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Geography of Rabies Rabies causes 60,000 deaths worldwide, half of which are in India. Countries completely free of rabies include: Australia, New Zealand, Japan, Honk Kong, Singapore, Great Britain, and some Scandinavian countries. The virus Rhabdoviridae Lyssavirus causes rabies. All mammals are capable of transmitting disease to other animals or people, but 99% of cases are transmitted from dogs.
Figure 10 Rabies distributions The Rabies vaccine may be recommended for travelers to areas in which rabies is endemic and for those who will have occupational or recreational exposure eg: veterinarians, spelunkers, or other contacts with livestock or wild animals. The presence and distribution of rabies can be determined by reviewing the rabies information on the CDC Web site (http://www.cdc.gov/travel), or the WHO Global Health Atlas Web site (http://globalatlas.who.int/). Animal commonly carrying rabies:
Rabies virus invasion Infections with rabies occur when the virus is first inoculated into the victim and then absorbed into a susceptible cell where it multiplies. The virus then enters nerve endings. The virus will migrate to the brain and once the virus has entered the brain rabies symptoms will begin to occur. Rabies is almost universally fatal afterwards. The term rabies refers only to when the person has the fatal condition. The average incubation time before the development of symptoms is 90 days, although it has developed in as little as 7-10 days to greater than a year. One case was known to have happened over 6 years after a bite. Children tend to develop symptoms faster because bites are closer to the brain (the virus has less distance to travel to arrive at the brain), and is often more severe. Symptoms of Rabies Symptoms of rabies in people are divided into 2 types - encephalitic (furious) and paralytic (dumb). Early symptoms may be vague and non-specific (fever, upset stomach). Local symptoms may occur at the bite site such as burning, numbness, tingling or itching. Characteristics of encephalitic (furious) rabies:
Rabies is 100% fatal although four people to date have survived but all with resultant neurological damage.
Human Rabies in the United States There have been 40 U.S. Acquired Infections 1980 - 2005: One from a Skunk (OK, 1981); Two from Dogs (TX, ‘91 and ‘94); Four From Human Organ Transplants (TX, ’94) The remaining 33 Have been determined by nucleotide analysis to have originated from bats (Aged 4 to 82; Six Children 4, 5, 11, 12, 13, and 15 Yrs) Only four had history of a bite; half had no Known bat contact (Many histories were vague).
Figure 11 Rabies distribution Human Rabies in Canada This is a much Smaller Problem Than in U.S. – 3,000 Post exposure prophylaxis’s Per Year; As Many as 40,000 in U.S. Only Twenty-two human infections since records began in 1925. Nine-Year old boy died of bat rabies in Quebec in 2000; Sixty-Four year old man died of bat rabies in British Columbia in 2003.
Human Rabies from Bats Transmission route is an enigma: vampire bats bite humans without awakening them. Can other bats do that also? They also have small, sharp teeth. Rabies may also be transmitted as an Aerosol via bat guano. Two men died after exploring a cave near Uvalde, Texas, in 1970’s and aerosol transmission to animals was subsequently demonstrated.
Current Recommendations regarding bats All Buildings should be “Bat-Proofed”. All bat contacts must be avoided. Any person who contacts a bat should receive post exposure prophylaxis unless bat is captured and examined for rabies. Anyone, particularly a child, who awakens from sleep and finds a bat in the room should receive PEP unless the bat is captured and examined.
Rabies in Wild Animals in North America U. S. and Canada are unique in having endemic rabies in a number of different wild animal species. This may also be true and exist undiscovered in developing countries U.S. Incidence Increased from 5,700 Infections per Year in 1980’s to as Many as 9,495 in 1994 Detected cases may represents 1 to 10 percent of wildlife rabies as most rabid animals die in the woods and are undetected
Table 12 Reported Animal Rabies infections in Canada
No rabies infections reported from Nova Scotia, North West Territories and the Yukon Territory. or lynx.
Rabies in Wild Animals Much of the U.S. surge resulted from an East Coast raccoon epizootic that started in Florida in the 1950’s. Animals transshipped to West Virginia in late 1970’s and the epizootic subsequently exploded In NY, the number of rabid animals encountered grew over 5,000% – 54 in 1989 to 2,746 in 1993. 2,444 (89 %) of those animals were raccoons. Well-vaccinated dog and cat pet population forms a buffer between raccoons and humans. One important feature may be that rabid raccoons are docile, not aggressive: people pick them up thinking them tame.
The U.S. Raccoon Epizootic Spread into Canada in 1999. Initial response by Ontario officials initiated a trapping program around site of infected animals; and a trap-vaccinate-release program with aerial vaccine drops Initially there were four Raccoon infections found in 2004; 45 Found in 2001; and a total of only 131 Infections since 1999. In New York number of raccoon infections climbed to 5,500 in Five years. Fox rabies is a much greater problem, but infections have dropped 97%; 1,500 in 1989 to 54 in 2004
The history of development of a human rabies vaccine The vaccine was first developed by Pasteur (and was also the first live virus vaccine) and was produced in rabbit spinal cords. The dried cords lose their infectivity after 15 Days so injections were started with 14-Day-Old cord material
Later the “Semple Vaccine” viruses were grown in animal brains (One-Day-Old mice) and neutralized with b-Propriolactone. Then 5 to 10 cc of simple saline suspension was injected – “Crudest” preparation used for humans and is the most widely used rabies vaccine used worldwide. This should be avoided in travelers. Human Diploid cell vaccines Human diploid cell vaccine (HDCV) was licensed In the U.S. in 1980 – and had almost no adverse side effects. 3 Patients (World-wide) have developed Guillain-Barre but recovered fully. Allergic reactions are mostly mild and have occurred with preexposure vaccination and they are attributed to Human Albumen in the preparation. HDCV is the “Gold Standard” vaccine with which other vaccines are compared. (2 Vaccines Licensed in Canada (Imovax® or Rabivert ®)) HDCV Production is produced by “a demanding technology- low virus yield, and enormous production costs per unit of vaccine.” This has made it remain expensive. Increased demand created by the raccoon epizootic strained production capacities and has created shortages from time to time. The cost is prohibitive in developing countries and HDCV is only sometimes available.
Other acceptable vaccines overseas A variety of Cell-Culture vaccines are used in the rest of the world. They are grown in primary cultures (hamster and dog kidney and chick embryo fibroblasts); grown in diploid cell lines (human or rhesus monkey); grown in continuous cell lines (green monkey and baby hamster kidney cells).
The Vero Cell Rabies Vaccine (VCRV) is grown on African green monkey (Vervet) kidney cells and is just as effective and safe as HDCV, and is far cheaper, but is not licensed in the United States or Canada.. For travelers who have been given a foreign vaccine series clinicians must determine if they received a quality vaccine abroad. If there is suspicion of substandard post bite prophylaxis consideration to switching to a HDCV treatment should be given. Rabies in travelers Rabies cases in travelers are rare but dog or monkey bites are not uncommon. Most cases of rabies in travelers follow a dog bite but other animals may also carry rabies such as monkeys, bats, foxes and mongoose. It should be recognized that many other animals might also carry rabies. Counseling travelers It is important that travelers are counseled about dog avoidance (and avoidance of other animals), thorough cleaning of all animal wounds with soap and water as soon as possible, and told to seek prompt medical evaluation. In areas where rabies is known to occur, medical advice for the correct postexposure prophylaxis for rabies should be sought Prevention and treatment of rabies Pre-exposure vaccination is giving the rabies vaccine to people who might be exposed to rabies. The 2 vaccines available in Canada and the US (Imovax, RabAvert) are both given in the deltoid (not gluteal) muscle at 0, 7 and 21 or 28 days. with a booster at 1 year and every 5 years after. It eliminates the need for post exposure immunoglobulin treatment after a rabid bite, which may not even be available in certain countries. It also simplifies post exposure treatment to only 2 vaccine doses after being bitten. People who should be vaccinated include researchers working with rabies, veterinarians, and remote travelers. Spulunkers may also be at risk of rabies from bats. Children of long-term travelers might also be at high risk of rabies in developing countries. Post bite treatment Cleaning bites is the most important step in preventing rabies. This should be done as soon as possible, first by flushing the wound with soap and water, followed by 70% alcohol, or tincture of iodine. Rabies exposures may be graded as: Type of Contact - Recommended Treatment
After a rabid bite the rabies vaccine is usually given on days 0, 3, 7, 21, and 28. The vaccine is given in the deltoid (or thigh in children). It is not to be given in the gluteal muscle because there is poor absorption of the vaccine when given in the gluteal area. Sometimes a double dose of the vaccine is given on day 0 if the patient is immune deficient or had a very bad bite. If a person who has been previously fully vaccinated within 5 years is bitten they only require 2 booster doses at days 0, 3 but do not need rabies immunoglobulin.
Rabies Immune Globulin Rabies immunoglobulin (RIG) is given to those people with severe bite(s) who have no prior antibodies that will bind to the virus to prevent them from entering the nerve tissue and spreading to the brain. RIG is a blood product and may not be available in developing countries. This should be given as soon as possible after being bitten since rabies has developed a few days after being bitten in some cases. People will begin to produce their own antibodies 7-10 days after being vaccinated. The immunoglobulin should be injected into the wound with a separate syringe from the rabies vaccine. Treatment should not be withheld while awaiting test results or quarantined animals. Be aware of Intradermal injections Intradermal injection of vaccine for post rabies exposure is done in some developing countries, which is much cheaper since less vaccine is given intradermally. The vaccine is given in day 0,3, and 7 in double doses; and days 28 and 90 at single doses. Some North American centres will give intradermal injections for pre-exposure since this is likewise cheaper. However when doing this these patients has to be followed closely by lab tests to confirm the effectiveness of this type of immunization with extra injections administered if a low immunoglobins titre is found. Important treatment summaries Rabies exposures are an important clinical situation where clinicians may not be familiar with specific protocols and plans of action for specific patient scenarios so the following are emphasized: Post bite management with prior rabies immunization A complete course of rabies vaccine prior to travel (given at days 0,7,and 21 or 28) eliminates the need for rabies immunoglobulin following an exposure but travelers will still require an additional 2 doses of the rabies vaccine after being bitten. Post bit management without prior rabies immunization If no rabies vaccination was given patients should receive post exposure rabies vaccine and Rabies immunoglobulin. Rabies Immunoglobulin of either human or equine origin may be very difficult to obtain in resource-poor regions of the world Pre-exposure vaccine has the additional theoretical benefit of protecting against unrecognized or unreported exposures. This may occur in children who are afraid to admit they were bitten. All travelers who have had an exposure, regardless of their pre-travel rabies vaccine history, require postexposure prophylaxis. Those who have had pretravel vaccine require an additional 2 doses, and those who have received no prior rabies vaccine require a complete course of vaccine (5 doses using the Human Rabies diploid cell vaccine) plus rabies immunoglobulin. Postexposure and boosting doses of rabies vaccine do not have to be administered using the original vaccine product. There are several rabies products available worldwide and with careful scrutiny of the type used, management may be continued using Canadian vaccines. There are also some vaccines of very dubious quality that are not recommended. If there is a reasonable suspicion that a rabies shot was not properly administrated or that a poor quality vaccine was used, the shot should not “count” and a new series of immunizations should be administered. Rabies immunization should be given IM in the deltoid muscle at a site apart from the RIG if co administered. Rabies vaccine given in the gluteal area is not effective and should not be injected there, as there have been many well-documented cases of vaccine failure in that instance. References Wilde H, Briggs DJ, Meslin FX, Hemachudha T, Sitprija V. Rabies update for travel medicine advisors. Clin Infect Dis 2003; 37:96–100. Centers for Disease Control and Prevention. Human rabies prevention—United States, 1999: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1999; 48(RR-1): 1–21. CDC Rabies http://www.cdc.gov/ncidod/dvrd/rabies/ Aventis Pasteur http://www.rabies.com/ WHO Rabnet http://www.who.int/GlobalAtlas/home.asp Health Canadahttp://www.hc-sc.gc.ca/pphb-dgspsp/tmp-pmv/info/rage_e.html Take home messages: Consider rabies in dog and wild animal encounters Notify city pound for follow up. They can follow up quarantine and evaluate if animal is possibly rabid. Consult infectious disease if not sure Educate children to not touch strange animals domestically and in travel. Pay attention to wound care- clean wound and consider tetanus. Evaluate if rabies immunization given was adequate (quality of vaccine used, administration use and not post expiry date) Administer rabies immunoglobulin if appropriate and within correct time window. Immunize pets against rabies to protect them and act as a buffer barrier to owners.
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