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Rabies is an irreversible, fatal disease most frequently characterized by acute encephalitis that causes approximately 55,000 deaths annually in Africa and Asia. Disease occurs when rabies virus, a Lyssavirus, is transmitted to a human via the saliva of an infected mammalian carnivore or bat, usually a dog, if it comes in contact with mucous membranes or enters the body via a bite, scratch, or lick on broken skin. Animal reservoirs for rabies exist in all continental areas worldwide. Deaths are presumed to be underreported in areas with poor access to medical facilities. Children are considered to be at a higher risk than adults.1,2 Although the risk of contracting rabies in developed countries is generally low, those who travel to areas with high epizootic endemicity are at increased risk of exposure and death. Steffen and co-workers evaluated the risk of rabies infection due to animal bites in travelers to developing countries and found an incidence rate per month between 0.1% and 1%.3 An epidemiological study of travelers presenting to GeoSentinel sites worldwide performed by the US Centers for Disease Control and Prevention (CDC) and the International Society of Travel Medicine (ISTM) found that 4.7% of this population required rabies post-exposure prophylaxis.4

After acquisition of the virus, the incubation period is variable, usually between 20 and 90 d, although occasionally disease develops after only a few days, and, in rare cases, more than a year following exposure. Usually patients develop a furious form of the disease, with episodes of generalized hyperexcitability separated by lucid periods. Encephalitis results from viral replication in the brain. In 20% of cases, a paralytic form of the disease results in progressive immobility. Both forms of rabies, furious and paralytic, are always fatal. One documented case of recovery from symptomatic disease has been reported; however, no cure has been reported in medical history.5 The incubation period often provides an opportunity for post-exposure prophylaxis to generate adequate immune defenses to avoid the onset of symptoms. These measures have a high rate of success.2

Although vaccination programs and animal control methods have led to a steep decline in canine rabies in many areas, viral reservoirs exist in wild animals, including bats, which cause a large proportion of cases in North America. Currently available rabies vaccines are propagated in cell cultures or embryonated eggs, and include the following types: human diploid cell vaccine, purified chick embryo cell-culture vaccine, purified duck embryo vaccine, and purified Vero cell rabies vaccine. These vaccines have well-established safety and efficacy profiles and can be administered either before or after an exposure occurs. Lyssavirus phylogroup I, which includes Rabies virus, Duvenhage virus, Australian bat lyssavirus, and European bat lyssavirus types 1 and 2, is covered by existing vaccines. The African genotypes, Mokola virus and Lagos bat virus, which comprise phylogroup II, and West Caucasian Bat Lyssavirus, which is supposed to be a third phylogroup, are assumed not to be covered.6–8

The WHO and the Advisory Committee on Immunization Practices (ACIP) recommend pre-exposure prophylaxis for travelers to rural areas with circulating rabies, especially if access to medical care may be limited.1,2,8 Pre-exposure prophylaxis recipients require a reduced course of vaccine, and no immunoglobulin, if exposed to rabies. Evidence suggests that many travelers and health-care providers ignore these recommendations.1,9–12

We report on the collection of all rabies deaths available in the clinical literature and other communications that occurred from 1990 to 2010 in persons traveling to areas with high rabies incidence.

Methods

  1. Top of page
  2. Methods
  3. Results
  4. Discussion
  5. Acknowledgments
  6. Declaration of Interests
  7. References

We systematically reviewed the clinical literature for all reports of imported deaths in travelers due to rabies and supplemented that information with personal communications regarding deaths in C.I.S. countries and a single report from PROMED, a body of international infectious disease experts which sends daily reports on infectious diseases in humans, plants, and animals. Imported deaths was defined as persons who contracted rabies while traveling and who subsequently died in the country where the report was made. Reports of travelers who contracted rabies and died in the country where the infection originated are not included in the current analysis. As the population was not predefined and all literature cases of people who died after contracting rabies abroad were reviewed and reported, our study included different types of travelers, including those visiting friends and relatives and guest workers, as well as ordinary travelers. For each reported imported human rabies death, information on the country where the disease was contracted, age of the patient, animal source and any information on medical intervention or treatment was collected.

Results

  1. Top of page
  2. Methods
  3. Results
  4. Discussion
  5. Acknowledgments
  6. Declaration of Interests
  7. References

Between 1990 and 2010, a total of 42 human deaths from rabies were reported in Europe, the United States, and Japan; all of these victims were assumed to have contracted the rabies infection abroad (Table 1).13–39 Of these imported human rabies cases, 36 (86%) were reported in the clinical literature, 5 (12%) via personal communication, and 1 case (2%) via PROMED. Twenty-seven deaths (64%) occurred after 2000. During the observation period, the greatest number of deaths were reported in European Union countries (n = 22), followed by the United States (n = 13), the former USSR (n = 5), and Japan (n = 2). One death, reported in Finland, was of a person from the country of rabies origin. No cases from Canada, Australia, and New Zealand were reported.

Table 1.  Forty-two human rabies deaths in Europe, Japan, and the United States caused by infection acquired during a visit to an endemic area, 1990 to 201013–39
YearOrigin of infectionAge of victimAnimal sourceMedical interventions (if known)First author, publication year
  1. PEP = post-exposure prophylaxis.

  2. *A.A. Movsesyants, personal communication, L.A. Tarassevich State Research Institute for Standardization and Control of Medical Biological Preparations, Moscow, Russian Federation, November 2010.

  3. The dog died soon after bite but was not tested for rabies.

  4. No medical intervention was sought in the country of infection after the bite was received.

  5. §No medical attention was sought before symptoms appeared.

  6. No information about medical interventions was specified.

  7. No PEP; no post-exposure prophylaxis.

  8. #Medical interventions not specified; however, three of six organ recipients from this patient subsequently died.

  9. **Reference states that medical personnel were not aware of rabies in the area and prophylaxis was not initiated.

  10. ††Reference specifies that the patient not seek wound cleansing or medical attention.

Austria
 2004Morocco23DogNone soughtStrauss 200513
Finland
 2007Philippines45DogNone sought§Rimhanen-Finne 201014
France
 1990Mexico28DogRotivel 200715
 1992Algeria3DogRotivel 200715
 1994Mali46DogRotivel 200715
 1996Algeria60DogRotivel 200715
 1996Algeria71DogRotivel 200715
 1996Madagascar3DogRotivel 200715
 1997India50DogRotivel 200715
 2003Gabon3DogNone sought[None listed] 200316
Germany
 1996Sri Lanka49DogNo PEPRoß 199717
 2004India51Dog/ monkeyNo PEPSummer 200418
 2004India26Dog#Johnson 200519
 2007Morocco55DogSought medical attention but vaccination not initiatedSchmiedel 200720
Netherlands
 1998Morocco49DogPost-exposure prophylaxis started in Morocco; however, vaccination was incomplete and no immunoglobulin was administeredGroen 199821
 2007Kenya34BatWound cleaned and medical treatment sought. No PEP was received.**van Thiel 200822
Russia
 2007Ukraine66FoxNone soughtMovsesyants 2010*
 2009Azerbaijan21DogNone soughtMovsesyants 2010*
 2009Kazakhstan58DogNone soughtMovsesyants 2010*
 2009Kyrgyzstan28DogNone soughtMovsesyants 2010*
Georgia
 2010Azerbaijan11DogReceived PEP, but interval after exposure is unknownPROMED 201021
Sweden
 2000Thailand19Dog (puppy)None soughtEkdahl 200024
United Kingdom
 1996Nigeria19DogNo PEPJohnson 200519
 2001Nigeria52DogInjections were received; provenance of the vaccine was unclearJohnson 200519
 2001Philippines55DogNone soughtJohnson 2005,19 Smith 200325
 2005India37DogNone sought,††Johnson 2005,19 Solomon 200526
 2008South Africa37Exposed to various animalsNo pre-exposure prophylaxis or PEPHunter 201027
Japan
 2006Philippines69DogNo PEPYamamoto 200828
 2006Philippines65DogNo PEPTobiume 200929
United States
 1992India11DogDSHS 200930
 1993Mexico69Dog or coyoteDSHS 200930
 1994Haiti51Dog or mongooseDSHS 200930
 1996Mexico26DogNone soughtCDC 199631
 1996Nepal32DogMedical treatment sought, but PEP not givenCDC 199732
 2000Ghana54DogCDC 200033
 2001Philippines72DogDSHS 2009,30 Krebs 200334
 2004El Salvador22No history of animal biteKrebs 200535
 2004Haiti41DogNone soughtCDC 200536
 2006Philippines11DogNo PEPCDC 2007,37 Blanton 201038
 2008Mexico16Dog or foxNo PEPBlanton 201038
 2009India42DogBlanton 201038
 2010MexicoUnknownNo PEPISID 201039

Among the 39 reports for whom the animal cause of rabies was known, 37 patients (95%) had had contact with a dog or puppy. One patient reported contact with a fox and one with a member of an unknown insectivorous bat species.

The most common continent of rabies origin was Asia (n = 19), followed by Africa (n = 14); in contrast, only eight cases were contracted in the Americas, and of those, seven were from the United States. At the country level, the most cases were contracted in India (n = 6) and the Philippines (n = 6), followed by Mexico (n = 5). The Philippines was the only source of disease common to the United States, Europe, and Japan.

Age was available for 41 of 42 cases. Twenty-eight deaths were in adults 19 to 64 y of age, nine were in children under 5 y of age, four were in children 11 to 18 y of age, and six were in persons 65 y of age or older.

Among cases for whom information about treatment and prophylaxis was available (n = 29), only a few received post-exposure prophylaxis. Twelve did not seek medical attention and six sought medical attention that was ineffective or denied because healthcare workers lacked supplies or knowledge about the disease.

Four of the cases we reviewed have not been previously published in the clinical literature. These cases were communicated by A.A. Movsesyants, Head of Rabies Department at the L. A. Tarassevich State Research Institute for Standardization and Control of Medical Biological Preparations in Moscow, Russian Federation. Three of these patients were bitten by stray or aggressive domestic dogs, and one was bitten by a fox. Exposures occurred in the Ukraine, Azerbaijan, Kazakhstan, or Kyrgyzstan. None of the male Russian patients, age 21 to 58 y, sought medical attention and all died (Table 1). An 11-y-old boy from Georgia, as described by PROMED, who received post-exposure prophylaxis after being bitten by a dog in Azerbaijan, died later in Georgia, probably because of an inappropriate interval between exposure and treatment.

Discussion

  1. Top of page
  2. Methods
  3. Results
  4. Discussion
  5. Acknowledgments
  6. Declaration of Interests
  7. References

Based on literature review and personal communications, we collected the most complete set of reports of imported rabies cases available to date. We reviewed 42 human deaths due to imported rabies, which we defined as rabies that was contracted outside the country where death occurred. We found that the risk for an individual traveler to contract rabies was small relative to the number of people traveling to such areas. For example, over 45 million international travelers went to Africa in 2009.40 We report 14 fatalities in travelers to Africa; however, there may be substantial underreporting. Interestingly, we only found published cases that had occurred in the United States, Europe, and Japan, countries where scientific publishing is very common. Of the 14 fatalities from Africa, 13 travelers came from Europe and 1 from the United States. To determine whether more human rabies cases occur in travelers within Asia or Africa would require further investigation by other means. Given that once symptoms of rabies are evident, the disease is expected to be fatal in virtually all cases, it is important to consider rabies prophylaxis and vaccination as a vital preparation to ensure the safety of those planning to visit areas with high rabies incidence.1,2,8–12

A striking finding in this review of cases was that in 38 of the 39 cases where the animal cause of rabies was known or strongly suspected, the patient had exposure to a member of the family Canidae.13–38 Given that contact with dogs is known to represent the highest risk for contracting rabies in humans, this finding is not surprising.1,2,8 Travelers to areas with a high prevalence of rabies in the animal population should be cautious when approaching dogs, including puppies. Healthcare providers should be trained prospectively when advising travelers, and those who seek advice at travel clinics or their general practitioner should be informed about the risk of contracting rabies and the very high mortality rate. Travelers who do not routinely seek medical advice could also be reached through travel agencies or the media.

We found it noteworthy that several persons who sought medical advice after an animal bite occurred received inappropriate care or ineffective care.13–39 This may highlight the need for greater educational measures for healthcare workers. However, while additional measures can be made in the countries reporting imported cases here, it is difficult to control education in poor and rural areas in developing countries. Therefore, it is very important for those planning to travel to areas with a high risk for rabies to educate themselves and receive pre-exposure prophylaxis. Obtaining pre-exposure vaccination can eliminate the need for immunoglobulin following an exposure and also reduces the number of vaccine doses required after exposure.2,8 Vaccination also reduces the risk of contracting rabies due to inappropriate management abroad.4 The vaccines recommended for travelers in North America, Europe, and Japan have been shown to be safe and effective in clinical use and clinical trials. Health-care provision to travelers, including both medical advice and any potential indicated pre-travel vaccination, should be based on a careful personal risk assessment and occur at an appropriate interval before departure. Advice should include an assessment of risk factors, destinations, type of travel, and the type and quality of health care available in the areas to be visited, and avoid focusing on the duration of stay. Previous guidelines only recommend vaccination to long-term travelers expecting to spend extensive time outdoors or expatriates, which may be questionable, as the cases here clearly demonstrate that travelers on short stays can die from rabies if prophylactic measures are omitted or are administered too late following exposure. Immediate access to appropriate medical care should be highlighted, and pre-exposure vaccination should be recommended if there is a likelihood that state-of-the-art post-exposure prophylaxis will not be guaranteed because of plans such as backpacking in remote areas, or due to an uncertain supply of biologicals.

This study has several limitations. We only report deaths that were available in clinical literature, including reports posted by the United States Centers for Disease Control and Prevention, or that had been reported to PROMED or the State Research Institute for Standardization and Control of Biological Preparations in Moscow. Therefore, our results are limited by the surveillance and reporting methods in various countries. It is possible that improved levels of reporting, for example, and not an actual increase in cases drove the larger proportion of cases reported during 2000 to 2010 relative to 1990 to 1999. Another limitation of this study is the absence of information about travelers who contracted rabies and then died in the country where infection was acquired.

We noted a large proportion of fatalities occurring in adults, with nearly as many cases in the elderly as in children.13–39 This indicates that travelers of all ages to rabies-endemic areas should be informed of the animal reservoirs for rabies, especially stray dogs, the risk of acquiring rabies and the consequences of the disease. Whether the epidemiology in travelers differs from that among persons living in countries with endemic rabies, or whether travelers exhibit different behavior and attitudes than people living in endemic areas should be further investigated. Pre-exposure prophylaxis should be administered to all travelers to areas with a high risk for rabies and where vaccine, immunoglobulin or even access to medical care in general is not available or may be delayed. All travelers must be made aware of the necessary medical treatment after contact with a potentially rabid animal. An awareness of the need for prompt treatment and appropriate levels of vaccination could help to save lives.

Acknowledgments

  1. Top of page
  2. Methods
  3. Results
  4. Discussion
  5. Acknowledgments
  6. Declaration of Interests
  7. References

The authors would like to thank Sandra Whitelaw PhD of Alpharmaxim Healthcare Communications for help with the literature search and the original tabulation of rabies cases. All interpretations and opinions expressed are those of the authors, who take editorial responsibility for the content of this manuscript.

Declaration of Interests

  1. Top of page
  2. Methods
  3. Results
  4. Discussion
  5. Acknowledgments
  6. Declaration of Interests
  7. References

The authors are full-time employees of Novartis Vaccines, a manufacturer of rabies vaccine.

References

  1. Top of page
  2. Methods
  3. Results
  4. Discussion
  5. Acknowledgments
  6. Declaration of Interests
  7. References