Thursday, November 23, 2006

RABIES

INTRODUCTION
Rabies is an infectious disease of animals caused by a bullet-shaped, enveloped RNA virus, 180 x 75 nm. Man is occasionally infected, and once infection is established in the CNS, the outcome is almost invariably fatal.

HUMAN RABIES
Is acquired from virus in saliva entering a bite wound caused by an infected animal, usually a rabid dog. The severity of the bite determines the risk of infection. The disease does not usually spread from man to man.
Incubation
After inoculation, the virus enters small nerve endings at the site of the bite. The virus slowly travels up the nerve to reach the CNS where it replicates and then travels down nerves to the salivary glands where there is further replication. The time it takes to do this depends upon the length of the nerve - a bite on the foot will have a very much longer incubation period than a bite on the face. The incubation period may last from two weeks to six months. Very often the primary wound is healed and forgotten by the time of clinical presentation.
Clinical Presentation

A) Furious Rabies
When the virus reaches the CNS the patient presents with headache, fever, irritability, restlessness and anxiety. This may progress to muscle pains, salivation and vomiting. After a few days to a week the patient may experience a stage of excitement and be wracked with painful muscle spasms, triggered sometimes by swallowing of saliva or water. Hence they drool and learn to fear water (* Hydrophobia). The patients are also excessively sensitive to air blown on the face. The stage of excitement lasts only a few days before the patient lapses into coma and death.
Once clinical disease manifests, there is a rapid, relentless progression to invariable death, despite all treatment.
B) Dumb Rabies
Starts in the same way, but instead of progressing into excitement, the subject retreats steadily and quietly downhill, with some paralysis, to death. Rabies diagnosis may easily be missed.

ANIMAL RABIES
Very similar picture to human rabies. In the stage of excitement the animal may bite vigorously and viciously at anything: sticks, stones, grass, other animals and humans, without provocation.
Wild animals may be abnormally tame or appear sick - beware of approaching or picking up such an animal ("dumb rabies").
Epidemiology
1. The disease is endemic in wild animals in most parts of the world although some countries (UK, Australia) are rabies free through vigorous control. The wild animal cycle constitutes the natural reservoir.
2. Wild animals may bite and infect domestic animals (cattle, horses, pigs, dogs and cats) which in turn may infect man. Occasionally wild animals may infect man directly.
3. In recent decades, a separate form of dog rabies (spread from dog to dog) has been recognised as spreading from West Africa eastwards and southwards in Africa. Via Mozambique, it reached Natal Kwazulu in the late 1970's and early 80's. Semi-wild dogs in Natal have formed the highest endemic rabies reservoir and source for human cases in the whole of the RSA.

ANIMAL RESERVOIR
• MONGOOSE (main reservoir in RSA in the wild)
• SURICATE
• JACKAL
• BAT (some evidence to suggest carrier status and droplet infection)
• FOX (in Europe)
• SKUNKS, RACCOONS (in USA)
• SEMI-WILD DOGS (in Natal)
Note: As in man, an infected animal becomes sick and dies. There is no substantial evidence of a true carrier status in apparently well animals, except perhaps in bats.

DIAGNOSIS
By assessment of:
1.Bite
Geographical area, type of animal, severity and site of bite.
2. Animal
Live - observe in cage:
If survives > 8 days, then NOT rabies.
Dead - brain sent to Onderstepoort
- Negri bodies
- IFA
- virus isolation
3. Man
Live - difficult diagnosis
- clinical picture, skin biopsy, corneal impression (antibodies only appear very late)
Dead - brain sent to Onderstepoort
"Negri bodies" in cytoplasm of brain cells;
immunofluorescence virus isolation

TREATMENT
• 1. Wash wound (soap, detergent and water)
• 2. Anti-rabies serum (human). Passive immunisation.
• 3. Vaccine (intensive course). Active immunisation.

RABIES VACCINE
A good but expensive killed virus vaccine (Human Diploid Cell Vaccine, HDCV) grown in human fibroblasts is available for safe use in man.
The unusually long incubation period of the virus permits the effective use of active immunisation with vaccine post-exposure. When used, vaccine has dramatically cut the rabies death rate. Supplied free by the State through district surgeons in South Africa.
(Older killed virus vaccines, made from infected neural tissues, were poorly immunogenic and had allergic encephalitic side effects, but are still used in developing countries.)
Prophylaxis
High-risk persons, eg. veterinarians, may be immunised before exposure, and then merely require one or two booster doses if they should be exposed to rabies.
Animal Vaccines
A range of live and killed virus vaccines are available for domestic animals (farm animals, cats and dogs).
Experimental vaccination of wildlife by using recombinant vaccinia vaccine (live) in bait for foxes in Europe and North America has been quite promising.

CONTROL OF RABIES (Government Department of Veterinary Services)
1. Education
2. Vaccination of dogs, cats and farm animals.
3. Notification
- animals (district vet officer, police, magistrate) - human (district surgeon)

Rabies
From Wikipedia, the free encyclopedia.
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This article is about the infectious disease. For the 1989 album by industrial band Skinny Puppy, see Rabies (album).
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Rabies virus
Virus classification

Group: Group V ((-)ssRNA)

Order: Mononegavirales

Family: Rhabdoviridae

Genus: Lyssavirus

Species: Rabies virus

Rabies (from a Latin word meaning rage) is a viral disease that causes acute encephalitis in animals and people. It can affect most species of warm-blooded animals, but is rare among non-carnivores. In unvaccinated humans, rabies is almost invariably fatal once full-blown symptoms have developed, but post-exposure vaccination can prevent symptoms from developing.
Contents
[hide]
• 1 Transmission and symptoms
• 2 The virus
• 3 Prevention
• 4 Prevalence
• 5 Recently publicised cases
o 5.1 Transmission by animal bites
o 5.2 Transmission through organ transplants
• 6 Transport of pet animals between countries
• 7 Rabies and domestic skunks in the United States
• 8 External links
o 8.1 Sources
o 8.2 Other links

[edit]
Transmission and symptoms


Micrograph with numerous rabies viruses (small dark-grey rod-like particles) and Negri bodies, larger cellular inclusions typical of Rabies infection
The stereotypical image of an infected ("rabid") animal is a "mad dog" foaming at the mouth, but cats, ferrets, raccoons, skunks, foxes and bats also become rabid. Squirrels, chipmunks, other rodents and rabbits are very seldom infected, perhaps because they would not usually survive an attack by a rabid animal. Rabies may also be present in a so-called 'paralytic' form, rendering the infected animal unnaturally quiet and withdrawn.
The virus is usually present in the saliva of a symptomatic rabid animal; the route of infection is nearly always by a bite. By causing the infected animal to be exceptionally aggressive, the virus ensures its transmission to the next host. Transmission has occurred via an aerosol through mucous membranes; transmission in this form may have happened in people exploring caves populated by rabid bats. Transmission from person to person is extremely rare, though it can happen through transplant surgery (see below for recent cases), or even more rarely through bites or kisses.
After a typical human infection by animal bite, the virus directly or indirectly enters the peripheral nervous system. It then travels along the nerves towards 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 pre-empt symptomatic rabies. Once the virus reaches the brain, it rapidly causes an encephalitis and symptoms appear. It may also inflame the spinal cord producing myelitis.
The period between infection and the first flu-like symptoms is normally 3-12 weeks, but can be as long as two years. Soon after, the symptoms expand to cerebral dysfunction, anxiety, insomnia, confusion, agitation, abnormal behaviour, hallucinations, progressing to delirium. 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 is known as "hydrophobia". Death almost invariably results 2-10 days after the first symptoms; the handful of people who are known to have survived the disease were all left with severe brain damage, with the recent exception of Jeanna Giese (see below).
[edit]
The virus
The Rabies virus is a Lyssavirus. 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 West Caucasian bat virus. Lyssaviruses have helical symmetry, so their infectious particles are approximately cylindrical in shape. This is typical of plant-infecting viruses; human-infecting viruses more commonly have cubic symmetry and take shapes approximating regular polyhedra.
The Lyssaviruses are the only viruses known to travel along the nerves after infection. Biopsy shows typical "Negri bodies" in the infected neurons.
The Rabies virus has a bullet-like shape with a length of about 180 nm and a cross-sectional diameter of about 75 nm.

Longitudinal and cross-sectional schematic view of Rabies virus
[edit]
Prevention
There is no known cure for symptomatic rabies, but it can be prevented by vaccination, both in humans and other animals. Virtually every infection with rabies was historically a death sentence, until Louis Pasteur developed the first rabies vaccination in 1886. Pasteur demonstrated its effectiveness by treating Joseph Meister, who had been bitten by a rabid dog.
Pasteur's vaccine consisted of a sample of the virus harvested from infected (and necessarily dead) rabbits, which was weakened by allowing it to dry. Similar nerve tissue-derived vaccines are still used today in developing 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.
Treatment after exposure (known as post-exposure prophylaxis or "PEP") is highly successful in preventing the disease if administered promptly, within 14 days after infection. In the United States, the treatment consists of a regimen of one dose of immunoglobulin and five doses of rabies vaccine over a 28-day period. Rabies immunoglobulin and the first dose of rabies vaccine should be given as soon as possible after exposure, with additional doses on days 3, 7, 14, and 28 after the first. The vaccinations are relatively painless and are given in one's arm, in contrast to previous treatments which were given through a large needle inserted into the abdomen. In case of animal bites it is also helpful to remove, by thorough washing, as much infectious material as soon as possible. Since the development of effective human vaccines and immunoglobulin treatments the US, death rate from rabies has dropped from 100 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.
PEP is effective in treating rabies because the virus must travel from the site of infection through the peripheral nervous system (nerves in the body) before infecting the central nervous system (brain and spinal cord) and glands to cause lethal damage. This travel along the nerves is usually slow enough that vaccine and immunoglobulin can be administered to protect the brain and glands from infection. The amount of time this travel requires is dependent on how far the infected area is from the brain: if the victim is bitten in the face, for example, the time between initial infection and infection of the brain is very short and PEP may not be successful.
[edit]
Prevalence
Between 40,000 and 70,000 human beings die annually from rabies, with about 90% of those cases occurring in Asia. About 6 million people receive treatment annually after suspected exposure to rabies.
Dog licensing, killing of stray dogs, muzzling and other measures contributed to the eradication of rabies from Great Britain in the early 20th century. More recently, large-scale vaccination of cats, dogs and ferrets has been successful in combatting rabies in some developed countries.


A rabid dog, with saliva dropping out of the mouth
Rabies virus survives in widespread, varied, rural wildlife reservoirs. However, in Asia, parts of Latin America and large parts of Africa, dogs remain the principal host. Mandatory vaccination of animals is less effective in rural areas. Especially in developing countries, animals may not be privately owned and their destruction may be unacceptable. Oral vaccines can be safely distributed in baits, and this has successfully impacted rabies in rural areas of France, Ontario, Texas, Florida and elsewhere. Vaccination campaigns may be expensive, and a cost-benefit analysis can lead those responsible to opt for policies of containment rather than elimination of the disease.
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[1]. The particular variant of the virus has been identified in the southeastern United States raccoon population since the 1950s, and is believed to have traveled to the northeast as the result of infected raccoons being among those caught and transported from the southeast to the northeast by hunters attempting to replenish the declining northeast raccoon population (Nettles VF, Shaddock JH, Sikes RK, Reyes CR. "Rabies in translocated raccoons". Am J Public Health 1979;69:601-2.). As a result, urban residents of these areas have become more wary of the large but normally unseen urban raccoon population. It has become the common assumption that any raccoon seen in daylight is infected; certainly the reported behavior of most such animals appears to show some sort of illness, and autopsies usually confirm rabies. Whether as a result of increased vigilance or just the normal avoidance reaction to any animal not seen in the course of day to day life, such as a raccoon, there have been no documented human rabies cases as a result of this variant. This does not include, however, the greatly increasing rate of prophylactic rabies treatments in cases of possible exposure, which numbered less than 100 persons annually in New York State before 1990, for instance, but rose to approximately 10,000 annually between 1990 and 1995. At approximately $1500 per course of treatment, this represents a considerable public health expenditure. Raccoons do constitute approximately 50% of the approximately 8,000 documented animal rabies cases in the United States (Krebs JW, Strine TW, Smith JS, Noah DL, Rupprecht CE, Childs JE. "Rabies surveillance in the United States during 1995". J Am Vet Med Assoc 1996;204:2031-44). Domestic animals constitute only 8% of rabies cases (ibid.), but are increasing at a rapid rate.
In the midwestern United States, skunks are the primary carriers of rabies, comprising 144 of the 237 documented animal cases in 1996. The most widely distributed reservoir of rabies in the United States, however, and the source of most human cases in the U.S., are bats. Nineteen of the 22 human rabies cases documented in the United States between 1980 and 1997 have been identified genetically as bat rabies. In many cases, victims are not even aware of having been bitten by a bat, assuming that a small puncture wound found after the fact was the bite of an insect or spider; in some cases, no wound at all can be found, leading to the hypothesis that in some cases the virus can be contracted via inhaling airborne aerosols from the vicinity of a bat or bats. For instance, the Centers for Disease Control and Prevention warned on May 9, 1997, that a woman who died in October, 1996 in Cumberland County, Kentucky and a man who died in December, 1996 in Missoula County, Montana were both infected with a rabies strain found in silver-haired bats; although bats were found living in the chimney of the woman's home and near the man's place of employment, neither victim could remember having had any contact with them. This inability to recognize a potential infection, in contrast to a bite from a dog or raccoon, leads to a lack of proper prophylactic treatment, and is the cause of the high mortality rate for bat bites.
In case of an attack by a possibly rabid animal, most states in the United States allow the killing of the attacking animal. Because a rabies diagnosis requires that the brain tissue be preserved, it is recommended that rabid animals are not to be shot in the head.

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