Clinical presentations

Symptoms of tularemia are principally related to the site of entry of the bacteria, the virulence of the F. tularensis strain, and the immune status of the host. Tularemia has several clinical forms in humans, including ulceroglandular, glandular, pneumonic, oropharyngeal, oculoglandular and systemic (typhoidal, intestinal). In the ulceroglandular form, a local skin lesion is often considered the route of entrance (scratch, cut, insect bite) and the disease progresses to the swelling of the regional lymph node, which may ulcerate and suppurate. The glandular form of this disease is similar to the ulcerglandular form, but no primary skin lesion is detected in these cases. The pneumonic form results from inhalation of F. tularensis, and affects one or both lungs. The oropharyngeal form of tularemia is linked to ingestion of contaminated food or water. Other clinical presentations of tularemia, such as septic or typhoidal, are infrequent in Europe [Reference Tarnvik26].

Case numbers, incidence and outbreaks

Overall, 18 343 human cases of tularemia were reported to the WHO-CISID or ECDC databases between 1992 and 2012. Sweden reported 25% of all reported cases, Finland 22%, Turkey 13% and the Czech Republic and Hungary around 9% each.

Highest overall case numbers in Europe for the study period were observed in 2000, 2003 and 2010 with 1657, 1865 and 2458 cases respectively (Fig. 1). However, the number of reporting countries has increased over time, and the reported case numbers represented 19, 27 and 31 reporting countries, respectively. When analysed by country, high case numbers were reported by Finland and Sweden in 2000 (917 and 464 cases, respectively) and 2003 (823 and 798 cases, respectively), by Sweden in 2010 (484 cases), Norway in 2011 (178 cases), Spain in 1997 and 2007 (585 and 493, cases respectively), and Turkey in 2010 (1531 cases). The average incidence rate in the study area for 2006–2012, i.e. number of cases per 100 000 inhabitants, was 0·04; however, notably higher average incidence rates were seen in some countries. The highest average incidence rates were observed in Finland, followed by Sweden (4·84 and 3·78, respectively); relatively high average rates were also observed in Norway and Slovakia (1·16 and 0·93, respectively). When the data was examined by year, it was determined that Turkey experienced a high incidence rate in 2010 (2·11), Hungary experienced relatively high rates in 2006 (1·38) and 2010 (1·26), and Spain also had a high incidence rate in 2007 (1·11). Large variations of incidence rates occurred between years for each country, but also within each country, and the latter can be visualized at higher geographical resolutions. For example, very high incidence rates (above 82/100 000 inhabitants) were observed in Norrbotten (northern Sweden) in 2012 and in Finnmark (northern Norway) in 2011.

Fig. 1. Number of cases of tularemia by country and by year reported to the European Centre for Disease Prevention and Control (ECDC) and WHO databases between 1992 and 2012. Each country is represented by a different colour. Data for this figure come from Austria, Bosnia & Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Finland, France, Germany, Hungary, Italy, Latvia, Lithuania, Norway, Poland, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland and Turkey, but not all countries reported for the entire period.

Additional epidemiological data compiled from the literature indicated that between 1992 and 1998 in Sweden, about 80% of the cases occurred in the northern part of the country, while in 1999 and particularly in 2000, a large proportion of cases also occurred in the middle and southern regions of the country [Reference Ekdahl and Twisselmann27]. During the period from 1995 to 2001, cases of tularemia in Finland were reported predominantly in the southern and western parts of the country (National Public Health Institute of Finland), while the northern and western parts of Finland have reported outbreaks since 2000 [Reference Kuusi, Klemets and Nuorti28]. The whole country of France seems to be affected, but some areas more heavily than others, a pattern which was similarly seen in the cases observed in hares [Reference Mailles29]. Similarly, more cases occurred in the western and southern parts of Germany, with an apparent increase in the number of cases after 2004 [Reference Splettstoesser and Seibold30]. In Norway, only the southern part of the country seems to have remained unaffected. Two war-related outbreaks occurred in Kosovo in 1999 and 2001 [Reference Grunow13], (WHO 2000). As indicated in Reintjes et al. [Reference Reintjes31], an outbreak of ulceroglandular tularemia, suspected to be associated with infected hares, was also reported in central and western Bosnia in 1995, in the aftermath of warfare. Serbia was also repeatedly affected in the early 2000s, in the region bordering Bulgaria. In Spain, in Castilla y Leon, two outbreak periods occurred at a 10-year interval (1997 and 2007); one isolated event happened in 1998 in Castilla la Mancha [Reference Diaz de Tuesta11]. In Turkey, outbreaks occurred in the northern half of the country in 2005 [Reference Akalin, Helvaci and Gedikoglu25], but during subsequent outbreaks in 2010–2012, the affected zone expanded to the more central parts of the country [Reference Balci12].

Outbreaks in humans are often sporadic and likely to be spatially and temporally variable, in addition to specific sites with potential for clusters of infection. Based on the reporting of human cases the major hotspots for tularemia at the European level are located in Scandinavia and Central Europe. According to data found in the literature, southeastern Europe (Slovakia, Serbia, Kosovo, Turkey) also show elevated incidences.

Trends

Data reporting has been inconsistent through the years and therefore trend analysis cannot be performed on all of ‘the countries’ at the same time. No clear trend was apparent in the data from 12 European countries which consistently reported cases between 1992 and 2012. The same was true for 23 countries which consistently reported between 2003 and 2010, and for EU MS, Norway and Iceland during the last 5 years (Fig. 2). However, trends were apparent in individual countries: Sweden, Norway, France, Germany and possibly Turkey (no recent data is available, but data from 2005 to 2010 was examined) showed a trend towards an increasing number of cases, while a trend of decreasing case numbers was apparent in Finland, Hungary, Bulgaria and Slovakia, and no trends appeared in data from Austria and the Czech Republic (Fig. 1, Table 2). An increase in case numbers was also reported for Switzerland [Reference Lyko and Chuard32].

Fig. 2. Number of cases of tularemia by month recorded in the European Centre for Disease Prevention and Control (ECDC) database, 2008 to 2012 (n = 4388), with a 12-month moving average. Data for this figure come from Austria, Belgium, Cyprus, the Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Norway, Poland, Romania, Slovakia, Slovenia, Spain, Sweden and the UK.

Table 2. Summary of data* on tularemia in humans in Europe

* Data extracted from the European Centre for Disease Prevention and Control (ECDC) and WHO databases or the literature review (in italic) between 1992 and 2012, by country (only countries reporting cases in the last 6 years/with published articles during the study period are included).

† Number of cases per 100 000 population per year.

‡ Insufficient case numbers to calculate trends.

Pathological presentations

According to previous publications, when infected with F. tularensis, the European brown hare develops chronic lesions [Reference Gyuranecz35], while the mountain hare typically develops acute fatal septicaemia [Reference Morner33, Reference Vikoren, Handeland and Djonne36–Reference Josefsen38]. However, studies from the last two decades indicate that the European brown hare can also develop acute disease [Reference Gyuranecz35, Reference Decors39]. In acute disease, necroses are distributed in multiple organs [Reference Morner33, Reference Decors39], while in chronic cases granulomatous inflammation can be seen in a more restricted number of organs, e.g. the kidney and lungs [Reference Gyuranecz35]. For other wildlife species, descriptions of the pathology and clinical presentations in naturally infected animals are still notably absent from the literature.

Serological investigations 1992–2012

Most of the serological investigations were conducted on samples from apparently healthy hunted or trapped animals. Results are presented in Table 3. Among the studied species, antibodies have been detected in European brown hare, red fox and wild boar. In Hungary, hares have been serologically surveyed yearly since 1984. For the period 1992–2010, the overall serological prevalence in 140 935 hares tested was 6·6% [Reference Gyuranecz34]. Studies finding serologically positive animals have also been published from Austria, the Czech Republic and Germany. In these studies, the prevalence in European brown hare, red fox and wild boar varied between 1·4% and 10·8% (Table 3). Serological investigations conducted during this time period in German and Hungarian small rodents, and in Swedish lynx did not detect any antibodies [Reference Gyuranecz40–Reference Ryser-Degiorgis42]. However, studies before 1992 did detect antibodies in Norwegian lemmings [Reference Berdal43] and Swedish beavers [Reference Morner, Sandstrom and Mattsson44, Reference Morner and Sandstedt45].

Detection of the bacterium F. tularensis 1992–2012

Table 3 summarizes results from investigations on the presence of the F. tularensis bacterium either in active surveillance studies or for diagnostic purposes, in single animals or small groups of animals. Many of the studies only diagnosed F. tularensis to species level, while others also determined the subspecies, which was holarctica in all reported studies. Apparently healthy hunted European brown hares were tested in Germany, with a detection rate for the bacterium varying between 0·3% and 2·9% [Reference Hauri46, Reference Runge47]. F. tularensis was detected in hares found dead in Germany [Reference Runge47], France [Reference Lamarque, Barrat and Moutou48] and Switzerland [Reference Haerer49]. In Germany, Runge et al. [Reference Runge47] also reported that 2·4% of wild European rabbits (Oryctolagus cuniculus) found dead tested positive for F. tularensis. Small rodents were investigated, primarily by trapping, in Austria, Bulgaria, Germany, Hungary, Kosovo, Slovakia and Sweden, and the detection rates varied greatly, from 0·7% up to 20·8%. Positive individuals were found among yellow-necked mice, wood mice, house mice, striped field mice, bank voles, common voles, water voles, field voles and black rats [Reference Kaysser41, Reference Broman50]. In one study in Austria, F. tularensis was detected in 1·3% of the submandibular lymph nodes of apparently healthy hunted red foxes [Reference Hofer9]. In Portugal, 212 migratory shore birds of varying species were examined for bacteria in their blood, which resulted in the identification of F. tularensis in one little stint (Calidris minuta) [Reference de Carvalho51].

Ticks

There is strong evidence that the tick is a biological vector of F. tularensis. The bacteria has been found in the midgut and salivary glands [Reference Reif63] of ticks and has also been shown to replicate within the tick [Reference Reif63]. Ticks have been shown to be capable of transmitting the infection during a blood meal [Reference Reif63, Reference Petrov64] and mechanically via interrupted feeding [Reference Petrov64]. Furthermore, transstadial transmission of F. tularensis has been demonstrated experimentally in ticks [Reference Petrov64, Reference Petersen, Mead and Schriefer65] and field studies have isolated F. tularensis from a number of adult male Dermacentor reticulatus ticks [Reference Hubalek and Halouzka54]. Given that adult male D. reticulates ticks do not take blood meals, this suggests that transstadial transmission may have occurred. Transovarial transmission of F. tularensis has however not been shown to occur experimentally in ticks, although there have been reports of infected unfed larvae in the field [Reference Petersen, Mead and Schriefer65].

The prevalence rates detected in ticks have been mostly between 0% and 3% (Table 4). However, it should be noted that some studies estimated prevalence based on the testing of individual ticks, while others estimated prevalence by testing a pooled set of ticks. The latter type of study may not accurately reflect the prevalence of the bacterium in the tick population. This is highlighted in two studies which reported unusually high prevalence rates of 16% [Reference Hubalek and Halouzka54] and 8% [Reference Gehringer60] which were based on pools of 8–13 ticks, and therefore may not be an accurate estimation of prevalence in the population of ticks tested. Furthermore, ticks have also been found to harbour Francisella-like endosymbionts (FLEs). FLEs are non-pathogenic bacteria which are closely related to F. tularensis [Reference de Carvalho58]. These FLEs pose a challenge for accurate identification of F. tularensis by PCR as the 16S rDNA gene sequence is highly conserved between these two species [Reference Michelet66]. Thus, studies that have not used tools capable of discriminating between F. tularensis and FLEs may overestimate the prevalence of F. tularensis in ticks.

Mosquitoes

In contrast to ticks, there is less information on the role of mosquitoes as biological vectors of F. tularensis.

Lundström and colleagues isolated F. tularensis subsp. holarctica from adult mosquitoes that were collected from the field as larvae and reared in the laboratory [Reference Lundstrom61]. This suggests that the larvae acquired F. tularensis in the field, and maintained the bacteria until they were tested as adults. Furthermore, mosquito larvae predate on protozoa that have been shown to harbour F. tularensis subsp. holarctica [Reference Abd67], suggesting that it is possible that mosquitoes may acquire the infection as larvae. Transstadial transmission was also confirmed in experimental studies by Thelaus et al. [Reference Thelaus68], where 25% of the adults of Aedes aegypti infected with F. tularensis subsp. holarctica as larvae maintained the bacteria. When uninfected mosquitoes fed on infected mice they were able to acquire the bacteria. In contrast, laboratory experiments by Triebenbach et al. [Reference Triebenbach69], infecting larvae from A. aegypti and Anopheles gambiae with F. tularensis subsp. novicida concluded that there was no evidence of transstadial transmission, that mosquitoes were unable to acquire the bacteria during a blood meal and that infected mosquitoes were not able to transmit the bacteria during a blood meal. Neither the study by Thelaus et al. or Triebenbach et al. could show transmission of the bacteria from infected mosquitoes to uninfected mammal hosts. They also agree that there is no evidence for active replication of the bacterium within the mosquitoes [Reference Thelaus68, Reference Triebenbach69].

There have been relatively few studies investigating the prevalence of F. tularensis in mosquitoes (Table 4). However, when prevalence of F. tularensis was estimated in mosquitoes, it was reported to be greater than that observed in ticks (a prevalence of 8–21%), although it should be noted that this was only based on one study [Reference Lundstrom61].

Susceptibility to disease in different animal species

Sensitivity to infection, and thus the severity of the resulting disease, differs between animal species. In the WHO Guidelines on tularemia [Reference Tarnvik26], a host's potential sensitivity to F. tularensis spp. (including subspecies tularensis and holarctica) infection is classified as ‘very sensitive’, ‘medium sensitive’ or ‘resistant’, based on data from experimental infections. According to the WHO Guidelines [Reference Tarnvik26], several small rodent species are considered very sensitive to the pathogen, which can be exemplified by the experimental infection conducted on common hamster (Cricetus cricetus) leading to septicaemic disease and death [Reference Gyuranecz70]. Experimentally infected lagomorphs, have been considered to be very sensitive and develop acute disease [Reference Tarnvik26]. In Europe this has been shown in experimentally and naturally infected hares with F. tularensis subsp. holarctica [Reference Morner33, Reference Decors39, Reference Borg71]. However, studies of naturally infected European brown hares (L. europaeus) have also described chronic disease [Reference Gyuranecz35], which suggests that the disease in hares does not always have an acute and fatal presentation. Antibodies against tularemia have been detected in Eurasian beavers (Castor fiber) [Reference Morner and Sandstedt45], but unfortunately there are no studies published on the disease in naturally infected Eurasian beavers in Europe. Olsufjev (Olsufjev, 1970, cited in [Reference Tarnvik26]) suggests that some resistant genera are Canis, Felis, Meles, Nyctereutes, Vulpes and Mustela. There are, however, occasional descriptions of naturally infected and diseased domestic cats and dogs [Reference Friend2]. Birds have been experimentally infected, and most species seem to be able to become infected, but are relatively resistant to developing clinical disease [Reference Friend2]. Humans are considered to be highly susceptible to infection, resulting in a disease that ranges from mild to severe [Reference Friend2, Reference Tarnvik26]. It is important to take into account the differences in sensitivity between species in order to understand the epidemiological role of the various possible host species, and to design appropriate surveillance strategies. However, the information available on the susceptibility of European hosts to F. tularensis subsp. holarctica is limited and there are few descriptions of experimental infections and natural disease. A large part the information available (see above) is outdated and often contains no information on the subspecies of F. tularensis involved.

Geographical distribution of tularemia in Europe 1992–2012

Tularemia is widely distributed in humans, wildlife and arthropod vectors in Europe. Figure 3 maps the distribution of F. tularensis subsp. holarctica across Europe; it clearly has a broad distribution, with areas of reported presence spanning from the northernmost European countries to the southernmost ones, and from the east across to the west. It can be clearly seen from Figure 3 that tularemia is present in both humans and wildlife in the majority of European countries. However, while human cases have been reported from Estonia, Latvia, Lithuania, Slovenia, Croatia, Bosnia & Herzegovina, Serbia, Turkey and Romania, there have been no reported cases in wildlife. In Belgium there have been reports of tularemia in wildlife, but not in humans, either in the databases or the literature. In Denmark, the only wildlife case reported was in a European brown hare, and there was a single human case described in the literature [Reference Bystrom72]. Tularemia cases in domestic animals have been reported from Bulgaria, the Czech Republic, Germany, Finland, France, Italy, Norway, Poland, Slovakia, Spain, Sweden and Switzerland. Many of these were in domestic lagomorphs. F. tularensis subsp. holarctica was only reported in arthropod vectors in some of the countries where outbreaks in other hosts were also observed. One possible explanation for these differences is that the only source of information on F. tularensis in vectors is published articles, while international databases have further information on the pathogen in humans, wildlife and domestic animals. It is difficult to compare the prevalence of tularemia, both between species (humans, wildlife, domestic animals and vectors) and between countries. There have been differences in the levels of surveillance between countries, and in the level of reporting engaged in by each country, ranging from no reporting to compulsory reporting, which affects the number of cases in the databases. Notification of animal cases is mandatory at the international level. The purpose of official notification of tularemia cases is to enable the veterinary authorities of a tularemia-free country to prohibit importation or transit of live hares through their territory from countries considered infected with tularemia. As a result, some countries are reluctant to report cases, as they might suffer economic disadvantages. A further explanation for differences in levels of tularemia in the different species may be attributable to the different methods of surveillance utilized: Human cases are recorded through passive surveillance systems, while wildlife and domestic animal reports result from both passive and active, and vectors from active surveillance.

Seasonality of disease

The majority of human cases reported between 2007 and 2012 in EU countries, Norway and Iceland occurred from July to November, with a peak typically occurring in August or September. However, some cases were also reported in February and March.

Tularemia thus appears to have a clear seasonal pattern in humans in the EU, with most cases occurring in the summer and early autumn months (Fig. 4, see also trend graph in Fig. 2). However, when examined at the individual country level, the pattern of seasonality appeared highly variable. In Italy, cases were more often reported in spring; in Hungary, in summer; in Sweden, Finland and Spain, in summer/autumn; in Norway, in autumn/winter; in Germany, in winter; and in Slovakia, France and the Czech Republic, all year round with a slight peak in winter (see Table 2). Data was either missing or insufficient to assess seasonality in the other countries. According to the literature reviewed, outbreaks were reported: in spring/summer/autumn in Bulgaria, Finland, Slovakia and Sweden; in autumn/winter/spring in Kosovo and Turkey; and in all seasons in France, Germany, Norway and Spain (see Table 2). Thus, in some countries, outbreaks occurred in periods during which the Europe-wide average reported incidence was low.

Fig. 4. Number of cases of tularemia by month recorded in the European Centre for Disease Prevention and Control (ECDC) database (n = 5715), 2007 to 2012. Data for this figure has been reported by Austria, Belgium, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Norway, Poland, Romania, Slovakia, Slovenia, Spain, Sweden and the UK.

In wildlife, previous studies have reported seasonal patterns of outbreaks in Northern Europe, which researchers have associated with the peak of the mosquito season [Reference Morner33]. From 1992 to 2012, a study was conducted on Norwegian mountain hares, which were found dead between May and November, and had died of tularemia [Reference Vikoren, Handeland and Djonne36–Reference Josefsen38]. These hares had septicaemic (acute) disease; as this form of tularemia results in death within a few days, it is likely they were infected shortly before death. Since the mosquito season spans from about June to September in Scandinavia, the timing for these infections would be consistent with the hypothesis that the mosquitoes played an important role in spreading the infection. Information from studies on European brown hares in Hungary, by contrast, have not been as informative with respect to the time of infection and identification of possible vectors. In Hungary, hares have been examined primarily during hunting season; in those infected with tularemia, the lesions were consistent with subacute to chronic disease, making it difficult to establish at what time point the hares contracted the infection [Reference Gyuranecz35]. Efforts have been made to detect F. tularensis in small rodents in endemic areas in Bulgaria, at the Austrian-Slovakian border, and in Hungary and Sweden (Table 3). Only two studies, both on the Austrian–Slovakian border, presented results by season [Reference Gurycova73, Reference Vyrostekova74]. The combined results showed a bacterial detection rate of 0% in January–June, 1·2–2·6% in June/July–September and 3·9–8·3% in October–December. It is not possible to determine if these results reflect a true seasonality, since the studies were small, and limited in both time and geographical location.

Reports of tularemia in domestic animals have been almost exclusively about farmed hares/rabbits [22, 23] and give no information on seasonality.

Human disease and risk factors

The most frequent clinical presentations of tularemia in humans in Europe, routes of infection, type of exposure, and risk factors are all summarized in Table 1. Oropharyngeal outbreaks were more frequent in autumn/winter/spring in most of the countries, associated with exposure to contaminated food or water, while ulceroglandular forms occurred mostly in summer or autumn, associated with exposure to infected vectors or hares (see also Table 2). The most frequently reported information on wildlife, associated with all forms of human outbreaks, was observations of increased numbers of rodents or dead hares, or contact with these (Table 2). Infection can indeed occur through direct contact, for example when hunters skin infected hares. Two outbreak investigations in Spain in 1998–1999 and 2007 mentioned handling of red crayfish as a risk factor for infection [Reference Anda75, Reference Allue76]. From the literature reviewed in the current study, the most frequently mentioned risks for humans in Europe to contract tularemia were from: consumption of contaminated water or food (mentioned 20 times), direct (skin) contact with infected animals – frequently wild ones (mentioned 19 times), vector bites from infected arthropods (mentioned 13 times), and exposure to infected environments via air (mentioned 10 times). Males in general and rural populations were found to be more often occupationally exposed (mentioned 11 times), urban populations to be affected through recreational outdoor activities, like hunting and fishing (mentioned 10 times). Contact with domestic animals has on occasion been implicated as a risk factor in connection with tularemia outbreaks in humans [Reference Leblebicioglu18, Reference Allue76–Reference Guercan79]. The few papers or case reports on seropositivity to F. tularensis in domestic animals in European countries (see Table 3) often resulted from investigations of potential risk factors for human outbreaks. Apart from those studies, evidence of the link between tularemia in domestic animals and humans in Europe was often circumstantial, and traced to reports of humans in whom infection was detected after they were scratched or bitten by cats [Reference Rodon80, Reference Yaqub, Bjørnholt and Enger81] or had been fleecing sheep [Reference Senol82]. The information regarding tularemia in zoo animals is scarce and describes mostly outbreaks or single cases in non-human primates. However, recently Kuehn et al. [Reference Kuehn10] performed serological investigations of 1122 German zoo animals representing 46 different species, most of them ungulates. Three (0·3%) tested positive for antibodies against tularemia. Contact between wild animals, e.g. small rodents, and zoo animals located in the same geographic area might enable transmission of tularemia between these animal groups. This study showed low seroprevalence and therefore the risk for humans to contract infection from zoo animals was likely low.

Sources of infection and routes of dissemination

Wild animals and arthropods appear to be important sources of infection with F. tularensis for humans and other animals. In theory, species that are moderately susceptible to tularemia, and maintain the infection for a prolonged time, may serve as reservoirs. In other hosts, bacterial amplification can occur, and they may serve as a source of infection to others [Reference Haydon83]. It has been shown that sensitivity to F. tularensis infection, and susceptibility to develop disease, varies between animal species. The sources of infection for animals have not been well investigated, but it is reasonable to hypothesize that they could be infected by routes similar to those for humans, i.e. through direct contact with secretions from infected animals, from ingestion of contaminated food or carcasses, via vectors, or from inhalation of the bacteria. Only a few studies have investigated the distribution of lesions in wildlife to determine in which organs lesions were present. Similarly, few studies have investigated possible routes of infection and shedding of F. tularensis in wildlife. In Hungary, hunted European brown hares with tularemia had subacute to chronic lesion in the lungs, pericardium, and kidneys [Reference Gyuranecz35]. Because lung involvement was a common finding, the authors postulated a respiratory route of infection. In terms of transmission of the disease, hares with chronic disease in the kidney could, in theory, shed bacteria in urine and thereby serve as a source of infection. This has not been shown in hares, but in experimental infection of meadow vole (Microtus pennsylvanicus) the animals developed bacteriuria [Reference Bell and Stewart84]. Olsufjev [Reference Olsufjev and Pavlovsky1] reported that the organs and blood of small rodents contained numerous bacteria, which could pose a risk for transmission to other animals either through shedding by the rodents during the acute phase of the disease, or as contaminated carcasses once the animals died. Most of the descriptions of transmission from small rodents to humans resulted from contact with dead infected animals, for example as reported through skinning of hamsters [Reference Munnich and Lakatos85]. There is very little information about their importance as live shedders or as reservoir hosts. Naturally infected small rodents have only been investigated for the presence of the agent, but not for lesions [Reference Reintjes31, Reference Gyuranecz40, Reference Kaysser41, Reference Broman50, Reference Gurycova73, Reference Christova and Gladnishka86, Reference Berdal87]. The fact that these small rodents were alive while harboring the bacterium might reflect that they acted as healthy carriers, had chronic disease, or had been recently infected and had not yet developed disease. Small rodents have also been implicated in the spread of tularemia through the contamination of food and water. In Norway, outbreaks of tularemia in humans have been attributed to drinking water from water-wells contaminated by dead lemmings or their excreta [Reference Larssen88]. Similarly, in Kosovo an outbreak of oropharyngeal tularemia in humans was attributed to contamination of food and water with rodent faeces [Reference Reintjes31]. From the studies conducted to date, it is not clear if small rodent species act as amplifiers of tularemia infection or might be reservoirs, or if their role differs in different areas, given that multiple factors are involved in the eco-epidemiology of tularemia. Red fox, wild boar and raccoon dog may contract infection (Table 3, [Reference Kuehn10]) when eating infected prey such as hares and small rodents and develop antibodies. However these species are not considered to be particularly susceptible to developing disease. Their potential role as asymptomatic carriers, shedding and/or spreading the infection in nature, has not been investigated [Reference Olsufjev and Pavlovsky1, Reference Hoflechner-Poltl7, Reference Hofer9, Reference Hubalek89, Reference Al90].