Risk for rabies importation from North Africa

A retrospective study conducted in France indicated that a large proportion of patients injured by potentially rabid animals while in North Africa did not seek pretravel advice, and some had not received proper rabies postexposure prophylaxis while in North Africa. As a result, imported human rabies cases are still being reported, and the need for postexposure prophylaxis after exposure in North Africa is not declining. Tourists are generally unaware of the danger of importing potentially rabid animals and of the rules governing the movement of pets. In France, for example, rabid dogs have frequently been imported from Morocco to France through Spain. This situation imposes heavy social and economic costs and impedes rabies control in Europe. Rabies surveillance and control should therefore be reinforced in North Africa, and travelers to North Africa should receive appropriate information about rabies risk and prevention.

and economic costs. The possibility of its reintroduction threatens western European countries, where terrestrial carnivores are presently rabies free (5,6).

Rabies in North Africa
Although rabies is endemic to North Africa (7), accurate data on incidence are scarce (8), and better surveillance is needed. Initiatives have recently been developed to share information and experiences, provide reliable rabies epidemiologic data, raise rabies awareness, improve access to prevention, and design programs for rabies control. These initiatives include the Africa Rabies Expert Bureau (www.afroreb.info), the global multidisciplinary European Union-funded RABMED CONTROL project (www. rabmedcontrol.org), and the Global Alliance for Rabies Control (www.rabiescontrol.net). Some of these initiatives are expected to provide detailed epidemiologic data about the rabies situation in North African countries. Although rabies incidence in North Africa is certainly underestimated (2,8,9), according to the most recent reports in the World Health Organization (WHO) RabNet database (www.who. int/globalatlas/default.asp), RABMED CONTROL data, and other sources (5,(9)(10)(11)(12), many human rabies cases are regularly reported in North Africa. The annual incidence varies from 0.02 cases/100,000 population in Tunisia to 0.1 cases/100,000 population in Egypt (Table 1). These disparities may result from differences in the epidemiologic status of animal rabies. More likely, however, they refl ect the combined effects of variations in the reliability of epidemiologic data, the implementation of primary wound care, and the accessibility of rabies postexposure prophylaxis (PEP). Indeed, rabies PEP accessibility is subject to large disparities; the lowest rates (0.4 persons receiving rabies PEP/1,000 population) are reported in Sudan, and the highest (3.3 persons receiving rabies PEP/1,000 population) are reported in Tunisia (Table 1).
In Morocco, 90% of human cases of rabies are caused by dog bites. Cases occur mainly in rural areas in Kenitra, Casablanca, and El Jadida (10). In Algeria, human deaths from rabies occur mostly in the coastal and northern part of the country (11). In Tunisia, human cases are localized in the northern (Bizerte and Béja), central and eastern rural (Siliana, Kairouan, Kasserine, Sidi Bouzid, and Gafsa), and southern coastal (Gabes and Medenine) parts of the country.
Most reported cases of rabies in animals are in dogs, which account for >40% of animals confi rmed rabid by laboratory investigations. Rabies cases are also reported for cats, cattle, goats, sheep, and horses. However, data collected for animal rabies (Table 1) are only partial and do not represent the true status of this infection in the fi eld (8). In Tunisia, mass vaccination campaigns directed at the canine population, together with the elimination of free-roaming dogs, has proven somewhat effective (13). However, rabies in dogs is still prevalent in Algeria, Morocco, and Tunisia (Table 1) because of ineffective implementation of rabies control and vaccination programs for these reservoir animals (5,8,14,15).
The information available from Egypt is clearly incomplete (16). Elimination of free-roaming cats and dogs has been conducted in Egypt with little effect (5). In Sudan, animal rabies is reported mainly in dogs but also in goats and donkeys (17,18). From Libya, no information about rabies in humans or animals has been available for many years; the country has declared itself free of canine rabies, although rabies is present in all neighboring countries (19). This description of the current rabies situation in North Africa is based on reported cases only and does not necessarily represent the real epidemiologic situation in the area, given the underreporting that results from nonexhaustive surveillance.

Risk for Importing Human Rabies from North Africa to Europe
North Africa is a popular tourist destination; in 2005, it accounted for 12% of all international travel from France. The most popular destinations were Morocco, Tunisia, and Egypt; these countries together accounted for 89% of travel to North Africa, with 950,000, 920,000, and 590,000 visits, respectively. Algeria accounted for 5% of travel to North Africa, with 140,000 visits. No data are available for Sudan or Libya (20). Persons who emigrated from North Africa to France also travel frequently to their countries of origin to visit friends and relatives. This travel pattern also creates a pathway for rabies reintroduction to France. During the fi rst half of the 20th century, canine rabies progressively disappeared from most countries in western and southern Europe (21). At the end of the 1940s, the epizootic of vulpine rabies spread from Poland into the rest of Europe (22). Today, oral vaccination of foxes has pushed vulpine rabies back into eastern Europe (23). Maintaining rabiesfree status among terrestrial carnivores, however, incurs considerable costs. Meanwhile, the legal and illegal importation of live animals imposes a continual risk for reimportation, as does the lack of awareness by travelers visiting rabies-endemic areas (6,24). In France, primary health care for patients seeking rabies PEP is delivered through an offi cial network of antirabies medical centers (ARMCs), which facilitate the accurate epidemiologic evaluation of animal-related injuries for which patients require rabies PEP. Since 1970, a total of 21 human deaths from rabies have been recorded in France; these cases resulted in a large number of rabies PEP treatments for contacts ( Table 2). Among these fatal cases, 19 were imported (50% originated in North Africa, mainly in Algeria and Morocco), 1 was acquired in French Guiana, and 1 was acquired through a cornea transplant from a donor infected in Egypt. During the past decade, 2 cases were acquired in Morocco by travelers from Austria and Germany (26,27). Other cases, imported to the United Kingdom, Germany, Sweden, and Finland, were acquired from India, Thailand, the Philippines, Nigeria, and South Africa (28)(29)(30)(31). These data refl ect the relevance of specifi c patterns of international travel between European and rabies-enzootic countries.
Of the 133,852 patients who consulted an ARMC in France during 1996-2009, a total of 6.7% of exposures to animals suspected of having rabies occurred while the patient was traveling outside France (French National Rabies Reference Centre, unpub. data). Persons who acquired animal-related injuries abroad accounted for 11.2% of patients who received rabies PEP during the same period, a fi gure that rose from 6.8% in 1996 to 17.8% in 2009 (Figure). Among treated patients who were injured abroad, 29.9% had returned from North Africa. This fi gure underscores the role of North Africa in rabies PEP epidemiology in France (Table 3). Need for rabies PEP seems to be particularly high after travel to Algeria. In 2005, only 5% of international tourists from France visited Algeria, but persons injured in Algeria accounted for 21.4% of patients seeking care in France after possible rabies exposure while abroad. Furthermore, 25% of all human rabies cases observed in mainland France since 1970 resulted from exposure in Algeria. In France, 94.7% of patients injured in North Africa received rabies PEP (Tables 3, 4), compared with 53% of those injured elsewhere, and 16.1% of rabies PEP given included rabies immunoglobulin, compared with only 5.8% given to persons injured elsewhere. This higher rate of rabies PEP among travelers injured in North Africa refl ects what is understood about rabies epidemiology in the region and the perception of the risk by physicians, which is largely infl uenced by the number of rabies infections that developed in France in persons exposed while in North Africa. Children are especially at risk. Since 1970, children <15 years of age have accounted for 50% of human rabies cases in mainland France; among these, 8 of 10 cases have occurred in children <6 years of age. Moreover, the proportion of children <15 of age years receiving rabies PEP in France is higher when their rabies exposure occurred in North Africa (Table 4). Regional variations also exist within France. In a recent study conducted among ≈424 international travelers seeking care for animal-associated injuries at the ARMC in Marseille, southern France, most (41.5%) had traveled to North Africa, and most injuries were from dogs and cats. A correlation was found between the country of exposure and the implicated species; in Algeria, the most implicated animals were dogs and in Tunisia, cats (32). During 2004-2010, among 90 patients exposed in North Africa and seeking care in Marseille, 53 (59%) had traveled for tourism and 35 (39%) had visited friends and relatives; however, 26 (69%) travelers injured in Algeria had visited friends and relatives ( Table 5). The French-speaking North African community is particularly large in Marseille, where it accounts for one third of the total immigrant population. Generally, only a few travelers to North Africa seek pretravel advice before departing, which is not surprising because specifi c vaccination and malaria prophylaxis are not required before travel to North Africa. In 2009 in the Paris ARMC, only 1 (1.2%) of 82 travelers from France who had been injured by animals while in North Africa had been vaccinated before traveling (Paris ARMC, unpub. data). Knowledge about rabies risk and preventive measures among persons traveling from France to rabiesendemic countries is limited (33).

Importation of Rabid Animals
Rabid animals have been repeatedly imported by travelers into France; most animals originated in Morocco and were transported through Spain by car (34)(35)(36)(37). During 2000-2009, a total of 8 imported rabies cases were reported. All infected animals were dogs imported from rabiesenzootic countries: 7 from Morocco and 1 from Gambia. Additionally, a dog that died in February 2008 had never traveled out of France. Epidemiologic investigations and molecular typing of the virus confi rmed that this case was indirectly linked to an imported dog from Morocco that had died in late 2007; the imported dog had not been examined for rabies. No secondary transmissions to humans resulted from these animal cases. However, the identifi cation of contacts at risk to ensure that they received appropriate care is costly and time-consuming (6). The sanitary regulation regarding rabies vaccination of all carnivores entering the European Union is essential for rabies control and must be strictly applied in areas of Europe that have been declared rabies free (38). This precaution applies to France in particular because the illegal pet importation route from Morocco through Spain to France is well known.

Availability of Rabies Vaccine and Immune Globulin in North Africa
Modern imported cell culture vaccines are available in Morocco, Egypt, Sudan, and Tunisia. No data are available from Libya. Algeria has been using mouse brain rabies  Similarly, in the Marseille ARMC during 1987-2005, among the 34 patients requiring rabies immunoglobulin whose PEP was started in North Africa, only 2 (5.9%) travelers received rabies immunoglobulin in the country of exposure and 23 (67.7%) travelers who received only vaccination in the country of exposure came to home clinics >7 days after receiving the fi rst vaccine injection.
After 7 days, administration of rabies immunoglobulin is useless and might even have a negative infl uence on active immune response (40).

Conclusions
We recommend that rabies control measures and, in particular, rabies control and vaccination programs in dogs be further implemented in North African countries. Meanwhile, the persistent risk for rabies in these countries exists for travelers, as shown for France. A large proportion of travelers exposed to potentially rabid animals in North Africa did not seek pretravel advice from travel clinics, thus missing the opportunity to learn about rabies risks and preventive measures. Furthermore, many of these patients did not receive rabies PEP and rabies immunoglobulin in accordance with WHO recommendations in the country of exposure. This problem reinforces the need to inform and train health professionals in these countries with regard to recommended practice for rabies prevention for humans.
Finally, rabies control in Europe is impeded by lack of tourist awareness of the threat of importing rabies from countries where it is enzootic and of the rules governing movement of pets. The sanitary regulations regarding rabies vaccination of all carnivores entering the European Union (38) are essential for rabies control and must be strictly applied in European areas that have been declared free of rabies in terrestrial carnivores. These regulations defi ne the requirements that dogs and cats must meet before entry into the European Union, with the aim of preventing entry of an infected but asymptomatic dog or cat from outside Europe.
We suggest that all travelers to North Africa be fully informed about rabies risk, adequate preventive measures, and risk of importing animals. For persons traveling to North Africa to visit relatives and who are at high risk for exposure to potentially rabid animals, rabies preexposure vaccination should be discussed; this precaution is especially wise for those undergoing repeated or long visits to places with no modern culture cell rabies vaccine and for groups at risk, such as children <15 years of age. As long as these measures and information are not properly implemented, costly capacities for surveillance of rabies in animals and humans, as well as for monitoring rabies exposures in humans, should be maintained.