Rabies Postexposure Prophylaxis in Returned Injured Travelers From France, Australia, and New Zealand: A Retrospective Study

Authors


Philippe Gautret, MD, PhD, Service des Maladies Infectieuses et Tropicales, AP-HM, Hôpital Nord, F-13015 Marseille, Cedex 05, France. E-mail: philippe.gautret@club-internet.fr

Abstract

Background There is little published information available describing rabies pre- and postexposure prophylaxis (PEP) in tourists returning to their home country and seeking care for animal-associated injuries, especially those associated with a rabies risk.

Method We analyzed 261 travelers seeking care on returning to their home country following an animal-related injury acquired abroad. Information on individual cases of rabies (PEP) including preexposure status, type of contact with a potentially rabid animal, type of animal, and the nature of rabies PEP was collected by retrospectively analyzing records from May 1997 to May 2005.

Results The majority of injuries were acquired in South-east Asia and North Africa. Only 6.8% of injured patients were previously vaccinated against rabies, while 75.4% of the cohort experienced a severe injurious contact with animals (World Health Organization category III). Of travelers who sustained a high-risk injury, only 24% received both vaccination and rabies immune globulin,(RIG) while 76% received vaccination only. Of the travelers who did not receive RIG, 43% had received a first dose of vaccine more than 7 days after return and before presenting to a clinic in their home country.

Conclusions This study highlights important deficiencies in rabies PEP for travelers who acquire high-risk, animal-associated injuries in rabies-endemic countries, with the majority not receiving adequate PEP or experiencing a substantial delay before receiving rabies vaccination.

A number of studies have been published on rabies pre- and postexposure prophylaxis (PEP) among long-term residents in the tropics,1–4 but to date, there have been almost no published data on rabies preimmunization coverage in short-term travelers, the characteristics of rabies PEP, or the type of animal-related injuries acquired abroad in tourists seeking care for rabies PEP on returning to their home country. One study reporting the experience of 56 tourists following potential rabies exposure and seen during their stay in Nepal found that only 21% of injured travelers received rabies preimmunization, while 80% experienced a superficial wound and 2% had sustained a high-risk injury located to the head or the face.4 The administration of PEP is often determined by the perceived risk of having sustained an injury associated with significant potential for rabies together with travel destination. To assess the risk of rabies for travelers, it is essential to examine available information on human disease occurrence, dog bite incidence, and prevalence of the disease in the main animal reservoirs.5 This information can be obtained from the World Health Organization (WHO) Rabnet database (http://www.who.int/globalatlas/default.asp) but requires a coordinated review of the available data.

The aim of this study was to examine the characteristics of rabies PEP administration in travelers returning from destinations in Africa, South-East Asia, and the Pacific region and presenting to travel clinics in three geographically distinct global locations.

Patients and methods

The overall epidemiology of animal-related injuries in travelers using network-wide surveillance data from 30 global sites has been recently published by the GeoSentinel Surveillance Network.6

The GeoSentinel Surveillance Network (http://www.istm.org/geosentinel/main.html) consists of specialized travel/tropical medicine clinics, primarily located within academic centers, on six continents recording information on ill travellers.7 Patients with imported illness are generally seen at these practices, although these sites are also the point of entry for many returned travelers who had pretravel medical consultations at the same clinic. Additional data were collected following a review of case records at three travel medicine clinics in Marseille (France), Auckland (New Zealand), and Melbourne (Australia). Each of these sites has a large volume of patients seeking rabies PEP care after sustaining an animal-related injury abroad. Anonymity of individual patient data was maintained by not linking GeoSentinel record numbers to the data obtained in the present study.

Patients were selected on the basis of having acquired an animal-related injury abroad and seeking care at one of the three clinics for rabies PEP on returning to their home country.

Information on individual cases of rabies PEP including preexposure status, type of contact with a potentially rabid animal, and the nature of rabies PEP was collected by retrospectively analyzing records from May 1997 to May 2005.

Three categories of animal contacts were defined according to the WHO guide for PEP:8

  • 1Category I (mild injury)—touching or feeding of animals, licks on intact skin.
  • 2Category II (moderate injury)—nibbling of uncovered skin, minor scratches or abrasions without bleeding.
  • 3Category III (severe injury)—single or multiple transdermal bites or scratches, licks on broken skin or mucous membranes, contact with bats.

Place of exposure was documented, and individual countries visited were grouped into 15 regions: North America, Central America, South America, Caribbean, Eastern Europe, Western Europe, Oceania, Australia–New Zealand, South Central Asia, South-East Asia, Eastern and North Asia, Western Asia (including the Middle East), North Africa, sub-Saharan Africa, and Antarctica.

Countries posing a potential rabies risk for travelers were determined from recent published studies and from the WHO and Centers for Disease Control sources as described elsewhere.6

All three centers use cell culture–derived rabies vaccine for pre- and postexposure vaccination (purified vero cell vaccine in France and New Zealand and human diploid cell vaccine in Melbourne). The WHO Essen intramuscular vaccination regimen (one dose on days 0, 3, 7, 14, and 28) is used in the three centers, and in addition, the WHO 2:1:1 intramuscular regimen (two doses on day 0 and one on days 7 and 21) is also used as an alternative to the WHO Essen regimen in Marseille. This was used predominantly in patients living far from the clinic to eliminate two clinic attendances. As a standard of practice in all three centers, human rabies immune globulin (RIG) is administered predominantly into and around the wounds.

Data were entered anonymously at individual sites and managed in Microsoft Access. Data analysis was carried out using EpiInfo 6.0 software (Centers for Diseases Control and Prevention, Atlanta, GA, USA). Differences in proportions were analyzed with the chi-square test. A p value of ≤0.05 was considered as significant. All p values were determined by two-tailed t-test.

Results

In total, data were available for 261 patients presenting to the three travel medicine clinics (Marseille, 62.1%; Auckland, 19.5%; and Melbourne, 18.4%). The region of travel and destination linked to an animal-associated injury was identified for each individual. The majority of cases were reported from Africa and South-East Asia (Figure 1).

Figure 1.

Region of exposure in 261 injured travelers.

The vast majority of patients who traveled to Africa were seen in Marseille (95.9%), while most of patients who traveled to South-East Asia were seen in Melbourne and Auckland (71.8%). Of the 261 cases, 238 occurred in rabies-endemic countries (91.2%). As shown in Table 1, the countries from which travelers had most frequently reported injuries included Morocco–Tunisia–Algeria (74 cases, 31.1%), Thailand (52 cases, 21.8%), India (14 cases, 5.9%), Vietnam (11 cases, 4.6%), and Indonesia (11 cases, 4.6%).

Table 1.  Place of exposure in 238 travelers injured by animals in rabies-endemic countries
CountryNumber of cases
Algeria19
Bolivia2
Brazil3
Burkina Faso1
Cambodia3
Cameroon1
Canada5
China8
Dominican Republic1
East Timor1
Ecuador1
El Salvador1
Ethiopia1
Guatemala1
India14
Indonesia11
Kenya4
Laos1
Madagascar4
Malaysia3
Mexico2
Mongolia1
Morocco30
Nepal2
Niger1
Peru7
Philippines3
Senegal6
South Africa1
Sri Lanka2
Swaziland1
Thailand52
Togo1
Tunisia25
Turkey5
United States2
Vietnam11
Zimbabwe1
Total238

Information regarding rabies preexposure prophylaxis was known for 259 patients (99.2%), and of these only 6.8% were vaccinated before traveling to rabies-endemic countries (Table 2).

Table 2.  Preexposure prophylaxis and type of contact with a potentially rabid animal and animal species in 261 injured travelers
Variablen (%)
  • RIG = rabies immune globulin.

  • *

    Category I: touching or feeding of animals, licks on intact skin; category II: nibbling of uncovered skin, minor scratches or abrasions without bleeding; category III: single or multiple transdermal bites or scratches, licks on broken skin or mucous membranes, contact with bats.

Rabies preexposure prophylaxis
 Unknown2 (0.8)
 None243 (93.1)
 Correct16 (6.1)
Type of contact with suspected or  confirmed rabid animal*
  Unknown14 (5.4)
  Category I14 (5.4)
  Category II36 (13.8)
  Category III197 (75.4)
Animal species
 Unknown3 (1.1)
 Bat8 (3.1)
 Cat52 (19.9)
 Cow3 (1.1)
 Dog139 (53.3)
 Lemur2 (0.8)
 Monkey43 (16.5)
 Rodent10 (3.8)
 Tiger1 (0.4)
Rabies postexposure prophylaxis
 None6 (2.3)
 Vaccination only199 (76.2)
 Vaccination + RIG56 (21.5)

As shown in Table 2, most of the injured travelers (75.4%) experienced severe category III contact with animals. The types of contact with animals in travelers according to the destinations most commonly reported to be associated with an injury are summarized in Table 3. No significant differences were observed in the proportion of travelers who experienced severe category III injuries in Africa and in Southeast Asia (79.4% vs 71.8%). Of the 197 travelers who experienced category III injuries, 20 (10.2%) had severe facial and hand injuries. The animal species associated with injuries were known in 258 cases (98.9%). The most common species were dogs (53.3%) and cats (19.9%), while monkeys caused 16.5% of the injuries (Table 2). Dogs were responsible for 50% of severe facial and hand bite, monkeys for 30%, and cats for 10%.

Table 3.  Types of contact with animals in travelers according to the destinations most commonly reported to be associated with an injury
Type of contact with suspected or confirmed rabid animal*Country of exposure, n (%)
Morocco–Tunisia–AlgeriaThailandIndiaVietnamIndonesia
  • *

    Category I: touching or feeding of animals, licks on intact skin; category II: nibbling of uncovered skin, minor scratches or abrasions without bleeding; category III: single or multiple transdermal bites or scratches, licks on broken skin or mucous membranes, contact with bats.

Unknown1 (1.4)5 (9.6)1 (9.1)1 (9.1)
Category I5 (6.8)3 (5.8)2 (18.2)
Category II11 (14.8)6 (11.5)3 (21.4)2 (18.2)1 (9.1)
Category III57 (77.0)38 (73.1)11 (78.6)6 (54.5)9 (81.8)

Among the travelers, 255 received rabies PEP (97.7%) (Table 2), and of these 199 individuals received vaccination only (76.2%) and 56 received both vaccination and RIG (21.5%). In travelers who received rabies PEP, 91.4% had traveled to rabies-endemic countries, while 8.6% had traveled to nonendemic countries. Of the 255 travelers who received rabies PEP, 133 received their first injection of vaccine in the country of exposure (52.2%), 120 on returning to their home country (47.1%), while in 2 cases (0.7%), this information was not available. The mean time between injury and first injection of vaccine was 1.3 days (range, 0–22 d) in travelers who began their treatment in the country of injury and 18.7 days (range, 1–420 d) in travelers who began their treatment on returning to their home country.

When considering the 170 travelers who experienced severe category III injuries in rabies-endemic countries and who were not vaccinated against rabies before travel (Figure 2), 19 received both vaccine and RIG in the country of exposure, while 81 received vaccine only and 2 were not treated. Twenty-two travelers began or completed their courses of vaccine and were injected with RIG on returning to their home country. Of the 129 travelers who did not receive RIG, 56 had received a first vaccine injection in the country of injury, more than 7 days before presenting to a clinic in their home country. Of the 20 travelers with severe facial and hand injuries, only 4 received both vaccine and RIG, and of the remaining 16, 7 had received vaccine only more than 7 days before presenting to a clinic in their home country. Finally, not a single case of rabies was observed in the 261 injured travelers included in this study.

Figure 2.

Rabies immunoglobulin management in 170 travelers presenting severe injuries acquired in countries endemic for rabies.

Discussion

Animal-associated injuries in travelers occurring in rabies-endemic countries are not an infrequent event6,9 and pose a serious health threat to individuals visiting such areas.5 In the present study, we have shown that the majority of animal-associated injuries in travelers were acquired in regions at risk for rabies in Asia and Africa, with the greatest proportion in South-East Asia. The countries from which animal attacks were the most frequently reported included Thailand, India, Vietnam, and Indonesia. Australians, New Zealanders, and West Europeans frequently travel to Thailand, and given that the majority of travelers were reported from Australia–New Zealand and France, it is not surprising that the majority of injuries occurred in Thailand. We also noted that a substantial number of the cases reported from Marseille sustained injuries in North African countries where rabies is endemic. North Africa is a common destination for Marseille travelers visiting friends and relatives or traveling for the reason of tourism. As a consequence, in our study, the geographical distribution of places of exposure for animal-related injuries reflects the habits of travelers in terms of destination and may not account for a higher risk of exposure to animal-related injuries in the destination countries. However, in our epidemiological survey of animal-related injuries reported to the GeoSentinel Surveillance Network, patients with animal-related injuries were significantly more likely to have traveled to South-East Asia and South Central Asia than those with other travel-associated diagnoses.6

In the present study, more than three quarters of the animal-related injuries were associated with a high-risk exposure, in contrast to previous findings.4 Of significant concern were the findings that (1) the vast majority of the cases involved individuals who had not received preexposure immunization and (2) RIG was administered in only 24% of high-risk injury cases and approximately half of cases experienced a delay in receiving their first dose of rabies vaccine.

Only a small proportion of travelers received RIG in the country of exposure, and a significant number of travelers who received vaccination only in the country of exposure came to our clinics more than 7 days after an animal-associated injury at a time when administration of RIG may be of reduced benefit or could even have a negative influence on the development of an active immune response.10,11 This probably reflects the fact that in most of the countries where related animal injury occurred in our study, human RIG is not readily available due to the associated high cost. Highly purified and safe equine RIG is now available in most developing countries to provide at least a partial solution to the problem of the cost and supply of human RIG.5 The fact that most travel clinics in developed countries insist on only using human RIG may discourage injured travelers at risk of rabies from allowing it to be used even when offered.

On the other hand, a large number of travelers presented to our clinics without any previous rabies PEP or less than 7 days after receiving vaccination alone and were still not given RIG. This highlights an inadequacy in current practices in RIG administration for injured travelers despite its availability. This is consistent with a previous study among experienced German travel health advisors who demonstrated deficiencies regarding the correct assessment of specific situations in which rabies PEP is appropriate.12

A combination of vaccine and RIG must be used in individuals not previously vaccinated against rabies, who have experienced severe category III contacts with potentially rabid animals, regardless of the location of injury.8,13,14 Treatment failure after incomplete PEP without administration of RIG has been reported.10,15,16 However, initiation of rabies PEP without RIG in the destination country may create a potential problem of reduced efficacy of PEP, with the subsequent administration of RIG on returning home.10,11 Strict adherence to the WHO recommended guidelines for optimal rabies PEP virtually guarantees protection from this disease.

Our results, together with the reports of cases of fatal imported rabies in travelers from Europe (26 cases in UK since 1946, 20 in France since 1970, 2 in Germany in 2004 and 2005, 1 in Austria in 2004, and 1 in Sweden in 2000),17–28 highlight an inadequacy in the use of pretravel immunization against rabies and reinforces the point that travelers should be adequately counseled about animal-associated injuries and rabies risk when visiting rabies-infected countries. Appropriate council regarding the availability of either human or equine RIG and its safety in the country of destination should be also provided. These recommendations can be based on published reports such as the current study, assessing the risk of rabies in travelers and support a preventive vaccination strategy against a disease that is effectively 100% fatal.

Acknowledgments

We thank David O. Freedman of GeoSentinel for guidance and comments on the manuscript.

Declaration of interests

The authors state that they have no conflicts of interest.

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