1.0 INTRODUCTION Rabies is a virus disease that causes acute inflammation of the brain in humans and other warm-blooded animals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness. Once symptoms appear it nearly always results in death. The time period between contracting the disease and the start of symptoms is usually one to three months; however, this time period can vary from less than one week to more than one year. The time is dependent on the distance the virus must travel to reach the central nervous system.
Rabies is caused by lyssaviruses including: rabies virus and Australian bat lyssavirus. Rabies is spread when an infected animal scratches or bites another animal or human. Saliva from an infected animal can also transmit rabies if the saliva comes into contact with the mouth, nose, or eyes. Overall dogs are the most common animal involved. More than 99% of rabies cases in countries where dogs commonly have the disease are caused by dog bites. In the Americas, bat bites are the most common source of rabies infections in humans, and less than 5% of cases are from dogs. Rodents are very rarely infected with rabies. The rabies virus travels to the brain by following the peripheral nerves. The disease can only be diagnosed 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 who are at high risk. The high-risk group includes people 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 a few people have survived a rabies infection after showing symptoms and this was with extensive treatment known as the Milwaukee protocol.

2.0 What are the causes of rabies?
The rabies virus is part of the Lyssavirus genus and infects other animals, including humans, through infected saliva, usually from a bite. Much less commonly, a person can become infected if an open wound or mucous membranes have contact with infected saliva. There have been recorded cases of people becoming infected after inhaling the air inside bat caves.
The virus lingers at the bite site for a while and then invades muscle and multiplies, eventually entering nerve endings and making its way to the central nervous system (spine and brain). From the central nervous system the virus spreads to vital organs and glands, such as the kidneys, lungs and salivary glands.
Dogs are still the main rabies carriers in Africa and Asia and are responsible for the majority of human infections and subsequent deaths worldwide, according to WHO (World Health Organization). Over the last decade bat rabies has been emerging as a problem in Europe and the Americas. Since 2003, wild bats have overtaken dogs as the main cause of human infection in South America.
The World Health Organization says that "Human rabies deaths following exposure to wild foxes, raccoons, skunks, jackals and wolves are very rare. Livestock, horses and deer can become infected with rabies, but although they could transmit the virus to other animals or people, this rarely occurs." The Centers for Disease Control and Prevention (CDC), USA, says that beavers, coyotes, monkeys, and woodchucks may also become infected and transmit to humans.
Pets and farm animals, such as cats, cows, dogs, ferrets, goats, horses and rabbits can become infected and there is a risk of transmission to humans. In most developed nations this risk is extremely small.

3.0 What are the signs and symptoms of rabies?
A symptom is something the patient senses and describes, while a sign is something other people, such as the doctor notice. For example, drowsiness may be a symptom, while dilated pupils may be a sign.

The period between initial infection and the onset of first symptoms (incubation period) can take from four to eight weeks, and sometimes over a year. The further the bite is from the head, the longer the incubation period tends to be.

The first symptoms to appear are flu-like ones, including fever, headache and fatigue. There will be tingling and/or pain at the bite site, as well as anorexia (loss of appetite).

Two possible types of rabies can develop; furious rabies or dumb rabies.

Symptoms of furious rabies: * progressive anxiety and agitation. * stiff neck * seizures * overproduction of tears and saliva (end stage) * convulsions * dilated pupils * photophobia - abnormal sensitivity to light * thermophobia - abnormal sensitivity to temperatures * hydrophobia - drinking water becomes increasingly difficult. When the patient tries to drink the throat muscles and the diaphragm go into a spasm. Eventually it becomes so bad that just the sound or sight of water can bring on spasms.

4.0 How is rabies diagnosed?
A PCR (polymerase chain reaction) or viral culture on brain samples after death can help diagnose rabies. Taking skin samples before death and analyzing them can help in reaching a reliable diagnosis.

Taking samples of saliva, urine or cerebrospinal fluid is a less sensitive way of testing for rabies. Inclusion of Negri bodies, which if detected are 100% diagnostic for rabies are only found in 80% of analyzed samples from infected patients.

If a human is bitten by an animal, there is no way rapid of finding out whether they have been infected. An animal suspected of rabies can be captured and monitored for 5 to 10 days. If no signs or symptoms are detected during this period, the animal does not have rabies, and the human who was bitten by that animal can stop receiving treatment.

4.0 What is the treatment for rabies? Anybody who is bitten by an animal that might have rabies needs to see a doctor immediately and receive treatment. If left untreated and symptoms eventually develop, the individual will die. In fact, even if you know the animal does not have rabies and you are bitten, see a doctor anyway as you may still need some other kind of treatment, and also a tetanus jab. After being bitten place the wound under a running tap and clean it thoroughly (use soap) for about five minutes. Exposed mucous membranes should be well rinsed with water. A virucidal antiseptic such as povidone-iodine, iodine tincture, aqueous iodine solution or alcohol (ethanol) should be applied after washing. If there is not profuse bleeding, do not try to close up or stitch the wound. Get medical help as soon as you can.

* If the patient was not vaccinated before being bitten the doctor will inject HRIG (human rabies immunoglobulin), mostly around the site of the wound and partly by deep intramuscular injection. Intramuscular injection should not be given into the gluteal area (buttocks) because it is linked to vaccination failure (injection must go into muscle, not fat). * The CDC (Centers for Disease Control and Prevention) says patients should receive 1 dose of HRIG and 4 doses of rabies vaccine over a 14-day period. The HRIG dosage should be no more than 20 units per kilogram of body weight. The vaccination site should be distant from the HRIG injection site. In infants (babies) the lateral thigh should be used for injection. If the patient is an adult, the arm can be used to give the vaccine. * The initial rabies vaccine should be given immediately, with the other doses on days 3, 7 and 14 after the first. * If a patient has already received pre-exposure vaccination, they should only receive the post-exposure vaccinations on days 0 and 2, and not be given the HRIG injections.
The National Health Service (NHS), UK warns all British people who have been bitten abroad and cannot get the vaccine in that country to return to the UK immediately for medical treatment.

5.0 How is rabies prevented?
Travelling - anybody travelling abroad into an area with rabies and know they will be in contact with possibly infected animals - for example, exploring bat caves - should have a pre-exposure anti-rabies vaccination. The vaccination gives the individual more time to get medical help; it does not offer full protection, but slows the virus down.

Contact with animals - do not touch unknown animals, no matter how friendly, furry, pretty and cute they seem. This is especially the case in areas that are not rabies-free. The National Health Service, UK informs that an early sign of rabies in an animal is unusual tameness.

Vaccinating animals - if you do not live in a rabies-free country or area, make sure your pets and farm animals' vaccinations are up-to-date. If you are not sure, talk to a veterinarian (animal doctor).The World Health Organization writes:

The most cost-effective strategy for preventing rabies in people is by eliminating rabies in dogs through animal vaccinations. A lack of awareness of the effectiveness and feasibility of this prevention approach hinders elimination of human cases. As shown in several countries - such as Japan and Malaysia - elimination of rabies in dogs can result in elimination of transmissions to people and other animals. Preventing human rabies through control of domestic dog rabies is a realistic goal for large parts of Africa and Asia.

Prevention of human rabies must be a community effort involving both veterinary and public health services. Rabies elimination efforts that focus on mass vaccinations of dogs are financially justified by the future savings of discontinuing post-exposure preventive treatment for people.

6.0 Where disease found and how can get it.
Rabies is most commonly spread among animals by the bite (direct contact) of an infected animal whose saliva contains the virus. The virus is not thought to be spread by blood, urine or feces.
People primarily get rabies from the bite (direct contact) of an infected animal. Less commonly, exposure to the virus occurs by entry of saliva, brain or spinal cord fluid of an infected animal into cuts or breaks in the skin or mucous membranes (e.g., eyes, nose, mouth). Rare exposures have occurred under special situations, such as aerosol in laboratory settings or organ transplantation. In most human cases, signs of rabies develop 1 to 3 months after exposure. Early symptoms include fever, headache, itching at the site of the bite, confusion and abnormal behavior. Hypersensitivity to light and sound, and difficulty swallowing can also occur. Once signs of disease begin, recovery is very rare. Death usually occurs within 2 to 10 days. Fortunately, treatment before signs develop is highly effective and life-saving. Rabies is transmitted through the saliva of an infected animal. Infection occurs primarily via bite wounds, or infected saliva entering an open cut or wound or mucous membrane, such as those in the mouth, nasal cavity or eyes. Infection through inhalation of the virus has been documented, for example, in the environment of a densely populated bat cave. The virus will generally remain at the entry site for a period of time before travelling along the nerves to the brain. In the brain, the virus multiplies quickly, resulting in clinical signs. The virus then moves from the brain along nerves to the salivary glands. The period of time before clinical signs appear in an infected animal can vary depending on the strain of virus and entry point. It is thus important to realise that the disease can be transmitted via the saliva of an infected animal to other animals and humans before the onset of clinical signs of the disease in the infected animal.

The rabies virus is present on all continents except Antarctica. Some countries have implemented vigilant control measures and succeeded in eradicating the disease to meet the OIE requirements for rabies free status. However, in some countries, the disease remains endemic with rabies present mainly in wild animal hosts. Although the infection of domestic livestock could have economic consequences in some countries, it is the occurrence of rabies in domestic dogs posing a threat to humans that is of major concern in several developing and in-transition countries. All mammals are susceptible to rabies, but only a limited number of species also act as reservoir hosts. They include members of the families Canidae (dogs, jackals, coyotes, wolves, foxes and raccoon dogs), Mustelidae (e.g., skunks), Viverridae (e.g., mongooses), and Procyonidae (raccoons), and the order Chiroptera (bats). Although cats can be affected by rabies, cat-adapted variants have not been seen. Each rabies variant is maintained in a particular host, and usually dies out during serial passage in species to which it is not adapted. However, any variant can cause rabies in other species. Occasionally, a virus adapted to one species becomes established in another. Rabies is maintained in two epidemiological cycles, one urban and one sylvatic. In the urban rabies cycle, dogs are the main reservoir host. This cycle predominates in areas where the proportion of unvaccinated and semi-owned or stray dogs is high, such as some parts of Africa, Asia, the Middle East and Latin America. The urban rabies cycle has been virtually eliminated in the U.S., Canada and Europe; although sporadic cases occur in dogs infected by wild animals, the urban cycle is not perpetuated in canine populations. However, the canine rabies variant is apparently established in some wildlife populations (e.g., foxes and skunks in North America) and it could be re-established in dogs from these reservoirs.

7.0 Transmission of Rabies.
People are usually infected following a deep bite or scratch by an infected animal. Dogs are the main host and transmitter of rabies. They are the cause of human rabies deaths in Asia and Africa.
Bats are the source of most human rabies deaths in the Americas. Bat rabies has also recently emerged as a public health threat in Australia and western Europe. Human deaths following exposure to foxes, raccoons, skunks, jackals, mongooses and other wild carnivore host species are very rare.
Transmission can also occur when infectious material – usually saliva – comes into direct contact with human mucosa or fresh skin wounds. Human-to-human transmission by bite is theoretically possible but has never been confirmed.
Rarely, rabies may be contracted by inhalation of virus-containing aerosol or via transplantation of an infected organ. Ingestion of raw meat or other tissues from animals infected with rabies is not a source of human infection.
Post-exposure prophylaxis (PEP)
Post-exposure prophylaxis (PEP) means the treatment of a bite victim that is started immediately after exposure to rabies in order to prevent rabies infection. This consists of: * local treatment of the wound, initiated as soon as possible after exposure; * a course of potent and effective rabies vaccine that meets WHO standards; and * the administration of rabies immunoglobulin, if indicated.
Effective treatment soon after exposure to rabies can prevent the onset of symptoms and death.

Local treatment of the wound
This involves first-aid of the wound that includes immediate and thorough flushing and washing of the wound for a minimum of 15 minutes with soap and water, detergent, povidone iodine or other substances that kill the rabies virus.
Recommended PEP
Depending on the severity of the contact administering with the suspected rabid animal, administration of PEP is recommended as follows (see table):

Table: Categories of contact and recommended post-exposure prophylaxis (PEP) | | | | | | | | | | Categories of contact with suspect rabid animal | Post-exposure prophylaxis measures | | | | | Category I – touching or feeding animals, licks on intact skin | None | | | | | Category II – nibbling of uncovered skin, minor scratches or abrasions without bleeding | Immediate vaccination and local treatment of the wound | | | | | Category III – single or multiple transdermal bites or scratches, licks on broken skin; contamination of mucous membrane with saliva from licks, contacts with bats. | Immediate vaccination and administration of rabies immunoglobulin; local treatment of the wound | | | | |

All category II and III exposures assessed as carrying a risk of developing rabies require PEP. This risk is increased if: * the biting mammal is a known rabies reservoir or vector species; * the animal looks sick or displays an abnormal behaviour; * a wound or mucous membrane was contaminated by the animal’s saliva; * the bite was unprovoked; and * the animal has not been vaccinated.
In developing countries, the vaccination status of the suspected animal alone should not be considered when deciding whether to initiate prophylaxis or not.
The Organization continues to promote human rabies prevention through the elimination of rabies in dogs as well as a wider use of the intradermal route for PEP which reduces volume and thereby the cost of cell-cultured vaccine by 60% to 80%.

8.0 Protecting your family and pets against rabies
Steps to protect your family and pets against rabies * Have your domestic pets vaccinated by a licensed veterinarian. * Warn your family, especially young children, to stay away from wild or stray animals. * Take measures to discourage wild animals from taking up residence in your home or on your property. For example, cover up potential entrances, such as uncapped chimneys and openings in attics, roofs, and decks. You might want to contact a professional for advice. * Do not keep wildlife as pets. * Report any animals behaving strangely to your local public health department or animal control office. * Do not attempt to nurse a sick animal back to health. Contact your local public health department or animal control office for assistance. * Report all dead animals found on your property to your local public health department. If you need to remove the carcass, wear protective gloves and use a shovel or other device to avoid direct contact. * If you think you or any member of your family has been in contact with a suspected rabid animal, immediately contact your local public health department or family physician, or go to your local emergency department for advice regarding the need for postexposure prophylaxis.

Appendix

9.0 Conclusion
While cases of rabies infection among humans are relatively rare in Canada, the potential for exposure to the virus still exists via domestic and wild animals, especially bats. Rabies also continues to be a substantial public health problem in developing countries, heightening the potential exposure for Canadians who travel internationally. Advise patients that preventive measures such as vaccinating domestic animals against rabies and avoiding contact with wild or stray animals are effective strategies to prevent viral spread. Frontline medical practitioners should be encouraged to report all animal-to-human exposures to local public health authorities so that a proper risk assessment for rabies can be made. By working together to identify suspected rabies exposures early, most human infections can be prevented.