Rabies
It is most commonly caused by a bite from an infected animal, but occasionally by other forms of contact. In some countries it is a significant killer of livestock.
The rabies virus makes its way to the brain by following the peripheral nerves. The incubation period of the disease depends on how far the virus must travel to reach the central nervous system, usually taking a few months.
In the beginning stages of rabies, the symptoms are malaise, headache, and fever, while in later stages it includes acute pain, violent movements, uncontrolled excitements, depressions, and the inability to swallow water (hence the name hydrophobia).
In the final stages, the patient begins to have periods of mania and lethargy, and coma. Death generally occurs due to respiratory insufficiency.
In non-vaccinated humans, rabies is almost invariably fatal after neurological symptoms have developed, but prompt post-exposure vaccination may prevent the virus from progressing. There are only six known cases of a person surviving symptomatic rabies, and only one known case of survival in which the patient received no rabies-specific treatment either before or after illness onset.
Virology
Classification
The rabies virus is a member of the Lyssavirus genus.
This genus of RNA viruses also includes the Aravan virus, Australian bat lyssavirus, Duvenhage virus, European bat lyssavirus 1, European bat lyssavirus 2, Irkut virus, Khujand virus, Lagos bat virus, Mokola virus and the West Caucasian bat virus.
Structure
Lyssaviruses have helical symmetry, so their infectious particles are approximately cylindrical in shape. Negri bodies in the infected neurons are pathognomonic.
The virus has a bullet-like shape with a length of about 180 nm and a cross-sectional diameter of about 75 nm.
One end is rounded or conical and the other end is planar or concave. Spikes do not cover the planar end of the virion (virus particle).
Beneath the envelope is the membrane or matrix (M) protein layer which may be invaginated at the planar end. The core of the virion consists of helically arranged ribonucleoprotein.
Genome
The genome is unsegmented linear antisense RNA.
Also present in the nucleocapsid are RNA dependent RNA transcriptase and some structural proteins.
Life cycle
From the source of wound of entry, the rabies virus travels quickly along the neural pathways to the central nervous system. Fatality can occur within anywhere from two days to five years from the time of initial infection.
Prevention
Rabies can be prevented by vaccination, both in humans and other animals.
Virtually every infection with rabies resulted in death, until Louis Pasteur and Emile Roux developed the first rabies vaccination in 1885. This vaccine was first used on a human on July 6, 1885 – nine-year old boy Joseph Meister (1876–1940) had been mauled by a rabid dog.
Their vaccine consisted of a sample of the virus harvested from infected (and necessarily dead) rabbits, which was weakened by allowing it to dry for 5 to 10 days.
Similar nerve tissue-derived vaccines are still used now in some countries, and while they are much cheaper than modern cell culture vaccines, they are not as effective and carry a certain risk of neurological complications.
The human diploid cell rabies vaccine (H.D.C.V.) was started in 1967. Human diploid cell rabies vaccines are made using the attenuated Pitman-Moore L503 strain of the virus.
Newer and less expensive purified chicken embryo cell vaccine, and purified Vero cell rabies vaccine are now available. Thoroughly washing the wound as soon as possible with soap and water for approximately five minutes is very effective at reducing the number of viral particles.
“If available, a virucidal antiseptic such as povidone-iodine, iodine tincture, 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, patients receive one dose of immunoglobulin and five doses of rabies vaccine over a twenty-eight day period.
Since the widespread vaccination of domestic dogs and cats and the development of effective human vaccines and immunoglobulin treatments, the number of recorded deaths in the U.S. This travel along the nerves is usually slow enough that vaccine and immunoglobulin can be administered to protect the brain and glands from infection.
may not be successful.
Pre-exposure prophylaxis
Currently pre-exposure immunization has been used on domesticated and normal non-human populations. Most tourists do not need such a vaccination, just those doing substantial non-urban activities.
It is harmless to humans and has been shown to be safe for various species of animals that might accidentally encounter it in the wild, including birds (gulls, hawks, and owls).
V-RG has been successfully used in the field in Belgium, France, and the United States to prevent outbreaks of rabies in wildlife. The plan for immunization of normal populations involves dropping bait containing food wrapped around a small dose of the live virus.
A strategy of vaccinating “neighborhood dogs” in Jaipur, India, (combined with a sterilization program) has also resulted in a large reduction in the number of human cases.
Symptoms
A patient with rabies, 1959.
The period between infection and the first flu-like symptoms is normally two to twelve weeks, but can be as long as two years. In addition, consideration should be given to the local epidemiology of encephalitis caused by arboviruses belonging to several taxonomic groups, including eastern and western equine encephalitis viruses, St.
Louis encephalitis virus, Powassan virus, the California encephalitis virus 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. Similarly, well-known viruses may be introduced into new locations, as is illustrated by the recent outbreak of encephalitis due to West Nile virus 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 be possible for low-income settings according to research reported on the Science and Development Network website in 2008. Accurate rabies diagnosis can be done ten times more cheaply, according to researchers from the Farcha Veterinary and Livestock Research Laboratory and the Support International Health Centre in N'Djamena, Chad.
After thirty-one days of isolation and seventy-six days of hospitalization, she was released from the hospital, having survived rabies.
Rodney Willoughby Jr., the primary care physician in this case published in the April 2007 issue of Scientific American. He notes that subsequent failures of what he calls the Milwaukee protocol did not use the cocktail of drugs used during the treatment of Giese. A point he makes for future research is the relationship of the virus to depletion of biopterin in the brain.
Later attempts to use the same treatment have failed, but in April, 2008, in Cali, Colombia, it was reported (by local newspapers) that an 11-year-old may have recovered successfully after induction of coma .
Rodents (mice, squirrels etc) are seldom infected.
The virus is usually present in the nerves and saliva of a symptomatic rabid animal. The route of infection is usually, but not necessarily, by a bite. In many cases the infected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behaviour. Transmission may also occur via an aerosol through mucous membranes; transmission in this form may have happened in people exploring caves populated by rabid bats.
Transmission between humans is extremely rare, although it can happen through transplant surgery (see below for recent cases), or, even more rarely, through bites, kisses or sexual relations.
After a typical human infection by bite, the virus enters the peripheral nervous system.
China introduced in the city of Beijing the “one-dog policy” 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.
Rabies was once rare in the United States outside the Southern states, but raccoons in the mid-Atlantic and northeast United States have been suffering from a rabies epidemic since the 1970s, which is now moving westwards into Ohio. In the midwestern United States, skunks are the primary carriers of rabies, composing 134 of the 237 documented non-human cases in 1996. The second stage is the excitative stage, which lasts three to four days.
Goran Klintmalm, a surgeon who oversees transplantation at Baylor University Medical Center, where the transplants occurred. Three other patients who received organs from the woman have not yet shown rabies symptoms.
Dozens of medical staff were vaccinated against rabies in the two hospitals as a precautionary measure.