Our analysis is a comprehensive survey addressing the epidemiology of animal-related exposures leading to rabies PEP among international travelers. The number of patients (2,697), duration of the study (16 years), and multicenter design (45 sites) provided robust data for this analysis. We found a small but significant rise in the proportion of travelers who sought care at GeoSentinel sites during 2003–2012 and who required rabies PEP, even after we eliminated the bias of increased number of sites by including only continuously reporting sites. It is known from World Tourism Organization data that tourist destinations are becoming more diverse (12); increased proportions of international tourists are traveling to countries that have emerging and developing economies and where rabies is endemic. Because the trend toward more exotic travel destinations is predicted to continue well into the future (12), demand for rabies pharmaceuticals and postexposure wound care among international travelers will probably continue to grow.

During the study period, 2,697 travelers sought care for animal exposure at GeoSentinel surveillance clinical sites and received rabies PEP. The number of travelers who seek rabies PEP is known to be an underestimate of the actual number of travelers exposed. In a recent survey conducted among 7,681 international travelers leaving the Bangkok airport, two thirds of travelers who reported having been bitten by a potentially rabid animal during their trip sought no medical care (13). Although exact figures do not exist, it can be supposed that the prevalence of exposure to potentially rabid animals among international tourists is substantial. The fact that 3 rabies diagnoses were entered into the GeoSentinel database during the study period confirms this supposition. More data defining the epidemiology of rabies exposure and disease among travelers are needed.

Our survey findings confirm those from an earlier GeoSentinel survey conducted among only 320 returned travelers (14). However, the inclusion criteria for the 2 analyses differed; the earlier analysis was conducted only among patients who sought care after travel, and 34% were patients who reported an animal exposure but did not receive rabies PEP. Additionally, the structure of the GeoSentinel network has evolved over time (6), so cautious interpretation of the comparison is warranted.

Most persons who report to GeoSentinel sites and require rabies PEP are young adult (15–44 years of age) tourists traveling from high-income regions to visit low- and low-middle–income regions. This profile corresponds to the overall traveler population seen at GeoSentinel sites (15). This apparent lack of distinction is important because the demographic characteristics of travelers exposed to potentially rabid animals did not differ from those of other ill travelers who seek medical care, which makes it challenging to identify specific travelers who might benefit from reinforced rabies pretravel preventive counseling. Although previous studies have found children to be at highest risk for animal bites requiring PEP (1), our results suggest that young adults may also be vulnerable and may also benefit from preventive counseling. We observed a small but significant seasonal pattern (especially for bat and cat exposures), which might be used to guide the pretravel advice given to summer tourist travelers.

The short median duration of travel (2 weeks) among returned travelers consulting for rabies PEP corroborates the World Health Organization recommendation that a travelers’ assessment for risk of an animal bite should not be influenced by the duration of travel (1). Our results, however, are not consistent with the current CDC recommendations that preexposure rabies vaccine recommendations should be based, at least in part, on longer durations of stay (16), a position that is shared by many countries (3). Additionally, among those seeking care at GeoSentinel sites during travel, exposure occurred within a median of 3 weeks of arriving in the country of exposure, which suggests that rabies vaccination may also be indicated for patients embarking on shorter trips.

Of travelers consulting for rabies PEP at a GeoSentinel site, 70% had been exposed while in Asia, most in Southeast Asia. Rabies is endemic to most countries in Asia (17). Of 10 patients, 6 were exposed in 5 countries (Thailand, Indonesia, Nepal, China, and India). Large numbers of human rabies cases among the local population are reported from these 5 countries, with the exception of Thailand (Technical Appendix), where only sporadic cases of rabies in humans are now reported (1,17–25; J.M. Shresta, 2012, pers. comm.). Rabies cases in humans are reported from almost all regions in India (rates are highest rates in Chhattisgarh, Uttar Pradesh, and Odisha states) and from almost all regions in China (rates are highest in Guizhou, Guangdong, Hunan, Guangxi, and Guangdong Provinces). In Thailand, rabies cases in humans show no specific geographic distribution. In Indonesia and Nepal, cases are concentrated in specific areas (1,17–25; P. Rupali, 2012, pers. comm.). Travel-associated rabies cases have been reported from all these countries except Indonesia; most such cases were acquired in India and China (2). Updated data about the incidence of rabies in many countries is difficult to find, which indicates a need for improved human rabies surveillance (1).

For travelers to these 5 countries, rabies vaccine is more accessible than rabies immunoglobulin. Tissue-cultured vaccine is locally produced (China and India) or imported (all 5 countries) and may be available in most cities. Equine rabies immunoglobulin is available from most public hospitals in China and Thailand but may be difficult to find in smaller hospitals, notably in remote rural areas. In India, Indonesia, and Nepal, equine rabies immunoglobulin may be available from large cities only. Human rabies immunoglobulin is generally unavailable except in limited circumstances and at specialized centers (26–32; P. Rupali, 2012, pers. comm.). All recent studies addressing rabies PEP management in exposed travelers indicate that <1 in 10 travelers received rabies immunoglobulin in the country of exposure (33–36). In this study, among those who received rabies immunoglobulin after returning to their home country, there was a substantial delay between exposure and administration of rabies immunoglobulin. Some exposed travelers returned home to clinics in their own countries, having received the first dose of vaccine—without rabies immunoglobulin—in the country of exposure >7 days earlier; at this time, administration of rabies immunoglobulin may have reduced benefits. Equine rabies immunoglobulin carries a very low risk for anaphylaxis and is safe and effective (37); travelers should be encouraged to accept it when available and prescribed.

Although few patients in our analysis were exposed while in Vietnam or Philippines, these rabies-endemic countries are among the top 10 tourist destinations in Asia (17), so travelers to these countries should also be informed about potential rabies exposure and benefits of pretravel vaccination. Given the complex mix of high travel volumes, rabies endemicity, and inconsistent availability of rabies pharmaceuticals, Asia may be a region of considerable rabies risk for travelers.

Although dogs remain the leading animal responsible for exposure among travelers, NHPs account for one quarter of the exposures among patients seen at GeoSentinel sites; this proportion is even higher among tourists, female travelers, and travelers to Southeast Asia. Although rabies cases do occur in NHPs, they are less frequently reported in the literature than are cases in humans. The occurrence of documented transmission of rabies virus from NHPs to humans suggests that rabies PEP is indicated for patients exposed to NHPs in rabies-enzootic countries (38).

As found in previous studies (3,4), we found that a substantial proportion of exposed travelers did not receive pretravel advice. Our data also suggest that only a small proportion had received preexposure rabies vaccination. However, vaccination data were missing for many patients. Public health professionals should work toward increasing the proportion of travelers who receive pretravel medical care, including a selective proportion who receive preexposure rabies vaccination.

This analysis has limitations. The GeoSentinel Surveillance Network captures data only for persons who visit specialized travel or tropical medicine clinics after travel for a travel-related illness or concern; these data do not represent all international travelers. GeoSentinel Surveillance data cannot be used to calculate absolute risk. The composition of travelers included in this analysis probably overrepresents persons traveling to or residing in Asia, as well as those residing in Australia, and underrepresents those residing in North America or traveling to Latin America. Children may also have been underrepresented. In addition, generalizability could be affected by site-specific differences in referral patterns, clinic volumes, patient populations, and travel destinations.

Encouraging travelers to undergo a pretravel risk assessment and prevention counseling may help identify persons who will be at higher risk for a rabies exposure when traveling. The pretravel consultation should educate and warn higher risk travelers to rabies-endemic regions in Asia, Africa, and Latin America about their destination- and itinerary-specific rabies risk profile and the need to avoid contact with animals, notably dogs, NHPs, and cats. Pretravel vaccination against rabies is expensive in many countries (37), although the long-lasting resulting immunity may make this investment attractive for some patients in light of cumulative risk from iterative travels (39). Schedules of less expensive intradermal preventive vaccination are recommended by the World Health Organization, for travelers as well as others. Several preliminary studies have shown shorter, less expensive preexposure vaccine sched­ules to be effective in several preliminary studies (37,40). However, they are not yet widely available to travelers, and further large-scale studies are needed before any recommendation can be made. Travel-health specialists should work to identify those for whom pretravel vaccination is most strongly indicated on the basis of risk characteristics. Travelers to rabies-endemic regions, particularly those in Asia, should be well educated about their potential rabies exposure, the importance of avoiding contact with animals, and the potential benefit of pretravel rabies vaccination, regardless of travel duration and traveler demographics.