# Technical Appendix

for

## Travel-Associated Rabies in Pets and Residual Rabies Risk, Western Europe

Florence Ribadeau-Dumas, Florence Cliquet, Philippe Gautret, Emmanuelle Robardet, Claude Le Pen, Hervé Bourhy

EID, Volume 22, Number 7—July 2016

### Author affiliations:

Université Paris Dauphine, PSL Research University Paris, France (F. Ribadeau Dumas, C. Le Pen), Institut Pasteur, Paris, France (F. Ribadeau Dumas, H. Bourhy)' French Agency for Food, Environmental and Occupational Health & Safety, Malzéville, France (F.Cliquet, E. Robardet), Assistance Publique Hôpitaux de Marseille, Marseille, France (P.Gautret), Aix Marseille University, Marseille, France (P. Gautret)

## Table of contents

<table><tr><td>1a: Rabies risk and its determinants in recent WE history</td><td>2</td></tr><tr><td>1b. Rabies situation in Western European countries until December 2013</td><td>4</td></tr><tr><td>1c: Relevance of human post-exposure prophylaxis (PEP) to reduce WE rabies risk</td><td>8</td></tr><tr><td>2: Methods</td><td>9</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Data and sources</td><td>9</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Inclusion and exclusion criteria</td><td>9</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Rabies risk calculation</td><td>9</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Key assumptions</td><td>10</td></tr><tr><td>&nbsp;&nbsp;&nbsp;&nbsp;Analyses</td><td>10</td></tr><tr><td>3: Factors for which correlation with P<sub>A</sub> has been studied</td><td>11</td></tr><tr><td>4a: Animal rabies cases in Western European countries related to a trip to or importation from an endemic country, 2001-2013</td><td>13</td></tr><tr><td>4b: Country of diagnosis and transit of pets diagnosed rabid in a Western European country. 2001-2013</td><td>18</td></tr><tr><td>4c: Complementary results</td><td>20</td></tr><tr><td>5: Evolution of the number of imported rabid pets and their secondary cases</td><td>20</td></tr><tr><td>6: Study limitations and robustness</td><td>21</td></tr><tr><td>7: Political implications</td><td>22</td></tr></table>
# Travel-Associated Rabies in Pets and Residual Rabies Risk, Western Europe

Florence Ribadeau-Dumas, Florence Cliquet, Philippe Gautret, Emmanuelle

Robardet, Claude Le Pen, Hervé Bourhy

► To cite this version:

Florence Ribadeau-Dumas, Florence Cliquet, Philippe Gautret, Emmanuelle Robardet, Claude Le Pen, et al.. Travel-Associated Rabies in Pets and Residual Rabies Risk, Western Europe. Emerging Infectious Diseases, 2016, 22 (7), pp.1268 - 1271. 10.3201/eid2207.151733. pasteur-01429541

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1a: Rabies risk and its determinants in recent WE history

Canine rabies was eliminated from Western Europe (WE) in the early 20th century, mainly due to public health measures such as controlling stray dogs, enforcing the wearing of muzzles and slaughtering suspect animals [1]. In the 1940s, after viral adaptation from dogs to foxes in Poland, rabies spread to nearly all of Europe. After implementation of biannual aerial distribution of vaccine baits, 12 European countries eliminated terrestrial rabies [1,2]. Two years after the last case, those countries (re-)acquired from the World Health Organisation for Animal Health (OIE) a rabies-free status for non-flying mammals [3]. Nevertheless, WE still faces 3 types of rabies risk in animals.

The first, related to bat rabies, is not a major epidemiologic risk in Europe. Unlike in the Americas, rabies in European bats has never been linked to RABV, the lyssavirus species responsible for canine rabies and over 99% of human cases. European Bat Lyssaviruses and the other two recently-discovered viruses—Bokeloh-Bat Lyssavirus and Lleida virus—are ill-adapted to spill over to non-flying species. No transmission between non-flying mammals and only 3 confirmed human fatalities linked with these viruses have been reported since 1954 in Europe (only 1 in WE (UK)) [4]. The second risk corresponds to cross-border reinfections of vulpine rabies from rabies-enzootic European countries and has been observed in Italy in 2008 [5], in the Republic of Macedonia in 2010[6], in Greece in 2012[7] and in Slovakia in 2013[8], highlighting the need for constant rabies surveillance. The third risk, illegal importations or movements of infected animals from rabies-enzootic countries, may cause indigenous rabies cases or, more seriously, a rabies resurgence. Thus, Spain in 1975 lost its rabies-free status when illegal importation of a rabid dog from Morocco led to rabies in 81 pets and 1 human in a single year [9,10]. To avoid rabies introduction from infected areas, a European Pet Movement Policy (EUPMP) has been implemented through successive EU regulations laying down, in particular since 2003, the conditions for non-commercial movements of pet animals prior to EU entry. Almost every year, rabid pets are reported [11] in Europe due to border control failures, ignorance or active subversion of these rules.

[1] Cliquet F, Picard-Meyer E, Robardet E. Rabies in Europe: what are the risks? Expert Rev Anti Infect Ther 2014;12:905-8. doi:10.1586/14787210.2014.921570.

[2] Freuling CM, Hampson K, Selhorst T, Schröder R, Meslin FX, Mettenleiter TC, et al. The elimination of fox rabies from Europe: determinants of success and lessons for the future. Philos Trans R Soc Lond B Biol Sci 2013;368:20120142. doi:10.1098/rstb.2012.0142.

[3] OIE - World Organisation for Animal Health, editor. Recommendations applicable to OIE Listed diseases and other diseases of importance to international trade. 23th ed. Paris: OIE; 2014.

[4] Dacheux L, Larrous F, Mailles A, Boisseleau D, Delmas O, Biron C, et al. European Bat Lyssavirus Transmission among Cats, Europe. Emerg Infect Dis 2009;15:280-4. doi:10.3201/eid1502.080637.

[5] Nouvellet P, Donnelly CA, De Nardi M, Rhodes CJ, De Benedictis P, Citterio C, et al. Rabies and Canine Distemper Virus Epidemics in the Red Fox Population of Northern Italy (2006-2010). PLoS ONE 2013;8:e61588. doi:10.1371/journal.pone.0061588.
# Travel-Associated Rabies in Pets and Residual Rabies Risk, Western Europe

Florence Ribadeau-Dumas, Florence Cliquet, Philippe Gautret, Emmanuelle Robardet, Claude Le Pen, Hervé Bourhy

In 2015, countries in western Europe were declared free of rabies in nonflying mammals. Surveillance data for 2001–2013 indicate that risk for residual rabies is not 0 because of pet importation from countries with enzootic rabies. However, the risk is so low (7.52 × 10⁻¹⁰) that it probably can be considered negligible.

Although western and northern Europe and most countries in central Europe have eliminated rabies in nonflying animals (https://zenodo.org/record/49670#) (1,2), alerts are regularly issued because of importation of rabid pets. Policy makers recommend postexposure prophylaxis (PEP) after exposure in Western Europe to bats or pet bites in areas with rabies alerts. However, the policy after exposure to these pets is unclear (https://zenodo.org/record/49670#).

Residual risk for rabies in pets in Western Europe is defined as no risk (no PEP necessary) or low risk (PEP recommended after exposure), depending on recommendations (e.g., no risk according to Public Health England and low risk according to the World Health Organization) (3). Thus, evaluation of residual rabies risk in western Europe caused by pet movement is needed. We evaluated residual rabies risk caused by pet movement in western Europe.

## The Study

We calculated the risk that a given pet in western Europe is contagious for rabies on a given day by the equation

$$P_A = \sum \frac{\text{No. contagious days for pets in the area during 2001-2013}}{\text{No. pets in the area} \times \text{no. days during 2001-2013}}$$

We describe factors associated with rabid pets (https://zenodo.org/record/49670#) and define pet transport as any noncommercial movement of a live cat, dog, or ferret and its owner or an authorized person across an administrative border.

Author affiliations: Université Paris Dauphine, Paris, France (F. Ribadeau-Dumas, C. Le Pen); Institut Pasteur, Paris (F. Ribadeau-Dumas, H. Bourhy); French Agency for Food, Environmental and Occupational Health and Safety, Malzéville, France (F. Cliquet, E. Robardet); Assistance Publique Hôpitaux de Marseille, Marseille, France (P. Gautret); Aix Marseille University, Marseille (P. Gautret)

DOI: http://dx.doi.org/10.3201/eid2207.151733

During 2001–2013, a total of 21 animal rabies cases attributed to pets from rabies-enzootic countries were reported in western Europe (https://zenodo.org/record/49670#), which represented 1.6 pets/year and 23 days/year of potential contagiousness. Fifteen dogs and 1 kitten originated from rabies-endemic countries outside western Europe. Five dogs raised in western Europe acquired rabies outside this region. One dog subsequently infected 2 indigenous dogs in France (4). All pet owners were identified. All owners except 1 (a Spanish man living in a van) were official residents of western Europe. Circumstances that led to pet examination and rabies diagnosis were clinical suspicion (14 pets), bitten humans (3 pets), border quarantine (2 pets), and retrospective data (2 pets with indigenous secondary cases during the alert in France in 2008).

Average contagious period was 16 days/pet: 14 days in western Europe (8 days without signs of rabies and 6 days with signs of rabies) and 2 days before arriving in western Europe. For 1 dog, signs of rabies appeared before the animal entered western Europe. For each rabid animal, an average of 34 (range 0–187) persons and other animals received PEPs. The maximum value of this range corresponds to an alert in France in 2004. After this alert, 1,200 animals were tested and 759 were observed for 1 year. Human and pet vaccinations led to vaccine shortages that required importing of vaccines not authorized for use in France (5).

We identified animal origin and mode of entry into western Europe (Table 1). Most rabies cases originated in Morocco and were recorded in France. Three cases were imported from eastern Europe to Germany, 1 from The Gambia to France, and 1 from Sri Lanka to the United Kingdom. Customs officials could not identify any of 11 cases in animals transported mainly by road (e.g., after a ferry trip from Morocco to Spain, Portugal, or France). Seven pets were transported through other countries in western Europe before arriving in the country of diagnosis (https://zenodo.org/record/49670#). Six puppies and 1 kitten were transported by air, of which only 2 were identified by customs officials (in the United Kingdom and Germany).

Of 19 transported rabid pets, 8 (42%) had no rabies vaccination, pet passport, or health certificate. Only 6 were vaccinated (0/2 infected in France, 3/3 imported but raised in western Europe, 3/7 imported by air, and 0/8 imported by road). Most vaccinated pets did not comply with recommended age for vaccination (≥12 weeks of age) or time between vaccination, serologic analysis, and transport. No reports mentioned valid rabies serologic analysis included in
[6] Kirandjiski T, Mrenoski S, Celms I, Mitrov D, Dzadzovski I, Cvetkovikj I, et al. First reported cases of rabies in the Republic of Macedonia. Vet Rec 2012;170:312. doi:10.1136/vr.100580.

[7] Tsiodras S, Douglas G, Baka A, Billinis C, Doudounakis S, Balaska A, et al. Re-emergence of animal rabies in northern Greece and subsequent human exposure, October 2012–March 2013. Euro Surveill 2013;18.

[8] Bires J. Rabies cases detected in Slovak Republic. Rabies - Bull - Eur n.d. http://www.who-rabies-bulletin.org/journal/Miscellaneous_Articles_4.aspx (accessed May 29, 2015).

[9] Pérez de Diego A, Vigo M, Monsalve J, Escudero A. The One Health approach for the management of an imported case of rabies in mainland Spain in 2013. Euro Surveill 2015;20:pii=21033.

[10] King AA. Historical perspective of rabies in Europe and the mediterranean basin: a testament to rabies by Dr. Arthur A. King. Paris: OIE; 2004.

[11] Johnson N, Freuling C, Horton D, Müller T, Fooks AR. Imported rabies, European Union and Switzerland, 2001–2010. Emerg Infect Dis 2011;17:751.
<table><caption>**Table 1.** Transport mode, country of origin, and country of diagnosis of 21 pets reported with rabies related to travel, 2000–2013</caption><thead><tr><th>Transport mode</th><th>No (%) rabid pets</th><th>Country of origin (no.)</th><th>Country of diagnosis (no.)</th></tr></thead><tbody><tr><td>Road</td><td>11 (52)</td><td>Morocco (9), Croatia (1), Bosnia and Herzegovina (1)</td><td>France (8), Germany (2), Spain (1)</td></tr><tr><td>Air</td><td>7 (33)</td><td>Morocco (4), Azerbaijan (1), Sri Lanka (1), The Gambia (1)</td><td>Germany (2), Belgium (1), France (2), The Netherlands (1), UK (1)</td></tr><tr><td>Unknown</td><td>1 (5)</td><td>Morocco (1)</td><td>Switzerland (1)</td></tr><tr><td>None</td><td>2 (10)</td><td>Dogs from France (secondary cases) (2)</td><td>France (2)</td></tr></tbody></table>

European Pet Movement Policy (Figure) for unlisted third countries (e.g., Morocco, the Gambia, Sri Lanka, or Azerbaijan) (6). Using data for 2001–2013, we calculated that, for contact on a given day with a pet in western Europe, the probability of the pet being contagious for rabies attributed to pet transport was $7.52 \times 10^{-10}$ (Table 2).

We observed a significant correlation between number of contagious days for dogs in a country and number of tourists traveling from this country to Morocco ($r = 0.73, p = 0.017$). We found no correlation with other variables tested (total dog population, dog population density, number of dogs per inhabitant).

## Conclusions

Risk for indigenous rabies has decreased in western Europe. During 2001–2013, because of appropriate control

<figure><img src="image_1.png" /></figure>

**Figure.** European Union (EU) regulations (no. 998/2003 and no. 576/2013, http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32013R0576) on movement of cats, dogs, and ferrets, 2003–2013. Before 2003, national rules applied (e.g., animal checked at destinations, rabies vaccination, animal identification, quarantine, health certification). EC, European community. *http://ec.europa.eu/food/animal/liveanimals/pets/list_third_en.htm. †A pet passport is required for pets transported in the EU. A health certificate provided by an official veterinarian is mandatory for pets transported from outside the EU.

of imported rabid pets, only 4 indigenous cases of human rabies were reported (3 in recipients of organs from a donor infected in India and 1 from a rabid bat in Scotland) (https://zenodo.org/record/49670#). Since 2011, no indigenous rabies cases have been reported in terrestrial mammals in western Europe. Because of increased travel (7), rabies imported by trips to rabies-enzootic countries has increased, and travel became the main source of rabies in humans (1.46 patients/year) (8) and pets (1.6 rabid pets/year) in 2001–2013. However, because of improved surveillance, although the number of imported rabies cases increased, the number of secondary cases decreased (https://zenodo.org/record/49670#).

Illegal importation of rabid animals is not limited to western Europe (9) or dogs and cats (10). This finding highlights the need for a global approach for regulation of animal movement worldwide and strengthening real-time reporting for animal and human rabies.

Risk for dog rabies being reintroduced into the European Union from Morocco was estimated as 0.21 cases/year (11). However, we estimate that 1.1 pets/year are entering western Europe after being infected in Morocco. Morocco has become the main source of pet rabies in western Europe, often through Ceuta and Melilla (Spanish enclaves in northern Morocco). Because no prophylaxis or specific vaccinations are needed for travel to northern Africa, few travelers seek pretravel advice and most have little knowledge of pet rabies (12,13).

Lack of awareness also increases importation of human rabies. Despite an efficient policy for preventing entry of rabid pets, the United Kingdom reported the highest number of patients with imported rabies during the study period (https://zenodo.org/record/49670#). Patients returning to this country did not believe that a correct PEP was needed after exposure abroad. None of the transported rabid pets fully satisfied European Pet Movement Policy, which raised questions about how to improve the current regulation application. Increasing international travel, expansion of the Schengen area (26 countries in Europe that have a common visa policy) into rabies-enzootic countries in eastern Europe, and development of internet animal trade (source of illegal importation) (14) are new challenges for ensuring compliance.

Because bat rabies is more difficult to control than dog rabies, and some developing countries still have difficulties
Technical Appendix 1b. Rabies situation in Western European countries until December 2013

<table><thead><tr><th>Country*</th><th>Date of last rabies case of indigenous origin in a human</th><th>Number of human cases 2001-2013[1]</th><th>Date of last indigenous rabies case in a non-flying mammal</th></tr></thead><tbody><tr><td>Belgium</td><td>1922 [2]</td><td>0*</td><td>1999 [2,3]</td></tr><tr><td>France</td><td>1924</td><td>1 (2003: 1 case from a dog in Gabon)</td><td>1998 (in 2008, 2 dogs acquired rabies in France but these were secondary cases from a rabid dog importation)</td></tr><tr><td>Germany</td><td></td><td>6[4] (2004: 1 case from a dog or monkey in India 2004: 1 case from a dog in India, source of 3 cases in 2005 in 3 transplant patients[5] 2007: 1 case from a dog bite in Morocco[4])</td><td>2006 [6] (361 cases from 2000 to 2006)</td></tr><tr><td>Ireland</td><td>Before 1904 [2]</td><td>1 (2008: 1 case from an animal in South Africa)</td><td>1903 [2]</td></tr><tr><td>Italy</td><td>1968 [7]</td><td>1 (2011: 1 case from a dog in India [8])</td><td>2011 (No cases from 1992 to 2007) Rabies-free status from 1995 [9] lost in 2008 due to resurgence with 287 cases from 2008 to 2011</td></tr><tr><td>Luxembourg</td><td>Before 1966[2]</td><td>0</td><td>1998</td></tr><tr><td>Netherlands</td><td>1923</td><td>02 (2007: 1 case from a bat bite in Kenya 2013: 1 case from a dog bite in Haiti)</td><td>1988 [10]</td></tr><tr><td>Portugal</td><td>1960 [2]</td><td>1 (2011: 1 case from a dog in Guinea Bissau [11])</td><td>1960 [2]</td></tr><tr><td>Spain</td><td>1975 [2]</td><td>0</td><td>1978'[2]</td></tr><tr><td>Switzerland</td><td>1977 [12]</td><td>1 (2012: 1 US soldier with US bat rabies [13])</td><td>1996 [14]</td></tr><tr><td>United Kingdom</td><td>1902[15,16]</td><td>6 [17,18] (2001: 1 case from a dog in the Philippines 2001: 1 case from a dog in Nigeria 2002: 1 case from a bat (EBLV 2) in Scotland 2005: 1 case from a dog in India 2008: 1 case from a dog in South Africa 2012: 1 case from a dog in India)</td><td>1922 [15]</td></tr></tbody></table>
<table><caption>**Table 2.** Risk that given dogs or cats are rabid on a given day in 10 countries in western Europe relative to pet transport, 2001–2013*</caption><thead><tr><th rowspan="3">Country†</th><th colspan="3">No. pets without signs of rabies</th><th colspan="6">No. days of pet contagiousness for rabies attributed to pet transport</th><th colspan="4">Estimation of probability in the event of contact on a given day with a pet that is contagious for rabies attributed to pet transport</th></tr><tr><th rowspan="2">Total</th><th colspan="2">Pets without rabies signs</th><th colspan="3">Total</th><th rowspan="2">Total</th><th rowspan="2">Total</th><th rowspan="2">Total</th><th rowspan="2">P<sub>A</sub>‡</th><th rowspan="2">Dogs, P<sub>AD</sub>§</th><th rowspan="2">Cats, P<sub>AC</sub>¶</th></tr><tr><th>Dogs</th><th>Cats</th><th>Total</th><th>Dogs</th><th>Cats</th></tr></thead><tbody><tr><td>Belgium</td><td>16</td><td>16</td><td>0</td><td>5</td><td>5</td><td>0</td><td>21</td><td>21</td><td>0</td><td>1.38 &times; 10<sup>-9</sup></td><td>3.32 &times; 10<sup>-9</sup></td><td>0</td></tr><tr><td>France</td><td>91</td><td>81</td><td>10</td><td>67</td><td>63</td><td>4</td><td>158</td><td>144</td><td>14</td><td>1.79 &times; 10<sup>-9</sup></td><td>3.99 &times; 10<sup>-9</sup></td><td>2.69 &times; 10<sup>-10</sup></td></tr><tr><td>Germany</td><td>32</td><td>32</td><td>0</td><td>31</td><td>31</td><td>0</td><td>63</td><td>63</td><td>0</td><td>9.83 &times; 10<sup>-10</sup></td><td>2.50 &times; 10<sup>-9</sup></td><td>0</td></tr><tr><td>Ireland</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Italy</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>The Netherlands</td><td>1</td><td>1</td><td>0</td><td>4</td><td>4</td><td>0</td><td>5</td><td>5</td><td>0</td><td>2.41 &times; 10<sup>-10</sup></td><td>7.05 &times; 10<sup>-10</sup></td><td>0</td></tr><tr><td>Portugal</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Spain</td><td>22</td><td>22</td><td>0</td><td>6</td><td>6</td><td>0</td><td>28</td><td>28</td><td>0</td><td>7.28 &times; 10<sup>-10</sup></td><td>1.25 &times; 10<sup>-9</sup></td><td>0</td></tr><tr><td>Switzerland</td><td>10</td><td>10</td><td>0</td><td>5</td><td>5</td><td>0</td><td>15</td><td>15</td><td>0</td><td>1.62 &times; 10<sup>-10</sup></td><td>7.10 &times; 10<sup>-9</sup></td><td>0</td></tr><tr><td>United Kingdom</td><td>6</td><td>6</td><td>0</td><td>3</td><td>3</td><td>0</td><td>9</td><td>9</td><td>0</td><td>1.18 &times; 10<sup>-10</sup></td><td>2.37 &times; 10<sup>-10</sup></td><td>0</td></tr><tr><td>Total</td><td>178</td><td>168</td><td>10</td><td>121</td><td>117</td><td>4</td><td>299</td><td>285</td><td>14</td><td>NA</td><td>NA</td><td>NA</td></tr><tr><td>Mean</td><td>18</td><td>17</td><td>1</td><td>12</td><td>12</td><td>0</td><td>30</td><td>29</td><td>1</td><td>7.52 &times; 10<sup>-10</sup></td><td>1.57 &times; 10<sup>-9</sup>#</td><td>6.48 &times; 10<sup>-11</sup></td></tr></tbody></table>

*NA, not applicable.

†We considered only countries in western Europe with a population >1 million persons.

‡P<sub>A</sub>, calculated risk that a given pet is rabid on a given day in a country in western Europe relative to pet transport.

§P<sub>AD</sub>, calculated risk that a given cat is rabid on a given day in a country in western Europe relative to pet transport.

¶P<sub>AD</sub>, calculated risk that a given dog is rabid on a given day in a country in western Europe relative to pet transport.

#P<sub>AD</sub> was lower if the dog had no signs of rabies (9.25 x 10<sup>-10</sup>–1.03 x 10<sup>-10</sup> for dogs with no signs of rabies and 6.44 x 10<sup>-9</sup>–6.44 x 10<sup>-6</sup> for dogs with signs of rabies assuming that 90%–99.99% had no signs of rabies on a given day).

controlling rabies, eradication of rabies is not a realistic objective. Awareness should be increased, and current regulations for pet transport should be applied to reduce rabies importation and ensure that risk in western Europe remains low.

To avoid unnecessary and costly PEP and optimize resource allocation, it should be clearly stated which WHO recommendations, Public Health England recommendations, or other practices most relevant after pet exposure should be applied. Low risks (<10<sup>-6</sup>) are usually considered acceptable or essentially 0 (3,15). The risk of a fatal car crash while traveling to PEP consultations was higher than the risk of rabies after exposure to a pet in France in 2001–2011 (3). The most pertinent policy in areas at low risk for rabies is probably that of the United Kingdom (i.e., no PEP outside alert areas that do not have asymptomatic animals or exposure to bats) (https://zenodo.org/record/49670#).

## Acknowledgments

We thank Karim Boubaker, Bernard Brochier, Laurent Dacheux, Juan Emilio Echavarria Mayo, Franco Mutinelli, Jacques-André Romand, and Reto Zanoni for providing information on rabies cases; Sylvie Tourdiat for providing assistance with formatting tables and the figure; and Delphine Libby-Claybrough for providing assistance with English editing.

Dr. Ribadeau-Dumas is a physician and doctoral candidate in economics at Paris Dauphine University, Paris, France. Her research interests are infectious diseases, public health, health economics, and rabies.

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10. Metlin AE, Holopainen R, Tuura S, Ek-Kommonen C, Huovilainen A. Imported case of equine rabies in Finland: clinical course of the disease and the antigenic and genetic characterization of the virus. Journal of Equine Veterinary Science. 2006;26:584–7. http://dx.doi.org/10.1016/j.jevs.2006.11.001
<footnote>*Only those parts of the country situated in Continental Europe are considered in this table</footnote>

<footnote>†38 cases in Ceuta and Melilla (Spain) between 2000 and 2013 were not considered in this table because they are enclaves in North Africa, not the Spanish peninsula</footnote>
11. Napp S, Casas M, Moset S, Paramio JL, Casal J. Quantitative risk assessment model of canine rabies introduction: application to the risk to the European Union from Morocco. Epidemiol Infect. 2010;138:1569-80. http://dx.doi.org/10.1017/S0950268810000415

12. Altmann M, Parola P, Delmont J, Gautret P. Knowledge, attitudes, and practices of French travelers from Marseille regarding rabies risk and prevention. J Travel Med. 2009;16:107-11. http://dx.doi.org/10.1111/j.1708-8305.2008.00283.x

13. Gautret P, Ribadeau-Dumas F, Parola P, Brouqui P, Bourhy H. Risk for rabies importation from north Africa. Emerg Infect Dis. 2011;17:2187-93. http://dx.doi.org/10.3201/eid1712.110300

14. RSPCA. Pushing at an open door: how the present UK controls on rabies are failing [cited 2015 Apr 24]. http://www.rspca.org.uk:

80/search?searchKey=Pushing+at+an+open++door+%E2%80%93+how+the++present+UK+controls+on+rabies+are+failing&x=0&y=0

15. Kelly KE, Cardon NC. The myth of 10⁻⁶ as a definition of acceptable risk. Presented at: 84th Annual Meeting and Exhibition of the Air and Waste Management Association; 1991 Jun 16-21; Vancouver, British Columbia, Canada.

Address for correspondence: Florence Ribadeau-Dumas, Laboratoire d'Economie de Dauphine/Laboratoire d'Economie et de Gestion des Organisations de Santé, Université Paris Dauphine, Place du Maréchal de Lattre deTassigny, Paris 75775, France, email: fribadeaudumas@gmail.com

<figure><img src="image_2.png" /></figure>
[1] Carrara P, Parola P, Brouqui P, Gautret P. Imported human rabies cases worldwide, 1990–2012. PLoS Negl Trop Dis 2013;7:e2209.

[2] King AA. Historical perspective of rabies in Europe and the mediterranean basin: a testament to rabies by Dr. Arthur A. King. Paris: OIE; 2004.

[3] Vitasek J. Review of rabies elimination in Europe. Vet Med-CZech 2004;5:171–85.

[4] Schmiedel S, Panning M, Lohse A, Kreymann KG, Gerloff C, Burchard G, et al. Case report on fatal human rabies infection in Hamburg, Germany, March 2007. Euro Surveill 2007;12:E070531.

[5] Maier T, Schwarting A, Mauer D, Ross RS, Martens A, Kliem V, et al. Management and Outcomes after Multiple Corneal and Solid Organ Transplantations from a Donor Infected with Rabies Virus. Clin Infect Dis 2010;50:1112–9. doi:10.1086/651267.

[6] Müller T, Bätza H-J, Freuling C, Kliemt A, Kliemt J, Heuser R, et al. Elimination of terrestrial rabies in Germany using oral vaccination of foxes. Berl Münch Tierärztl Wschr 2012;13:178–90.

[7] Rabbia | n.d. http://www.izsvenezie.it/temi/malattie-patogeni/rabbia/ (accessed April 16, 2015).

[8] De Benedictis P, Perboni G, Gentili C, Gaetti L, Zaffanella F, Mutinelli F, et al. Fatal case of human rabies imported to Italy from India highlights the importance of adequate post-exposure prophylaxis, October 2011. Euro Surveill 2012;17:pii=20168.
[9] Mutinelli F. Rabies control in Italy. WHO Meet. Rabies Control Middle East Eur. Ctries. Kosice Slovak. Sept. 25-27 2002, 2002.

[10] van Rijckevorsel GG, Swaan CM, van den Bergh JP, Goorhuis A, Baayen D, Isken L, et al. Rabid puppy-dog imported into the Netherlands from Morocco via Spain, February 2012. Euro Surveill 2012;17:pii=20112.

[11] Santos A, Cale E, Dacheux L, Bourhy H, Gouveia J, Vasconcelos P. Fatal case of imported human rabies in Amadora, Portugal, August 2011. Euro Surveill 2011;17:pii=20130.

[12] Groupe de travail rage, Commission Suisse pour les vaccinations. Prophylaxie pré- et post-expositionnelle de la rage chez l'homme. Berne: Office fédéral de la santé publique; 2004.

[13] Deubelbeiss AN, Trachsel C, Bachli EB, Kuffer A, Budka H, Eniseyskiy P, et al. Imported human rabies in Switzerland, 2012: a diagnostic conundrum. J Clin Virol Off Publ Pan Am Soc Clin Virol 2013;57:178-81.
doi:10.1016/j.jcv.2013.02.001.

[14] Breitenmoser U, Müller U, Kappeler A, Zanoni RG. [The final stage of rabies in Switzerland]. Schweiz Arch Für Tierheilkd 2000;142:447-54.

[15] Muir P, Roome A. Indigenous rabies in the UK. The Lancet 2005;365:2175. doi:10.1016/S0140-6736(05)66769-4.

[16] Rabies: the green book, chapter 27 - Publications - GOV.UK n.d.
https://www.gov.uk/government/publications/rabies-the-green-book-chapter-27 (accessed April 16, 2015).

[17] Banyard AC, Hartley M, Fooks AR. Reassessing the risk from rabies: A continuing threat to the UK? Virus Res 2010;152:79-84. doi:10.1016/j.virusres.2010.06.007.

[18] Johnson N, Brookes SM, Fooks AR, Ross RS. Review of human rabies cases in the UK and in Germany. Vet Rec 2005;157:715.
1c: Relevance of human post-exposure prophylaxis (PEP) to reduce WE rabies risk

Human rabies encephalitis—always fatal—can be prevented through PEP, including rabies vaccines sometimes prescribed with rabies immunoglobulins. As dogs and cats can be contagious up to 10 days before clinical signs, [1,2] the need for PEP must be evaluated even after exposure to asymptomatic pets. In most WE countries where rabies was recently eliminated (see Technical Appendix 1b), PEP recommendations are based on the WHO, which considers WE as a “low rabies-risk area” (mainly because European bat rabies is not differentiated from bat rabies in the Americas) [3–5]. Consequently, PEP is recommended for patients injured by local unobservable pets. The lack of specific “very low risk area” recommendations leads to discrepancies in practices and expenses not always based on epidemiologic reasoning [6]. For example, in the UK, the position of Public Health England (PHE) is based on WE OIE rabies-free status for terrestrial mammals. PHE considers that there is “no risk” of rabies following infection by WE dogs or cats, and consequently does not recommend PEP [7] (unless there is an alert in the area). PHE does not consider the history of OIE rabies-free status, whether long (e.g. the UK) or short (e.g. France, Belgium, Switzerland). However, because of sporadic cases of imported rabid animals, many WE countries, including France [8], Germany [9] and Switzerland [10], still recommend the WHO position and so PEP after exposure to an unobservable dog in their country. Residual risk in WE pets being defined as “no risk” (no PEP necessary) or “low risk” (PEP recommended after exposure to an unobservable pet) depending on stakeholders, it appears necessary to better rationalize and harmonize PEP recommendations in WE.

[1] Compendium of Animal Rabies Prevention and Control, 2011 n.d.

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6006a1.htm (accessed May 14, 2014).

[2] OIE - World Organisation for Animal Health. Infection with rabies virus. Terr. Anim. Health Code, n.d.

[3] World Health Organization. Rabies vaccines: WHO position paper—Recommendations. Vaccine 2010;28:7140–2. doi:10.1016/j.vaccine.2010.08.082.

[4] World Health Organization. International travel and health. Vaccine-preventable diseases and vaccine. WHO 2012. http://www.who.int/ith/fr/ (accessed April 4, 2014).

[5] World Health Organization. WHO Expert Consultation on Rabies. Second report. World Health Organ Tech Rep Ser 2013:1–139.

[6] Ribadeau Dumas F, N'Diaye DS, Paireau J, Gautret P, Bourhy H, Le Pen C, et al. Cost-effectiveness of rabies post-exposure prophylaxis in the context of very low rabies risk: A decision-tree model based on the experience of France. Vaccine 2015. doi:10.1016/j.vaccine.2015.02.075.

[7] Health Protection Agency. Rabies risks in terrestrial animals, by country n.d.

http://www.hpa.org.uk/web/HPAweb&HPAwebStandard/HPAweb_C/1259152458758 (accessed February 28, 2014).

[8] Comité technique des vaccinations. Direction Générale de la Santé. Guide des vaccinations 2012. INPES

2012. http://www.inpes.sante.fr/nouveautes-editoriales/2012/guide-vaccination-2012.asp (accessed February 28, 2014).

[9] RKI - STIKO-Recommendations - Recommendations of the Standing Committee on Vaccination (STIKO) at the Robert Koch Institute/Effective: August 2014 n.d.

http://www.rki.de/EN/Content/Prevention/Vaccination/recommandations/34_2014_engl_19215.html (accessed April 16, 2015).

[10] Groupe de travail rage, Commission Suisse pour les vaccinations. Prophylaxie pré- et post-expositionnelle de la rage chez l'homme. Berne: Office fédéral de la santé publique; 2004.
# 2: Methods

## Data and sources

Epidemiologic data on WE rabies cases among pets due to travel were first obtained from a literature review using PubMed (MEDLINE) from 2001 to April 2014 (cross-referencing "rabies" "importation" "travel" "dog" "cat" and "ferret") and ProMED alert systems supplemented by peer-reviewed papers. Additional disease reporting systems were used, including the OIE World Animal Health Information Database (WAHID) interface (http://www.oie.int/wahis_2/public/wahid.php/Diseaseinformation/WI), the European Food Safety Agency's annual report, and reports of the European Standing Committee on the Food Chain and Animal Health [1]. When lacking specific information on included cases, national records or rabies reference centers were consulted. Information was considered valid if not invalidated by any national or European rabies reference center and if found in at least 2 different reporting systems or published in peer-reviewed journals. Data collected concerned chronology, animal characteristics, rabies vaccination history, pet passport and health certificate, transportation mode, country of origin and destination, and number of PEP related to each case. Data on dog and cat populations per country were obtained from the European Pet Food Industry Federation [2].

## Inclusion and exclusion criteria

We considered all rabid pets reported in WE, whether directly or indirectly linked to pet travel. The WE countries studied were Belgium, France, Germany, Ireland, Italy, the Netherlands, Portugal, Spain, Switzerland and the United Kingdom, restricted to continental Europe (Spain's Ceuta and Melilla enclaves were excluded, for example, as was French Guiana). We did not consider countries with <1,000,000 inhabitants.

Bat and wildlife rabies cases were excluded (Germany before 2006 and Italy from 2008 to 2011 being concerned by wildlife rabies [3,4]).

Pet travel is herein defined as any non-commercial movement across an administrative border by a live cat, dog or ferret with its owner or authorized person. Thus, a rabid animal confirmed by WE reference laboratories but diagnosed in samples from animals that died outside WE [5] were not included. This concerned 2 dog cadavers imported for diagnosis: 1 from Afghanistan to France in 2009 and 1 from Nepal to Germany in 2001.

## Rabies risk calculation

The number of contagious days over the study period was calculated for each country and for all WE according to review data. For each area (country or WE), the animals' contagious period included period of contagiousness in the area before symptoms and from first symptoms to death. We defined then calculated P<sub>A</sub> for each country and all WE according to a previous study in France [6]:
$$P_A = \frac{\sum \text{number of contagious days for pets in the area between 2001 and 2013}}{\text{number of pets in the area} * \text{number of days between 2001 and 2013}}$$

## Key assumptions

It was assumed that the number of cats and dogs (based on data from 2010 [2]) was stable over the study period (2001-2013). Dogs and cats were considered to be contagious 10 days before initial symptoms [7-9].

## Analyses

Correlation tests were performed to assess the relationship between different parameters (dog population, density of dogs, dogs per inhabitant, number of tourists visiting Morocco) and P<sub>A</sub> or number of contagious days. Considering un-normality and the limited size of the dataset (10 countries), a non-parametric Spearman-Rank Correlation test was used. Analyses were undertaken using Excel2013© (Microsoft.Inc) and R 3.0.1 (R Development Core Team, 2006).

[1] European Food Safety Authority. The European Union summary report on trends and sources of zoonoses, zoonotic agents and food-borne outbreaks in 2013. EFSA J 2015;13.

[2] The European Pet Food Industry-FEDIAF. Facts and figures 2010 n.d. http://www.google.fr/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CCkQFjAB&url=http%3A%2F%2Fwww.fediaf.org%2Ffileadmin%2Fuser_upload%2Ffacts_and_figures_2010.pdf&ei=DYRxVdG-IIHlUaLOgcAF&usg=AFQjCNFzcqh4D_o_cJ1XbUaXimxFelDclw&sig2=XM30honrglT2uxDAk3uvJA&bvm=bv.95039771,d.ZGU (accessed June 5, 2015).

[3] Müller T, Bätza H-J, Freuling C, Kliemt A, Kliemt J, Heuser R, et al. Elimination of terrestrial rabies in Germany using oral vaccination of foxes. Berl Münch Tierärztl Wschr 2012;13:178-90.

[4] Nouvellet P, Donnelly CA, De Nardi M, Rhodes CJ, De Benedictis P, Citterio C, et al. Rabies and Canine Distemper Virus Epidemics in the Red Fox Population of Northern Italy (2006-2010). PLoS ONE 2013;8:e61588. doi:10.1371/journal.pone.0061588.

[5] Johnson N, Freuling C, Horton D, Müller T, Fooks AR. Imported rabies, European Union and Switzerland, 2001-2010. Emerg Infect Dis 2011;17:751.

[6] Ribadeau Dumas F, N'Diaye DS, Paireau J, Gautret P, Bourhy H, Le Pen C, et al. Cost-effectiveness of rabies post-exposure prophylaxis in the context of very low rabies risk: A decision-tree model based on the experience of France. Vaccine 2015. doi:10.1016/j.vaccine.2015.02.075.

[7] Compendium of Animal Rabies Prevention and Control, 2011 n.d. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6006a1.htm (accessed May 14, 2014).

[8] OIE - World Organisation for Animal Health. Infection with rabies virus. Terr. Anim. Health Code, n.d.

[9] World Health Organization. WHO Expert Consultation on Rabies. Second report. World Health Organ Tech Rep Ser 2013:1-139.
## 3: Factors for which correlation with P<sub>A</sub> has been studied

<table><caption>Technical Appendix 3: Factors for which correlation with P<sub>A</sub> has been studied</caption><thead><tr><th rowspan="2">Country</th><th colspan="3">Population size</th><th rowspan="2">Area*<br>(km²)</th><th rowspan="2">Dog/capita</th><th rowspan="2">Cat/capital</th><th rowspan="2">Dog/km²</th><th rowspan="2">Cat/km²</th><th rowspan="2">Number of<br>tourists to<br>Morocco<br>in 2011</th></tr><tr><th>Human [1]<br>1.1. 2011</th><th>Dogs [2]<br>2010</th><th>Cats [2]<br>2010</th></tr></thead><tbody><tr><td>Switzerland</td><td>8,037,000</td><td>445,000</td><td>1,507,000</td><td>41,290</td><td>0.06</td><td>0.19</td><td>11</td><td>36</td><td>&lt;200,000</td></tr><tr><td>France</td><td>64,994,000</td><td>7,595,000</td><td>10,965,000</td><td>547,030</td><td>0.12</td><td>0.17</td><td>14</td><td>20</td><td>1,776,000</td></tr><tr><td>Belgium</td><td>11,000,000</td><td>1,331,000</td><td>1,884,000</td><td>30,528</td><td>0.12</td><td>0.17</td><td>44</td><td>62</td><td>258,000</td></tr><tr><td>Germany</td><td>81,751,000</td><td>5,300,000</td><td>8,200,000</td><td>357,021</td><td>0.06</td><td>0.10</td><td>15</td><td>23</td><td>219,000</td></tr><tr><td>Spain</td><td>46,152,000</td><td>4,720,000</td><td>3,385,000</td><td>505,580</td><td>0.10</td><td>0.07</td><td>9</td><td>7</td><td>693,000</td></tr><tr><td>Netherlands</td><td>16,655,000</td><td>1,493,000</td><td>2,877,000</td><td>41,526</td><td>0.09</td><td>0.17</td><td>36</td><td>69</td><td>&lt;200,000</td></tr><tr><td>United<br>Kingdom</td><td>62,515,000</td><td>8,000,000</td><td>8,000,000</td><td>244,820</td><td>0.13</td><td>0.13</td><td>33</td><td>33</td><td>352,000</td></tr><tr><td>Ireland</td><td>4,570,000</td><td>425,000</td><td>310,000</td><td>70,280</td><td>0.09</td><td>0.07</td><td>6</td><td>4</td><td>&lt;200,000</td></tr><tr><td>Italy</td><td>60,626,000</td><td>7,000,000</td><td>7,400,000</td><td>301,230</td><td>0.12</td><td>0.12</td><td>23</td><td>25</td><td>211,000</td></tr><tr><td>Portugal</td><td>10,572,000</td><td>1,940,000</td><td>991,000</td><td>92,042</td><td>0.18</td><td>0.09</td><td>21</td><td>11</td><td>&lt;200,000</td></tr><tr><td>All WE</td><td>366,872,000</td><td>38,249,000</td><td>45,519,000</td><td>2,231,347</td><td>0.10</td><td>0.12</td><td>17</td><td>20</td><td>-</td></tr><tr><td>Mean</td><td>36,687,200</td><td>3,824,900</td><td>4,551,900</td><td>223,135</td><td>-</td><td>-</td><td>-</td><td>-</td><td>-</td></tr></tbody></table>

P<sub>A</sub>: Calculated risk that a given pet (dog or cat) is rabid on a given day in a Western European country in relation to pet travel

WE= Western Europe

*http://fr.wikipedia.org/wiki/Liste_des_pays_d%27Europe_par superficie
[1] Silvia Andueza Robustillo, Corsini V, Marcu M, Vasileva K, DG ESTAT, Marchetti E, et al. EU employment and social situation. Quarterly Review Special Supplement on Demographic Trends. European Commission; 2013.

[2] The European Pet Food Industy-FEDIAF. Facts and figures 2010 n.d.
http://www.google.fr/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CCkQFjAB&url=http%3A%2F%2Fwww.fediaf.org%2Ffileadmin%2Fuser_upload%2Ffacts_and_figures_2010.pdf&ei=DYRxVdG-IIHIUaLOgcAF&usg=AFQjCNFzcqh4D_o_cJ1XbUaXimxFelDclw&sig2=XM30honrglT2uxDAk3uvJA&bvm=bv.95039771,d.ZGU (accessed June 5, 2015).
<table><thead><tr><th>Year</th><th>Country of</th><th>Date of</th><th>Date of entry in</th><th>Date of</th><th>Date of</th><th>Species</th><th>Age</th><th>Conditions</th><th>Circumstances</th><th>Vaccination*</th><th>Pet passport</th><th>Health</th><th>Travel mode</th><th>Count</th></tr></thead><tbody></tbody></table>

4a: Animal rabies cases in Western European countries related to a trip to or importation from an endemic country, 2001-2013.
<table><thead><tr><th></th><th>declaration</th><th>ownership</th><th>final country</th><th>first symptoms</th><th>animal death</th><th></th><th>of ownership in the endemic country</th><th>of dog diagnosis</th><th>*</th><th></th><th>Certificate</th><th>rabies</th></tr></thead><tbody><tr><td>2001</td><td>France</td><td>03/26/2001</td><td>03/31/2001</td><td>5/19/2001</td><td>5/21/2001</td><td>dog</td><td>puppy 3 mo</td><td>Adoption</td><td>Sick</td><td>No</td><td>?</td><td>No</td><td>Road</td><td>Moro</td></tr><tr><td>2002</td><td>Germany</td><td>November (before the 10th) 2001</td><td>12/21/2001</td><td>12/23/2001</td><td>01/9/2002</td><td>dog</td><td>puppy 1 mo</td><td>Adoption</td><td>Sick</td><td>Yes</td><td>No</td><td>Yes</td><td>Plane</td><td>Azerb</td></tr><tr><td>2002</td><td>France</td><td>?</td><td>08/16/2002</td><td>08/29/2002</td><td>09/2/2002</td><td>dog</td><td>puppy 2.5 mo</td><td>Gift</td><td>Sick</td><td>No</td><td>?</td><td>Yes</td><td>Road</td><td>Moro</td></tr><tr><td>2003</td><td>Switzerland</td><td>06/25/2003</td><td>05/,?/2003</td><td>007/15/2003</td><td>07/19/2003</td><td>dog*</td><td>puppy 2 mo</td><td>Adoption from a shelter*</td><td>Sick</td><td>?</td><td>?</td><td>?</td><td>?</td><td>Moro</td></tr><tr><td>2004</td><td>Germany</td><td>before January 2004</td><td>01/6/2004</td><td>02/2/2004</td><td>02/7/2004</td><td>dog</td><td>puppy 8 mo</td><td>?</td><td>Customs control (quarantine)</td><td>No</td><td>No</td><td>No</td><td>Plane</td><td>Moro</td></tr><tr><td>2004</td><td>France (Through Melilla and Spain)</td><td>NA</td><td>01/?/2004</td><td>01/23/2004</td><td>01/26/2004</td><td>dog†</td><td>adult 4y</td><td>NA French dog</td><td>Sick</td><td>Yes</td><td>No</td><td>No</td><td>Road</td><td>Moro</td></tr><tr><td>2004</td><td>France (Through Ceuta and Spain)</td><td>?</td><td>07/11/2004</td><td>08/17/2004</td><td>08/21/2004</td><td>dog</td><td>puppy 4 mo</td><td>Adoption</td><td>Bite</td><td>No</td><td>?</td><td>No</td><td>Road</td><td>Moro</td></tr><tr><td>2004</td><td>France (Through Spain)</td><td>05/9/2012</td><td>05/11/2004</td><td>05/10/2004</td><td>05/15/2004</td><td>dog</td><td>puppy 6 mo</td><td>Gift</td><td>Sick</td><td>No</td><td>?</td><td>?</td><td>Road</td><td>Moro</td></tr><tr><td>2007</td><td>France (Through Portugal and Spain)</td><td>NA</td><td></td><td>10/20/2007 in Spain then 2-3 days in Portugal then 10/23/2007 in Spain then 10/28/2007 in</td><td>11/2/2007</td><td>11/12/2007</td><td>dog†</td><td>adult</td><td>NA French dog</td><td>Sick</td><td>Yes</td><td>No</td><td>No</td><td>Road</td><td>Moro</td></tr></tbody></table>
France

<table><tr><td>2007</td><td>Belgium</td><td>07/?/2007</td><td>07/7/2007</td><td>10/16/2007</td><td>10/20/2007</td><td>dog</td><td>puppy<br>1 mo</td><td>Adoption</td><td>Sick</td><td>No</td><td>No</td><td>Yes</td><td>Plane</td><td>Moro</td></tr><tr><td>2008</td><td>France</td><td>NA</td><td>NA</td><td>01/2/2008</td><td>01/5/2008</td><td>dog†</td><td>adult</td><td>NA<br>French dog</td><td>Retrospective<br>(secondary<br>cases)</td><td>No</td><td>?</td><td>?</td><td>NA</td><td>France</td></tr><tr><td>2008</td><td>France</td><td>NA</td><td>NA</td><td>02/15/2008</td><td>02/19/2008</td><td>dog†</td><td>puppy<br>9 mo</td><td>NA<br>French dog</td><td>Retrospective<br>(secondary<br>cases)</td><td>No</td><td>?</td><td>?</td><td>NA</td><td>France</td></tr><tr><td>2008</td><td>France<br>(Through Belgium)</td><td>01/4/2008</td><td>04/07/2008 in<br>Belgium<br>04/13/2008 in<br>France</td><td>04/16/2008</td><td>04/21/2008</td><td>dog</td><td>puppy<br>4 mo</td><td>Adoption<br>found</td><td>Sick</td><td>Yes</td><td>No<br>(microchip)</td><td>Yes</td><td>Plane then<br>Road from<br>Belgium to<br>France</td><td>Gamb</td></tr><tr><td>2008</td><td>United Kingdom</td><td>04/12/2008</td><td>04/17/2008</td><td>04/23/2008</td><td>04/25/2008</td><td>dog</td><td>puppy<br>2.5 mo</td><td>Adoption<br>found</td><td>Customs<br>control<br>(quarantine)</td><td>Yes</td><td>No</td><td>?</td><td>Plane</td><td>Sri La</td></tr><tr><td>2008</td><td>France<br>(Through Spain)</td><td>10/12/2008</td><td>10/12/2008</td><td>10/30/2008</td><td>11/10/2008</td><td>dog</td><td>puppy<br>3 mo</td><td>Adoption<br>found</td><td>Sick</td><td>No</td><td>?</td><td>No</td><td>Road</td><td>Moro</td></tr><tr><td>2008</td><td>Germany</td><td>07/15/2008</td><td>07/15/2008</td><td>12/27/2008</td><td>12/29/2008</td><td>dog</td><td>puppy<br>1.5 mo</td><td>Bought</td><td>Sick</td><td>No</td><td>No</td><td>?</td><td>Road</td><td>Croat</td></tr><tr><td>2010</td><td>Germany</td><td>02/27/2010</td><td>02/27/2010</td><td>3/18/2010</td><td>03/21/2010</td><td>dog</td><td>puppy<br>2 mo</td><td>Bought</td><td>Sick</td><td>No</td><td>Yes</td><td>Yes</td><td>Road</td><td>Bosnia<br>Herz</td></tr><tr><td>2011</td><td>France</td><td>07/11/2011</td><td>08/1/2011</td><td>08/5/2011</td><td>08/7/2011</td><td>dog</td><td>puppy<br>3 mo</td><td>Adoption<br>found</td><td>Sick</td><td>No</td><td>No</td><td>No</td><td>Road</td><td>Moro</td></tr><tr><td>2012</td><td>Netherlands<br>(Through Spain)</td><td>1/28/2012</td><td>02/04/2012 in<br>Spain<br>02/11/2012 in<br>the Netherlands</td><td>2/12/2012</td><td>2/15/2012</td><td>dog</td><td>puppy<br>2 mo</td><td>Bought</td><td>Bite</td><td>No</td><td>Morocco:<br>No<br>(microchip)<br>Spain: Yes</td><td>Yes</td><td>Road to<br>Spain then<br>Plane to<br>Netherlands</td><td>Moro</td></tr></table>
<table><tr><td>2013</td><td>Spain#</td><td>NA</td><td>04/13/2013</td><td>05/27/2013</td><td>6/1/2013</td><td>dog†</td><td>adult<br>4y</td><td>NA<br>Spanish<br>dog</td><td>Bite</td><td>Yes</td><td>Yes<br>(microchip)</td><td>?</td><td>Road</td><td>Moro</td></tr><tr><td>2013</td><td>France</td><td>10/25/2013</td><td>10/13/2013</td><td>10/25/2013</td><td>10/28/13</td><td>cat</td><td>kitten<br>2 mo</td><td>Adoption<br>found</td><td>Sick</td><td>No</td><td>No</td><td>Yes</td><td>Plane</td><td>Moro</td></tr></table>

NA = Not Applicable

? = Data unavailable

WE= West Europe

mo= month

*Animal from an endemic country bought or adopted from a shelter

†Animal raised in the Western European country where rabies was diagnosed

‡For the calculation of the number of contagious days: day of entry in the country and day of death are included, but day of departure from the country is not

§The owners lived in a van

¶Approximation based on incomplete available data

\#2 months before the dog's owners had tried to cross the border legally, but were denied entry because the seroneutralisation assay according to EU regulation had not been done before the trip to Morocco

** Animals are considered as vaccinated whether the rabies vaccination is up-to-date or not (this information is unavailable most of the time)
[1] Bruyere-Masson V, Barrat J, Cliquet F, Rotivel Y, Bourhy H, Brie P. A Puppy Illegally Imported from Morocco Brings Rabies to France. Rabies Bull Eur 2001;25:12-3.

[2] Suess J, Weber A, Berg H, Keller B, Schmahl W. Rabies in a Vaccinated Dog Imported from Azerbaijan to Germany. Rabies Bull Eur 2001;25:14-5.

[3] Mailles A, Boisseleau D, Dacheux L, Michalewicz C, Gloaguen C, Ponçon N, et al. Rabid dog illegally imported to France from Morocco, August 2011. Euro Surveill 2011;16:pii=19946.

[4] Cliquet F. 3rd quarter 2002. Rabies Bull Eur n.d.;26:5.

[5] Johnson N, Freuling C, Horton D, Müller T, Fooks AR. Imported rabies, European Union and Switzerland, 2001-2010. Emerg Infect Dis 2011;17:751.

[6] Barrat J, Picard-Meyer E, Cliquet F, Bourhy H, Melik N. Cas de rage importé sur un chien du Morbilhan 2004.

[7] Zanini V. Rage dans le Morbilhan: le chien n'était plus vacciné depuis 2001 2004. http://www.upv.be/actualites/~un-nouveau-cas-de-rage-a-ete-constate-et-diagnostique-dans-le-morbihan-mars-2004.htm?lng=fr (accessed April 16, 2015).

[8] Servas V, Mailles A, Neau D, Castor C, Manetti A, Fouquet E, et al. An imported case of canine rabies in Aquitaine: investigation and management of the contacts at risk, August 2004-March 2005. Euro Surveill 2005;10:222-5.

[9] Servas V, Mailles A, Neau D, Castor C, Manetti A, Fouquet E, et al. Importation d'un cas de rage canine en Aquitaine : recherche et prise en charge des contacts à risque, août 2004-mars 2005. Bull Epidémiologique Hebd 2005;36:179-80.

[10] Note de service DGAL/SDSPA/N2008-8104 : Situation de la rage au 30 avril 2008. DGAL; 2008.

[11] Le Roux I, Van Gucht S. Two cases of imported canine rabies in the Brussels area within six months time. Rabies Bull Eur 2008;32:5-6.

[12] French and Belgian multidisciplinary investigation teams. Identification of a rabid dog illegally introduced from the Republic of the Gambia to Belgium and France. Euro Surveill 2008;13.

[13] Nicholas Johnson AN. Investigation of an Imported Case of Rabies in a Juvenile Dog with Atypical Presentation. Animals 2011;1:402-13.

[14] Catchpole M, Thomas L, Morgan D, Brown K, Turbitt D, Kirkbride H. Imported rabies in a quarantine centre in the United Kingdom. Euro Surveill 2008;13:pii=18868.

[15] Zanini V. Un cas de rage sur un chiot importé d'Espagne en Isère. Sem Vét n.d.:44.

[16] van Rijckevorsel GG, Swaan CM, van den Bergh JP, Goorhuis A, Baayen D, Isken L, et al. Rabid puppy-dog imported into the Netherlands from Morocco via Spain, February 2012. Euro Surveill 2012;17:pii=20112.

[17] Pérez de Diego A, Vigo M, Monsalve J, Escudero A. The One Health approach for the management of an imported case of rabies in mainland Spain in 2013. Euro Surveill 2015;20:pii=21033.

[18] Anonymous. Rabies confirmed in an imported kitten in France. Vet Rec 2013;173:435. doi:10.1136/vr.f6683.
<table><caption>Technical Appendix 4b: Country of diagnosis and transit of pets diagnosed rabid in a Western European country. 2001-2013</caption><thead><tr><th>Country<br>=21)</th><th>Number of rabid pets<br>with the following<br>country of diagnosis<br>n (%)</th><th>Number of rabid pets<br>with the following WE country<br>of transit between infection<br>and diagnosis<br>n<sub>t</sub></th><th>Total of pets with<br>transit or diagnosis<br>in the country<br>n<sub>td</sub> = n+n<sub>t</sub></th><th>Mean number of rabid pets<br>linked with travel in 100<br>years<br>m<sup>‡</sup></th></tr></thead><tbody><tr><td>Belgium</td><td>1 (5%)</td><td>1</td><td>2</td><td>15</td></tr><tr><td>France</td><td>10+2 secondary cases (57%)</td><td>0</td><td>12</td><td>92</td></tr><tr><td>Germany</td><td>4 (19%)</td><td>0</td><td>4</td><td>31</td></tr><tr><td>Italy</td><td>0 (0%)</td><td>0</td><td>0</td><td>-</td></tr><tr><td>Malta</td><td>0 (0%)</td><td>0</td><td>0</td><td>-</td></tr><tr><td>Netherlands</td><td>1 (5%)</td><td>0</td><td>1</td><td>8</td></tr><tr><td>Portugal</td><td>0 (0%)</td><td>1*</td><td>1</td><td>8</td></tr><tr><td>Spain</td><td>1 (5%)</td><td>6<sup>†</sup></td><td>7</td><td>54</td></tr><tr><td>Switzerland</td><td>1 (5%)</td><td>0</td><td>1</td><td>8</td></tr><tr><td>United<br>Kingdom</td><td>1 (5%)</td><td>0</td><td>1</td><td>8</td></tr><tr><td>WE</td><td>21 (100%)</td><td>7 pets with a transit country<br>(of which 1 has 2 transit<br>countries)</td><td>21 pets<br>(of which 8 transits<br>where reported)</td><td>162 pets<br>(of which 62 transits would<br>be reported)</td></tr></tbody></table>

‡ = Western Europe

A dog from Morocco diagnosed rabid in France in 2007 transited through Portugal and Spain. The period of contagiousness started in Spain after transit through Portugal so it is reported in this table but no days with a rabid dog were taken into account in Portugal for this event.

For some dogs from Morocco that arrived in France via Spain, no days of attendance in Spain are reported. Those cases are reported in this table. ‡m=n<sub>td</sub>×100/13, m is calculated under the assumption that, during the 100-year period, the mean annual number of rabid pets transited with travel is the same as that observed between 2001 and 2013.

4b: Country of diagnosis and transit of pets diagnosed rabid in a Western European country. 2001-2013
4c: Complementary results

Fifteen dogs (all puppies under 6 months) and 1 kitten originated from endemic countries outside WE: 12 (75%) were found or gifted in the endemic country, 3 were bought abroad and 1 was adopted from a shelter (in Switzerland where it had been illegally imported). Five dogs raised in WE (4 adults, 1 puppy) acquired rabies outside WE, including 3 in Morocco.

Without contamination dates, it was impossible to calculate the average incubation period, but it was over 33 days as the average period between an animal entering WE and first symptoms was 33 days [IC95: 10-56]. The average contagious period was 16 days, starting 2 days before entering WE, and including 14 days in WE (8 asymptomatic and 6 symptomatic). For 1 dog, symptoms began before entering WE.

5: Evolution of the number of imported rabid pets and their secondary cases

Only 1/19, i.e. 5%, of 2001-2013 imported rabid pets led to secondary cases (2 cases in dogs) compared to 4/17, i.e. 24%, in the 1968-1995 period (with 1 to 7 secondary cases per alert) and to the Spanish situation in 1975, when a rabid Moroccan dog infected 81 pets and 1 human [1,2].

[1] Pérez de Diego A, Vigo M, Monsalve J, Escudero A. The One Health approach for the management of an imported case of rabies in mainland Spain in 2013. Euro Surveill 2015;20:pii=21033.

[2] King AA. Historical perspective of rabies in Europe and the mediterranean basin: a testament to rabies by Dr. Arthur A. King. Paris: OIE; 2004.
## 6: Study limitations and robustness

We did not consider whether the contagious period occurred during quarantine (as in the 2008 UK case), during veterinary observation or outside those contexts. Risk management is easier during quarantine and veterinarian observation. First, because—unlike the general population—veterinarians and quarantine workers should be vaccinated prior to exposure [1], and second, because risky contacts are limited and more easily and quickly handled. Thus the UK rabies risk is probably over-estimated in our study (1 rabid pet imported in 13 years, compared to 1 in 170 following a DEFRA assessment [2] (DEFRA assumed 90% compliance with EUPMP and did not consider a rabid pet in quarantine as entering the UK). We considered, based on the WHO post-exposure animal observation period, that the asymptomatic contagious period was 10 days rather than 14 (Spain's observation period) or 15 (UK and France's period). However, had we considered a 15-day period for the 14/20 dogs which started their contagious period in WE, we would have had 238 instead of 168 asymptomatic contagious dog days in WE. Thus $P_A$ would have increased to $1.96 \times 10^{-9}$ which is still very low. Our review could suffer from missing information regarding imported animal cases. However, our results are probably near-exhaustive since rabies notification is mandatory in WE, and the quality of health watch and reporting networks is satisfactory. From 2001 to 2013, no human fatalities were observed after contact with 1 of the 21 rabid pets. Therefore, the average individual risk of rabies linked with pet travel is $<2.10 \times 10^{-10}/year$, which is notably less than the $8.2 \times 10^{-6}/year$ individual risk of rabies in the world and very low even regarding other risks considered very low, such as death from dog bites ($7.1 \times 10^{-8}$), road accidents ($8.3 \times 10^{-6}$) or lightning ($5.2 \times 10^{-8}$) [2,3].

[1] World Health Organization. WHO Expert Consultation on Rabies. Second report. World Health Organ Tech Rep Ser 2013:1-139.

[2] Veritas DN. Interpretation of Rabies Risk Assessment: Final Report. Report for Defra (UK) 2011. http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.394.8967&rep=rep1&type=pdf (accessed May 19, 2014).

[3] Kelly KE, Cardon NC. The myth of 10-6 as a definition of acceptable risk. 84th Annu. Meet. Exhib. Air Waste Manag. Assoc. Vanc. BC, 1991, p. 16-21.
## 7: Political implications

Finally, EU and WE countries should:

- Improve information to travelers to or from rabies-enzootic countries (especially North Africa) about the risk of rabies if exposed abroad or traveling with pets. For example, information about rabies risks could be made available on transport from rabies-enzootic countries to WE (on tickets, in the line for customs or boarding or on posters in ferries and airports).

- Enhance information to professionals (especially veterinary and customs services) involved in the application of EUMP as initiated recently with training courses organized by the European Commission (http://www.foodinfo-europe.com/training-programs/mdc-presentation).

- Check in each country, but especially in areas with non-rabies-free borders (such as Ceuta and Melilla) and ports, airports and land border crossings with heavy traffic to/from enzootic countries, that sufficient human resources and equipment are available for reliable border controls of all pets.

- Help the main countries involved in rabies importation to improve and successfully control indigenous canine rabies, possibly through partnerships. The EU could, for example, promote mass dog vaccination campaigns in those countries as it has already promoted mass oral vaccination campaigns for wildlife in neighboring Eastern and Southern European countries with fox rabies. Those countries' residents and European travelers would no longer be exposed to rabies, WE patients would be saved from unnecessary and possibly harmful PEP and the WE public health system would avoid costly alert management.