Open Access

Prevalence of tick-borne encephalitis virus in Ixodes ricinus ticks in northern Europe with particular reference to Southern Sweden

  • John H-O Pettersson1,
  • Irina Golovljova2,
  • Sirkka Vene3 and
  • Thomas GT Jaenson1Email author
Parasites & Vectors20147:102

https://doi.org/10.1186/1756-3305-7-102

Received: 2 January 2014

Accepted: 16 February 2014

Published: 11 March 2014

Abstract

Background

In northern Europe, the tick-borne encephalitis virus (TBEV) of the European subtype is usually transmitted to humans by the common tick Ixodes ricinus. The aims of the present study are (i) to obtain up-to-date information on the TBEV prevalence in host-seeking I. ricinus in southern and central Sweden; (ii) to compile and review all relevant published records on the prevalence of TBEV in ticks in northern Europe; and (iii) to analyse and try to explain how the TBE virus can be maintained in natural foci despite an apparently low TBEV infection prevalence in the vector population.

Methods

To estimate the mean minimum infection rate (MIR) of TBEV in I. ricinus in northern Europe (i.e. Denmark, Norway, Sweden and Finland) we reviewed all published TBEV prevalence data for host-seeking I. ricinus collected during 1958–2011. Moreover, we collected 2,074 nymphs and 906 adults of I. ricinus from 29 localities in Sweden during 2008. These ticks were screened for TBEV by RT-PCR.

Results

The MIR for TBEV in nymphal and adult I. ricinus was 0.28% for northern Europe and 0.23% for southern Sweden. The infection prevalence of TBEV was significantly lower in nymphs (0.10%) than in adult ticks (0.55%). At a well-known TBEV-endemic locality, Torö island south-east of Stockholm, the TBEV prevalence (MIR) was 0.51% in nymphs and 4.48% in adults of I. ricinus.

Conclusions

If the ratio of nymphs to adult ticks in the TBEV-analysed sample differs from that in the I. ricinus population in the field, the MIR obtained will not necessarily reflect the TBEV prevalence in the field. The relatively low TBEV prevalence in the potential vector population recorded in most studies may partly be due to: (i) inclusion of uninfected ticks from the ‘uninfected areas’ surrounding the TBEV endemic foci; (ii) inclusion of an unrepresentative, too large proportion of immature ticks, compared to adult ticks, in the analysed tick pools; and (iii) shortcomings in the laboratory techniques used to detect the virus that may be present in a very low concentration or undetectable state in ticks which have not recently fed.

Keywords

Ixodes ricinus Minimum infection rate Real-time PCR Sweden Norway Denmark Finland TBE Tick-borne encephalitis virus Virus prevalence

Background

The common tick Ixodes ricinus is the most important arthropod vector of pathogens of human diseases in Europe [1, 2]. One of these pathogens potentially causing human disease is the tick-borne encephalitis virus (TBEV), a member of the tick-borne group within the genus Flavivirus[3], family Flaviviridae [4]. Tick-borne encephalitis (TBE) is a potentially fatal disease syndrome of humans and some other mammals [5]. TBE is endemic in central, eastern, and northern Europe eastwards through Russian Siberia and China [68]. During the last two decades, 1990–2009, an annual mean incidence of 2,815 cases of human TBE was recorded for Europe, while a corresponding annual mean incidence of 5,682 human TBE cases was reported from Russia [7].

Currently, the TBEV complex is considered to encompass three virus subtypes; the European (TBEV-Eu), the Far-Eastern (TBEV-Fe), and the Siberian TBEV (TBEV-Sib) [4, 5, 9]. TBEV-Eu is mainly vectored by I. ricinus while I. persulcatus is the primary vector of the Siberian and Far Eastern subtypes [5]. The European subtype is present in certain foci in Sweden, Norway, Denmark, Finland, Russia, the Baltic countries and southwards through several east, central and south European countries [7]. The Far-Eastern subtype, in contrast to the Siberian subtype, has not yet been found in Northern Europe. However, it is present in populations of I. persulcatus in the Baltic area [10] and western Russia not far from the Finnish border. Its geographical range extends eastwards to China and Japan [9, 11]. The Siberian subtype is found in Siberia, eastern Europe and western Russia [9, 10, 12], but also in Finland [13]. All three subtypes are known to co-circulate in areas where the geographical ranges of I. ricinus and I. persulcatus overlap [14, 15]. The European subtype is the only subtype so far found in ticks in Sweden [1618], Norway [19] and Denmark [20]. In Finland, both the European and Siberian viruses have been detected in I. persulcatus. Only the former virus subtype has been recorded from I. ricinus in Finland [13, 21, 22].

More than 70% of TBEV infections in humans are without symptoms [5]. Virulence and disease symptoms exhibit characteristic differences related to virus subtype. The overt disease caused by TBEV-Eu may range from a relatively mild influenza-like infection to a severe, life-threatening disease with paralytic long-lasting sequelae. The mortality rate caused by infections with TBEV-Eu is about 1–2% while that of the Siberian subtype rarely exceeds 8% [5]. The Far-Eastern subtype often causes a monophasic disease with a high rate of severe neurologic sequelae and a mortality rate that sometimes exceeds 20% [5, 6, 2325].

In Sweden the first human TBE case was described in 1954 [26]. Four years later the virus was isolated from I. ricinus ticks and from a patient. Since then, the annual incidence of human TBE has increased from 60–80 cases/year before the 1990s to more than 100 cases/year since 2000, thereafter increasing even further to more than 150 cases/year since 2006 with a significant increasing trend during 2000–2012 [27]. This rise in TBE incidence in Sweden is attributed to a combination of biotic and climatological factors, particularly high abundance of roe deer and other cervids in southern Sweden since the mid-1980s and a warmer climate with a prolonged vegetation period [27, 28]. Based on data for the year 2009 for the Scandinavian countries, Sweden has the highest TBE incidence (2.3 per 100 000), followed by Finland (0.5 per 100 000), Norway (0.2 per 100 000), and Denmark (0.02 per 100 000) [7]. The only regional estimates of TBEV prevalence in I. ricinus published so far refer to southwestern Sweden. They range from 0.10% to 0.42% [29].

Despite the great public health importance of TBE, some aspects of the ecology of TBEV have not been adequately investigated. One characteristic of the ecology of the TBE virus is its irregular distribution over a large geographical range with a patchy occurrence in restricted foci of limited size [3033]. This is in contrast to several other Ixodes-transmitted pathogens, such as Anaplasma phagocytophilum[34, 35] and some genospecies in the Borrelia burgdorferi sensu lato complex, the endemic regions of which are extensive and sometimes even include whole countries [36, 37]. Another peculiarity of TBEV, which has puzzled scientists for a long time, is the low prevalence of the virus, usually <1%, in the I. ricinus population. This phenomenon also differs from the usually significantly higher prevalence of most of the bacteria vectored by I. ricinus[34, 35, 37, 38]. Thus, the question arises how the virus can be maintained in a small focus for many years despite such apparently low infection prevalence in I. ricinus.

Here we present TBEV prevalence data based on virus screening of I. ricinus collected at 29 localities in the main TBEV-endemic regions of southern Sweden during 2008. We also provide a summary of all relevant, published TBEV-prevalence data for I. ricinus collected in Sweden and its three neighbouring countries Denmark, Norway and Finland.

Methods

Tick collection

Between May-September 2008, host-seeking (that usually do not contain any visible blood in the gut) I. ricinus were collected at 29 localities in southern and central Sweden (Figure 1, Additional file 1: Table S1) as previously described [39]. In short, a total of 2,074 nymphs and 906 adult ticks (481 females and 425 males) were collected by a person pulling a 1 × 1 (1 m2) white flannel cloth placed horizontally on the ground vegetation in deciduous or mixed deciduous/coniferous woodland biotopes [40]. At Norbo Finnmark, 12 adult I. ricinus, four of which were fully engorged, were removed from a pet dog (Canis lupus domesticus) (Table 1). All ticks were identified as I. ricinus based on morphological criteria according to [41, 42]. The words “tick” and “ticks”, when used in this article, denote I. ricinus.
Figure 1

Map of southern and central Sweden. The numbers refer to localities where nymphs and adults of Ixodes ricinus ticks were collected. These ticks were subsequently analysed for TBEV infection. The name of each numbered locality and its GPS coordinates can be found in Table 1 and Additional file 1: Table S1, respectively.

Table 1

Summary of published and unpublished data on I. ricinus ticks collected in Sweden, Norway, Finland and Denmark analysed for TBE virus infection

   

Number of collected ticks

Number of TBEV-positive

Prevalence estimate (%)

  

Country

Collection year

Locality

Nymphs

Males

Females

Total

Pools

Positive pools

Positive nymphs

Positive adults

MIR nymphs

MIR adults

MIR all

Method

Reference

Sweden

1958

96 km NE of Stockholm (9 sites)

35

898

933

24

4

1

3

2.86

0.33

0.42

MBI*

[43]

Sweden

2003

Torö

106

9

115

1

1

0.87

RT-PCR

[17]

Sweden

2003

Combined central Sweden (3 sites)

167

23

190

1

1

0.53

RT-PCR

[17]

Sweden

2006

3 sites south of Vänern (T1-T3)

4380

220

220

4820

263

11

9

2

0.21

0.45

0.23

RT-PCR

[29]

Sweden

2004

South-western Sweden (T4)

2740

70

2810

144

7

6

1

0.22

1.43

0.25

RT-PCR

[29]

Sweden

2008

Hudiksvall (1)

30

6

5

41

14

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Stenö/Källskär (2)

300

90

92

482

202

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Gävle (3)

4

1

0

5

2

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Trödje (4)

3

2

2

7

4

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Skutskär (5)

29

11

15

55

27

1

0

1

0

3.85

1.82

RT-PCR

This study

Sweden

2008

Älvkarleby (6)

10

6

13

29

20

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Borlänge (7)

7

4

4

15

9

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Vikmanshyttan (8)

15

2

4

21

7

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Östhammar (9*)

94

10

15

119

31

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Norbo Finnmark (10)

11

11

12

34

24

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Väddö (11*)

32

10

6

48

18

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Skebobruk (12*)

40

13

19

72

34

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Morga (13*)

300

31

55

386

114

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Rimbo (14*)

8

2

4

14

7

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Kapellskär (15*)

373

59

70

502

151

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Kolarvik (16*)

158

57

49

264

115

1

1

0

0.63

0

0.38

RT-PCR

This study

Sweden

2008

Västerås (17*)

137

11

24

172

47

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Strängnäs (18*)

37

27

22

86

51

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Eskilstuna (19*)

27

4

7

38

13

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Karlstad (20)

9

5

3

17

9

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Värmdö (21*)

46

3

6

55

16

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Askersund (22)

36

0

5

41

9

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Herrhamra (23*)

196

31

36

263

99

4

1

3

0.51

4.48

1.52

RT-PCR

This study

Sweden

2008

Kapellängen, GS (24) (P)

24

21

2

47

25

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Gamla gården, GS (25) (P)

5

2

2

9

4

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Jönköping (26)

30

2

1

33

5

1

0

1

0

33.33

3.03

RT-PCR

This study

Sweden

2008

Västervik (27)

14

4

5

23

10

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Änggårdsbergen (28)

31

0

1

32

3

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Särö Västerskog (29) (P)

68

0

2

70

8

0

0

0

0

0

0

RT-PCR

This study

Sweden

2008

Combined central Sweden, 12 sites*

1448

258

313

2019

258

5

2

3

0.14

0.53

0.25

RT-PCR

This study

Sweden

2008

Combined Sweden, 29 sites

2074

425

481

2980

1074

7

2

5

0.10

0.55

0.23

RT-PCR

This study

Sweden

1958–2008

Combined Sweden, 4 studies, 45 sites

9396

2337

11733

1510

30

18

11

0.19

0.47

0.26

*/PCR

[17, 29, 43], this study

Finland

1957–1960, 1964

Archipelago of southern-western Finland

4932

391

389

8131

249

18

0.22

MBI**

[44]

Finland

1957-1960, 1964

Southern Finland

124

9

0

133

7

0

0

MBI**

[44]

Finland

1957–1960, 1964

South-eastern Finland

1308

39

84

1643

51

1

0.06

MBI**

[44]

Finland

1996–1997

Isosaari (Mjölö) island, Helsinki

69

70

139

20

1

0.72

RT-PCR

[45]

Finland

1996–1997

Åland islands

203

247

450

48

1

0.22

RT-PCR

[45]

Finland

1996–1997

Helsinki city parks

74

123

726

130

0

0

RT-PCR

[45]

Finland

2004

Kokkola (Karleby) archipelago (10 sites)

72

539

570

1181

122

13

1.10

RT-PCR

[13]

Finland

2003

Kumlinge

454

46

4

0.88

RT-PCR

[21]

Finland

2005

Isosaari (Mjölö) island, Helsinki

96

11

1

1.04

RT-PCR

[21]

Finland

2007

Turku (Åbo) archipelago

1039

315

1

0.10

RT-PCR

[21]

Finland

2005

Lappeenranta (Villmanstrand)

292

29

2

0.68

RT-PCR

[21]

Finland

2008

Närpiö (Närpes)

36

0

0

RT-PCR

[21]

Finland

1957–2008

Combined Finland, 4 studies, ≥ 27 sites

   

14320

2490

42

0.29

**/PCR

[13, 21, 44, 45]

Norway

2003

Vest-Agder and Hordaland county

360

  

1

0.28

RT-PCR

[19]

Norway

2004

Vest-Agder and Hordaland county

450

  

1

0.22

RT-PCR

[19]

Norway

2009

Risør, Dalen (S1)

900

900

90

1

1

0.11

0.11

RT-PCR

[46]

Norway

2009

Arendal (S2–S3)

1350

1350

135

8

8

0.59

0.59

RT-PCR

[46]

Norway

2009

Mandal (S4–S5)

1520

1520

152

9

9

0.59

0.59

RT-PCR

[46]

Norway

2009

Lyngdal (S6–S7)

1860

1860

186

6

6

0.32

0.32

RT-PCR

[46]

Norway

2003–2009

Combined Norway, 2 studies, 9 sites

   

6440

≥ 563

26

0.40

RT-PCR

[19, 46]

Denmark

1999

Bornholm (7 sites)

3843

215

4058

 

2

0.05

RT-PCR

[47]

Denmark

2002–2003

Northern Zealand

50

25

30

105

3

1

1

2.00

0.95

RT-PCR

[48]

Denmark

2002–2003

3 different sites

62

62

9

0

 

RT-PCR

[48]

Denmark

2011

Tokkekøb (3 sites, Jun.)

854

22

20

896

24

3

2

1

0.23

2.38

0.33

RT-PCR

[20]

Denmark

2011

Tokkekøb (3 sites, Sept.)

700

15

15

730

8

5

5

0

0.71

0.68

RT-PCR

[20]

Denmark

2011

Grib Forest

183

9

6

198

13

0

0

0

RT-PCR

[20]

Denmark

2011

Bornholm (3 sites)

738

37

41

816

13

0

0

0

RT-PCR

[20]

Denmark

1999–2011

Combined Denmark, 3 studies , ≥ 18 sites

   

6865

≥ 70

11

0.16

RT-PCR

[20, 47, 48]

All four countries

1957–2011

All sites (≥ 99) included in references

   

39358

3171

109

    

0.28

 

[13, 17, 1921, 29, 4348], this study

Numbers within parenthesis for the present study correspond to sampling localities in Figure 1.

MIR, Minimum Infection Rate (%). P, adult ticks were pooled.

MBI*, Mouse brain inoculation and tissue cultures followed by neutralization tests and complement fixation tests [43].

MBI**, Mouse brain inoculation followed by haemagglutination and haemagglutination-inhibition tests [44].

RNA extraction and detection of TBEV

RNA was extracted, amplified and screened for TBEV in nymphs and adults of I. ricinus using a Real-Time Reverse Transcription Polymerase Chain Reaction (RT-PCR) targeting a certain region in the 3′-terminal of the TBEV genome modified after Schwaiger and Cassinotti [49] as previously described for the detection of TBEV in nymphs [50] and adult [29]Ixodes ticks, respectively. Each RNA extraction was made from a pool of ~20 nymphs, or a single adult tick, except for adult ticks collected at Gotska Sandön and Särö Västerskog, which were pooled as shown with the letter P in Table 1.

Statistical analyses

The prevalence of TBEV infection in I. ricinus ticks of a certain stage collected at a certain locality was estimated using the Minimum Infection Rate (MIR), i.e. the minimum infected proportion expressed as a percentage:
MIR = p / N × 100 %

where:

p = the number of positive pools

N = the total number of ticks tested

The MIR is considered acceptable for the present type of data on arboviruses occurring in their vector populations at low prevalences [5153]. This method assumes that only one infected tick is present in each positive pool [51]. The MIR also permits comparison of prevalence estimates from different investigations in which different tick collection strategies were used, and where the number of positive pools and the total number of ticks analysed are known. Fisher’s exact test was used to test if there is a significant difference, based on a two-tailed hypothesis, between two MIR estimates.

Gathering of TBEV prevalence data from previous studies

TBEV prevalence data were included in our review if the study reported at least the total number of ticks and/or tick stage(s) collected, and the total number of TBEV positive pools and/or individual ticks. We included only publications presenting TBEV-analyses of ticks collected in Denmark, Finland, Norway or Sweden.

Results

TBEV in nymphs or adult ticks in Sweden

A total of 2,074 nymphs and 906 adults of I. ricinus were collected from 29 study localities in Sweden during 2008 (Figure 1). Among 108 pools of nymphs tested two pools were TBEV-positive, as indicated by RT-PCR (Table 1): One pool originated from Kolarvik and the other from Herrhamra. Five of 906 adult ticks tested individually were TBEV-positive by RT-PCR (Figure 1, Table 1): One tick originated from Jönköping, three ticks from Herrhamra on the island of Torö, and one from Skutskär. The MIR calculated was 0.10% for the nymphs and 0.55% for the adult females (Fisher’s test: P = 0.030). Four of 7 TBEV-positive ticks originated from the same small island, Torö, which is a well-known TBEV-endemic focus. At Torö, we detected the TBEV infection in both nymphs (MIR = 0.51%) and adults of both sexes (MIR = 4.48%) of I. ricinus (Fisher’s test: P = 0.0521).

Based on all nymphs and adults of I. ricinus from the 29 localities the TBEV prevalence, calculated as a MIR, was 0.23% (7 positive pools; 1,007 negative pools; N = 2,980 ticks analysed). For ticks collected in the northern part of southern Sweden (Eskilstuna, Herrhamra, Kapellskär, Kolarvik, Morga, Rimbo, Skebobruk, Strängnäs, Väddö, Värmdö, Västerås, Östhammar) (Figure 1, Table 1), the MIR was 0.25%. This infection prevalence comes from 5 positive pools (2 nymphal pools and 3 adult ticks; 84 negative nymphal pools and 568 negative specimens) out of 2,019 ticks tested (1,448 nymphs and 571 adults).

TBEV in ticks from the four countries

The overall mean MIR estimate for TBEV in I. ricinus for the four neighbouring countries, Denmark, Sweden Norway and Finland, was 0.28% (109 TBEV-positive pools of 39,358 ticks tested, Table 1), which corresponds to approximately one TBEV-positive tick in each sample of 360 ticks. However, it should be noted that this is an overall mean MIR for the four countries and is based on both nymphs and adult ticks. The reason for combining these life stages is that in several of the publications analysed information about the tick stage(s) analysed was not stated. In the total data set (Table 1), the nymphal to adult ratio is approximately 5:1. This is within the range of the ratio of nymphs to adults that can be found in research on population ecology of I. ricinus[40, 5456].

Discussion

TBEV prevalence in Sweden and neighbouring Nordic countries

The overall mean TBEV prevalence for I. ricinus in the four Scandinavian countries was 0.28%. This corresponds to almost one TBEV-positive specimen in each sample of 360 ticks collected. It should be emphasised that the latter percentage, 0.28%, for Scandinavia refers to a mixture of pools containing both nymphs and adult ticks. It is well known that the infection prevalence of adult female ticks is usually significantly higher than that of nymphs [57]. This is most likely mainly due to the fact that, during their development from larva to adult tick, the questing adult tick female has usually blood-fed twice, i.e. on two different, potentially TBEV-infected host individuals. In contrast, the questing nymphs have fed only once [58, 59]. This is also indicated in the present study by the data from Herrhamra where the MIR was 0.51% for nymphs and 4.48% for adults. Thus, if we had analysed relatively more adult ticks from Herrhamra it is likely that the overall TBEV infection prevalence estimate would have appeared even higher. The estimated mean TBEV prevalence is similar to those estimated for another I. ricinus- transmitted pathogen, B. miyamotoi, in Sweden [60] and Estonia [50] but lower than those usually recorded for other pathogens vectored by I. ricinus, such as B. afzelii, B. garinii and B. valaisiana[37, 60], and A. phagocytophilum[34, 35, 39, 61].

The estimated infection prevalence increased when the TBEV analysis was restricted to ticks collected only from one locality, Herrhamra on the island of Torö. This is a well-known TBEV-enzootic area, where many people have contracted neuroinvasive TBE. The island seems to be an example of such a focus, as described by Dobler and co-workers [33] in which the TBEV occurs permanently within a restricted geographical area. Consequently, if a larger number of ticks had been collected outside of the TBEV focus and had been included in the virological analysis the TBEV prevalence estimate would have been reduced. Furthermore, another obvious problem with the use of the MIR estimate on pooled samples occurs when ticks are collected in a habitat where the infection rate is relatively high. Here, several virus-infected tick specimens could be present in one pool; yet, such a positive pool would be considered to contain only one infected tick, thereby reducing the prevalence estimate to fall below the actual prevalence [5153].

Maintenance of TBEV in nature

The TBE virus is maintained and transmitted in natural foci mainly in five ways: (i) by ticks becoming infected when feeding on viraemic hosts whereby infective ticks, in a subsequent stage, may transmit the virus to susceptible, new hosts; (ii) by transovarial transmission in ticks; (iii) by transstadial transmission in ticks; (iv) by sexual transmission from a male tick to a female tick; and (v) by non-viraemic transmission from infective tick(s) co-feeding adjacent to susceptible ticks on a non-infected and/or non-viraemic host [6265].

Transmission of the TBEV can take place when tick larvae or nymphs feed on (I) viraemic Apodemus mice or Myodes voles. Apodemus mice are regarded as the optimal transmission hosts for this mode of TBEV transfer, since they do not rapidly become resistant to the feeding ticks [66]. This is in contrast to bank voles, which rapidly become resistant to the feeding ticks [67]. Furthermore, it is generally accepted that any viraemia in rodents, infective to feeding ticks, will only last for a few days. Therefore, this mode of TBEV transmission is not considered sufficiently effective to solely maintain the virus in the I. ricinus populations [65, 68, 69]. Still, rodents can act as TBEV reservoirs since TBEV can be detected in infected rodents for periods of several months, including during the winter period [70, 71].

Even ticks act as reservoirs for the TBEV due to their capacity of transovarial and transstadial transmission. Once infected, the tick will usually remain infected throughout its life [65]. However, transovarial transmission only occurs at a low frequency and is, therefore, on its own considered not sufficiently effective to maintain TBEV in the vector population [72]. Sexual transmission occurs when TBEV-infected tick males infect females by transferring infectious saliva and/or seminal fluid during copulation [73]. It is not known if transovarial and sexual transmission are necessary for the long-term persistence of the virus in the ecosystem. Possibly, they may have evolved to function as auxiliary modes of transmission by which the TBEV can ‘survive’ in the ecosystem during periods when the availability of vertebrate virus transmission hosts and vertebrate virus reservoirs are unavailable for the questing ticks to feed on. Non-viraemic transmission is generally regarded as the main mode of transmission by which TBEV is transmitted to infectible ticks and maintained in nature. Non-viraemic transmission may occur when one or more susceptible ticks are feeding in close proximity to an infective tick [62, 65, 68, 74]. In this way, transmission of TBEV takes place when infective ticks, typically nymphs, are feeding on the host. TBE virions will be transferred with the saliva, which is injected by the blood-feeding, virus-infective nymphs into the feeding site. Here, virions may be phagocytosed by leukocytes. Some of these virus-infected blood cells may then be ingested by susceptible ticks, typically larvae, which in this manner become infected [62]. It should be noted that for virus transmission to occur among co-feeding ticks it is not necessary that a viraemia is present in the host [63]. However, synchronous questing activity of infective ticks and susceptible ticks is necessary for the TBE virus to be transmitted in this way [75]. Non-viraemic transmission supported by a low degree of transovarial transmission is considered sufficient to maintain the TBEV at the prevalence levels at which it generally occurs in I. ricinus[76].

There is some evidence that goats are not competent hosts either for viraemic or non-viraemic transmission of TBEV among co-feeding ticks [77]. However, to our knowledge, there exists no experimental evidence that cervids are incompetent hosts for non-viraemic transmission of TBEV among co-feeding ticks. Although the TBEV viraemia in deer may be of a short duration and of insufficient magnitude in cervids we should not yet reject the possibility that co-feeding transmission via non-viraemic cervids might take place. In TBE-endemic areas both domesticated and wild ungulates, especially roe deer, usually have antibodies to TBEV [78] and the seroprevalence in TBEV foci can be high in such mammals [77]. Labuda and co-workers demonstrated that natural hosts, which have neutralizing antibodies to the TBEV and apparently are immune to TBEV (i.e., without any viraemia) still can support transmission of this virus from infective to uninfected ticks feeding close together on the same host [63]. All stages of I. ricinus preferentially attach to the neck and head region of roe deer and both larvae and nymphs occur at the highest densities on the head of this important tick maintenance host [79]. These facts support the idea that the roe deer is one of the most important host species for adult I. ricinus ticks. These facts also support the notion that roe deer possibly can support the non-viraemic transmission of TBEV to uninfected ticks. Indeed, roe deer abundance may be a useful indicator of the risk for people in TBEV-endemic areas to contract a TBE virus infection. Along these lines, Zeman and Januska [80] showed that the risk of TBE was associated with the abundance of roe deer and mice (Apodemus spp.).

Is the TBEV prevalence in the tick population unexpectedly low?

Two important questions are: (I) Is the infection prevalence of TBEV in the I. ricinus populations exceptionally low? (II) How can the virus persist in nature despite such ‘low’ infection prevalence? Prevalence rates of TBEV in I. ricinus populations in endemic areas usually range from 0.1–5% [7, 10, 57, 81] and the prevalence usually fluctuates from year to year and among regions [57]. It is likely that both viraemic and non-viraemic transmission of TBEV to uninfected ticks occur more frequently during years of peak abundance of small mammals [27]. So these fluctuations in TBEV infection prevalence are presumably to some degree due to the varying densities of reservoir-competent vs. reservoir-incompetent tick hosts. Both TBEV and B. miyamotoi seem to have geographical distributional ranges composed of a patchwork of relatively small enzootic foci. Here, both pathogens seem to be present at low prevalences in their invertebrate reservoir and vector, i.e. I. ricinus. Both pathogens rely, to a small extent, on transovarial transmission. It might be a trait, which has evolved in TBEV and in B. miyamotoi, to enable these human pathogens to ‘survive’ independent from vertebrate transmission hosts during periods when the availability of such tick hosts, i.e. small mammals, is low or non-existent.

One reason for the low apparent prevalence recorded in many investigations may be due to inclusion of ticks from non-endemic areas adjacent to the relatively confined TBEV-infected foci [33]. If the limits of such a focus are known and ticks are collected only from within the borders of this TBEV focus, the virological analysis of these ticks is likely to give a higher TBEV prevalence estimate than if ticks from outside the TBE focus were included in the analysis.

It has been known for many years that TBEV infection rates of blood-fed ticks, collected from humans or other hosts, are usually higher than those of unfed, questing ticks collected from the vegetation in the same area [81, 82]. In a series of experiments, it was shown that TBEV-infected ticks become more active in their host-searching behaviour compared to that of uninfected ticks [83, 84]. It was also suggested that TBEV might occur in undetectable concentrations in infected ticks in nature, and that it is not until the tick is feeding, that virus quantities can increase 100-fold [83] so that TBEV becomes detectable [84]. It may be that the virus occurs in an undetectable, seemingly ‘latent’ state, in the host-seeking TBEV-infected tick. Components in the blood and/or the increased temperature might be triggering immature virions to become mature virions. Another possibility is that the amount of virions in the non-blood-fed tick is below the detection limit of the methodology ordinarily used. Different methods for detecting viruses and microorganisms can have different sensitivities [85, 86]. Thus, it has been emphasized that if the sensitivity of the PCR-based detection method used is not optimal, it is likely that the infection prevalence will be underestimated [57]. The PCR method that we used, which is a modification of the method described by Schwaiger and Cassinotti [49], has a detection limit of 1–10 copies per reaction. Therefore, the TBEV prevalences of the ticks collected in Sweden and analysed by us, are most likely not underestimated.

The observed, relatively low TBEV prevalence in I. ricinus in nature is likely explained by a combination of such factors as just mentioned. Future studies should aim to explain in more detail the relative importance of the different environmental, pathogen-, tick-, and vertebrate-related factors, which are necessary for an area to be a long-term TBEV enzootic focus.

Conclusions

If the ratio of nymphs to adult ticks in the TBEV-analysed sample differs from that in the I. ricinus population in the field, the MIR obtained will not necessarily reflect the TBEV prevalence in the field. The relatively low TBEV prevalence in the potential vector population recorded in most studies may partly be due to: (i) inclusion of uninfected ticks from the ‘uninfected areas’ surrounding the TBEV endemic foci; (ii) inclusion of an unrepresentative, too large proportion of immature ticks, compared to adult ticks, in the analysed tick pools; and (iii) shortcomings in the laboratory techniques used to detect the virus that may be present in a very low concentration or undetectable state in ticks which have not recently fed.

Declarations

Acknowledgements

We are grateful to Allison Perrigo, Uppsala University, for many valuable suggestions on the manuscript; to Isabella Fröjdman, Helsingfors University, for invaluable assistance with collection of ticks; and to Anders Larsson for help with constructing the map. TJ’s and JP’s research on ticks and tick-borne infections is funded by Carl Trygger’s Stiftelse, Helge Ax:son Johnson’s stiftelse, Längmanska Kulturfonden, Magnus Bergvall’s Stiftelse and Stiftelsen Lars Hierta’s Minne (all in Stockholm, Sweden); IG’s research is funded by the Estonian Ministry of Education and Research (project SF0940033s09).

This article is an extended, revised version of an article published as part of a PhD dissertation at Uppsala University. The thesis was publicly examined on 10th January 2014 for the degree of Doctor of Philosophy. The full reference of the PhD thesis is:

Pettersson, J. H.-O. 2013. The origin of the genus Flavivirus and the ecology of tick-borne pathogens. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 1100. 60 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-8814-7.

Authors’ Affiliations

(1)
Medical Entomology Unit, Subdepartment of Systematic Biology, Department of Organismal Biology, Evolutionary Biology Centre, Uppsala University
(2)
Department of Virology, National Institute for Health Development
(3)
Public Health Agency of Sweden

References

  1. Granström M: Tick-borne zoonoses in Europe. Clin Microbiol Infect. 1997, 3: 156-169. 10.1111/j.1469-0691.1997.tb00592.x.View ArticlePubMedGoogle Scholar
  2. Charrel RN, Attoui H, Butenko AM, Clegg JC, Deubel V, Frolova TV, Gould EA, Gritsun TS, Heinz FX, Labuda M, Lashkevich VA, Loktev V, Lundkvist A, Lvov DV, Mandl CW, Niedrig M, Papa A, Petrov VS, Plyusnin A, Randolph S, Süss J, Zlobin VI, de Lamballerie X: Tick-borne virus diseases of human interest in Europe. Clin Microbiol Infect. 2004, 10: 1040-1055. 10.1111/j.1469-0691.2004.01022.x.View ArticlePubMedGoogle Scholar
  3. Gritsun TS, Nuttall PA, Gould EA: Tick-borne flaviviruses. Adv Virus Res. 2003, 61: 317-371.View ArticlePubMedGoogle Scholar
  4. International Committee on Taxonomy of Viruses: Virus Taxonomy. 2012, Release. Available: http://ictvonline.org/virusTaxonomy.asp?version=2012 Accessed on: 2013-04-22Google Scholar
  5. Gritsun TS, Lashkevich VA, Gould EA: Tick-borne encephalitis. Antiviral Res. 2003, 57: 129-146. 10.1016/S0166-3542(02)00206-1.View ArticlePubMedGoogle Scholar
  6. European Centre for Disease Prevention and Control: Epidemiological situation of tick-borne encephalitis in the European Union and European Free Trade Association countries. ECDC. 2012, doi: 10.2900/62311. Available: http://ecdc.europa.eu/en//publications/publications/tbe-in-eu-efta.pdfGoogle Scholar
  7. Süss J: Tick-borne encephalitis, epidemiology, risk areas, and virus strains in Europe and Asia-an overview. Ticks Tick Borne Dis. 2010, 2011 (2): 2-15.Google Scholar
  8. Wu X-B, Na RH, Wei S-S, Zhu J-S, Peng H-J: Distribution of tick-borne diseases in China. Parasit Vectors. 2013, 6: 119-10.1186/1756-3305-6-119.PubMed CentralView ArticlePubMedGoogle Scholar
  9. Ecker M, Allison SL, Meixner T, Heinz FX: Sequence analysis and genetic classification of tick-borne encephalitis viruses from Europe and Asia. J Gen Virol. 1999, 80 (Pt 1): 179-185.View ArticlePubMedGoogle Scholar
  10. Katargina O, Russakova S, Geller J, Kondrusik M, Zajkowska J, Zygutiene M, Bormane A, Trofimova J, Golovljova I: Detection and characterization of tick-borne encephalitis virus in Baltic countries and eastern Poland. PLoS ONE. 2013, 8: e61374-10.1371/journal.pone.0061374.PubMed CentralView ArticlePubMedGoogle Scholar
  11. Kovalev SY, Kokorev VS, Belyaeva IV: Distribution of Far-Eastern tick-borne encephalitis virus subtype strains in the former Soviet Union. J Gen Virol. 2010, 91: 2941-2946. 10.1099/vir.0.023879-0.View ArticlePubMedGoogle Scholar
  12. Kovalev SY, Chernykh DN, Kokorev VS, Snitkovskaya TE, Romanenko VV: Origin and distribution of tick-borne encephalitis virus strains of the Siberian subtype in the Middle Urals, the north-west of Russia and the Baltic countries. J Gen Virol. 2009, 90 (Pt 12): 2884-2892.View ArticlePubMedGoogle Scholar
  13. Jääskeläinen AE, Tikkakoski T, Uzcategui NY, Alekseev AN, Vaheri A, Vapalahti O: Siberian subtype tick-borne encephalitis virus, Finland. Emerg Infect Dis. 2006, 12: 1568-1571. 10.3201/eid1210.060320.PubMed CentralView ArticlePubMedGoogle Scholar
  14. Lundkvist Å, Vene S, Golovljova I, Mavtchoutko V, Forsgren M, Kalnina V, Plyusnin A: Characterization of tick-borne encephalitis virus from Latvia: evidence for co-circulation of three distinct subtypes. J Med Virol. 2001, 65: 730-735. 10.1002/jmv.2097.View ArticleGoogle Scholar
  15. Golovljova I, Vene S, Sjölander KB, Vasilenko V, Plyusnin A, Lundkvist Å: Characterization of tick-borne encephalitis virus from Estonia. J Med Virol. 2004, 74: 580-588. 10.1002/jmv.20224.View ArticlePubMedGoogle Scholar
  16. Haglund M, Vene S, Forsgren M, Günther G, Johansson B, Niedrig M, Plyusnin A, Lindquist L, Lundkvist A: Characterisation of human tick-borne encephalitis virus from Sweden. J Med Virol. 2003, 71: 610-621. 10.1002/jmv.10497.View ArticlePubMedGoogle Scholar
  17. Melik W, Nilsson AS, Johansson M: Detection strategies of tick-borne encephalitis virus in Swedish Ixodes ricinus reveal evolutionary characteristics of emerging tick-borne flaviviruses. Arch Virol. 2007, 152: 1027-1034. 10.1007/s00705-006-0922-9.View ArticlePubMedGoogle Scholar
  18. Norberg P, Roth A, Bergström T: Genetic recombination of tick-borne flaviviruses among wild-type strains. Virology. 2013, 440: 105-116. 10.1016/j.virol.2013.02.017.View ArticlePubMedGoogle Scholar
  19. Skarpaas T, Golovljova I, Vene S, Ljøstad U, Sjursen H, Plyusnin A, Lundkvist A: Tickborne encephalitis virus, Norway and Denmark. Emerging Infect Dis. 2006, 12: 1136-1138. 10.3201/eid1207.051567.PubMed CentralView ArticlePubMedGoogle Scholar
  20. Fomsgaard A, Fertner ME, Essbauer S, Nielsen AY, Frey S, Lindblom P, Lindgren P-E, Bødker R, Weidmann M, Dobler G: Tick-borne encephalitis virus, Zealand, Denmark, 2011. Emerging Infect Dis. 2013, 19: 1171-1173. 10.3201/eid1907.130092.PubMed CentralView ArticlePubMedGoogle Scholar
  21. Jääskeläinen AE, Sironen T, Murueva GB, Subbotina N, Alekseev AN, Castrén J, Alitalo I, Vaheri A, Vapalahti O: Tick-borne encephalitis virus in ticks in Finland, Russian Karelia and Buryatia. J Gen Virol. 2010, 91 (Pt 11): 2706-2712.View ArticlePubMedGoogle Scholar
  22. Jääskeläinen AE, Tonteri E, Sironen T, Pakarinen L, Vaheri A, Vapalahti O: European subtype tick-borne encephalitis virus in Ixodes persulcatus ticks. Emerging Infect Dis. 2011, 17: 323-325. 10.3201/eid1702.101487.PubMed CentralView ArticlePubMedGoogle Scholar
  23. Kaiser R: Tick-borne encephalitis. Infect Dis Clin North Am. 2008, 22: 561-575. 10.1016/j.idc.2008.03.013.View ArticlePubMedGoogle Scholar
  24. Lindquist L, Vapalahti O: Tick-borne encephalitis. Lancet. 2008, 371: 1861-1871. 10.1016/S0140-6736(08)60800-4.View ArticlePubMedGoogle Scholar
  25. Mansfield KL, Johnson N, Phipps LP, Stephenson JR, Fooks AR, Solomon T: Tick-borne encephalitis virus–a review of an emerging zoonosis. J Gen Virol. 2009, 90 (Pt 8): 1781-1794.View ArticlePubMedGoogle Scholar
  26. Holmgren EB, Forsgren M: Epidemiology of tick-borne encephalitis in Sweden 1956-1989: a study of 1116 cases. Scand J Infect Dis. 1990, 22: 287-295. 10.3109/00365549009027050.View ArticlePubMedGoogle Scholar
  27. Jaenson TGT, Hjertqvist M, Bergström T, Lundkvist A: Why is tick-borne encephalitis increasing? A review of the key factors causing the increasing incidence of human TBE in Sweden. Parasit Vectors. 2012, 5: 184-10.1186/1756-3305-5-184.PubMed CentralView ArticlePubMedGoogle Scholar
  28. Jaenson TGT, Jaenson DGE, Eisen L, Petersson E, Lindgren E: Changes in the geographical distribution and abundance of the tick Ixodes ricinus during the past 30 years in Sweden. Parasit Vectors. 2012, 5: 8-10.1186/1756-3305-5-8.PubMed CentralView ArticlePubMedGoogle Scholar
  29. Brinkley C, Nolskog P, Golovljova I, Lundkvist Å, Bergström T: Tick-borne encephalitis virus natural foci emerge in western Sweden. Int J Med Microbiol. 2008, 298, Supplement 1: 73-80.View ArticleGoogle Scholar
  30. Blaskovic D, Nosek J: The ecological approach to the study of tick-borne encephalitis. Prog Med Virol. 1972, 14: 275-320.PubMedGoogle Scholar
  31. Nosek J, Kožuch O, Mayer V: Spatial distribution and stability of natural foci of tick-borne encephalitis virus in Central Europe. Beiträge zur Geoökologie der Zentraleuropäischen Zecken-Encephalitis. Edited by: Jusatz HJ. 1978, Berlin, Heidelberg: Springer Berlin Heidelberg, 60-74.View ArticleGoogle Scholar
  32. Kupča AM, Essbauer S, Zoeller G, de Mendonça PG, Brey R, Rinder M, Pfister K, Spiegel M, Doerrbecker B, Pfeffer M, Dobler G: Isolation and molecular characterization of a tick-borne encephalitis virus strain from a new tick-borne encephalitis focus with severe cases in Bavaria, Germany. Ticks Tick Borne Dis. 2010, 1: 44-51. 10.1016/j.ttbdis.2009.11.002.View ArticlePubMedGoogle Scholar
  33. Dobler G, Hufert F, Pfeffer M, Essbauer S: Tick-borne encephalitis: From microfocus to human disease. Progress in Parasitology. Edited by: Mehlhorn H. 2011, Berlin, Heidelberg: Springer Berlin Heidelberg, 323-331.View ArticleGoogle Scholar
  34. Skarphédinsson S, Lyholm BF, Ljungberg M, Søgaard P, Kolmos HJ, Nielsen LP: Detection and identification of Anaplasma phagocytophilum, Borrelia burgdorferi, and Rickettsia helvetica in Danish Ixodes ricinus ticks. APMIS. 2007, 115: 225-230. 10.1111/j.1600-0463.2007.apm_256.x.View ArticlePubMedGoogle Scholar
  35. Stuen S, Granquist EG, Silaghi C: Anaplasma phagocytophilum—a widespread multi-host pathogen with highly adaptive strategies. Front Cell Infect Microbiol. 2013, 3: 31-doi:10.3389/fcimb.2013.0031PubMed CentralView ArticlePubMedGoogle Scholar
  36. Hubálek Z, Halouzka J: Distribution of Borrelia burgdorferi sensu lato genomic groups in Europe, a review. Eur J Epidemiol. 1997, 13: 951-957. 10.1023/A:1007426304900.View ArticlePubMedGoogle Scholar
  37. Blaschitz M, Narodoslavsky-Gföller M, Kanzler M, Walochnik J, Stanek G: Borrelia burgdorferi sensu lato genospecies in questing Ixodes ricinus ticks in Austria. Int J Med Microbiol. 2008, 298: 168-176.View ArticleGoogle Scholar
  38. Parola P, Paddock CD, Socolovschi C, Labruna MB, Mediannikov O, Kernif T, Abdad MY, Stenos J, Bitam I, Fournier P-E, Raoult D: Update on tick-borne rickettsioses around the world: a geographic approach. Clin Microbiol Rev. 2013, 26: 657-702. 10.1128/CMR.00032-13.PubMed CentralView ArticlePubMedGoogle Scholar
  39. Wallménius K, Pettersson JH-O, Jaenson TGT, Nilsson K: Prevalence of Rickettsia spp., Anaplasma phagocytophilum, and Coxiella burnetii in adult Ixodes ricinus ticks from 29 study areas in central and southern Sweden. Ticks Tick Borne Dis. 2012, 3: 100-106. 10.1016/j.ttbdis.2011.11.003.View ArticlePubMedGoogle Scholar
  40. Mejlon HA, Jaenson TGT: Seasonal prevalence of Borrelia burgdorferi in Ixodes ricinus in different vegetation types in Sweden. Scand J Infect Dis. 1993, 25: 449-456. 10.3109/00365549309008526.View ArticlePubMedGoogle Scholar
  41. Arthur DR: British Ticks. 1963, London: ButterworthsGoogle Scholar
  42. Filippova NA: Fauna of the SSSR, Paukoobraznye: Arachnidea. Ixodid ticks of subfamily Ixodinae. 1977, Russian: Leningrad: Nauka, 4(4):Google Scholar
  43. Von Zeipel G: Isolation of viruses of the Russian spring summer encephalitis-louping ill group from Swedish ticks and from a human case of meningoencephalitis. Arch Gesamte Virusforsch. 1959, 9: 460-469. 10.1007/BF01242853.View ArticlePubMedGoogle Scholar
  44. Brummer-Korvenkontio M, Saikku P, Korhonen P, Oker-Blom N: Arboviruses in Finland: I: isolation of tick-borne encephalitis (TBE) virus from arthropods, vertebrates, and patients. Am J Trop Med Hyg. 1973, 22: 382-389.PubMedGoogle Scholar
  45. Han X, Aho M, Vene S, Peltomaa M, Vaheri A, Vapalahti O: Prevalence of tick-borne encephalitis virus in Ixodes ricinus ticks in Finland. J Med Virol. 2001, 64: 21-28. 10.1002/jmv.1012.View ArticlePubMedGoogle Scholar
  46. Andreassen A, Jore S, Cuber P, Dudman S, Tengs T, Isaksen K, Hygen HO, Viljugrein H, Anestad G, Ottesen P, Vainio K: Prevalence of tick borne encephalitis virus in tick nymphs in relation to climatic factors on the southern coast of Norway. Parasit Vectors. 2012, 5: 177-10.1186/1756-3305-5-177.PubMed CentralView ArticlePubMedGoogle Scholar
  47. Jensen PM: Tætheder af skovflåten (Ixodes ricinus) og koeksistens af Louping ill-virus og tick borne encephalitis-virus på Bornholm. Ugeskr Laeger. 2004, 166: 2563-2565.PubMedGoogle Scholar
  48. Fomsgaard A, Christiansen C, Bodker R: First identification of tick-borne encephalitis in Denmark outside of Bornholm, August 2009. Euro Surveill. 2009, 14: 36-Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19325Google Scholar
  49. Schwaiger M, Cassinotti P: Development of a quantitative real-time RT-PCR assay with internal control for the laboratory detection of tick borne encephalitis virus (TBEV) RNA. J Clin Virol. 2003, 27: 136-145. 10.1016/S1386-6532(02)00168-3.View ArticlePubMedGoogle Scholar
  50. Geller J, Nazarova L, Katargina O, Leivits A, Järvekülg L, Golovljova I: Tick-borne pathogens in ticks feeding on migratory passerines in western part of Estonia. Vector Borne Zoonotic Dis. 2013, 13: 443-448. 10.1089/vbz.2012.1054.PubMed CentralView ArticlePubMedGoogle Scholar
  51. Cowling DW, Gardner IA, Johnson WO: Comparison of methods for estimation of individual-level prevalence based on pooled samples. Prev Vet Med. 1999, 39: 211-225. 10.1016/S0167-5877(98)00131-7.View ArticlePubMedGoogle Scholar
  52. Speybroeck N, Williams CJ, Lafia KB, Devleesschauwer B, Berkvens D: Estimating the prevalence of infections in vector populations using pools of samples. Med Vet Entomol. 2012, 26: 361-371. 10.1111/j.1365-2915.2012.01015.x.View ArticlePubMedGoogle Scholar
  53. Ebert TA, Brlansky R, Rogers M: Reexamining the pooled sampling approach for estimating prevalence of infected insect vectors. Ann Entomol Soc Am. 2010, 103: 827-837. 10.1603/AN09158.View ArticleGoogle Scholar
  54. Randolph SE, Green RM, Hoodless AN, Peacey MF: An empirical quantitative framework for the seasonal population dynamics of the tick Ixodes ricinus. Int J Parasitol. 2002, 32: 979-989. 10.1016/S0020-7519(02)00030-9.View ArticlePubMedGoogle Scholar
  55. Tälleklint L, Jaenson TG: Infestation of mammals by Ixodes ricinus ticks (Acari: Ixodidae) in south-central Sweden. Exp Appl Acarol. 1997, 21: 755-771. 10.1023/A:1018473122070.View ArticlePubMedGoogle Scholar
  56. Dobson ADM, Finnie TJR, Randolph SE: A modified matrix model to describe the seasonal population ecology of the European tick Ixodes ricinus: Ixodes ricinus population model. J Appl Ecol. 2011, 48: 1017-1028. 10.1111/j.1365-2664.2011.02003.x.View ArticleGoogle Scholar
  57. Süss J, Schrader C, Abel U, Voigt WP, Schosser R: Annual and seasonal variation of tick-borne encephalitis virus (TBEV) prevalence in ticks in selected hot spot areas in Germany using a nRT-PCR: results from 1997 and 1998. Zentralbl Bakteriol. 1999, 289: 564-578. 10.1016/S0934-8840(99)80010-3.View ArticlePubMedGoogle Scholar
  58. Milne A: The ecology of the sheep tick, Ixodes ricinus L. Parasitology. 1950, 40: 35-45. 10.1017/S0031182000017832.View ArticlePubMedGoogle Scholar
  59. Needham GR, Teel PD: Off-host physiological ecology of ixodid ticks. Annu Rev Entomol. 1991, 36: 659-681. 10.1146/annurev.en.36.010191.003303.View ArticlePubMedGoogle Scholar
  60. Fraenkel C-J, Garpmo U, Berglund J: Determination of novel Borrelia genospecies in Swedish Ixodes ricinus ticks. J Clin Microbiol. 2002, 40: 3308-3312. 10.1128/JCM.40.9.3308-3312.2002.PubMed CentralView ArticlePubMedGoogle Scholar
  61. Severinsson K, Jaenson TG, Pettersson J, Falk K, Nilsson K: Detection and prevalence of Anaplasma phagocytophilum and Rickettsia helvetica in Ixodes ricinus ticks in seven study areas in Sweden. Parasit Vectors. 2010, 3: 66-10.1186/1756-3305-3-66.PubMed CentralView ArticlePubMedGoogle Scholar
  62. Labuda M, Jones LD, Williams T, Danielova V, Nuttall PA: Efficient transmission of tick-borne encephalitis virus between cofeeding ticks. J Med Entomol. 1993, 30: 295-299.View ArticlePubMedGoogle Scholar
  63. Labuda M, Kozuch O, Zuffová E, Elecková E, Hails RS, Nuttall PA: Tick-borne encephalitis virus transmission between ticks cofeeding on specific immune natural rodent hosts. Virology. 1997, 235: 138-143. 10.1006/viro.1997.8622.View ArticlePubMedGoogle Scholar
  64. Gould EA, de Lamballerie X, Zanotto PM, Holmes EC: Origins, evolution, and vector/host coadaptations within the genus Flavivirus. Adv Virus Res. 2003, 59: 277-314.View ArticlePubMedGoogle Scholar
  65. Nuttall PA, Labuda M: Dynamics of infection in tick vectors and at the tick-host interface. Adv Virus Res. 2003, 60: 233-272.View ArticlePubMedGoogle Scholar
  66. Randolph SE: Population regulation in ticks: the role of acquired resistance in natural and unnatural hosts. Parasitology. 1979, 79: 141-156. 10.1017/S0031182000052033.View ArticlePubMedGoogle Scholar
  67. Dizij A, Kurtenbach K: Clethrionomys glareolus, but not Apodemus flavicollis, acquires resistance to lxodes ricinus L, the main European vector of Borrelia burgdorferi. Parasite Immunol. 1995, 17: 177-183. 10.1111/j.1365-3024.1995.tb00887.x.View ArticlePubMedGoogle Scholar
  68. Randolph SE, Gern L, Nuttall PA: Co-feeding ticks: epidemiological significance for tick-borne pathogen transmission. Parasitol Today (Regul Ed). 1996, 12: 472-479. 10.1016/S0169-4758(96)10072-7.View ArticleGoogle Scholar
  69. Achazi K, Růžek D, Donoso-Mantke O, Schlegel M, Ali HS, Wenk M, Schmidt-Chanasit J, Ohlmeyer L, Rühe F, Vor T, Kiffner C, Kallies R, Ulrich RG, Niedrig M: Rodents as sentinels for the prevalence of tick-borne encephalitis virus. Vector Borne Zoonotic Dis. 2011, 11: 641-647. 10.1089/vbz.2010.0236.PubMed CentralView ArticlePubMedGoogle Scholar
  70. Tonteri E, Jääskeläinen AE, Tikkakoski T, Voutilainen L, Niemimaa J, Henttonen H, Vaheri A, Vapalahti O: Tick-borne encephalitis virus in wild rodents in winter, Finland, 2008–2009. Emerg Infect Dis. 2011, 17: 72-75. 10.3201/eid1701.100051.PubMed CentralView ArticlePubMedGoogle Scholar
  71. Bakhvalova VN, Dobrotvorsky AK, Panov VV, Matveeva VA, Tkachev SE, Morozova OV: Natural tick-borne encephalitis virus infection among wild small mammals in the southeastern part of western Siberia, Russia. Vector Borne Zoonotic Dis. 2006, 6: 32-41. 10.1089/vbz.2006.6.32.View ArticlePubMedGoogle Scholar
  72. Danielová V, Holubová J: Transovarial transmission rates of tick-borne encephalitis virus in Ixodes ricinus ticks. Modern Acarology. Edited by: Dusbabek F, Bukva V. 1991, Prague, Czech Republic: SPB Academic Publishing, 7-10. 2Google Scholar
  73. Alekseev AN: Ecology of tick-borne encephalitis virus: part of Ixodidae ticks males in its circulation. Ecol Parasitol. 1992, 1: 48-58.Google Scholar
  74. Jones LD, Davies CR, Steele GM, Nuttall PA: A novel mode of arbovirus transmission involving a nonviremic host. Science. 1987, 237: 775-777. 10.1126/science.3616608.View ArticlePubMedGoogle Scholar
  75. Randolph SE, Miklisová D, Lysy J, Rogers DJ, Labuda M: Incidence from coincidence: patterns of tick infestations on rodents facilitate transmission of tick-borne encephalitis virus. Parasitology. 1999, 118 (Pt 2): 177-186.View ArticlePubMedGoogle Scholar
  76. Nonaka E, Ebel GD, Wearing HJ: Persistence of pathogens with short infectious periods in seasonal tick populations: the relative importance of three transmission routes. PLoS ONE. 2010, 5: e11745-10.1371/journal.pone.0011745.PubMed CentralView ArticlePubMedGoogle Scholar
  77. Labuda M, Elečková E, Ličková M, Sabó A: Tick-borne encephalitis virus foci in Slovakia. Int J Med Microbiol. 2002, 291: 43-47.View ArticlePubMedGoogle Scholar
  78. Skarphédinsson S, Jensen PM, Kristiansen K: Survey of tickborne infections in Denmark. Emerg Infect Dis. 2005, 11: 1055-1061. 10.3201/eid1107.041265.PubMed CentralView ArticlePubMedGoogle Scholar
  79. Kiffner C, Lödige C, Alings M, Vor T, Rühe F: Attachment site selection of ticks on roe deer, Capreolus capreolus. Exp Appl Acarol. 2010, 53: 79-94.PubMed CentralView ArticlePubMedGoogle Scholar
  80. Zeman P, Januška J: Epizootiologic background of dissimilar distribution of human cases of Lyme borreliosis and tick-borne encephalitis in a joint endemic area. Comp Immunol Microbiol Infect Dis. 1999, 22: 247-260. 10.1016/S0147-9571(99)00015-6.View ArticlePubMedGoogle Scholar
  81. Süss J, Schrader C, Falk U, Wohanka N: Tick-borne encephalitis (TBE) in Germany–epidemiological data, development of risk areas and virus prevalence in field-collected ticks and in ticks removed from humans. Int J Med Microbiol. 2004, 293 (Suppl 37): 69-79.PubMedGoogle Scholar
  82. Bormane A, Lucenko I, Duks A, Mavtchoutko V, Ranka R, Salmina K, Baumanis V: Vectors of tick-borne diseases and epidemiological situation in Latvia in 1993–2002. Int J Med Microbiol. 2004, 293 (Suppl 37): 36-47.PubMedGoogle Scholar
  83. Alekseev AN, Chunikhin SP: The experimental transmission of the tick-borne encephalitis virus by ixodid ticks (the mechanisms, time periods, species and sex differences). Parazitologia. 1990, 24: 177-185.PubMedGoogle Scholar
  84. Belova OA, Burenkova LA, Karganova GG: Different tick-borne encephalitis virus (TBEV) prevalences in unfed versus partially engorged ixodid ticks—evidence of virus replication and changes in tick behavior. Ticks Tick Borne Dis. 2012, 3: 240-246. 10.1016/j.ttbdis.2012.05.005.View ArticlePubMedGoogle Scholar
  85. Kuypers J, Wright N, Ferrenberg J, Huang M-L, Cent A, Corey L, Morrow R: Comparison of real-time PCR assays with fluorescent-antibody assays for diagnosis of respiratory virus infections in children. J Clin Microbiol. 2006, 44: 2382-2388. 10.1128/JCM.00216-06.PubMed CentralView ArticlePubMedGoogle Scholar
  86. Morozova OV, Dobrotvorsky AK, Livanova NN, Tkachev SE, Bakhvalova VN, Beklemishev AB, Cabello FC: PCR detection of Borrelia burgdorferi sensu lato, tick-borne encephalitis virus, and the human granulocytic ehrlichiosis agent in Ixodes persulcatus ticks from western Siberia, Russia. J Clin Microbiol. 2002, 40: 3802-3804. 10.1128/JCM.40.10.3802-3804.2002.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Pettersson et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Advertisement