Rabies
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Rabies is a
viral disease A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Structural Characteristics Basic structural characteristics, ...
that causes encephalitis in humans and other
mammals Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and
loss of consciousness Loss may refer to: Arts, entertainment, and media Music * ''Loss'' (Bass Communion album) (2006) * ''Loss'' (Mull Historical Society album) (2001) *"Loss", a song by God Is an Astronaut from their self-titled album (2008) * Losses "(Lil Tjay son ...
. Once symptoms appear, the result is virtually always death, regardless of treatment. The time period between contracting the disease and the start of symptoms is usually one to three months but can vary from less than one week to more than one year. The time depends on the distance the virus must travel along
peripheral nerves The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain an ...
to reach the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
. Rabies is caused by
lyssavirus ''Lyssavirus'' (from the Ancient Greek, Greek ''lyssa'' "rage, fury, rabies" and the Latin ''Virus#Etymology, vīrus'') is a genus of RNA viruses in the family ''Rhabdoviridae'', order ''Mononegavirales''. Mammals, including humans, can serve ...
es, including the
rabies virus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lys ...
and
Australian bat lyssavirus ''Australian bat lyssavirus'' (''ABLV''), originally named ''Pteropid lyssavirus'' (''PLV''), is a zoonotic virus closely related to the rabies virus. It was first identified in a 5-month-old juvenile black flying fox ('' Pteropus alecto'') col ...
. It is spread when an infected animal bites or scratches a human or other animals. Saliva from an infected animal can also transmit rabies if the saliva comes into contact with the eyes, mouth, or nose. Globally, dogs are the most common animal involved. In countries where dogs commonly have the disease, more than 99% of rabies cases are the direct result of
dog bites A dog bite is a bite upon a person or other animal by a dog, including from a rabid dog. More than one successive bite is often called a dog attack, although dog attacks can include knock-downs and scratches. Though some dog bites do not result ...
. In the
Americas The Americas, which are sometimes collectively called America, are a landmass comprising the totality of North and South America. The Americas make up most of the land in Earth's Western Hemisphere and comprise the New World. Along with th ...
,
bat Bats are mammals of the order Chiroptera.''cheir'', "hand" and πτερόν''pteron'', "wing". With their forelimbs adapted as wings, they are the only mammals capable of true and sustained flight. Bats are more agile in flight than most ...
bites are the most common source of rabies infections in humans, and less than 5% of cases are from dogs.
Rodent Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are na ...
s are very rarely infected with rabies. The disease can be diagnosed only after the start of symptoms. Animal control and vaccination programs have decreased the risk of rabies from dogs in a number of regions of the world. Immunizing people before they are exposed is recommended for those at high risk, including those who work with bats or who spend prolonged periods in areas of the world where rabies is common. In people who have been exposed to rabies, the
rabies vaccine The rabies vaccine is a vaccine used to prevent rabies. There are a number of rabies vaccines available that are both safe and effective. They can be used to prevent rabies before, and, for a period of time, after exposure to the rabies virus, ...
and sometimes
rabies immunoglobulin Rabies immunoglobulin (RIG) is a medication made up of antibodies against the rabies virus. It is used to prevent rabies following exposure. It is given after the wound is cleaned with soap and water or povidone-iodine and is followed by a cours ...
are effective in preventing the disease if the person receives the treatment before the start of rabies symptoms. Washing bites and scratches for 15 minutes with soap and water,
povidone-iodine Povidone-iodine (PVP-I), also known as iodopovidone, is an antiseptic used for skin disinfection before and after surgery. It may be used both to disinfect the hands of healthcare providers and the skin of the person they are caring for. It may ...
, or detergent may reduce the number of viral particles and may be somewhat effective at preventing transmission. , only fourteen people were documented to have survived a rabies infection after showing symptoms. However, research conducted in 2010 among a population of people in Perú with a self-reported history of one or more bites from
vampire bats Vampire bats, species of the subfamily Desmodontinae, are leaf-nosed bats found in Central and South America. Their food source is blood of other animals, a dietary trait called hematophagy. Three extant bat species feed solely on blood: the com ...
(commonly infected with rabies), found that out of 73 individuals reporting previous bat bites, 7 people had rabies virus-neutralizing antibodies (rVNA). Since only one member of this group reported prior vaccination for rabies, the findings of the research suggest previously undocumented cases of infection and viral replication followed by an abortive infection. This could indicate that in rare cases people may have an exposure to the virus without treatment and develop natural antibodies as a result. Rabies causes about 59,000 deaths worldwide per year, about 40% of which are in children under the age of 15. More than 95% of human deaths from rabies occur in Africa and Asia. Rabies is present in more than 150 countries and on all continents but Antarctica. More than 3 billion people live in regions of the world where rabies occurs. A number of countries, including Australia and Japan, as well as much of Western Europe, do not have rabies among dogs. Many Pacific islands do not have rabies at all. It is classified as a
neglected tropical disease Neglected tropical diseases (NTDs) are a diverse group of tropical disease, tropical infections that are common in low-income populations in Developing country, developing regions of Africa, Asia, and the Americas. They are caused by a variety ...
.


Etymology

The name rabies is derived from the
Latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
''rabies'', "madness". This, in turn, may be related to the Sanskrit ''rabhas'', "to rage". The Greeks derived the word ''lyssa'', from ''lud'' or "violent"; this root is used in the genus name of the rabies virus, ''Lyssavirus''.


Signs and symptoms

Man with rabies displaying hydrophobia Animals with "dumb" rabies appear depressed, lethargic, and uncoordinated The
period Period may refer to: Common uses * Era, a length or span of time * Full stop (or period), a punctuation mark Arts, entertainment, and media * Period (music), a concept in musical composition * Periodic sentence (or rhetorical period), a concept ...
between infection and the first symptoms (incubation period) is typically 1–3 months in humans. This period may be as short as four days or longer than six years, depending on the location and severity of the wound and the amount of virus introduced. Initial symptoms of rabies are often nonspecific such as fever and headache. As rabies progresses and causes inflammation of the brain and meninges, symptoms can include slight or partial paralysis,
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
,
insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
,
confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"
, agitation, abnormal behavior,
paranoia Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy co ...
, terror, and
hallucination A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...
s. The person may also have fear of water. The symptoms eventually progress to delirium, and coma. Death usually occurs 2 to 10 days after first symptoms. Survival is almost unknown once symptoms have presented, even with intensive care. Rabies has also occasionally been referred to as hydrophobia ("fear of water") throughout its history. It refers to a set of symptoms in the later stages of an infection in which the person has difficulty swallowing, shows panic when presented with liquids to drink, and cannot quench their thirst. Any mammal infected with the virus may demonstrate hydrophobia. Saliva production is greatly increased, and attempts to drink, or even the intention or suggestion of drinking, may cause excruciatingly painful spasms of the muscles in the throat and
larynx The larynx (), commonly called the voice box, is an organ in the top of the neck involved in breathing, producing sound and protecting the trachea against food aspiration. The opening of larynx into pharynx known as the laryngeal inlet is about ...
. Since the infected individual cannot swallow saliva and water, the virus has a much higher chance of being transmitted, because it multiplies and accumulates in the
salivary gland The salivary glands in mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands ( parotid, submandibular, and sublingual), as well as hundreds of minor salivary glands. Salivary ...
s and is transmitted through biting. Hydrophobia is commonly associated with furious rabies, which affects 80% of rabies-infected people. The remaining 20% may experience a paralytic form of rabies that is marked by muscle weakness, loss of sensation, and paralysis; this form of rabies does not usually cause fear of water.


Cause

Rabies is caused by a number of
lyssavirus ''Lyssavirus'' (from the Ancient Greek, Greek ''lyssa'' "rage, fury, rabies" and the Latin ''Virus#Etymology, vīrus'') is a genus of RNA viruses in the family ''Rhabdoviridae'', order ''Mononegavirales''. Mammals, including humans, can serve ...
es including the
rabies virus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lys ...
and
Australian bat lyssavirus ''Australian bat lyssavirus'' (''ABLV''), originally named ''Pteropid lyssavirus'' (''PLV''), is a zoonotic virus closely related to the rabies virus. It was first identified in a 5-month-old juvenile black flying fox ('' Pteropus alecto'') col ...
. Duvenhage lyssavirus may cause a rabies-like infection. The rabies virus is the
type species In zoological nomenclature, a type species (''species typica'') is the species name with which the name of a genus or subgenus is considered to be permanently taxonomically associated, i.e., the species that contains the biological type specimen ...
of the ''
Lyssavirus ''Lyssavirus'' (from the Ancient Greek, Greek ''lyssa'' "rage, fury, rabies" and the Latin ''Virus#Etymology, vīrus'') is a genus of RNA viruses in the family ''Rhabdoviridae'', order ''Mononegavirales''. Mammals, including humans, can serve ...
''
genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In the hierarchy of biological classification, genus com ...
, in the family''
Rhabdoviridae ''Rhabdoviridae'' is a family of negative-strand RNA viruses in the order ''Mononegavirales''. Vertebrates (including mammals and humans), invertebrates, plants, fungi and protozoans serve as natural hosts. Diseases associated with member viru ...
'', order ''
Mononegavirales ''Mononegavirales'' is an order of negative-strand RNA viruses which have nonsegmented genomes. Some common members of the order are Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. A ...
''. Lyssavirions have helical symmetry, with a length of about 180  nm and a cross-section of about 75 nm. These virions are enveloped and have a single-stranded
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
genome with negative sense. The genetic information is packed as a
ribonucleoprotein Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins. Structures Nucleoproteins tend to be positively charged, facilitating int ...
complex in which RNA is tightly bound by the viral nucleoprotein. The
RNA genome Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydr ...
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). To enter cells, trimeric spikes on the exterior of the membrane of the virus interact with a specific cell receptor, the most likely one being the
acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
receptor. The cellular membrane pinches in a procession known as
pinocytosis In cellular biology, pinocytosis, otherwise known as fluid endocytosis and bulk-phase pinocytosis, is a mode of endocytosis in which small molecules dissolved in extracellular fluid are brought into the cell through an invagination of the cell ...
and allows entry of the virus into the cell by way of an
endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...
. The virus then uses the acidic environment, which is necessary, of that endosome and binds to its membrane simultaneously, releasing its five proteins and single-strand RNA into the cytoplasm. Once within a muscle or nerve cell, the virus undergoes replication. The L protein then transcribes five mRNA strands and a positive strand of RNA all from the original negative strand RNA using free nucleotides in the cytoplasm. These five mRNA strands are then translated into their corresponding proteins (P, L, N, G and M proteins) at free ribosomes in the cytoplasm. Some proteins require post-translative modifications. For example, the G protein travels through the rough endoplasmic reticulum, where it undergoes further folding, and is then transported to the
Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...
, where a sugar group is added to it ( glycosylation). When there are enough viral proteins, the viral polymerase will begin to synthesize new negative strands of RNA from the template of the positive-strand RNA. These negative strands will then form complexes with the N, P, L and M proteins and then travel to the inner membrane of the cell, where a G protein has embedded itself in the membrane. The G protein then coils around the N-P-L-M complex of proteins taking some of the host cell membrane with it, which will form the new outer envelope of the virus particle. The virus then buds from the cell. From the point of entry, the virus is neurotropic, traveling along the neural pathways into the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
. The virus usually first infects muscle cells close to the site of infection, where they are able to replicate without being 'noticed' by the host's immune system. Once enough virus has been replicated, they begin to bind to
acetylcholine receptor An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter. Classification Like other transmembrane receptors, acetylcholine receptors are classified according ...
s at the neuromuscular junction. The virus then travels through the nerve cell axon via
retrograde transport Axonal transport, also called axoplasmic transport or axoplasmic flow, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other organelles to and from a neuron's cell body, through the cytoplas ...
, as its P protein interacts with dynein, a protein present in the cytoplasm of nerve cells. Once the virus reaches the cell body it travels rapidly to the central nervous system (CNS), replicating in motor neurons and eventually reaching the brain. After the brain is infected, the virus travels centrifugally to the peripheral and autonomic nervous systems, eventually migrating to the salivary glands, where it is ready to be transmitted to the next host.


Transmission

All
warm-blooded Warm-blooded is an informal term referring to animal species which can maintain a body temperature higher than their environment. In particular, homeothermic species maintain a stable body temperature by regulating metabolic processes. The onl ...
species, including humans, may become infected with the rabies virus and develop symptoms.
Bird Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweigh ...
s were first artificially infected with rabies in 1884; however, infected birds are largely, if not wholly, asymptomatic, and recover. Other bird species have been known to develop rabies antibodies, a sign of infection, after feeding on rabies-infected mammals. The virus has also adapted to grow in cells of cold-blooded vertebrates. Most animals can be infected by the virus and can transmit the disease to humans. Worldwide, about 99% of human rabies cases come from domestic dogs. Other sources of rabies in humans include
bat Bats are mammals of the order Chiroptera.''cheir'', "hand" and πτερόν''pteron'', "wing". With their forelimbs adapted as wings, they are the only mammals capable of true and sustained flight. Bats are more agile in flight than most ...
s,
monkey Monkey is a common name that may refer to most mammals of the infraorder Simiiformes, also known as the simians. Traditionally, all animals in the group now known as simians are counted as monkeys except the apes, which constitutes an incomple ...
s,
raccoon The raccoon ( or , ''Procyon lotor''), sometimes called the common raccoon to distinguish it from other species, is a mammal native to North America. It is the largest of the procyonid family, having a body length of , and a body weight of ...
s,
fox Foxes are small to medium-sized, omnivorous mammals belonging to several genera of the family Canidae. They have a flattened skull, upright, triangular ears, a pointed, slightly upturned snout, and a long bushy tail (or ''brush''). Twelve sp ...
es,
skunk Skunks are mammals in the family Mephitidae. They are known for their ability to spray a liquid with a strong, unpleasant scent from their anal glands. Different species of skunk vary in appearance from black-and-white to brown, cream or ginge ...
s,
cattle Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referred to as cows and adult mal ...
,
wolves The wolf (''Canis lupus''; plural, : wolves), also known as the gray wolf or grey wolf, is a large Canis, canine native to Eurasia and North America. More than thirty subspecies of Canis lupus, subspecies of ''Canis lupus'' have been reco ...
,
coyotes The coyote (''Canis latrans'') is a species of canis, canine native to North America. It is smaller than its close relative, the wolf, and slightly smaller than the closely related eastern wolf and red wolf. It fills much of the same ecologica ...
,
cat The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of ...
s, and
mongoose A mongoose is a small terrestrial carnivorous mammal belonging to the family Herpestidae. This family is currently split into two subfamilies, the Herpestinae and the Mungotinae. The Herpestinae comprises 23 living species that are native to so ...
s (normally either the small Asian mongoose or the yellow mongoose). Rabies may also spread through exposure to infected
bears Bears are carnivoran mammals of the family Ursidae. They are classified as caniforms, or doglike carnivorans. Although only eight species of bears are extant, they are widespread, appearing in a wide variety of habitats throughout the North ...
, domestic farm animals,
groundhog The groundhog (''Marmota monax''), also known as a woodchuck, is a rodent of the family Sciuridae, belonging to the group of large ground squirrels known as marmots. The groundhog is a lowland creature of North America; it is found through mu ...
s,
weasel Weasels are mammals of the genus ''Mustela'' of the family Mustelidae. The genus ''Mustela'' includes the least weasels, polecats, stoats, ferrets and European mink. Members of this genus are small, active predators, with long and slender bo ...
s, and other wild carnivorans. However,
lagomorphs The lagomorphs are the members of the taxonomic order Lagomorpha, of which there are two living families: the Leporidae ( hares and rabbits) and the Ochotonidae (pikas). The name of the order is derived from the Ancient Greek ''lagos'' (λα ...
, such as
hare Hares and jackrabbits are mammals belonging to the genus ''Lepus''. They are herbivores, and live solitarily or in pairs. They nest in slight depressions called forms, and their young are able to fend for themselves shortly after birth. The ge ...
s and
rabbit Rabbits, also known as bunnies or bunny rabbits, are small mammals in the family Leporidae (which also contains the hares) of the order Lagomorpha (which also contains the pikas). ''Oryctolagus cuniculus'' includes the European rabbit speci ...
s, and small
rodent Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are na ...
s, such as
chipmunk Chipmunks are small, striped rodents of the family Sciuridae. Chipmunks are found in North America, with the exception of the Siberian chipmunk which is found primarily in Asia. Taxonomy and systematics Chipmunks may be classified either as ...
s,
gerbil The Mongolian gerbil or Mongolian jird (''Meriones unguiculatus'') is a small rodent belonging to the subfamily Gerbillinae. Their body size is typically , with a tail, and body weight , with adult males larger than females. The animal is use ...
s,
guinea pig The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus ''Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ani ...
s,
hamster Hamsters are rodents (order Rodentia) belonging to the subfamily Cricetinae, which contains 19 species classified in seven genera.Fox, Sue. 2006. ''Hamsters''. T.F.H. Publications Inc. They have become established as popular small pets. The b ...
s,
mice A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
, rats, and
squirrel Squirrels are members of the family Sciuridae, a family that includes small or medium-size rodents. The squirrel family includes tree squirrels, ground squirrels (including chipmunks and prairie dogs, among others), and flying squirrels. Squ ...
s, are almost never found to be infected with rabies and are not known to transmit rabies to humans. Bites from mice, rats, or squirrels rarely require rabies prevention because these rodents are typically killed by any encounter with a larger, rabid animal, and would, therefore, not be carriers. The
Virginia opossum The Virginia opossum (''Didelphis virginiana''), also known as the North American opossum, is the only opossum living north of Mexico, its range extending south into Central America. It is the northernmost marsupial in the world. In the United S ...
(a marsupial, unlike the other mammals named in this paragraph, which are all eutherians/
placental Placental mammals (infraclass Placentalia ) are one of the three extant subdivisions of the class Mammalia, the other two being Monotremata and Marsupial Marsupials are any members of the mammalian infraclass Marsupialia. All extant marsup ...
), has a lower internal body temperature than the rabies virus prefers and therefore is resistant but not immune to rabies.
Marsupials Marsupials are any members of the mammalian infraclass Marsupialia. All extant marsupials are endemic to Australasia, Wallacea and the Americas. A distinctive characteristic common to most of these species is that the young are carried in a po ...
, along with
monotremes Monotremes () are prototherian mammals of the order Monotremata. They are one of the three groups of living mammals, along with placentals (Eutheria), and marsupials (Metatheria). Monotremes are typified by structural differences in their brains, ...
(
platypuses The platypus (''Ornithorhynchus anatinus''), sometimes referred to as the duck-billed platypus, is a semiaquatic, egg-laying mammal endemic to eastern Australia, including Tasmania. The platypus is the sole living representative or monotyp ...
and
echidnas Echidnas (), sometimes known as spiny anteaters, are quill-covered monotremes (egg-laying mammals) belonging to the family Tachyglossidae . The four extant species of echidnas and the platypus are the only living mammals that lay eggs and the ...
), typically have lower body temperatures than similarly sized eutherians. The virus is usually present in the nerves and
saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...
of a symptomatic rabid animal. The route of
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
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. This is an example of a viral pathogen modifying the behavior of its host to facilitate its transmission to other hosts. After a typical human infection by bite, the virus enters the
peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...
. It then travels retrograde along the
efferent nerve Efferent nerve fibers refer to axonal projections that ''exit'' a particular region; as opposed to afferent projections that ''arrive'' at the region. These terms have a slightly different meaning in the context of the peripheral nervous syste ...
s toward the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
. 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 A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
, it rapidly causes encephalitis, the prodromal phase, which is the beginning of the symptoms. Once the patient becomes symptomatic, treatment is almost never effective and mortality is over 99%. Rabies may also inflame the
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
, producing
transverse myelitis Transverse myelitis (TM) is a rare neurological condition wherein the spinal cord is inflamed. The adjective ''transverse'' implies that the spinal inflammation (myelitis) extends horizontally throughout the cross section of the spinal cord; the ...
. Although it is theoretically possible for rabies-infected humans to transmit it to others by biting or otherwise, no such cases have ever been documented, because infected humans are usually hospitalized and necessary precautions taken. Casual contact, such as touching a person with rabies or contact with non-infectious fluid or tissue (urine, blood, feces), does not constitute an exposure and does not require post-exposure prophylaxis. But as the virus is present in sperm and vaginal secretions, it might be possible for rabies to spread through sex. There are only a handful of recorded cases of human-to-human transmission of rabies, and all occurred through
organ transplant Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transpo ...
s from infected donors.


Diagnosis

Rabies can be difficult to diagnose because, in the early stages, it is easily confused with other diseases or even with a simple aggressive temperament. The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an
immunohistochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...
procedure, which is recommended by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO). The FAT relies on the ability of a detector molecule (usually fluorescein isothiocyanate) coupled with a rabies-specific antibody, forming a conjugate, to bind to and allow the visualisation of rabies antigen using fluorescent microscopy techniques. Microscopic analysis of samples is the only direct method that allows for the identification of rabies virus-specific antigen in a short time and at a reduced cost, irrespective of geographical origin and status of the host. It has to be regarded as the first step in diagnostic procedures for all laboratories. Autolysed samples can, however, reduce the sensitivity and specificity of the FAT. The RT PCR assays proved to be a sensitive and specific tool for routine diagnostic purposes, particularly in decomposed samples or archival specimens. The diagnosis can be reliably made from brain samples taken after death. The diagnosis can also be made from saliva, urine, and cerebrospinal fluid samples, but this is not as sensitive or reliable as brain samples. Cerebral inclusion bodies called
Negri bodies Negri bodies are eosinophilic, sharply outlined, pathognomonic inclusion bodies (2–10 μm in diameter) found in the cytoplasm of certain nerve cells containing the virus of rabies, especially in pyramidal cells within Ammon's horn of t ...
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. Some
light microscopy Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of micr ...
techniques may also be used to diagnose rabies at a tenth of the cost of traditional fluorescence microscopy techniques, allowing identification of the disease in less-developed countries. A test for rabies, known as LN34, is easier to run on a dead animal's brain and might help determine who does and does not need post-exposure prevention. The test was developed by the CDC in 2018. The
differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...
in a case of suspected human rabies may initially include any cause of encephalitis, in particular infection with viruses such as herpesviruses,
enterovirus ''Enterovirus'' is a genus of positive-sense single-stranded RNA virus An RNA virus is a virusother than a retrovirusthat has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA ( ssRNA) but it ma ...
es, and
arboviruses Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term ''arbovirus'' is a portmanteau word (''ar''thropod-''bo''rne ''virus''). ''Tibovirus'' (''ti''ck-''bo''rne ''virus'') is sometimes used to more sp ...
such as
West Nile virus West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family ''Flaviviridae'', from the genus ''Flavivirus'', which also contains the Zika virus, dengue virus, and yellow fever virus. The virus ...
. The most important viruses to rule out are
herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names ''Human alphaherpesvirus 1'' and '' Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral inf ...
type one,
varicella zoster virus Varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3) or ''Human alphaherpesvirus 3'' (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting chil ...
, and (less commonly) enteroviruses, including
coxsackievirus Coxsackieviruses are a few related enteroviruses that belong to the ''Picornaviridae'' family of viral envelope, nonenveloped, linear, positive-sense single-stranded RNA viruses, as well as its genus ''Enterovirus'', which also includes poliovi ...
es,
echovirus Echovirus is a polyphyletic group of viruses associated with enteric disease in humans. The name is derived from "enteric cytopathic human orphan virus". These viruses were originally not associated with disease, but many have since been identifie ...
es,
poliovirus A poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species ''Enterovirus C'', in the family of ''Picornaviridae''. There are three poliovirus serotypes: types 1, 2, and 3. Poliovirus is composed of an ...
es, and human enteroviruses 68 to 71. New causes of viral encephalitis are also possible, as was evidenced by the 1999 outbreak in Malaysia of 300 cases of encephalitis with a mortality rate of 40% caused by
Nipah virus Nipah virus, scientific name ''Nipah henipavirus'', is a bat-borne virus that causes Nipah virus infection in humans and other animals, a disease with a high mortality rate. Numerous disease outbreaks caused by Nipah virus have occurred in Sout ...
, a newly recognized paramyxovirus. Likewise, well-known viruses may be introduced into new locales, as is illustrated by the outbreak of encephalitis due to West Nile virus in the eastern United States.


Prevention

Almost all human exposure to rabies was fatal until a vaccine was developed in 1885 by
Louis Pasteur Louis Pasteur (, ; 27 December 1822 – 28 September 1895) was a French chemist and microbiologist renowned for his discoveries of the principles of vaccination, microbial fermentation and pasteurization, the latter of which was named afte ...
and
Émile Roux Pierre Paul Émile Roux FRS (17 December 18533 November 1933) was a French physician, bacteriologist and immunologist. Roux was one of the closest collaborators of Louis Pasteur (1822–1895), a co-founder of the Pasteur Institute, and respon ...
. 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. Less expensive purified chicken embryo cell vaccine and purified
vero cell Vero cells are a lineage of cells used in cell cultures. The 'Vero' lineage was isolated from kidney epithelial cells extracted from an African green monkey (''Chlorocebus'' sp.; formerly called ''Cercopithecus aethiops'', this group of monkeys ha ...
rabies vaccine are now available. A
recombinant vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.
called V-RG has been used in Belgium, France, Germany, and the United States to prevent outbreaks of rabies in undomesticated animals. Immunization before exposure has been used in both human and nonhuman populations, where, as in many jurisdictions, domesticated animals are required to be vaccinated. The Missouri Department of Health and Senior Services Communicable Disease Surveillance 2007 Annual Report states the following can help reduce the risk of contracting rabies: * Vaccinating dogs, cats, and ferrets against rabies * Keeping pets under supervision * Not handling wild animals or strays * Contacting an animal control officer upon observing a wild animal or a stray, especially if the animal is acting strangely * If bitten by an animal, washing the wound with soap and water for 10 to 15 minutes and contacting a healthcare provider to determine if post-exposure prophylaxis is required 28 September is
World Rabies Day World Rabies Day is an international awareness campaign coordinated by the Global Alliance for Rabies Control, a non-profit organization with headquarters in the United States. It is a United Nations Observance and has been endorsed by internatio ...
, which promotes the information, prevention, and elimination of the disease. In Asia and in parts of the Americas and Africa, dogs remain the principal host. Mandatory vaccination of animals is less effective in rural areas. Especially in developing countries, pets may not be privately kept and their destruction may be unacceptable. Oral vaccines can be safely distributed in baits, a practice that has successfully reduced rabies in rural areas of
Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...
,
France France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...
, and the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
. In
Montreal Montreal ( ; officially Montréal, ) is the List of the largest municipalities in Canada by population, second-most populous city in Canada and List of towns in Quebec, most populous city in the Provinces and territories of Canada, Canadian ...
, Quebec, Canada, baits are successfully used on raccoons in the Mount-Royal Park area. Vaccination campaigns may be expensive, but cost-benefit analysis suggests baits may be a cost-effective method of control. In
Ontario Ontario ( ; ) is one of the thirteen provinces and territories of Canada.Ontario is located in the geographic eastern half of Canada, but it has historically and politically been considered to be part of Central Canada. Located in Central Ca ...
, a dramatic drop in rabies was recorded when an aerial bait-vaccination campaign was launched. The number of recorded human deaths from rabies in the United States has dropped from 100 or more annually in the early 20th century to one or two per year due to widespread vaccination of domestic dogs and cats and the development of human vaccines and immunoglobulin treatments. Most deaths now result from bat bites, which may go unnoticed by the victim and hence untreated.


Treatment


After exposure

Treatment after exposure can prevent the disease if given within 10 days. The rabies vaccine is 100% effective if given early, and still has a chance of success if delivery is delayed. Every year, more than 15 million people get vaccinated after potential exposure. While this works well, the cost is significant. In the US it is recommended people receive one dose of human rabies
immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
(HRIG) and four doses of rabies vaccine over a 14-day period. HRIG is expensive and makes up most of the cost of post-exposure treatment, ranging as high as several thousand dollars. In the UK, one dose of HRIG costs the National Health Service £1,000, although this is not flagged as a "high-cost medication". A full course of vaccine costs £120–180. As much as possible of HRIG should be injected around the bites, with the remainder being given by deep intramuscular injection at a site distant from the vaccination site. People who have previously been vaccinated against rabies do not need to receive the immunoglobulin—only the postexposure vaccinations on days 0 and 3. The side effects of modern cell-based vaccines are similar to the side effects of flu shots. The old nerve-tissue-based vaccination required multiple injections into the abdomen with a large needle but is inexpensive. It is being phased out and replaced by affordable World Health Organization intradermal-vaccination regimens. In children less than a year old, the lateral thigh is recommended. Thoroughly washing the wound as soon as possible with soap and water for approximately five minutes is effective in reducing the number of viral particles.
Povidone-iodine Povidone-iodine (PVP-I), also known as iodopovidone, is an antiseptic used for skin disinfection before and after surgery. It may be used both to disinfect the hands of healthcare providers and the skin of the person they are caring for. It may a ...
or alcohol is then recommended to reduce the virus further. Awakening to find a bat in the room, or finding a bat in the room of a previously unattended child or mentally disabled or intoxicated person, is an indication for
post-exposure prophylaxis Post-exposure prophylaxis, also known as post-exposure prevention (PEP), is any preventive medical treatment started after exposure to a pathogen in order to prevent the infection from occurring. COVID-19 In 2021, the FDA has approved bamlanivi ...
(PEP). The recommendation for the precautionary use of PEP in bat encounters where no contact is recognized has been questioned in the medical literature, based on a
cost–benefit analysis Cost–benefit analysis (CBA), sometimes also called benefit–cost analysis, is a systematic approach to estimating the strengths and weaknesses of alternatives. It is used to determine options which provide the best approach to achieving benefits ...
. However, a 2002 study has supported the protocol of precautionary administration of PEP where a child or mentally compromised individual has been alone with a bat, especially in sleep areas, where a bite or exposure may occur with the victim being unaware.


After onset

At least two treatment schemes have been proposed for treating rabies after the onset of symptoms, the Milwaukee Protocol and the Recife Protocol. The Milwaukee Protocol was first used in 2004 on Jeanna Giese, who became the first person known to have survived rabies without preventive treatments before symptom onset. The protocol puts a person into a chemically induced coma and uses antiviral medications to prevent fatal
dysautonomia Dysautonomia or autonomic dysfunction is a condition in which the autonomic nervous system (ANS) does not work properly. This may affect the functioning of the heart, bladder, intestines, sweat glands, pupils, and blood vessels. Dysautonomia has m ...
. The overall protocol is complex; the sixth version of the protocol last updated in 2018 consists of 17 pages with 22 steps of treatment, detailed monitoring, and a timeline of expected complications. The Recife Protocol follows the same principle but differs in details like termination of sedation and supplementary medication.


Prognosis

Vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
after exposure, PEP, is highly successful in preventing rabies. In unvaccinated humans, rabies is virtually always fatal after
neurological Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...
symptoms have developed.


Epidemiology

In 2010, an estimated 26,000 people died from rabies, down from 54,000 in 1990. The majority of the deaths occurred in Asia and Africa. , India, followed by China (approximately 6,000) and the Democratic Republic of the Congo (5,600), had the most cases. A 2015 collaboration between the World Health Organization, World Organization of Animal Health (OIE), Food and Agriculture Organization of the United Nation (FAO), and Global Alliance for Rabies Control has a goal of eliminating deaths from rabies by 2030.


India

India India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
has the highest rate of human rabies in the world, primarily because of stray dogs, whose number has greatly increased since a 2001 law forbade the killing of dogs. Effective control and treatment of rabies in India is hindered by a form of
mass hysteria Mass psychogenic illness (MPI), also called mass sociogenic illness, mass psychogenic disorder, epidemic hysteria, or mass hysteria, involves the spread of illness symptoms through a population where there is no infectious agent responsible for c ...
known as
puppy pregnancy syndrome Puppy pregnancy syndrome (PPS) is a psychosomatic illness in humans brought on by mass hysteria. People suffering from PPS believe that shortly after being bitten by a dog, puppies are conceived within their abdomen. The syndrome is thought to be ...
(PPS). Dog bite victims with PPS, male as well as female, become convinced that puppies are growing inside them, and often seek help from
faith healer Faith healing is the practice of prayer and gestures (such as laying on of hands) that are believed by some to elicit divine intervention in spiritual and physical healing, especially the Christian practice. Believers assert that the healing ...
s rather than medical services. An estimated 20,000 people die every year from rabies in India, more than a third of the global total.


Australia

Australia has an official rabies-free status, although
Australian bat lyssavirus ''Australian bat lyssavirus'' (''ABLV''), originally named ''Pteropid lyssavirus'' (''PLV''), is a zoonotic virus closely related to the rabies virus. It was first identified in a 5-month-old juvenile black flying fox ('' Pteropus alecto'') col ...
(ABLV), discovered in 1996, is a strain of rabies prevalent in Australian native bat populations.


United States

Canine-specific rabies has been eradicated in the United States. But rabies is common among wild animals in the United States, and an average of 100 dogs become infected from other wildlife each year. Due to high public awareness of the virus, efforts at vaccination of domestic animals and curtailment of feral populations, and availability of
postexposure prophylaxis Post-exposure prophylaxis, also known as post-exposure prevention (PEP), is any preventive medical treatment started after exposure to a pathogen in order to prevent the infection from occurring. COVID-19 In 2021, the FDA has approved bamlanivi ...
, incidence of rabies in humans is very rare in the United States. From 1960 to 2018, a total of 125 human rabies cases were reported in the United States; 36 (28%) were attributed to dog bites during international travel. Among the 89 infections acquired in the United States, 62 (70%) were attributed to bats. The most recent rabies death in the United States was an Illinois man who refused treatment after waking up in the night with a bat on his neck; the man died a month later. Occurring in 2021, it was the first case of human rabies in the United States in nearly three years.


Europe

Either no or very few cases of rabies are reported each year in Europe; cases are contracted both during travel and in Europe. In Switzerland the disease was virtually eliminated after scientists placed chicken heads laced with live
attenuated vaccine An attenuated vaccine (or a live attenuated vaccine, LAV) is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live"). Attenuation takes an infectious agent and alters it so that it becomes harmless or less ...
in the
Swiss Alps The Alpine region of Switzerland, conventionally referred to as the Swiss Alps (german: Schweizer Alpen, french: Alpes suisses, it, Alpi svizzere, rm, Alps svizras), represents a major natural feature of the country and is, along with the Swiss ...
. The foxes of Switzerland, proven to be the main source of rabies in the country, ate the chicken heads and immunized themselves. Italy, after being declared rabies-free from 1997 to 2008, has witnessed a reemergence of the disease in wild animals in the
Triveneto The Triveneto (), or Tre Venezie () ( vec, Tre Venesie, german: Venetien), is a historical region of Italy. The area included what has become the three Italian regions of ''Venezia Euganea'', ''Venezia Giulia'' and ''Venezia Tridentina''. This ter ...
regions (
Trentino-Alto Adige/Südtirol it, Trentino (man) it, Trentina (woman) or it, Altoatesino (man) it, Altoatesina (woman) or it, Sudtirolesegerman: Südtiroler (man)german: Südtirolerin (woman) , population_note = , population_blank1_title = Official ...
,
Veneto Veneto (, ; vec, Vèneto ) or Venetia is one of the 20 regions of Italy. Its population is about five million, ranking fourth in Italy. The region's capital is Venice while the biggest city is Verona. Veneto was part of the Roman Empire unt ...
and
Friuli-Venezia Giulia (man), it, Friulana (woman), it, Giuliano (man), it, Giuliana (woman) , population_note = , population_blank1_title = , population_blank1 = , demographics_type1 = , demographics1_footnotes = , demographics1_t ...
), due to the spreading of an epidemic in the
Balkans The Balkans ( ), also known as the Balkan Peninsula, is a geographical area in southeastern Europe with various geographical and historical definitions. The region takes its name from the Balkan Mountains that stretch throughout the who ...
that also affected Austria. An extensive wild animal vaccination campaign eliminated the virus from Italy again, and it regained the rabies-free country status in 2013, the last reported case of rabies being reported in a red fox in early 2011. The United Kingdom has been free of rabies since the early 20th century except for a rabies-like virus (EBLV-2) in a few
Daubenton's bat Daubenton's bat or Daubenton's myotis (''Myotis daubentonii'') is a Eurasian bat with rather short ears. It ranges from Ireland to Japan (Hokkaido) and is considered to be increasing its numbers in many areas. This bat was first described in 181 ...
s. There has been one fatal case of EBLV-2 transmission to a human. There have been four deaths from rabies, transmitted abroad by dog bites, since 2000. The last infection in the UK occurred in 1922, and the last death from indigenous rabies was in 1902. Sweden and mainland Norway have been free of rabies since 1886. Bat rabies antibodies (but not the virus) have been found in bats. On Svalbard, animals can cross the arctic ice from Greenland or Russia.


Mexico

Mexico was certified by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
as being free of dog-transmitted rabies in 2019 because no case of dog-human transmission had been recorded in two years.


History

Rabies has been known since around 2000 BC. The first written record of rabies is in the Mesopotamian Codex of Eshnunna (), which dictates that the owner of a dog showing symptoms of rabies should take preventive measures against bites. If another person were bitten by a rabid dog and later died, the owner was heavily fined. In Ancient Greece, rabies was supposed to be caused by
Lyssa In Greek mythology, Lyssa (; Ancient Greek: Λύσσα ''Lússā''), called Lytta (; Λύττα ''Lúttā'') by the Athenians, was the spirit of mad rage, frenzy, and rabies in animals. She was closely related to the Maniae, the spirits of madness ...
, the spirit of mad rage. Ineffective folk remedies abounded in the medical literature of the ancient world. The physician
Scribonius Largus Scribonius Largus (c. 1-c. 50) was the court physician to the Roman emperor Claudius. About 47 AD, at the request of Gaius Julius Callistus, the emperor's freedman, he drew up a list of 271 prescriptions (''Compositiones''), most of them his own, ...
prescribed a poultice of cloth and hyena skin;
Antaeus Antaeus (; Ancient Greek: Ἀνταῖος ''Antaîos'', "opponent", derived from , ''antao'' – 'I face, I oppose'), known to the Berbers as Anti, was a figure in Berber and Greek mythology. He was famed for his defeat by Heracles as part o ...
recommended a preparation made from the skull of a hanged man. Rabies appears to have originated in the Old World, the first
epizootic In epizoology, an epizootic (from Greek: ''epi-'' upon + ''zoon'' animal) is a disease event in a nonhuman animal population analogous to an epidemic in humans. An epizootic may be restricted to a specific locale (an "outbreak"), general (an "epi ...
in the New World occurring in Boston in 1768. Rabies was considered a scourge for its prevalence in the 19th century. In France and Belgium, where
Saint Hubert Hubertus or Hubert ( 656 – 30 May 727 A.D.) was a Christian saint who became the first bishop of Liège in 708 A.D. He is the patron saint of hunters, mathematicians, opticians and metalworkers. Known as the "Apostle of the Ardennes", he w ...
was venerated, the "
St Hubert's Key St. Hubert’s Key (, ) is a sacramental in the form of a metal nail, cross, or cone. 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, opt ...
" was heated and applied to cauterize the wound. By an application of
magical thinking Magical thinking, or superstitious thinking, is the belief that unrelated events are causally connected despite the absence of any plausible causal link between them, particularly as a result of supernatural effects. Examples include the idea that ...
, dogs were branded with the key in hopes of protecting them from rabies. It was not uncommon for a person bitten by a dog merely suspected of being rabid to commit suicide or to be killed by others. In ancient times the attachment of the tongue (the
lingual frenulum The frenulum of tongue or tongue web (also lingual frenulum or frenulum linguæ; also fraenulum) is a small fold of mucous membrane extending from the floor of the mouth to the midline of the underside of the tongue. Development The tongue start ...
, a mucous membrane) was cut and removed, as this was where rabies was thought to originate. This practice ceased with the discovery of the actual cause of rabies. Louis Pasteur's 1885 nerve tissue vaccine was successful, and was progressively improved to reduce often severe side-effects. In modern times, the fear of rabies has not diminished, and the disease and its symptoms, particularly agitation, have served as an inspiration for several works of
zombie A zombie (Haitian French: , ht, zonbi) is a mythological undead corporeal revenant created through the reanimation of a corpse. Zombies are most commonly found in horror and fantasy genre works. The term comes from Haitian folklore, in whic ...
or similarly themed fiction, often portraying rabies as having mutated into a stronger virus which fills humans with murderous rage or incurable illness, bringing about a devastating, widespread pandemic. File:Cantigas de Santa Maria-275-5.jpg, Miniature of the ''Cantiga'' #275 depicting two monks hospitaller with rabies being carried before St. Mary of Terena. File:Middle Ages rabid dog.jpg, A
woodcut Woodcut is a relief printing technique in printmaking. An artist carves an image into the surface of a block of wood—typically with gouges—leaving the printing parts level with the surface while removing the non-printing parts. Areas that ...
from the
Middle Ages In the history of Europe, the Middle Ages or medieval period lasted approximately from the late 5th to the late 15th centuries, similar to the post-classical period of global history. It began with the fall of the Western Roman Empire a ...
showing a rabid dog File:Sauvages de la Croix, François Boissier de – Dissertation sur la nature et la cause de la Rage, 1777 – BEIC 3001126.jpg,
François Boissier de Sauvages de Lacroix François Boissier de Sauvages de Lacroix (May 12, 1706 – February 19, 1767) was a French physician and botany, botanist who was a native of Alès. He was the brother of naturalist Pierre Augustin Boissier de Sauvages (1710—1795). He received ...
, ''Della natura e causa della rabbia'' (''Dissertation sur la nature et la cause de la Rage''), 1777 File:Medieval rabies folio.jpg, alt=An ancient folio from the medieval times depicting a rabid dog biting a man. circa 1224, An Arabic
folio The term "folio" (), has three interconnected but distinct meanings in the world of books and printing: first, it is a term for a common method of arranging sheets of paper into book form, folding the sheet only once, and a term for a book ma ...
from the
medieval In the history of Europe, the Middle Ages or medieval period lasted approximately from the late 5th to the late 15th centuries, similar to the Post-classical, post-classical period of World history (field), global history. It began with t ...
times depicting a rabid
dog The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. Do ...
biting a man. circa 1224


Other animals

Rabies is infectious to
mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
s; three stages of central nervous system infection are recognized. The first stage is a one- to three-day period characterized by behavioral changes and is known as the prodromal stage. The second is the excitative stage, which lasts three to four days. This stage is often known as "furious rabies" for the tendency of the affected animal to be hyper-reactive to external stimuli and bite at anything near. The third is the paralytic stage and is caused by damage to
motor neuron A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectl ...
s. Incoordination is seen, owing to rear limb paralysis, and drooling and difficulty swallowing is caused by paralysis of facial and throat muscles. Death is usually caused by
respiratory arrest Respiratory arrest is a sickness caused by apnea (cessation of breathing) or respiratory dysfunction severe enough it will not sustain the body (such as agonal breathing). Prolonged apnea refers to a patient who has stopped breathing for a long p ...
.


Research


Biotechnological use

The outer shell of the rabies virus, stripped of its RNA contents and thus unable to cause disease, may be used as a
vector Vector most often refers to: *Euclidean vector, a quantity with a magnitude and a direction *Vector (epidemiology), an agent that carries and transmits an infectious pathogen into another living organism Vector may also refer to: Mathematic ...
for the delivery of unrelated genetic material in a research setting. It has the advantage over other
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, also called a pseudovirus. With this method, the foreign viral envelope proteins can ...
methods for gene delivery in that the cell targeting (
tissue tropism Tissue tropism is the range of cells and tissues of a host that support growth of a particular pathogen, such as a virus, bacterium or parasite. Some bacteria and viruses have a broad tissue tropism and can infect many types of cells and tissues. ...
) is more specific for the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
, a difficult-to-reach site, obviating the need for invasive delivery methods. It is also capable of infecting neighboring "upstream" cells, moving from one cell to
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
s of the next at
synapses In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...
, and is thus used for
retrograde tracing Retrograde tracing is a research method used in neuroscience to trace neural connections from their point of termination (the synapse) to their source (the cell body). Retrograde tracing techniques allow for detailed assessment of neuronal connec ...
in neuronal circuits.


Potential treatment

Evidence indicates artificially increasing the permeability of the
blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
, which normally does not allow most immune cells across, promotes viral clearance.


See also

*
Global Alliance for Rabies Control The Global Alliance for Rabies Control (GARC) is a non-profit organization that aims to eliminate deaths from canine rabies by 2030. Rabies is a neglected disease of poverty, which is almost 100% fatal, but can also be prevented with available v ...
*
Rabies in Haiti Rabies is a viral disease that exists in Haiti and throughout the world. It often causes fatal inflammation of the brain in humans and other mammals, such as dogs and mongooses in Haiti. The term "rabies" is derived from a Latin word that mean ...
*
Eradication of infectious diseases Eradication is the reduction of an infectious disease's prevalence in the global host population to zero. Two infectious diseases have successfully been eradicated: smallpox in humans, and rinderpest in ruminants. There are four ongoing progra ...
*
Madstone (folklore) In the folklore of the early United States, a madstone was a special medicinal substance that, when pressed into an animal bite, was believed to prevent rabies by drawing the "poison" out. The ''Encyclopedia Americana'' described it as "a vegetable ...


References


Further reading

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


External links

* *
Virus Pathogen Database and Analysis Resource (ViPR): Rhabdoviridae

OIE's Rabies Portal

Aerophobia and Hydrophobia in Rabies Videos
* {{Authority control Articles containing video clips Bat diseases Cat diseases Dog diseases Neurological disorders Wikipedia infectious disease articles ready to translate Slow virus diseases Tropical diseases Vaccine-preventable diseases Viral encephalitis Viral infections of the central nervous system Wikipedia medicine articles ready to translate Zoonoses Infectious diseases Mammal diseases