Rabies is a viral disease that causes inflammation of the brain in humans and other mammals. Early symptoms can include fever and abnormal sensations at the site of exposure, which are followed by nausea, vomiting, violent movements, uncontrolled excitement, fear of water, inability to move parts of the body, confusion, and loss of consciousness. Once symptoms appear, the result is virtually always death. The time period between contracting the infection 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 to reach the central nervous system.
Rabies is caused by lyssaviruses, including the rabies virus and Australian bat lyssavirus. It is spread when an infected animal bites or scratches a human or other animals. Even in the absence of a bite or a scratch, saliva from an infected animal coming into contact with the eyes, mouth, or nose can transmit rabies. Rabies can also be transmitted through tears and nervous tissues."Frequently asked questions about rabies for the General Public ". World Health Organization. 14 February 2018. Globally, dogs are the most common animal involved. In countries where dogs commonly have the disease, more than 99% of rabies cases in humans are the direct result of dog bites. In the Americas, bat bites are the most common source in humans, and less than 5% of cases are from dogs. Rodents are very rarely infected with rabies. The disease can be diagnosed only after the start of symptoms, but prompt preventative treatment is recommended for anyone who has had contact with a rabid animal.
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 and sometimes rabies immunoglobulin 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, 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.
Rabies causes about 59,000 human 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. The global cost is estimated at US$8.6 billion per year in lost lives, medical care, and associated costs, besides the psychological trauma.
Signs and symptoms
The time between infection and the first symptoms is typically one to three months in humans. 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, insomnia, confusion, agitation, abnormal behavior, paranoia, terror, and hallucinations. The infected person may also fear drinking water.
The symptoms eventually progress to delirium and coma. Death usually occurs two to ten days after first symptoms. Survival is almost unknown once symptoms have presented, even with intensive care.
Two forms of the disease are recognized, furious rabies and dumb rabies. The furious form affects 80% of rabies victims. This form of rabies causes irrational aggression in the host, which aids in the spreading of the virus through animal bites. This form of rabies has also been called hydrophobia ("fear of water"; see also aquaphobia) throughout its history. In the later stages of a furious infection, the victim has difficulty swallowing, often panics when presented with liquids to drink, and cannot quench their thirst. 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. Since the victim cannot swallow saliva and water, the virus has a much higher chance of being transmitted, because it multiplies and accumulates in the salivary glands and is transmitted through biting. Such overproduction of saliva and inability to swallow it may cause "foaming at the mouth," much associated with rabies in the public perception and in popular culture.
The remaining 20% often experience the dumb form, a progressive paralytic condition marked by muscular weakness, loss of sensation, and paresis that resembles Guillain–Barré syndrome in its symptomatology. This form of rabies does not usually cause fear of water.
Cause Virus
Rabies is caused by a number of lyssaviruses including the rabies virus and Australian bat lyssavirus. Duvenhage lyssavirus may cause a rabies-like infection.
The rabies virus is the type species of the Lyssavirus genus, in the family Rhabdoviridae, order Mononegavirales. 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 genome with negative sense. The genetic information is packed as a ribonucleoprotein 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).
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 receptor. The cellular membrane pinches in a procession known as pinocytosis and allows entry of the virus into the cell by way of an endosome. 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-translational 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, 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 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 receptors at the neuromuscular junction. The virus then travels through the nerve cell axon via retrograde transport, 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 species, including humans, may become infected with the rabies virus, which has also adapted to grow in cells of cold-blooded vertebrates. Birds were first artificially infected with rabies in 1884; however, infected birds are largely, if not wholly, asymptomatic, and recover. Some bird species have been known to develop rabies antibodies, a sign of infection, after feeding on rabies-infected mammals.
Most animals can be infected by the virus and can transmit the disease to humans. Worldwide, however, about 99% of human rabies cases come from dogs. Other sources of rabies in humans include bats, monkeys, raccoons, foxes, skunks, cattle, wolves, coyotes, cats, and mongooses (normally either the small Asian mongoose or the yellow mongoose).
Rabies may also spread through exposure to infected bears, domestic farm animals, groundhogs, weasels, and other wild carnivorans. However, lagomorphs, such as hares and rabbits, and small rodents, such as chipmunks, gerbils, guinea pigs, hamsters, mice, rats, and squirrels, 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. Non-placental mammals such as the Virginia opossum, a marsupial, have a lower body temperature than similarly-sized placentals and so tend to resist the rabies virus, which thrives at a higher temperature, although they are not immune to it. In 2024, rabies was found to be spreading in South African Cape fur seals, possibly making it the first outbreak documented in marine mammals.
The virus is usually present in the nerves and saliva of a symptomatic rabid animal. The route of infection 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. It then travels retrograde along the efferent nerves toward the central nervous system. 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, 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, producing transverse myelitis.