Department of Community Medicine Al Kindy College of Medicine RABIES Dr. Wijdan Akram FICM/CM Department of Community Medicine Al Kindy College of Medicine

RABIES Acute, usually fatal infectious disease of warm-blooded animals that attacks the central nervous system. It is spread by contact with an infected animal's saliva, usually from a bite. The rhabdovirus that causes it spreads along nerve tissue from the wound to the brain. Symptoms usually appear four to six weeks later, often beginning with irritability and aggressiveness. Wild animals lose their fear of humans and are easily provoked to bite, as are pets.

Microbiology Lyssavirus genus prototype 7 rabies groups in genus Single-stranded, negative-sense, nonsegmented RNA. 7 rabies groups in genus Classic rabies virus – common rabies 6 others with less than 10 reported human cases of disease.

Rabies is widely distributed across the globe Rabies is widely distributed across the globe. More than 55 000 people die of rabies each year. About 95% of human deaths occur in Asia and Africa. Most human deaths follow a bite from an infected dog. Between 30% to 60% of the victims of dog bites are children under the age of 15.

Rabies Rabies ranks number 10 worldwide as a cause of mortality. 50,000 – 60,000 deaths annually worldwide Rare human cases in US but 35,000 people provided prophylaxis annually.

Pathophysiology Virus course Initial uptake of virus by monocytes in 48-96 hours Crosses motor end-plate to travel up the axon to the dorsal root ganglia to the spinal cord and the CNS Then spreads outward via peripheral nerves to infect almost all tissue of the body

Incubation period: In human average 4-6 weeks but range from 5 days to more than one year I.P. up to 6 years have been confirmed by antigenic typing and nucleotide sequencing of strain.

Epidemiology Dogs: Less than 5% of animal cases in US, Canada and Europe. Greater than 90% of animal cases in developing countries. Very rare documented rabies in: Squirrels, hamsters, guinea pigs, gerbils, rats, mice, domesticated rabbits and other small rodents. Almost never requires post exposure prophylaxis

Wound cleansing and immunizations, done as soon as possible after suspect contact with an animal and following WHO recommendations, can prevent the onset of rabies in virtually 100% of exposures. Once the signs and symptoms of rabies start to appear, there is no treatment and the disease is almost always fatal.

The signs and symptoms of rabies The first symptoms of rabies may be very similar to those of the flu including general weakness or discomfort, fever, or headache. These symptoms may last for days. There may be also discomfort or a prickling or itching sensation at the site of bite, progressing within days to symptoms of cerebral dysfunction, anxiety, confusion, agitation. As the disease progresses, the person may experience delirium, abnormal behavior, hallucinations, and insomnia. The acute period of disease typically ends after 2 to 10 days

Epidemiology Transmission Saliva though bite of an rabid animal most common Aerosolized in bat caves Mucus membrane transmission also reported Bites and scratches Risk of developing rabies dependant on the location injury, depth, and number of bites

Infection Risk Risk of infection Multiple bites around the face 80-100% Single bite 15-40% Superficial bite on the extremity 5-10% Contamination of open wound by saliva 0.1% Transmission via fomites (e.g. tree branch, or animal) 0%

Who is most at risk? People most at risk of rabies live in rural areas of Africa and Asia. An estimated 31 000 people die from dog rabies in Asia each year. In Africa the annual death is 24 000. Dog rabies is responsible for more than 14 million courses of post-exposure treatment to prevent the onset of disease. Globally, the most cost-effective strategy for preventing rabies in people is by eliminating rabies in dogs through animal vaccinations.

Disease prevention: includes administration of both passive antibody, through an injection of human immune globulin and a round of injections with rabies vaccine. Once a person begins to exhibit signs of the disease, survival is rare. To date less than 10 documented cases of human survival from clinical rabies have been reported and only two have not had a history of pre- or post exposure prophylaxis.

Demographics Cases of rabies in humans are very infrequent in the United States, averaging one or two a year (down from over 100 cases annually in 1900), but the worldwide incidence is estimated to be between 30,000 and 50,000 cases each year. These figures are based on data collected by the World Health Organization (WHO) in 1997 and updated in 2002. Rabies is most common in developing countries in Africa, Latin America, and Asia, particularly India

Dog bites are the major origin of infection for humans in developing countries, but other important host animals are the wolf, and bat. Most deaths from rabies in the United States result from bat bites. People whose work frequently brings them in contact with animals are also considered to be at higher risk than the general population. This group includes those in the *fields of veterinary medicine, animal control, wildlife work, and *laboratory work involving live rabies virus. People in these occupations and *residents of or travelers to areas where rabies is a widespread problem should consider being immunized

Diagnosis After the onset of symptoms: blood tests. cerebrospinal fluid (CSF) analysis tests will be conducted. CSF will be collected during a procedure called a lumbar puncture in which a needle is used to withdraw a sample of CSF from the area around the spinal cord. The CSF tests do not confirm diagnosis but are useful in ruling out other potential causes for the patient's altered mental state. The two most common diagnostic tests are the fluorescent antibody test . 3. isolation of the rabies virus from an individual's saliva or throat culture.

Treatment Because of the extremely serious nature of a rabies infection, the need for rabies immunizations should be carefully considered for anyone who has been bitten by an animal, based on a personal history and results of diagnostic tests. If necessary, treatment includes the following: The wound is washed thoroughly with medicinal soap and water. Deep puncture wounds should be flushed with a catheter and soapy water. Unless absolutely necessary, a wound should not be sutured.

Tetanus toxoid and antibiotics will usually be administered Tetanus toxoid and antibiotics will usually be administered. Rabies vaccination may or not be given, based on the available information. If the individual was bitten by a* domestic animal and the animal was captured, the animal will be placed under observation in quarantine for ten days. If the animal does not develop rabies within four to seven days, then no immunizations are required. *If the animal is suspected of being rabid, it is killed, and the brain is examined for evidence of rabies infection. *In cases involving bites from domestic animals in which the animal is not available for examination, the decision for vaccination is made based on the prevalence of rabies within the region where the bite occurred.

* If the bite was from a wild animal and the animal was captured, it is generally killed because the incubation period of rabies is unknown in most wild animals.  In those rare instances in which rabies has progressed beyond the point where immunization would be effective, the patient is given medication to prevent seizures, relieve some of the anxiety, and relieve painful muscle spasms. Pain relievers are also given. In the later stages, aggressive supportive care will be provided to maintain breathing and heart function. Survival is rare but can occur.

Prognosis If preventative treatment is sought promptly, rabies need not be fatal. Immunization is almost always effective if started within two days of the bite. Chance of effectiveness declines, however, the longer vaccination is put off. Local treatment of the wound Removing the rabies virus at the site of the infection by chemical or physical means is an effective means of protection. Therefore, prompt local treatment of all bite wounds and scratches that may be contaminated with rabies virus is important. Recommended first-aid procedures include 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

Available Vaccines The rabies vaccine is available as: Human diploid cell vaccine (HDCV) Purified chick embryo cell vaccine (PCECV) History of the Vaccine The first rabies vaccine was developed in the early 1960’s. All rabies vaccines currently available for humans are made from killed rabies virus.

Who Should and Should Not Receive the Vaccine Who should receive the vaccine pre-exposure? Vaccination before exposure (pre-exposure) should be offered to people in high risk groups such as veterinarians, animal handler/caretakers, or laboratory workers who may be exposed to the rabies virus. Pre-exposure vaccination may be considered for: 1- People whose activities bring them into frequent contact with rabies virus or potentially rabid animals (e.g., bats, raccoons, skunks, ferrets, cats, dogs). 2-Travelers who will spend more than one month in countries with a high rate of rabies infection, if they are likely to come in contact with rabid animals and immediate access to appropriate medical care is limited

Who should receive the vaccine post-exposure? Vaccination after exposure (post-exposure) is recommended for all individuals who have had contact with an animal (e.g., bites or abrasions) that they believe may be, or which is proven to be, rabid. Vaccination should be initiated as soon after exposure as possible and should be accompanied by proper wound management and the administration of RIG, human. Pregnant women who are exposed to rabies may receive the vaccine

Who should not receive the vaccine? The rabies vaccines are not recommended for routine use. People who are moderately or severely ill should consult with their physician before receiving any vaccine Dose Schedule Pre-exposure rabies vaccines are administered by a series of three injections: The first dose may be given at any time The second dose should be given seven days later The third dose should be given 21 or 28 days after the first dose

Booster doses of vaccine are recommended every two years for those individuals who continue to be at increased risk of contracting rabies to maintain protective antibody levels. People that work with live rabies virus in laboratory settings should be tested every six months to ensure that they have adequate antibody levels, and receive boosters as necessary When post-exposure rabies vaccines are administered: The number of doses required is determined by the previous immunization status of the individual 1- Previously unvaccinated people should receive the vaccine intramuscularly at 0, 3, 7, and 14  days.

For adults the vaccine is given in the deltoid area; for children, it may be given in the anterolateral aspect of the thigh. They should also receive rabies immune globulin (RIG) at the same time as the first dose of the vaccine to provide rapid protection that persists until the vaccine works. 2- Previously vaccinated people should receive two doses of the vaccine intramuscularly—the first immediately, the other three days later. RIG is unnecessary and should not be given. An immunized person is anyone who has received a complete series of vaccine, or a person who has received a pre-exposure or post-exposure series of any rabies vaccine who has an adequate rabies antibody level  

Effectiveness of the Vaccine There are no controlled trials of rabies vaccine but studies of persons who had bitten by an animal that was proven to be rabid and who received both RIG and a full course of one of these modern rabies vaccines, there have been no cases of rabies. Previously immunized people still must receive two additional doses of the vaccine if exposed to the virus, and the vaccine is almost 100% effective in these cases as well.

Known Side Effects 1- Mild reactions such as pain, redness, swelling, or itching at injection site are reported among 30%-74% of those vaccinated. 2- Headache, nausea, abdominal pain, muscle aches, and dizziness are reported in 5-40% of those vaccinated. 3- Serious events after vaccination are rare. However, allergic reactions including swelling and mild difficulty breathing developed in 6% of patients who received booster doses of Human Diploid Cell Rabies Vaccine. In addition, three cases of neurologic illness resembling Guillain-Barre Syndrome, a progressive disorder affecting the nervous system, have been reported in people who received the Human Diploid Cell Rabies Vaccine. In these cases, all patients recovered within three months

Related Issues What should you do if bitten by a rabid or suspicious animal? 1) Wash all bites and scratches immediately and thoroughly with soap and water and a solution that kills viruses (such as a povidone-iodine solution). Wound cleansing alone will markedly reduce the chances of getting rabies. 2) Go to a health care provider for a medical assessment regarding the need for a tetanus shot (if it needs to be updated), rabies vaccination, and administration of RIG, human. Two rabies immune globulins are licensed for use in the U.S. Each year approximately 18,000 people in the U.S. receive vaccination and immune globulin, and none of them has developed rabies. 3) Notify the state or local health department.

Vaccination and appropriate immune globulin therapy can protect you after you have been bitten. Vaccination before exposure merely simplifies therapy by eliminating the need for RIG and decreasing the number of vaccine doses needed. Effective rabies control measures include routine immunization of dogs, cats, and ferrets, and control of stray dogs and selected wildlife. A fully vaccinated dog or cat is unlikely to become infected or to transmit rabies.

Key facts Rabies occurs in more than 150 countries and territories. Worldwide, more than 55 000 people die of rabies every year. 40% of people who are bitten by suspect rabid animals are children under 15 years of age. Dogs are the source of 99% of human rabies deaths. Wound cleansing and immunization within a few hours after contact with a suspect rabid animal can prevent the onset of rabies and death. Every year, more than 15 million people worldwide receive a post-exposure preventive regimen to avert the disease – this is estimated to prevent 327 000 rabies deaths annually.

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