PEP = post-exposure prophylaxis.
Imported Human Rabies Cases in Europe, the United States, and Japan, 1990 to 2010
Version of Record online: 4 OCT 2011
© 2011 International Society of Travel Medicine
Journal of Travel Medicine
Volume 18, Issue 6, pages 402–407, November/December 2011
How to Cite
Malerczyk, C., DeTora, L. and Gniel, D. (2011), Imported Human Rabies Cases in Europe, the United States, and Japan, 1990 to 2010. Journal of Travel Medicine, 18: 402–407. doi: 10.1111/j.1708-8305.2011.00557.x
- Issue online: 24 OCT 2011
- Version of Record online: 4 OCT 2011
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.
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.
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.
|Year||Origin of infection||Age of victim||Animal source||Medical interventions (if known)||First author, publication year|
|2004||Morocco||23||Dog†||None sought‡||Strauss 200513|
|2007||Philippines||45||Dog||None sought§||Rimhanen-Finne 201014|
|2003||Gabon||3||Dog||None sought‡||[None listed] 200316|
|1996||Sri Lanka||49||Dog||No PEP¶||Roß 199717|
|2004||India||51||Dog/ monkey||No PEP¶||Summer 200418|
|2007||Morocco||55||Dog||Sought medical attention but vaccination not initiated||Schmiedel 200720|
|1998||Morocco||49||Dog||Post-exposure prophylaxis started in Morocco; however, vaccination was incomplete and no immunoglobulin was administered||Groen 199821|
|2007||Kenya||34||Bat||Wound cleaned and medical treatment sought. No PEP was received.**||van Thiel 200822|
|2007||Ukraine||66||Fox||None sought‡||Movsesyants 2010*|
|2009||Azerbaijan||21||Dog||None sought‡||Movsesyants 2010*|
|2009||Kazakhstan||58||Dog||None sought‡||Movsesyants 2010*|
|2009||Kyrgyzstan||28||Dog||None sought‡||Movsesyants 2010*|
|2010||Azerbaijan||11||Dog||Received PEP, but interval after exposure is unknown||PROMED 201021|
|2000||Thailand||19||Dog (puppy)||None sought‡||Ekdahl 200024|
|1996||Nigeria||19||Dog||No PEP||Johnson 200519|
|2001||Nigeria||52||Dog||Injections were received; provenance of the vaccine was unclear||Johnson 200519|
|2001||Philippines||55||Dog||None sought‡||Johnson 2005,19 Smith 200325|
|2005||India||37||Dog||None sought‡,††||Johnson 2005,19 Solomon 200526|
|2008||South Africa||37||Exposed to various animals||No pre-exposure prophylaxis or PEP||Hunter 201027|
|2006||Philippines||69||Dog||No PEP¶||Yamamoto 200828|
|2006||Philippines||65||Dog||No PEP¶||Tobiume 200929|
|1993||Mexico||69||Dog or coyote||‖||DSHS 200930|
|1994||Haiti||51||Dog or mongoose||‖||DSHS 200930|
|1996||Mexico||26||Dog||None sought‡||CDC 199631|
|1996||Nepal||32||Dog||Medical treatment sought, but PEP not given||CDC 199732|
|2001||Philippines||72||Dog||‖||DSHS 2009,30 Krebs 200334|
|2004||El Salvador||22||No history of animal bite||‖||Krebs 200535|
|2004||Haiti||41||Dog||None sought‡||CDC 200536|
|2006||Philippines||11||Dog||No PEP¶||CDC 2007,37 Blanton 201038|
|2008||Mexico||16||Dog or fox||No PEP¶||Blanton 201038|
|2010||Mexico||—||Unknown||No PEP¶||ISID 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.
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.
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
The authors are full-time employees of Novartis Vaccines, a manufacturer of rabies vaccine.
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