Abstract

Main tick-borne diseases in Europe are reviewed with particular emphasis to emerging, zoonotic rickettsial, ehrlichial and spirochetal infections. "New" species of bacteria have been isolated from animals and ticks and are now considered emergent as a consequence of the global changing of climate, of land exploitation for human activities and ecology of ticks and infection reservoirs.

Since the beginning of this century, ticks have been described as vectors of human and animal diseases, including, bacterial (spotted fever rickettsioses, recurrent fever borreliosis, tularemia, Q fever), viral and protozoan zoonoses (Parola and Raoult, 2001). Ticks are considered to be second only to mosquitoes as vectors of such diseases in the world (Sonenshine, 1991). The first demonstration that ticks were able to transmit infectious diseases was made when Boophilus annulatus was considered as the vector of the protozoan Babesia bigemina, the agent of Texas cattle fever (Smith and Kilbourne 1893).

Canine babesiosis is widely spread in Europe, and the Mediterranean is most affected (Spain, South of France, Italy, Greece, Turkey) including several continental areas in eastern Europe such as Hungary are at high risk of infection (Horvath and Papp, 1996). The protozoa is transmitted mainly by ticks Rhipicephalus sanguineus and Dermacentor reticulates, which also act as reservoir. The prevalence of infection in canine populations is strongly affected by the relative humidity which influence the abundance of ticks in the environment. Furthermore, the yearly prevalence may range from less than 5% to >15% in the same endemic area as a consequence of climatic conditions (Traldi et al., 1988; Puccini et al., 1998). Most clinical cases are diagnosed between April and May. Babesia canis canis and B. canis vogeli are the species usually found in the European dogs (CacciÁ et al., 2002; Criado-Fornelio et al., 2002). B. gibsoni has till now only been found in imported animals.

Bacterial diseases

Since Smith and Kilbourne's findings (1893), ticks have been identified as vectors of numerous human bacterial diseases such as Borrelia duttonii, the agent of Tick relapsing fever (Dutton and Todd, 1905) or Rickettsia rickettsii, the agent of the Rocky Mountain spotted fever (Ricketts, 1909). The first cases of Mediterranean spotted fever were reported in Tunis in 1910 (Conor and Bruch, 1910), but the role of R. sanguineus as the vector of the disease was established later (Brumpt 1932). The Lyme borreliosis, one of the most important vector-borne disease in both United States and Europe, caused by the spirochete Borrelia burgdorferi, was described in 1984 (Johnson et al., 1984). In recent decades, numerous tick-borne bacterial diseases have been reported worldwide (Raoult and Roux, 1997).

Ticks can act as vectors and also as reservoirs of tick-transmitted bacteria, including spotted fever group rickettsiae, recurrent fever Borreliae and Francisella tularensis. In these cases, ticks transfer the bacteria to vertebrates via salivary secretions and between themselves transstadially and transovarially. The prevalence of these tick-borne diseases are primarily dependent on the geographic distribution of host ticks, which act both as vector and reservoir.

Some endosymbiont bacteria, such as a member of the Francisella genus found in Dermacentor andersoni by Niebylski et al., (1997), are transmitted transovarially but since they do not infect the tick salivary glands, they cannot then be transmitted to vertebrate hosts during blood feeding. Furthermore, some bacteria apparently can damage the tick host itself, as it has been demonstrated for R. rickettsii (Niebylski et al., 1999).

Among the numerous bacterial agents transmitted by ticks in Europe, some of them are considered as emerging in the last decades (Parola and Raoult 2001):

Rickettsioses are caused by obligate intracellular bacteria belonging to the genus Rickettsia (Raoult and Roux, 1997). Before 1974, only four tick-borne rickettsioses were known (R. rickettsii in the Americas, R. conorii in Europe, southwest Asia, and Africa, R. sibirica in Siberia and western Russia and R. australis in Australia) (Raoult and Roux, 1997). More recently, the increased use of molecular-based identification methods has resulted in new pathogenic tick-borne rickettsiae being described (Raoult and Roux, 1997; Raoult et al., 1997; Nilsson et al., 1999). Examples are R. helvetica (Nilsson et al., 1999; Fournier et al., 2000), R. slovaca (Raoult et al., 2002), R. mongolotimonae (Fournier et al., 2000), or the Israeli spotted fever Rickettsia (R. conorii complex) (Giammanco et al., 2003). R. Helvetica, R. slovaca, R. africae, R. aeshlimanni and the Israeli spotted fever Rickettsia have been detected in ticks from Italy (Beninati et al., 2002; Beninati et al., 2004; Giammanco et al., 2003).

The detection of antibodies against R. conorii in dogs has been used in epidemiological studies due to the high levels of exposure to R. sanguineus and to the intense antibody response to the organism encountered in dogs (Segura-Porta et al., 1998; Mannelli et al., 2003). In Italy, high seroprevalences of R. conorii has been found in several survey in healthy dogs throughout the country (30-80%), with the highest values in dogs aged more than 2 years (Melgrati et al., 1999; Mannelli et al., 2003). Though the clinical signs of infection are practically absent in dogs and dogs cannot act as a reservoir (as do ticks), seroprevalence data can useful as a sensitive indicator for the risk of infection for humans. To note that R. rickettsii, the agent of Rocky Mountain spotted fever, has never been isolated from humans, dogs or ticks in Europe, but diagnosed in patients after returning from USA (Reinauer et al, 1990).

Although ehrlichiae were known for long time as veterinary pathogens, they have recently been recognized as emerging tick-borne pathogens also in humans (Nuti et al. 1998). In particular, Human Granulocytic Ehrlichiosis (HGE), first described in USA (Dumler and Bakken 1998), has emerged in Europe. The causative agent is Anaplasma (formerly Ehrlichia) phagocytophila. In Europe the tick vector is Ixodes ricinus and the reservoirs are small rodents such as Apodemus or Clethrionomys spp. (Liz et al., 2000). The first documented human case of HGE in Europe was reported in Slovenia in 1997 (Petrovec et al., 1997), and later the A. phagocytophila agent was detected in different European countries (Parola and Raoult 2001). To date, there are no reports on the presence of E. chaffeensis or E. ewingii in Europe, described in USA as an agent of human ehrlichioses (Parola and Raoult, 2001). Other ehrlichiae of veterinary importance, including Ehrlichia canis and Ehrlichia ruminantium, are widely distributed on the continent, and these organisms are known to cross-react with E. chaffeensis in serological tests. The presence of antibodies against E. canis in dogs from Italy has been reported (Buonavoglia et al., 1995).

Lyme borreliosis is caused by Borrelia burgdorferi sensu stricto, B. garinii and B. afzelii, all species within the B. burgdorferi sensu lato complex. Recently, a pathogenic role for B. valaisiana in humans has also been considered (Ryffel et al. 1999). In Europe, Apodemus spp. are considered the most important reservoirs of the bacteria. Much less is known about LymeBorreliosis in animals than is known about the disease in humans. The most common symptom of the disease in dogs is migratory arthritis (Magnarelli et al. 1987). Other but less common symptoms reported in dogs are carditis, glomerulonephritis and neuritis (Goossens et al. 2001). B. burgdorferi infections or serologic evidence of B. burgdorferi infections have been reported in dogs in the United States (Magnarelli et al. 1987). In Europe, relatively few reports exist on Lyme borreliosis in animals. A recent study by Goossens et al. (2001) carried out in The Netherlands found no positive correlation between the seropositivity of hunters and the seropositivity of their huntering dogs. For this reason, direct transfer of ticks between dog and humans does not seem important and owning a dog should not be considered a risk factor for Lyme Borreliosis.

In Europe and Africa, tick-borne relapsing fever is caused by Borrelia crocidurae, B. hispanica, and B. duttoni and is transmitted by Argasid ticks of the genus Ornithodoros (Parola and Raoult 2001). Recently, a "Spain strain" of this spirochete was implicated in human disease (Anda et al. 1996). Moreover, the discovery of a Borrelia species associated with relapsing fever in hard ticks has challenged the assumption that these organisms are associated only with soft ticks (Anda et al. 1996).

Conclusion

Since the beginning of the 1980s, more than 15 new tick-borne bacterial diseases have been described in the world. The increasing number of pathogens recently discovered may be as a consequence of the use of new molecular biological tools, which have facilitated studies of the epidemiology of emerging tick-borne diseases all over the world. Moreover, a number of Rickettsia, Borrelia, and Ehrlichia have been found in ticks only, and their pathogenicity in humans or animals is yet to be determined. However, the new trend in human activity leading to and increased frequentation of wilderness has increased the risk of tick infestations and infection transmission. Furthermore, the increased abundance of wild animal reservoir such as deer and rodents and the global changing of climate have resulted in a tremendous increase of tick populations, accelerating the ecological cycle of pathogenic microorganisms and in a dramatic surge in disease incidence.

References

1.  Anda P, W Sanchez-Yebra, et al. (1996). A new Borrelia species isolated from patients with relapsing fever in Spain. Lancet 348(9021): 162-5.

2.  Beninati T, N Lo, et al. (2002). First detection of spotted fever group rickettsiae in Ixodes ricinus from Italy. Emerg Infect Dis 8: 983-6.

3.  Beninati T, N Lo, et al (2004) Molecular characterization of Spotted Fever Group rickettsiae in Ixodid ticks from Sicily. Emerg Infect Dis in press.

4.  Brumpt E (1932). Longevité du virus de la fièvre boutonneuse (Rickettsia conorii, n. sp.) chez la tique Rhipicephalus sanguineus. C R Soc Biol 110: 1197-9.

5.  Buonavoglia, D, P Sagazio, et al. (1995). Serological evidence of Ehrlichia canis in dogs in southern Italy. New Microbiol 18(1): 83-6.

6.  CacciÁ SM, B Antunovic, et al. (2002). Molecular characterization of Babesia canis canis and Babesia canis vogeli from naturally infected European dogs. Vet Parasitol 106: 285-292.

7.  Conor A and A Bruch (1910). Une fièvre éruptive observée en Tunisie." Bull Soc Pathol Exot Filial 8: 492-6.

8.  Criado-Fornelio A, A Martinez-Marcos et al. (2002). Molecular studies on Babesia, Theileria and Hepatozoon in southern Europe. Part I. Epizootiological aspects. Vet Parasitol 113: 189-201

9.  Dumler JS and JS Bakken (1998). Human ehrlichioses: newly recognized infections transmitted by ticks. Ann Rev Med 49: 201-13.

10. Dutton JE and JL Todd (1905). The nature of tick fever in the eastern part of the Congo Free State, with notes on the distribution and bionomics of the tick. Br Med J 2: 1259-60.

11. Fournier PE, F Grunnenberger, et al. (2000). Evidence of Rickettsia helvetica infection in humans, eastern France. Emerg Infect Dis 6(4): 389-92.

12. Fournier PE, H Tissot-Dupont, et al. (2000). Rickettsia mongolotimonae: a rare pathogen in France. Emerg Infect Dis 6(3): 290-2.

13. Giammanco G, S Mansueto, et al. (2003). Israeli spotted fever Rickettsia in Sicilian Rhipicephalus sanguineus ticks. Emerg Infect Dis 9(7): 892-3.

14. Goossens HA, AE van den Bogaard et al. (2001). Dogs as sentinels for human Lyme borreliosis in The Netherlands. J Clin Microbiol 39: 844-8.

15. Horvath L, L Papp (1996) Prevalence, symptoms and treatment of canine babesiosis. Magyar All Lapja 51: 180-187.

16. Johnson RC, GP Schmid et al. (1984). Borrelia burgdorferi sp. nov.: etiological agent of Lyme disease. Int J Syst Bacteriol 34: 496-7.

17. Liz JS, L Anderes et al. (2000). PCR detection of granulocytic ehrlichiae in Ixodes ricinus ticks and wild small mammals in western Switzerland. J. Clin. Microbiol. 38: 1002-7.

18. Magnarelli LA, JF Anderson et al. (1987). Clinical and serologic studies of canine borreliosis. J Am Vet Med Assoc 191(9): 1089-94.

19. Mannelli A, ML Mandola et al. (2003). Associations between dogs that were serologically positive for Rickettsia conorii relative to the residences of two human cases of Mediterranean spotted fever in Piemonte (Italy). Prev Vet Med 60: 13-26.

20. Melgrati E, M Pilla et al (1999) Seroprevalence of anti-Rickettisa colorii antibody in dogs from north-west of Province of Milan following some cases of autochthonous infections in humans. Giornale Italiano Malattie Infettive 5: 34-39.

21. Niebylski ML, MG Peacock et al. (1997). Characterization of an endosymbiont infecting wood ticks, Dermacentor andersoni, as a member of the genus Francisella. Appl Environ Microbiol 63(10): 3933-40.

22. Niebylski ML, MG Peacock et al. (1999). Lethal effect of Rickettsia rickettsii on its tick vector (Dermacentor andersoni). Appl Environ Microbiol 65: 773-8.

23. Nilsson K, O Lindquist et al. (1999). Association of Rickettsia helvetica with chronic perimyocarditis in sudden cardiac death. Lancet 354(9185): 1169-73.

24. Nuti M, DA Serafini et al (1998). Ehrlichia infection in Italy. Emerg Infect Dis 4(4): 663-5.

25. Parola P and D Raoult (2001). Ticks and tickborne bacterial diseases in humans: an emerging infectious threat. Clin Infect Dis 32(6): 897-928.

26. Parola P and D Raoult (2001). Tick-borne bacterial diseases emerging in Europe. Clin Microbiol Infect 7(2): 80-3.

27. Petrovec M, S Lotric Furlan et al. (1997). Human disease in Europe caused by a granulocytic Ehrlichia species. J Clin Microbiol 35: 1556-9.

28. Puccini V, Fasanella A et al (1998) Canine babesiosis in Puglia. Prevalence, risk factors and tick species involved in the transmission. Obiettivi e Documenti Veterinari 19: 55-61.

29. Raoult D, P Berbis et al. (1997). A new tick-transmitted disease due to Rickettsia slovaca. Lancet 350(9071): 112-3.

30. Raoult D, A Lakos et al. (2002). Spotless rickettsiosis caused by Rickettsia slovaca and associated with Dermacentor ticks. Clin Infect Dis 34(10): 1331-6.

31. Raoult D and V Roux (1997). Rickettsioses as paradigms of new or emerging infectious diseases. Clin Microbiol Rev 10(4): 694-719.

32. Ricketts, HT (1909). Some aspects of Rocky Mountain spotted fever as shown by recent investigations. Med Rec 16: 843-55.

33. Ryffel K, O Peter et al. (1999). Scored antibody reactivity determined by immunoblotting shows an association between clinical manifestations and presence of Borrelia burgdorferi sensu stricto, B. garinii, B. afzelii, and B. valaisiana in humans. J Clin Microbiol 37(12): 4086-92.

34. Segura-Porta F, G Diestre-Ortin et al. (1998). Prevalence of antibodies to spotted fever group rickettsiae in human beings and dogs from and endemic area of mediterranean spotted fever in Catalonia, Spain. Eur J Epidemiol 14(4): 395-8.

35. Smith T and FL Kilbourne (1893). Investigators into the nature, causation, and prevention of Texas or southern cattle fever. Bull Bur Anim Ind, US Dept Agric 1: 301.

36. Sonenshine DE (1991). Biology of ticks. New York, Oxford University Press.

37. Traldi G, MH Ahmed, M Mazzucchelli (1988). Diffusione di Babesia canis in 2 province del nord Italia. Parassitologia 30 (Suppl 1): 209-210.