Rabies—A public health emergency
Any possible human exposure to rabies constitutes an emergency, and physicians must be aware of local protocols for accessing rabies post-exposure prophylaxis (RPEP) quickly. In BC, the exposure of greatest concern is that associated with bats. The threshold for intervention related to such encounters is low and has recently been lowered further. The real-life scenario described in the accompanying sidebar (“A mishandled bat attack [9]”) highlights the need for clinicians to be circumspect around human-bat encounters reported to them.

Ultimately, rabies causes encephalitis and death in humans and most other mammals. After being deposited in body tissues by the bite of an infected animal or the salivary contamination of a wound or mucous membrane, the virus replicates at the site of injury or invades nerve endings directly.[1] It is highly neurotropic. Progression is determined by the richness of nerve endings at the site of replication and the distance the virus must travel from the periphery to the central nervous system. Migration occurs at a rate of about 8 mm to 20 mm per day. In the case of bites involving the head, or exposure of membranes of the eyes, mouth, or nose, rabies virus may migrate directly to the brain.[1] The reported incubation period for rabies varies from a few days to over 19 years, but 75% of patients become ill in the first 90 days after exposure.[2] 

Rabies is primarily a disease of animals—humans are not natural hosts but they can become infected by bites from rabid animals. According to best estimates, worldwide more than 30 000 human deaths from rabies occur annually, principally following bites from rabid dogs. Each year, approximately 4 million people require rabies post-exposure prophylaxis.[1,2] 

The unwitting role played by bats
Since 1925, 21 human deaths due to rabies have been reported in Canada. Of the five cases indigenously acquired since 1960, three have been bat-related.[1] Rabies is enzootic in foxes and striped skunks, and these represent the primary wildlife reservoirs elsewhere in Canada. During 1999, raccoon rabies emerged in Ontario—an alarming finding with implications for other provinces.

Bats are a natural reservoir throughout Canada and are the only reservoir in BC. Contact with any wild animal, and particularly any animal exhibiting aberrant behavior, should be avoided since any mammal can become infected following a bite or scratch by another infected host. However, direct contact with bats is of greatest concern in this province. The last human death in BC due to rabies was in 1985—the result of transmission from a bat. A 25-year-old male was bitten and scratched about the face and arms while camping in Alberta. He did not seek medical attention and returned to BC, where he died 4 months later.

Respecting bats and maintaining a safe distance
Bats are a protected species under the BC Provincial Wildlife Act and are important to our ecology.[3] They consume large numbers of flying insects and as such are a natural asset to agriculture and gardening. Using sophisticated echolocation, an individual bat weighing as little as 6 grams can find and consume 600 insects in an hour. Twenty species inhabit Canada and 16 species live in British Columbia.[4] In protecting humans from the risk of rabies, it is not necessary to malign these animals. Nevertheless, mutual respect and a safe distance are beneficial to both in the bat-human relationship. Ensuring a safe distance includes barring bats from human dwellings by sealing openings as small as 2 cm and placing screens on windows. Professional bat control advice may be necessary where homes are already inhabited.[5]

What is the risk associated with bats?
Bat rabies was first identified in North America in Florida in 1953 and in Canada in BC in 1957.[1] Although 4% to 10% of BC bats submitted for testing prove to be infected, this is probably an over-estimate since such bats are a priori ill, dead, or behaving abnormally. Recent random bat surveys are lacking but past surveys show prevalence below 1%.[1] In fact, the true prevalence varies depending upon testing protocol, the species of bat, its social preferences (colonial versus solitary), and migratory patterns.

The behavior demonstrated by rabid bats may not be dramatically altered. While some may become aggressive, others may simply become disoriented, lose their flying ability, and appear clumsy. Bats are night creatures and it is unusual for them to fly in daylight. Those active during the day should be considered particularly suspect, as should any found on the ground.

Bat rabies has been identified as the most rapidly increasing source of human rabies infection in North America. Nucleotide sequencing has made this determination possible by identifying bat variant rabies where the source was previously unknown.[2] Bat teeth are very fine and their bites may be undetectable as pinpoint puncture marks a millimeter or less in diameter. Most bat-inflicted scratch marks are less than a centimeter long.[6] Such minor evidence of contact may be difficult to recall or elicit from a person dying from rabies. Since 1980, 21 of the 36 rabies deaths among humans in the United States have been due to bat-variant rabies. In only 10 to 12 of these bat-associated cases was there any apparent contact with a bat, and in only one or two was a bite reported.[7]

Changing recommendations around bat encounters
Recent recognition that indigenous human rabies cases in North America are largely bat-associated and that even direct contact may not be recognized has prompted changes in the way human-bat encounters are handled. The burden of proof has shifted—unless physical contact with a bat can be strictly ruled out, RPEP should be considered. RPEP is recommended for all persons with a known bite, scratch, or mucous membrane exposure unless prompt testing demonstrates the bat is negative for evidence of rabies. In addition, since May 1997, the Centre for Disease Control has advised that RPEP should be considered in all situations in which there is a reasonable probability that physical contact with a bat /may/ have occurred, unless prompt laboratory testing has ruled out rabies.[7] This includes cases in which a person may not be aware that direct contact has occurred, such as those in which a bat is found in the same room as a sleeping person, an unattended child, or a mentally disabled or intoxicated person.[7] 

What to do following a bat encounter
In all instances of potential human exposures involving bats, the bat should be safely collected undamaged, if possible, and submitted for rabies diagnosis. If the bat is alive, it should be placed in a sealable container and kept in a cool, dry place away from pets or humans until testing can be arranged. A Styrofoam cooler with small air holes or a tin can covered with cardboard given air holes works well. Indirect handling with a tool is preferred since a bat will usually bite when held. Protective clothing including thick gloves should be worn if direct contact is a possibility.[5]

Since the brain and/or spinal cord are required for testing, the animal should be humanely euthanised by a veterinarian in such a way as to preserve these tissues. Even if the bat is already dead, direct handling should be avoided, but testing is still possible unless the carcass is clearly putrid. The local health unit or one of the Animal Health District Offices of the Canadian Food Inspection Agency (CFIA) can provide further advice around testing.

Immediate and thorough washing of all bite wounds and scratches with soap and water and a virucidal agent such as povidone-iodine solution are important first measures for preventing rabies.[7] If iodine solution is not available, a 20% soap solution can be used. Thorough wound cleansing can reduce the risk of rabies by up to 90%.[2] The local health unit (consult the Blue Pages under Health Authorities) or, after hours, the provincial microbiologist on-call (604 661-7033) should be contacted in all cases where human rabies exposure is suspected. In some instances, the recommendation will be made to proceed with RPEP before laboratory tests are known. The local medical health officer, in making the recommendation for RPEP, requests its release from the BC Centre for Disease Control. RPEP is then couriered on an emergency basis to the administering clinician.

Pet owners should ensure their pets are up to date with rabies immunization. Whenever pet exposure to a bat or other potentially rabid animal is suspected, the exposure should be discussed with the district veterinarian (see list [10]) who can provide proper handling, testing, and follow-up guidance. All situations where human exposure may also be a concern should be discussed with public health staff.

Rabies post-exposure prophylaxis—The protocol
Standard RPEP in a person previously unimmunized against rabies consists of 5 spaced doses of human diploid cell rabies vaccine (given on days 0, 3, 7, 14, and 28) and a single dose of rabies immune globulin (RIG) given on day 0. RIG provides immediate protection while the active antibody response is stimulated by vaccine. The dose of RIG is based on weight and should not be exceeded because of possible interference with active antibody production. As much as possible of the RIG is infiltrated into the wound site, if visible.[7] A template instruction sheet for RPEP administration is included here [11]. This routine is very safe and effective when followed correctly. Failure rates of 1 in 80 000 have been estimated in developed countries and between 1 in 12 000 and 1 in 30 000 in developing countries.[2] Failures predominantly occur where the protocol has been breached in some way.

The RPEP experience
Following the 1997 revised recommendations for handling bat exposure there was a two- to three-fold increase in RPEP release in BC (55 in 1995, 69 in 1996, 119 in 1997, 158 in 1998). The proportion of RPEP released for bat exposures increased to 62.2% in 1997 and 75.3% in 1998 compared to 26.1% in 1996 and 45.5% in 1995. The average proportion of RPEP release related to bat exposures from 1988 to 1994 was 24.6%. While bites, scratches, and salivary contact accounted for most canine-associated RPEP releases, bat-related RPEP releases were predominantly for suspect contacts such as handling or being in the same room as a bat where direct contact could not be ruled out. Most contacts occur in the summer months, with bats generally emerging from hibernation during the warmer temperatures of May or June.[3]

The bottom line
The cost-effectiveness of the revised approach to bat exposures is difficult to assess. The complete RPEP series for the average 70 kg adult costs approximately $700 in biological products alone without reference to administration fees. There is no evidence that bat rabies has increased in prevalence in BC, and this province was without a case of rabies for many years prior to the revised recommendations.

Nevertheless, when dealing with a uniformly fatal illness such as rabies, extreme prudence is warranted. Recent case reports in the US with minimal known contact preceding bat-associated rabies in humans cannot be ignored. It is hoped that by increasing awareness of the benefit to both bat and human in respecting a safe distance, the opportunities for exposure, the need for RPEP, and the risk of this dreaded disease will be minimized.

Acknowledgments
The authors gratefully acknowledge the contribution and editorial assistance provided by Dr Brian P. Emerson, medical health officer; Ms Laura Friis, Ministry of Environment, Lands and Parks, British Columbia; Dr Don Olson, program officer, Animal Health, Canadian Food Inspection Agency; Dr Robert M.R. Barclay, Biological Sciences, University of Calgary; and Dr Helen Schwantje, wildlife veterinarian, Wildlife Branch, MELP.

Dr Skowronski is a physician epidemiologist at the BC Centre for Disease Control. Dr Srour is a community medicine resident in the department of Health Care and Epidemiology at UBC.