which is in the order Mononegavirales. The name is derived from the Greek rhabdos meaning rod referring to the shape of the viral particles. Rhabdoviruses infect a broad range of hosts throughout the animal and plant kingdoms...

, order Mononegavirales
Mononegavirales
The order Mononegavirales is the taxonomic home of numerous related viruses. Members of the order that are commonly known are, for instance, Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. All of these viruses cause significant disease in...

. Lyssaviruses have helical symmetry, with a length of about 180 nm and a cross-sectional diameter of about 75 nm. These viruses are enveloped
Viral envelope
Many viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...

 and have a single-stranded RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 genome with negative-sense. The genetic information is packaged as a ribonucleoprotein
Ribonucleoprotein
Ribonucleoprotein is a nucleoprotein that contains RNA, i.e. it is an association that combines ribonucleic acid and protein together. A few known examples include the ribosome, the enzyme telomerase, vault ribonucleoproteins, and small nuclear RNPs , which are implicated in pre-mRNA splicing and...

 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).

Once inside a muscle or nerve cell, the virus undergoes replication. The trimeric spikes on the outside of the membrane of the virus interact with a specific cell receptor, the most likely one being the acytlcholine receptor. The cell membrane pinches in a process known as pinocytosis
Pinocytosis
In cellular biology, pinocytosis is a form of endocytosis in which small particles are brought into the cell—forming an invagination, and then suspended within small vesicles that subsequently fuse with lysosomes to hydrolyze, or to break down, the particles...

 and allows entry of the virus into the cell by way of an endosome. The virus then utilizes the acidic environment of that endosome and binds to its membrane simultaneously releasing its five proteins and single strand RNA into the cytoplasm. The L protein then transcribes 5 mRNA strands and a positive strand of RNA all from the original negative strand RNA using free nucleotides in the cytoplasm. These 5 mRNA strands are then translated into their corresponding proteins (P,L,N,G,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
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

 where it undergoes further folding, and is then transported to the Golgi Apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....

 where a sugar group is added to it (glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...

). Where there are enough 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 were 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 cell.

From the point of entry, the virus is neurotropic
Neurotropic virus
A neurotropic virus is a virus which is capable of infecting nerve cells, or which does so preferentially. Such viruses thereby largely evade the usual immune response—which acts only within the blood system.- Terminology :...

, traveling quickly along the neural pathways into the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 (CNS), and then further into other organs. The salivary glands receive high concentrations of the virus, thus allowing further transmission.

Diagnosis


The reference method
Gold standard (test)
In medicine and statistics, gold standard test refers to a diagnostic test or benchmark that is the best available under reasonable conditions. It does not have to be necessarily the best possible test for the condition in absolute terms...

 for diagnosing rabies is by performing PCR
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....

 or viral culture on brain samples taken after death. The diagnosis can also be reliably made from skin samples taken before death. It is also possible to make the diagnosis from saliva, urine and cerebrospinal fluid samples, but this is not as sensitive
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...

. Cerebral inclusion bodies called Negri bodies
Negri bodies
Negri bodies are eosinophilic, sharply outlined, pathognomonic inclusion bodies found in the cytoplasm of certain nerve cells containing the virus of rabies, especially in Ammon's horn of the hippocampus. Often also found in the cerebellar cortex of postmortem brain samples of rabies victims.They...

 are 100% diagnostic for rabies infection, but are found in only about 80% of cases. If possible, the animal from which the bite was received should also be examined for rabies.

The differential diagnosis
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

 in a case of suspected human rabies may initially include any cause of encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...

, in particular infection with viruses such as herpesviruses
Herpesviridae
The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein , referring to the latent, recurring infections typical of this group of viruses...

, enteroviruses, and arboviruses (e.g., West Nile virus
West Nile virus
West Nile virus is a virus of the family Flaviviridae. Part of the Japanese encephalitis antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, domestic...

). The most important viruses to rule out are herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...

 type 1, varicella-zoster virus, and (less commonly) enteroviruses, including coxsackieviruses, echovirus
Echovirus
An ECHO virus, is a type of RNA virus that belongs to the genus Enterovirus of the Picornaviridae family...

es, poliovirus
Poliovirus
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is...

es, and human enterovirus
Enterovirus
Enteroviruses are a genus of ssRNA viruses associated with several human and mammalian diseases. Serologic studies have distinguished 66 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the...

es 68 to 71. In addition, consideration should be given to the local epidemiology
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...

 of encephalitis caused by arboviruses belonging to several taxonomic
Taxonomy
Taxonomy is the science of identifying and naming species, and arranging them into a classification. The field of taxonomy, sometimes referred to as "biological taxonomy", revolves around the description and use of taxonomic units, known as taxa...

 groups, including eastern and western equine encephalitis virus
Equine Encephalitis
Equine encephalitis may be caused by several viruses:* Eastern equine encephalitis virus* Western equine encephalitis virus*West Nile virus* Venezuelan equine encephalitis virus...

es, St. Louis encephalitis
St. Louis Encephalitis
St. Louis Encephalitis is a disease caused by the Culex mosquito borne St. Louis Encephalitis virus. St. Louis encephalitis virus is related to Japanese encephalitis virus and is a member of the Flaviviridae subgroup. This disease mainly affects the United States...

 virus, Powassan virus
Powassan virus
The Powassan virus is a tick-borne encephalitis virus related to the classic TBE flavivirus. This disease had its earliest origins in the town of Powassan, Ontario, found in a young boy who eventually died from it....

, the California encephalitis virus
California encephalitis virus
California encephalitis virus was discovered in Kern County, California and causes encephalitis in humans. Encephalitis is an acute inflammation of the brain that can cause minor symptoms, such as headaches, to more severe symptoms such as seizures...

 serogroup, and La Crosse virus.

New causes of viral encephalitis are also possible, as was evidenced by the recent outbreak in Malaysia of some 300 cases of encephalitis (mortality rate, 40%) caused by Nipah virus, a newly recognized paramyxovirus
Paramyxovirus
Paramyxoviruses are viruses of the Paramyxoviridae family of the Mononegavirales order; they are negative-sense single-stranded RNA viruses responsible for a number of human and animal diseases.-Genera:*Subfamily Paramyxovirinae**Genus Avulavirus Paramyxoviruses (from Greek para-, beyond, -myxo-,...

. Likewise, well-known viruses may be introduced into new locations, as is illustrated by the recent outbreak of encephalitis due to West Nile virus
West Nile virus
West Nile virus is a virus of the family Flaviviridae. Part of the Japanese encephalitis antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, domestic...

 in the eastern United States. Epidemiologic factors (e.g., season, geographic location, and the patient's age, travel history, and possible exposure to animal bites, rodents, and ticks) may help direct the diagnostic workup.

Cheaper rabies diagnosis will become possible for low-income settings: accurate rabies diagnosis can be done at a tenth of the cost of traditional testing using basic light microscopy techniques.

Prevention


All human cases of rabies were fatal until a vaccine was developed in 1885 by Louis Pasteur
Louis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...

 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. Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines. The human diploid cell rabies vaccine was started in 1967; however, a new and less expensive purified chicken embryo cell vaccine and purified vero cell rabies vaccine are now available. A recombinant vaccine called V-RG has been successfully used in Belgium, France, Germany, and the United States to prevent outbreaks of rabies in wildlife
Wildlife
Wildlife includes all non-domesticated plants, animals and other organisms. Domesticating wild plant and animal species for human benefit has occurred many times all over the planet, and has a major impact on the environment, both positive and negative....

. Currently pre-exposure immunization has been used in both human and non-human populations, whereas in many jurisdictions domesticated animals are required to be vaccinated.

In the USA, since the widespread vaccination of domestic dogs and cats and the development of effective human vaccines and immunoglobulin treatments, the number of recorded deaths from rabies has dropped from one hundred or more annually in the early 20th century, to 1–2 per year, mostly caused by bat bites, which may go unnoticed by the victim and hence untreated.

The Missouri Dept. of Health and Senior Services Communicable Disease Surveillance 2007 Annual Report states that the following can help reduce the risk of exposure to rabies:
  • Vaccinating dogs, cats, and ferrets against rabies
  • Keeping pets under supervision
  • Not handling wild animals or strays
  • Contacting an animal control officer, if you see a wild animal or a stray, especially if the animal is acting strangely.
  • Washing the wound with soap and water between 10 and 15 minutes, if you do get bitten by an animal, and contacting your healthcare provider to see whether you need rabies post-exposure prophylaxis.
  • Getting pets spayed or neutered
    Neutering
    Neutering, from the Latin neuter , is the removal of an animal's reproductive organ, either all of it or a considerably large part. The process is often used in reference to males whereas spaying is often reserved for females. Colloquially, both terms are often referred to as fixing...

    . Pets that are sterile are less likely to leave home, become strays, and reproduce more stray animals.


September 28 is World Rabies Day
World Rabies Day
World Rabies Day is an international campaign coordinated by the Global Alliance for Rabies Control, a non-profit organization with headquarters in the United States and the United Kingdom...

, which promotes information on, and prevention and elimination of the disease.

Post-exposure prophylaxis


Treatment after exposure, known as post-exposure prophylaxis
Post-exposure prophylaxis
Post-exposure prophylaxis is any prophylactic treatment started immediately after exposure to a pathogen , in order to prevent infection by the pathogen and the development of disease.-Rabies:...

 (PEP), is highly successful in preventing the disease if administered promptly, in general within ten days of infection. Thoroughly washing the wound as soon as possible with soap and water for approximately five minutes is very effective in reducing the number of viral particles. "If available, a virucidal antiseptic such as povidone-iodine, iodine tincture
Tincture of iodine
Tincture of iodine is a disinfectant, usually 2–7% elemental iodine, along with potassium iodide or sodium iodide, dissolved in a mixture of ethanol and water. As in the case of Lugol's iodine, the role of iodide and water in the solution is to increase the solubility of the elemental iodine, by...

, aqueous iodine solution, or alcohol (ethanol) should be applied after washing. Exposed mucous membranes such as eyes, nose or mouth should be flushed well with water."

In the United States, the Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

 (CDC) recommend patients receive one dose of human rabies immunoglobulin (HRIG) and four doses of rabies vaccine over a fourteen-day period. The immunoglobulin dose should not exceed 20 units per kilogram body weight. HRIG is very expensive and constitutes the vast majority of the cost of post-exposure treatment, ranging as high as several thousand dollars. As much as possible of this dose should be infiltrated around the bites, with the remainder being given by deep intramuscular injection at a site distant from the vaccination site. The first dose of rabies vaccine is given as soon as possible after exposure, with additional doses on days three, seven and fourteen after the first. Patients who have previously received pre-exposure vaccination do not receive the immunoglobulin, only the post-exposure vaccinations on day 0 and 2.

Modern cell-based vaccines are similar to flu shots in terms of pain and side-effects. The old nerve-tissue-based vaccinations that require multiple painful injections into the abdomen with a large needle are cheap, but are being phased out and replaced by affordable WHO ID (intradermal) vaccination regimens.

Intramuscular vaccination should be given into the deltoid, not gluteal area, which has been associated with vaccination failure due to injection into fat rather than muscle. In infants, the lateral thigh is used as for routine childhood vaccinations.

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 regarded as an indication for post-exposure prophylaxis. The recommendation for the precautionary use of post-exposure prophylaxis in occult bat encounters where there is no recognized contact has been questioned in the medical literature, based on a cost-benefit analysis. However, recent studies have further confirmed the wisdom of maintaining the current protocol of precautionary administering of PEP in cases where a child or mentally compromised individual has been left alone with a bat, especially in sleep areas, where a bite or exposure may occur while the victim is asleep and unaware or awake and unaware that a bite occurred. This is illustrated by the September 2000 case of a nine-year-old boy from Quebec who died from rabies three weeks after being in the presence of a sick bat, even though there was no apparent report of a bite, as shown in the following conclusion made by the doctors involved in the case:

Despite recent criticism (45), the dramatic circumstances surrounding our patient's history, as well as increasingly frequent reports of human rabies contracted in North America, support the current Canadian guidelines that state that RPEP [PEP] is appropriate in cases where a significant contact with a bat cannot be excluded (45). The notion that a bite or an overt break in the skin needs to be seen or felt for rabies to be transmitted by a bat is a myth in many cases.


It is highly recommended that PEP be administered as soon as possible. Begun with little or no delay, PEP is 100% effective against rabies. In the case in which there has been a significant delay in administering PEP, the treatment should be administered regardless of that delay, as it may still be effective.

Blood-brain barrier


During lethal rabies infection of mice, the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

 (BBB) does not allow anti-viral immune cells to enter the brain, the primary site of rabies virus replication. This aspect contributes to the pathogenicity of the virus and artificially increasing BBB permeability promotes viral clearance. Opening the BBB during rabies infection has been suggested as a possible novel approach to treating the disease, even though no attempts have yet been made to determine whether or not this treatment could be successful.

Induced coma


In 2004, American teenager Jeanna Giese
Jeanna Giese
The Milwaukee protocol is an experimental course of treatment of an acute infection of rabies in a human being. The treatment involves putting the patient into a chemically induced coma and administering antiviral drugs. It was developed and named by Dr. Rodney Willoughby, Jr., M.D., following the...

 survived an infection of rabies unvaccinated. She was placed into an induced coma
Induced coma
A barbiturate-induced coma, or barb coma, is a temporary coma brought on by a controlled dose of a barbiturate drug, usually pentobarbital or thiopental...

 upon onset of symptoms and given ketamine
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...

, midazolam
Midazolam
Midazolam is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic,...

, ribavirin
Ribavirin
Ribavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...

, and amantadine
Amantadine
Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...

. Her doctors administered treatment based on the hypothesis that detrimental effects of rabies were caused by temporary dysfunctions in the brain and could be avoided by inducing a temporary partial halt in brain function that would protect the brain from damage while giving the immune system time to defeat the virus. After thirty-one days of isolation and seventy-six days of hospitalization, Giese was released from the hospital. She survived with almost no permanent sequela
Sequela
A sequela) is a pathological condition resulting from a disease, injury, or other trauma.Chronic kidney disease, for example, is sometimes a sequela of diabetes, and neck pain is a common sequela of whiplash or other trauma to the cervical vertebrae. Post-traumatic stress disorder may be a...

e and as of 2009 was starting her third year of university studies.

Giese's treatment regimen became known as the "Milwaukee protocol", which has since undergone revision (the second version omits the use of ribavirin
Ribavirin
Ribavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...

). There were 2 survivors out of 25 patients treated under the first protocol. A further 10 patients have been treated under the revised protocol and there have been a further 2 survivors. The anesthetic drug ketamine
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...

 has shown the potential for rabies virus inhibition in rats, and is used as part of the Milwaukee protocol.

On April 10, 2008 in Cali
Calì
Calì, also written in English as Cali, is an Italian surname, widespread mainly in the Ionian side of Sicily.For the surname Calì is assumed the origin of the Greek word kalos , or from its Sanskrit root kali, "time."The surname refers to:...

, Colombia
Colombia
Colombia, officially the Republic of Colombia , is a unitary constitutional republic comprising thirty-two departments. The country is located in northwestern South America, bordered to the east by Venezuela and Brazil; to the south by Ecuador and Peru; to the north by the Caribbean Sea; to the...

, an eleven-year-old boy was reported to survive rabies and the induced coma without noticeable brain damage.

On June 12, 2011, Precious Reynolds, an eight-year-old girl from Humboldt County, California
Humboldt County, California
Humboldt County is a county in the U.S. state of California, located on the far North Coast 200 miles north of San Francisco. According to 2010 Census Data, the county’s population was 134,623...

, became the third reported person in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

 to have recovered from rabies without receiving post-exposure prophylaxis.

Prognosis


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. Begun with little or no delay, PEP is 100% effective against rabies. In the case in which there has been a significant delay in administering PEP, the treatment should be administered regardless of that delay, as it may still be effective.

In unvaccinated humans, rabies is usually fatal after neurological symptoms have developed, but prompt post-exposure vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...

 may prevent the virus from progressing. Rabies kills around 55,000 people a year, mostly in Asia and Africa.

Survival data using the Milwaukee protocol are available from the rabies registry. As of 2011, seven people have been saved by this induced coma treatment, for details see the section above- Rabies#Induced coma).

Epidemiology



Transmission


Any warm-blooded animal (including humans) may become infected with the rabies virus and develop symptoms (although birds have only been known to be experimentally infected). Indeed the virus has even been adapted to grow in cells of poikilotherm
Poikilotherm
A poikilotherm is an organism whose internal temperature varies considerably. It is the opposite of a homeotherm, an organism which maintains thermal homeostasis. Usually the variation is a consequence of variation in the ambient environmental temperature...

ic ("cold-blooded") vertebrates. Most animals can be infected by the virus and can transmit the disease to humans. Infected bat
Bat
Bats are mammals of the order Chiroptera "hand" and pteron "wing") whose forelimbs form webbed wings, making them the only mammals naturally capable of true and sustained flight. By contrast, other mammals said to fly, such as flying squirrels, gliding possums, and colugos, glide rather than fly,...

s, monkey
Monkey
A monkey is a primate, either an Old World monkey or a New World monkey. There are about 260 known living species of monkey. Many are arboreal, although there are species that live primarily on the ground, such as baboons. Monkeys are generally considered to be intelligent. Unlike apes, monkeys...

s, raccoon
Raccoon
Procyon is a genus of nocturnal mammals, comprising three species commonly known as raccoons, in the family Procyonidae. The most familiar species, the common raccoon , is often known simply as "the" raccoon, as the two other raccoon species in the genus are native only to the tropics and are...

s, fox
Fox
Fox is a common name for many species of omnivorous mammals belonging to the Canidae family. Foxes are small to medium-sized canids , characterized by possessing a long narrow snout, and a bushy tail .Members of about 37 species are referred to as foxes, of which only 12 species actually belong to...

es, skunk
Skunk
Skunks are mammals best known for their ability to secrete a liquid with a strong, foul odor. General appearance varies from species to species, from black-and-white to brown or cream colored. Skunks belong to the family Mephitidae and to the order Carnivora...

s, cattle
Cattle
Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...

, wolves, coyotes, dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...

s, mongoose
Mongoose
Mongoose are a family of 33 living species of small carnivorans from southern Eurasia and mainland Africa. Four additional species from Madagascar in the subfamily Galidiinae, which were previously classified in this family, are also referred to as "mongooses" or "mongoose-like"...

 (normally yellow mongoose) or cat
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...

s present the greatest risk to humans. Rabies may also spread through exposure to infected domestic farm animals
Livestock
Livestock refers to one or more domesticated animals raised in an agricultural setting to produce commodities such as food, fiber and labor. The term "livestock" as used in this article does not include poultry or farmed fish; however the inclusion of these, especially poultry, within the meaning...

, groundhog
Groundhog
The groundhog , also known as a woodchuck, whistle-pig, or in some areas as a land-beaver, is a rodent of the family Sciuridae, belonging to the group of large ground squirrels known as marmots. Other marmots, such as the yellow-bellied and hoary marmots, live in rocky and mountainous areas, but...

s, weasel
Weasel
Weasels are mammals forming the genus Mustela of the Mustelidae family. They are small, active predators, long and slender with short legs....

s, bear
Bear
Bears are mammals of the family Ursidae. Bears are classified as caniforms, or doglike carnivorans, with the pinnipeds being their closest living relatives. Although there are only eight living species of bear, they are widespread, appearing in a wide variety of habitats throughout the Northern...

s and other wild carnivores
Carnivora
The diverse order Carnivora |Latin]] carō "flesh", + vorāre "to devour") includes over 260 species of placental mammals. Its members are formally referred to as carnivorans, while the word "carnivore" can refer to any meat-eating animal...

. Small rodents such as squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice and lagomorphs like rabbits and hares are almost never found to be infected with rabies and are not known to transmit rabies to humans. The Virginia opossum is resistant but not immune to rabies.

The virus is usually present in the nerves and saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...

 of a symptomatic rabid animal. The route of infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

 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.

Transmission between humans is extremely rare. A few cases have been recorded through transplant surgery
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...

.

After a typical human infection by bite, the virus enters the peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...

. It then travels along the nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...

s toward the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

. During this phase, the virus cannot be easily detected within the host, and vaccination may still confer cell-mediated immunity to prevent symptomatic rabies. When the virus reaches the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

, it rapidly causes encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...

. This is called the prodromal phase, and is the beginning of the symptoms. Once the patient becomes symptomatic, treatment is almost never effective and mortality is over 99%. Rabies may also inflame the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

, producing transverse myelitis
Myelitis
Myelitis is a disease involving inflammation of the spinal cord, which disrupts central nervous system functions linking the brain and limbs. The name is derived from Greek referring to the "spinal cord", and the suffix -itis, which denotes inflammation....

.

Prevalence


The rabies virus survives in widespread, varied, rural fauna reservoirs. It is present in the animal populations of almost every country in the world, except in Australia and New Zealand. In some countries, like those in western Europe and Oceania, rabies is considered to be prevalent among bat populations only.

In Asia, parts of the Americas, and large parts of Africa, dogs remain the principal host. Mandatory vaccination of animals is less effective in rural areas. Especially in developing countries, pets may not be privately kept and their destruction may be unacceptable. Oral vaccines can be safely distributed in baits, a practice that has successfully reduced rabies in rural areas of Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...

, France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...

, and the USA
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

. In Montréal
Montreal
Montreal is a city in Canada. It is the largest city in the province of Quebec, the second-largest city in Canada and the seventh largest in North America...

, Canada, baits are successfully used on raccoons in the Mont-Royal Park area. Vaccination campaigns may be expensive, and cost-benefit analysis suggests that baits may be a cost effective method of control.

There are an estimated 55,000 human deaths annually from rabies worldwide, with about 31,000 in Asia, and 24,000 in Africa. One of the sources of recent flourishing of rabies in East Asia
East Asia
East Asia or Eastern Asia is a subregion of Asia that can be defined in either geographical or cultural terms...

 is the pet boom. China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...

 introduced the "one-dog policy" in the city of Beijing
Beijing
Beijing , also known as Peking , is the capital of the People's Republic of China and one of the most populous cities in the world, with a population of 19,612,368 as of 2010. The city is the country's political, cultural, and educational center, and home to the headquarters for most of China's...

 in November 2006 to control the problem. India has been reported as having the highest rate of human rabies in the world, primarily because of stray dogs. , Vietnam had the second-highest rate, followed by Thailand; in these countries the virus is primarily transmitted through canines (feral dogs and other wild canine species).

Rabies is common among wild animals in the United States. Bat
Bat
Bats are mammals of the order Chiroptera "hand" and pteron "wing") whose forelimbs form webbed wings, making them the only mammals naturally capable of true and sustained flight. By contrast, other mammals said to fly, such as flying squirrels, gliding possums, and colugos, glide rather than fly,...

s, raccoon
Raccoon
Procyon is a genus of nocturnal mammals, comprising three species commonly known as raccoons, in the family Procyonidae. The most familiar species, the common raccoon , is often known simply as "the" raccoon, as the two other raccoon species in the genus are native only to the tropics and are...

s, skunk
Skunk
Skunks are mammals best known for their ability to secrete a liquid with a strong, foul odor. General appearance varies from species to species, from black-and-white to brown or cream colored. Skunks belong to the family Mephitidae and to the order Carnivora...

s and fox
Fox
Fox is a common name for many species of omnivorous mammals belonging to the Canidae family. Foxes are small to medium-sized canids , characterized by possessing a long narrow snout, and a bushy tail .Members of about 37 species are referred to as foxes, of which only 12 species actually belong to...

es account for almost all reported cases (98% in 2009). Rabid bats are found in all 48 contiguous states. Other reservoirs are more limited geographically: for example, the raccoon rabies virus variant is only found in a relatively narrow band along the East Coast. Due to a high public awareness of the virus, efforts at vaccination of domestic animals and curtailment of feral populations, and availability of post-exposure prophylaxis
Post-exposure prophylaxis
Post-exposure prophylaxis is any prophylactic treatment started immediately after exposure to a pathogen , in order to prevent infection by the pathogen and the development of disease.-Rabies:...

, incidents of rabies in humans are very rare. There was a total of 45 cases of the disease in the country in 1995-2010; of these, 9 are thought to have been acquired abroad. Almost all domestically acquired cases are attributed to bat bites.

Etymology


The term is derived from the Latin
Latin
Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...

 rabies, "madness". This, in turn, may be related to the Sanskrit rabhas, "to do violence". The Greeks derived the word "lyssa", from "lud" or "violent"; this root is used in the name of the genus of rabies lyssavirus.

Impact



Because of its potentially violent nature, rabies has been known since c.2000 B.C. The first written record of rabies is in the Mesopotamian Codex of Eshnunna
Laws of Eshnunna
The Laws of Eshnunna are inscribed on two cuneiform tablets discovered in Tell Abū Harmal, Baghdad, Iraq. The Iraqi Directorate of Antiquities headed by Taha Baqir unearthed two parallel sets of tablets in 1945 and 1947. The two tablets are separate copies of an older source and date back to ca....

 (ca. 1930 BC), which dictates that the owner of a dog showing symptoms of rabies should take preventive measure against bites. If another person was bitten by a rabid dog and later died, the owner was heavily fined.

Rabies was considered a scourge for its prevalence in the 19th century. In France and Belgium, where Saint Hubert
Hubertus
Saint Hubertus or Hubert , called the "Apostle of the Ardennes" was the first Bishop of Liège...

 was venerated, the "St Hubert's Key
St Hubert's Key
St Hubert’s Key took the form of a metal nail or bar with a decorative head. It was used in Europe until the early 20th century as a traditional cure for rabies and was named for St Hubert, the patron saint of hunters, mathematicians, opticians and metalworkers....

" was heated and applied to cauterize the wound; by an application of magical thinking
Magical thinking
Magical thinking is causal reasoning that looks for correlation between acts or utterances and certain events. In religion, folk religion, and superstition, the correlation posited is between religious ritual, such as prayer, sacrifice, or the observance of a taboo, and an expected benefit or...

, dogs were branded with the key in hopes of protecting them from rabies. Fear of rabies related to methods of transmissions was almost irrational; however, this gave Louis Pasteur
Louis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...

 ample opportunity to test post-exposure treatments from 1885.
In ancient medical times, the attachment of the tongue (the frenum linguae, a mucous membrane) was cut and removed from where they thought the rabies came from. This changed once they found the actual cause of rabies.

In other animals


Rabies is infectious to mammals. Three stages of rabies are recognized in dogs and other animals. The first stage is a one- to three-day period characterized by behavioral changes and is known as the prodromal stage
Prodrome
In medicine, a prodrome is an early symptom that might indicate the start of a disease before specific symptoms occur. It is derived from the Greek word prodromos or precursor...

. The second stage is the excitative stage, which lasts three to four days. It is this stage that is often known as furious rabies for the tendency of the affected animal to be hyperreactive to external stimuli and bite at anything near. The third stage is the paralytic stage and is caused by damage to motor neuron
Motor neuron
In vertebrates, the term motor neuron classically applies to neurons located in the central nervous system that project their axons outside the CNS and directly or indirectly control muscles...

s. Incoordination is seen owing to rear limb paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...

 and drooling and difficulty swallowing is caused by paralysis of facial and throat muscles. Death is usually caused by respiratory arrest
Respiratory arrest
Respiratory arrest is the cessation of breathing. It is a medical emergency and it usually is related to or coincides with a cardiac arrest. Causes include opiate overdose, head injury, anaesthesia, tetanus, or drowning...

.

Research and gene therapy uses


Rabies has the advantage over other pseudotyping
Pseudotyping
Pseudotyping is the process of producing viruses or viral vectors in combination with foreign viral envelope proteins. The result is a pseudotyped virus particle.. With this method, the foreign viral envelope proteins can be used to alter host tropism or an increased/decreased stability of the...

 methods for gene delivery in that the cell targeting (tissue tropism
Tissue tropism
Tissue tropism is a term most often used in virology to define the cells and tissues of a host which support growth of a particular virus. Bacteria and other parasites may also be referred to as having a tissue tropism....

) is more specific for difficult to reach sites such as the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 without invasive delivery methods as well as capable of retrograde tracing
Retrograde tracing
Retrograde tracing is a research method which is used in neuroscience to trace neural connections from their point of termination to their source . The opposite technique is anterograde tracing, which is used to trace neural connections from their source to their point of termination...

 (i.e. going against the flow of information at synapses) in neuronal circuits.

See also

  • Global Alliance for Rabies Control
    Global Alliance for Rabies Control
    The Global Alliance for Rabies Control is a non-profit organization that aims to increase awareness of the continuing threat of rabies around the world...

  • Rabies in popular culture
    Rabies in popular culture
    Rabies has been the main plot device or a significant theme in many fictional works. Due to the long history of the virus as well as the neurotropic nature, rabies has been a potent symbol of madness, irrationalism, or simply an unstoppable plague.-Novels and films:...

  • World Rabies Day
    World Rabies Day
    World Rabies Day is an international campaign coordinated by the Global Alliance for Rabies Control, a non-profit organization with headquarters in the United States and the United Kingdom...


External links