Statement on travellers and rabies vaccine

Postexposure management of the patient with an apparent rabies contact as described in the Canadian Immunization Guide[2] is summarized in Table 1.

                          Immune
                       (vaccinated)          Nonimmune
Treatment                 patient             patient

Wound care (cleaning        Yes                 Yes
and leaving open)

Rabies immune globulin      No                  Yes
 (day 0)

Vaccination             2 doses             5 doses
(postexposure)          (days 0 and 3)      (days 0,3,7,14 and 28)

It is noteworthy that pre-exposure prophylaxis does not eliminate the need for wound management and for postexposure vaccination. Two issues are considered in this statement: (1) risks posed to Canadian expatriates by pets and stray animals, and (2) pre-exposure prophylaxis.

Domestic animals

• Pets may become rabid through contact with local domestic animals.
• Vaccination of pets may not be universal.
• Pet owners may be scratched or bitten by other animals while separating their pets from these animals.
• Guard dogs represent a particular problem. Although they may fulfil an important security function, they may be in greater contact with other animals.

Recommendations

1. Canadian expatriates should keep no pets, i.e., no dogs, cats or other animals, that may leave the house and might develop rabies (strength of recommendation: C; category of evidence: III[3]).
2. Guard dogs should not be kept unless they are vaccinated according to North American standards (strength of recommendation: C; category of evidence: III).
3. Expatriates should be informed not to touch any stray animals (strength of recommendation: C; category of evidence: III).

Pre-exposure prophylaxis

Vaccination may protect against inapparent infection or any infection in individuals in whom postexposure treatment is delayed. By eliminating the need for human rabies immune globulin and reducing the need for vaccination in the field, pre-exposure vaccination can reduce problems related to the unavailability or toxicity of these therapies.

Rabies is common in much of the developing world and occurs in both urban and rural areas. An estimated 50 000 cases -- one per 10 000 of the population -- occur in India per year.[1] The disease is rare in North American travellers. There has been one case of rabies being acquired abroad by a Canadian in the seven decades since statistics have been kept, i.e., since 1924.[5] In the United States during the period 1980-92, 10 travellers acquired rabies outside the country.[6]

The number of courses of postexposure prophylaxis given to North Americans abroad is unknown. Of 4014 at-risk US Peace Corps volunteers, 175 received postexposure treatments during the 12-month period from 1 November, 1987, to 31 October, 1988 -- an overall postexposure treatment rate of 43.6 per 1000 volunteers per year, which is considered to be an exceptionally high rate.[7]

The number of Canadians sojourning in developing countries for 30 days or more is not known. There are approximately 10 000 Canadians on long-term aid or diplomatic postings. The number of postexposure treatments is unknown.

Vaccine is conventionally administered intramuscularly (i.m.) in three doses. No failures to attain protective antibody levels have been reported in North American recipients. Because of the high cost of vaccine, intradermal (i.d.) vaccination, using one-tenth the i.m. dose, has been used in the United States. It is generally highly immunogenic. Concurrent administration of chloroquine results in impaired antibody response to i.d. vaccination, giving titres that are approximately half the normal value.[8] There has been at least one case of rabies reported among individuals who were vaccinated while taking chloroquine.[9] There are no data on the effect of mefloquine on the response to rabies vaccine.

Risk of vaccination is estimated to be minor. Although 6% of human diploid cell vaccine recipients are reported to develop allergic reactions, serious reactions are uncommon. In the United States there were 108 reports of systemic allergic reactions (mostly type III [antigen-antibody-complex-mediated reactions]) in one 46-month period, an estimated rate of 11 per 10 000 vaccinees. There were "few" hospitalizations and no deaths.[10]

The cost to a hospital for three 1-mL doses of i.m. vaccine is about $220. There is no approved preparation for i.d. dosing in Canada. The National Advisory Committee on Immunization has approved i.d. dosing in the event that such a preparation were to become available.[11]

A conservative estimate of the cost of i.m. vaccine per life saved can be based on the assumption that universal vaccination of 10 000 people at risk each year would save one more life over 70 years: $220 × 70 (years) × 10 000, or $154 million; a minimum estimate for i.d. vaccine, 1/10 of the i.m. figure, would be $15 million.

In the Peace Corps cohort the cost of pre-exposure prophylaxis was estimated to be 1.8 to 4.2 times greater than that of postexposure prophylaxis, despite the high rate of intervention. The break-even point was at a vaccine cost of US$21 for three doses.[7]

It must be concluded that rabies pre-exposure prophylaxis cannot be recommended to the general population of long-term travellers to endemic areas in order to prevent rabies. Rabies is being effectively prevented despite the minimal, albeit highly targeted, use of vaccine. Pre-exposure prophylaxis can be advocated for the broader population of expatriates only to prevent postexposure prophylaxis. The following are recommendations for pre-exposure prophylaxis of long-term travellers to areas of high endemicity.

• Limit the use of rabies vaccine to those with greater risk of animal exposure, e.g., veterinarians, farm workers and spelunkers.
• Children too young to understand their need to avoid animals or to report a traumatic contact should also be considered at greater risk of animal exposure. The dose of vaccine for children is the same as for adults.

Recommendations

1. The possibility of developing for use in Canada rabies vaccine for intradermal use should be explored with Connaught-Mérieux and the Bureau of Biologics. With reasonable pricing of such a product, recommended use might be broadened (strength of recommendation: D; category of evidence: III).
2. The interaction of rabies vaccine and other antimalarial agents, i.e., mefloquine, should be studied (strength of recommendation: D; category of evidence: III).

References

1. Warrell DA, Warrell MJ: Rabies and related viruses. In Strickland GT (ed): Hunter's Tropical Medicine, 7th ed, WB Saunders, Philadelphia, 1991: 219-227
2. National Advisory Committee on Immunization: Canadian Immunization Guide, 4th ed (cat no H49-8/1993E), Health Canada in collaboration with the Canadian Medical Association, Ottawa, 1993: 101-108
3. Evidence-based medicine. Can Commun Dis Rep 1994; 20: 145-147 [also in CMAJ 1995; 152: 201-202]
4. Cases of specified notifiable diseases, United States, weeks ending January 5, 1991, and January 6, 1990. MMWR 1991; 40: 11
5. Rabies surveillance in Canada. Can Dis Wkly Rep 1985; 11: 205-208
6. Human rabies -- California, 1992. MMWR 1992; 41: 461-463
7. Bernard KW, Fishbein DB: Pre-exposure rabies prophylaxis for travellers: Are the benefits worth the cost? Vaccine 1991; 9: 833-836
8. Pappaioanou M, Fishbein DB, Dreesen DW et al: Antibody response to preexposure human diploid cell rabies vaccine given concurrently with chloroquine. N Engl J Med 1986; 314: 280-284
9. Human rabies -- Kenya. MMWR 1983; 32: 494-495
10. Systemic allergic reactions following immunization with human diploid cell rabies vaccine. MMWR 1984; 33: 185-187
11. Intradermal administration of human diploid cell rabies vaccine (HDCV). Can Dis Wkly Rep 1982; 8: 149

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