Parasitology Research

, Volume 103, Supplement 1, pp 29–43

Mosquito-borne viruses in Europe

Authors

    • Institute of Vertebrate BiologyAcademy of Sciences
Mosquitoes

DOI: 10.1007/s00436-008-1064-7

Cite this article as:
Hubálek, Z. Parasitol Res (2008) 103: 29. doi:10.1007/s00436-008-1064-7
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Abstract

The number of mosquito-borne viruses (‘moboviruses’) occurring in Europe since the twentieth century now stands at ten; they belong to three families—Togaviridae (Sindbis, Chikungunya), Flaviviridae (West Nile, Usutu, Dengue), and Bunyaviridae (Batai, Ťahyňa, Snowshoe hare, Inkoo, Lednice). Several of them play a definite role in human or animal pathology (Sindbis, Chikungunya, Dengue, West Nile, Ťahyňa). Mobovirus outbreaks are strictly determined by the presence and/or import of particular competent vectors of the disease. Ecological variables affect moboviruses considerably; the main factors are population density of mosquito vectors and their vertebrate hosts, intense summer precipitations or floods, summer temperatures and drought, and presence of appropriate habitats, e.g., wetlands, small water pools, or intravillan sewage systems. A surveillance for moboviruses and the diseases they cause in Europe is recommendable, because the cases may often pass unnoticed or misdiagnosed not only in free-living vertebrates but also in domestic animals and even in humans.

Introduction

Mosquito-borne viruses (‘moboviruses’) belong to an ecological group of viruses characterized by their specific biological transmission via competent hematophagous arthropods—mosquitoes (Culicidae) to homoiothermous (endotherm) vertebrates. Competent vectors are those arthropods that are able to imbibe the virus in the course of blood-feeding on an infected donor host, to support the multiplication of the virus in their organism, and to deliver a sufficiently large inoculum to the recipient host. Usually, certain minimum level of viremia (‘infection threshold’) in a donor vertebrate host is necessary for an efficient infection of particular arthropod vectors. Therefore, only those vertebrate species that produce viremia have been regarded as ‘true’ or ‘amplifying’ hosts of particular moboviruses (Bárdoš 1979). Many moboviruses can be transmitted from male to female during copulation (venereal or horizontal transmission, VT) or even from female to the offspring (transovarial or vertical transmission, TOT). These modes are extremely important ecologically, e.g., under conditions of TOT, the mosquito vector also plays the role of a long-term reservoir of the virus. Majority of moboviruses have probably evolved from viral symbionts of these arthropods, while only a minority could have originated as true vertebrate viruses (Lvov et al. 1989b).

All moboviruses registered in the International Catalogue of Arboviruses (Karabatsos 1985) that have occurred in Europe since the beginning of the twentieth century are listed here, including their standard abbreviations according to the Catalogue, synonyms, and classification into the families, genera, and antigenic groups. The number of the ‘European’ moboviruses (excluding synonymous, duplicate viruses) stands at ten, but some of them are rather ephemeral in their occurrence in Europe (e.g., Dengue and Chikungunya viruses). For experimental pathogenicity of these viruses for some vertebrates and cell cultures, see Tables 1 and 2, respectively.
Table 1

Experimental pathogenicity of ‘European’ moboviruses (Karabatsos 1985; Hubálek and Halouzka 1996)

 

SM i.c.

SM i.p.

M i.c.

M i.p.

H i.c.

H i.p.

GP i.c.

GP i.p.

C s.c.

CE y.s.

Other

SINV

2–4

2–4

+

1–3

RM i.c. −

CHIKV

4

+

(−)

(−)

nd

RM s.c. (−)

WNV

2–5

4–5

3–5

4–9

+

+

(+)

2–4

RM, sheep i.c. (+) horse, birds s.c. (+)

USUV

5–6

6–11

 

DENV

3–6

(−)

5–20

RM i.c. +

BATV

3–5

4–8

4–8

(−)

10

3–5

RM i.c. (−) pig, sheep i.c. −

TAHV

2–3

2–5

3–6

(−)

4–9

3–8

RM i.c. − (fever)

SSHV

2–3

2–4

3–6

(−)

+

+

nd

nd

nd

2–5

 

INKV

3

7

6

nd

nd

nd

nd

nd

nd

 

LEDV

4–5

6–13

3–4

RM, birds s.c. −

The figures show the average survival time (days) of the viruses established after several passages

+ Death, (+) irregular death, (−) irregular encephalitis or pareses, but survival, no death, nd not done, SM suckling mouse, M adult mouse, H adult hamster, GP guinea pig, C chick (newly hatched), CE chick embryo (into yolk sac), RM rhesus monkey, i.c. intracerebrally, i.p. intraperitoneally, s.c. subcutaneously

Table 2

Susceptibility of cell cultures to ‘European’ moboviruses (Karabatsos 1985; Hubálek and Halouzka 1996)

 

CEC, DEC

BHK

VERO

CV-1

GMK

LLC-MK2

PS

HeLa

XTC

AA

SINV

+

+

+

+

+

+

+

+

+

(+)

CHIKV

+

+

+

nd

nd

+

+

+

nd

m

WNV

+

(+)

+

+

+

+

+

(+)

+

(+)

USUV

+

(m)

+

nd

nd

m

m

m

nd

nd

DENV−1

(p)

(p)

+

+

(p)

(+)

(−)

(+)

BATV

P

+

+

+

nd

+

+

+

+

m

TAHV

+

+

+

+

+

+

+

+

+

m

SSHV

+

+

+

+

+

+

+

nd

+

nd

INKV

m

+

+

nd

nd

+

+

+

+

m

LEDV

+

+ CPE and plaques produced, (+) faint CPE formed, p plaques produced (under overlay) but no CPE, (p) indistinctive plaques produced, usually no CPE, neither CPE nor plaques produced (data on multiplication missing), m multiplication without CPE/plaques production, CPE cytopathic effect, nd not done, AA Aedes albopictus cells

Three categories of mosquito-borne viruses can be distinguished in Europe: (i) human pathogenic and autochthonous, (ii) human pathogenic and imported, and (iii) pathogenic for other vertebrates than humans. This review briefly summarizes the present knowledge about the European mosquito-borne viruses; for more details, see, e.g., Theiler and Downs (1973), Karabatsos (1985), Aspöck (1996), Hubálek and Halouzka (1996), Lundström (1999), Medlock et al. (2007), and Gratz (2006).

Mosquito-borne human pathogenic viruses autochthonous in Europe

Sindbis virus (Alphavirus, Togaviridae); synonyms or subtypes: Ockelbo, Pogosta, Karelian fever, Babanki, and Kyzylagach viruses

Sindbis virus (SINV) is a member of the American Western equine encephalomyelitis (WEE) antigenic complex of alphaviruses, together with the closely related Australian Whataroa virus (Calisher et al. 1988). This similarity caused in the past some unsubstantiated reports about the occurrence of WEE in Europe. It was originally isolated from Culex univittatus mosquitoes collected in Sindbis village, Nile Delta (Egypt) in 1952 (prototype strain Eg-339; Taylor et al. 1955); first European isolation was reported from a reed warbler (Acrocephalus scirpaceus) caught in Western Slovakia in 1971 (European topotype strain R-33; Ernek et al. 1973). Ockelbo (Edsbyn 5/82) and Karelian fever (LEIV-9298 ‘Karelia’) strains are identical to prototype SINV by complement fixation and hemagglutination inhibition tests and by polypeptide composition (Uryvaev et al. 1990) but distinguishable by neutralization test (Niklasson et al. 1984; Lvov et al. 1988). However, the overall divergence between Ockelbo and EgAr-339 strains is only 6% and 3% in the sequences of nucleotides and amino acids, respectively (Shirako et al. 1991). Certain antigenic and genetic differences have additionally been described among other SINV strains isolated in different geographic areas (Olson and Trent 1985; Lundström et al. 2001). SINV is very widely distributed; it occurs in Africa, Eurasia and Australia. Distribution in Europe was shown in Fig. 1.
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Fig. 1

Geographic distribution of moboviruses in Europe. Explanation: black points, the virus isolation; white circles and hachures, specific antibodies detected

Vectors are largely ornithophilic mosquitoes. In Europe, these are Culex pipiens, Culex torrentium (principal enzootic vector in Sweden), Culiseta morsitans, Coquillettidia richiardii, Ochlerotatus communis, Ochlerotatus excrucians, Aedes cinereus, and Anopheles hyrcanus (Berezin et al. 1972; Francy et al. 1989; Lundström et al. 1990a, b; Turell et al. 1990; Lvov et al. 1984, 1985). Laboratory transmission of SINV was documented also in Aedes albopictus (Dohm et al. 1995). Exceptional are isolations reported from Hyalomma marginatum (Grešíková et al. 1978) and H. anatolicum ticks.

Vertebrate hosts are largely wild passeriform birds, e.g., Turdidae, Fringillidae, Emberizidae, Corvus corone, Motacilla alba, Ardeola ralloides, Somateria mollissima, Anas platyrhynchos, Vanellus vanellus, Streptopelia turtur, Gallinago gallinago, Fulica atra, Acrocephalus scirpaceus, Sturnus vulgaris (Taylor et al. 1955; Uryvaev et al. 1992; Lundström et al. 1993a, 2001), occasionally rodents, and amphibians (Rana ridibunda; Kožuch et al. 1978). Migratory birds play an important role in the wide geographic distribution of the virus (Calisher et al. 1988; Ernek et al. 1973, 1977; Lvov and Ilyichev 1979; Lvov et al. 1989b; Nir et al. 1968; Nosek and Folk 1977; Shirako et al. 1991; Uryvaev et al. 1992), including its probable introduction in Fennoscandia. Long-term persistence (53 days) of SINV in the central nervous system (CNS) of an experimentally inoculated pigeon was observed (Semenov et al. 1973).

Natural foci of SINV infections occur mainly in wetland ecosystems of diverse biomes (principally an avian-mosquito cycle; Ernek et al. 1973/1974).

In animals, the virus can cause sporadic illness in birds (pigeon—encephalitis) and irregular deaths in old chickens (while newborn chicks are very susceptible at intracerebral and intraperitoneal inoculations).

Human disease is fever for 3–4 days with headache, myalgia, arthralgia (polyarthritis), malaise, conjunctivitis, pharyngitis, and rash (skin vesicles on the trunk and limbs while the face remains usually unaffected). Acute illness lasts up to 10 days, but fatigue and tendon pains may persist for several weeks or months, and chronic arthritis may develop in some patients (Laine et al. 2004; Kurkela et al. 2005, 2007). No mortality has been observed. A great input for the study of SINV in Europe has been outbreaks with hundreds of cases in Fennoscandia since 1981 that repeat at about 7-year periodicity (1974, 1981/1982, 1988, 1995, 2002). The disease has been called variably according to the region involved as ‘Ockelbo’ (Sweden), ‘Pogosta’ (Finland), or ‘Karelian’ (NW Russia) fever (Lvov et al. 1982, 1985, 1988; Skogh and Espmark 1982; Espmark and Niklasson 1984; Niklasson et al. 1984, 1988; Niklasson and Vene 1996). The average annual incidence of SINV fever in Finland, 1995–2003, was the highest in North Karelia with 25.7 cases per 100,000 population, while in other parts of the country, it varied between 0.4 and 14.8 cases/100,000 population. The mean human seroprevalence was 5.2% at the same time, reaching 15.4% in the age group of 60–69 years (Kurkela et al. 2008). The highest incidence in Sweden was 2.9 per 100,000 population in an eastern area, and mean annual number of cases was 31 in the whole country during 1981 through 1988 (Lundström et al. 1991). In 1995, there were 47 cases in Sweden and as many as 1,352 cases in Finland (Lundström 1999). Hundreds of SINV fever cases have also occurred in South Africa, Uganda, and Australia (due to closely related Whataroa virus on the latter continent).

West Nile virus (Flavivirus, Flaviviridae); synonym Rabensburg virus

West Nile virus (WNV) is a member of the Japanese encephalitis group of flaviviruses, originally isolated from the blood of a febrile woman in the West Nile district in Uganda in 1937 (Smithburn et al. 1940) and later from a child in Egypt in 1950 (Melnick et al. 1951). Prototype (B-956 from a man in Uganda, 1937) belongs to lineage 2, while the Egyptian topotype Eg-101 (child in Egypt, 1950) belongs to lineage 1 of WNV. European topotypes are Sambuc (man in France, 1964) and Hp-94 (H. marginatum, South Russia, 1963). WNV was soon recognized as one of the most widespread flaviviruses distributed through Africa, Asia, Europe, and Australia, also present in America, since 1999. In Europe, it was first recovered from H. marginatum ticks in Astrakhan, southern Russia in 1963 (strain Hp-94; Chumakov et al. 1968) and from patients and mosquitoes in Camargue, South France in 1964 (Hannoun et al. 1964), later in several other European countries (e.g., Labuda et al. 1974; Hubálek and Halouzka 1996, 1999; Murgue et al. 2002). Distribution in Europe was shown in Fig. 2.
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Fig. 2

Geographic distribution of moboviruses in Europe. Explanation: black points, the virus isolation; black squares, human infections; white circles and hachures, specific antibodies detected

Only the lineage 1 WNV isolates were known in Europe before 1997. However, two identical strains of WNV (‘Rabensburg’) were isolated in Czechland from Culex pipiens mosquitoes in 1997 and 1999 (Hubálek et al. 1998, 2000), which were later sequenced and found to represent a new, third genomic lineage of WNV (Bakonyi et al. 2005). In addition, a lineage 2 WNV strain was isolated from a dead goshawk fledgling in Hungary recently (Bakonyi et al. 2006).

In Europe, WNV was isolated from largely ornithophilic mosquitoes Culex pipiens (TOT; Anderson and Main 2006), Culex modestus, and Coquillettidia richiardii. Occasional vectors are Ochlerotatus cantans and Anopheles maculipennis group (Hannoun et al. 1964, 1969; Berezin et al. 1971, 1972; Filipe 1972; Labuda et al. 1974; Murgue et al. 2002), while certain Hyalomma, Argas, and Ornithodoros tick species could play a subsidiary role in dry ecosystems of southern Russia (Lvov et al. 1989b).

Vertebrate hosts are largely wild birds. In Europe, WNV was isolated from Ardeola ralloides, Plegadis falcinellus, Anas querquedula, Fulica atra, Tringa ochropus, Vanellus vanellus, Larus ridibundus, Streptopelia turtur, Corvus corone, Corvus frugilegus, and Sturnus vulgaris. High and/or long-term viremias were observed in experimentally infected birds of many species, e.g., Anas acuta (up to 101 days; Fedorova and Stavskiy 1972), Aythya ferina, and Corvus frugilegus, with an occasional fatal encephalitis in the latter species (Stavskiy et al. 1972). WNV could persist in the organs (liver, spleen, CNS) of domestic pigeons for at least 20 days (Semenov et al. 1973). Migratory birds play a role in the widespread geographic distribution of WNV (Nir et al. 1968; Hannoun et al. 1969; Ernek et al. 1977; Nosek and Folk 1977; Rappole et al. 2000; Rappole and Hubálek 2003). Occasional hosts may be mammals like cattle, camel, horse (Schmidt and Mansoury 1963; Hannoun et al. 1969), or frogs Rana ridibunda (viremia confirmed experimentally; Kostyukov et al. 1985).

Natural foci are situated largely in wetland ecosystems, principally an avian-mosquito cycle. However, argasid and some metastriate ticks may act as potential substitute vectors in certain dry and warm habitats of the Palaearctic (Lvov and Ilyichev 1979).

Animal disease is a febrile illness and encephalomyelitis in horses, with approximately 25% lethality, usually as epizootics in France, Portugal, Italy, and outside Europe (Egypt, Morocco, North America). Occasionally, fatal systemic disease included encephalitis in birds (corvids, raptors, and some other avian groups) especially in North America where highly virulent WNV strain has caused epornithics.

Human disease is were moderate to high abrupt fever (3–6 days, sometimes biphasic), headache, sore throat, backache, myalgia, arthralgia, fatigue, anorexia, nausea (vomiting), conjunctivitis, retrobulbar pain, maculopapular rash (spreading from the trunk to the face and extremities), lymphadenopathy, insomnia, acute aseptic meningitis, or encephalitis; less often myocarditis, pancreatitis, or hepatitis; and mortality rate of 5–10% with a majority of fatal cases recorded in persons aging >60 years old. First recorded epidemics occurred in Israel in 1950’s and then in South Africa with at least 3,000 cases in 1974. In Europe, epidemics with tens to hundreds of cases have been observed in southern Russia, South France, Spain, and Romania (1996–1998, >500 cases in the latter country), while sporadic cases in, e.g., Czechland (Hubálek et al. 1999). In the late 1990’s, outbreaks of WNV fever also occurred in Israel and southern Russia. The incidence of WNV infections in Europe is unknown but except for outbreaks probably rather low. An exception may be South Russia (Butenko et al. 1968), Romania, South France (Hannoun 1971; Murgue et al. 2001), and Spain (Filipe and Andrade 1990), where epidemics with tens of human cases have been observed. Hundreds of cases have occurred outside Europe. For instance, WNV is the most common arbovirus infection in Senegal or in South Africa (e.g., a large outbreak in 1974). In North America, WNV disease of humans (and animals) has spread from the East to the West Coast within 4 years after its introduction in 1999.

Ťahyňa virus (California group, Orthobunyavirus, Bunyaviridae); synonyms Lumbo, Trojica

Ťahyňa virus (TAHV) is a member of the California antigenic group, closely related to North American LaCrosse and Snowshoe Hare viruses (Casals 1962; Calisher 1983). Genetic reassortment with all possible combinations of the three RNA segments has been demonstrated among them (Bishop et al. 1980) and the reassortants can appear during a mixed infection of a vector mosquito (Chandler et al. 1991). TAHV was originally isolated (prototype strain Ť-92) from Aedes vexans and Ochlerotatus caspius mosquitoes in Ťahyňa and Križany villages, eastern Slovakia in 1958 (Bárdoš and Danielová 1959). This is the very first mobovirus pathogenic to humans that was isolated in Europe. An antigenically identical virus Lumbo was reported from Mozambique later in 1960 (Kokernot et al. 1962). TAHV occurs outside Europe in Asia (southern Siberia and the Far East, Turkey, Armenia, Azerbaijan, Tadjikistan, Uzbekistan; antibodies were detected in Sri Lanka and China) and Africa (Tunisia, Morocco, Egypt, Ethiopia, Mozambique, Uganda, Kenya, Angola, South Africa, West Africa). Distribution in Europe was shown in Fig. 3.
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Fig. 3

Geographic distribution of moboviruses in Europe. Explanation: black points, the virus isolation; white circles and hachures, specific antibodies detected

Arthropod vectors are culicine mosquitoes Aedes vexans, Aedes cinereus, Ochlerotatus caspius, Ochlerotatus cantans, Ochlerotatus punctor, Ochlerotatus communis (northern Europe), Ochlerotatus flavescens, Ochlerotatus excrucians, Culiseta annulata, Culex modestus, and Culex pipiens, and Anopheles hyrcanus in southern Europe (Kolman et al. 1964; Aspöck and Kunz 1966, 1967; Hannoun et al. 1966; Danielová et al. 1966; Lvov et al. 1972, 1987, 1989a, b; Arcan et al. 1974; Gligic and Adamovic 1976; Traavik et al. 1978, 1985; Rosický and Málková 1980; Pilaski and Mackenstein 1985; Danielová 1992). Transovarial transmission was documented in Aedes vexans (Danielová and Ryba 1979) and Culiseta annulata (Bárdoš et al. 1975b), while overwintering in female Culex modestus (Chippaux et al. 1970) and Culiseta annulata (Danielová and Minář 1969).

Principal vertebrate hosts are lagomorphs (brown hare Lepus europaeus and rabbits), hedgehogs (Erinaceus roumanicus), and rodents. Experimental viremia has been demonstrated in juv. lagomorphs, Erinaceus concolor, Citellus citellus, Glis glis, Ondatra zibethicus, Sciurus vulgaris, Martes foina, Putorius eversmanni, Vulpes vulpes, Meles meles, Vespertilio murinus, and piglets (Aspöck and Kunz 1970b; Rödl et al. 1979, 1987; Rosický and Málková 1980).

Natural foci of Valtice fever occur in inundated lowland habitats (floodplain forest ecosystem) in diverse biomes, sometimes including periurban areas (Labuda and Kožuch 1982; Málková et al. 1984).

Animal disease is unknown. However, several cases of encephalitis of young dogs caused by LaCrosse virus were described in the USA (Black et al. 1994; Tatum et al. 1999); experimental infection of puppies led to fatal CNS disease (Godsey et al. 1988).

Human disease caused by TAHV, ‘Valtice fever’, is an influenza-like illness occurring in summer and early autumn mainly in children, with a sudden onset of fever (3–5 days), headache, malaise, conjunctivitis, pharyngitis, myalgia, nausea, gastrointestinal disorders, anorexia, occasional arthralgia, stiff neck, or other signs of the CNS involvement (meningitis), sometimes bronchopneumonia. No mortality has been described, contrary to the North American La Crosse virus. Very high frequency (60–80%) of neutralizing antibodies is reported regularly in elderly persons in endemic foci (Bárdoš 1974; Hubálek et al. 1979, 2000). At least 200 documented cases of Valtice fever have been published in the Czechland and Slovakia since 1963 (Bárdoš and Sluka 1963; Mittermayer et al. 1964; Sluka 1969; Sluka and Šimková 1972; Šimková and Sluka 1973, 1977; Bárdoš 1974, 1977; Bárdoš et al. 1975a, 1980; Rosický and Málková 1980), but many cases have remained undiagnosed (this is not a notifiable infectious disease in Europe). For comparison, a total of 263 cases of the California group virus infection were diagnosed in European Russia between 1986 and 1993 (Kolobukhina et al. 1989a, b, 1990; Demikhov et al. 1991, D. K. Lvov, personal communication). The disease also occurs in other European countries (e.g., France; Janbon et al. 1974) and outside Europe, e.g., in Tadjikistan (Lvov et al. 1977). The closely related LaCrosse virus is the main cause of arbovirus encephalitis in children in the USA, whereas Jamestown Canyon virus of the same serogroup is more often associated with illness in adults. Between 1963 and 1981, a total of 1,348 human cases of California encephalitis were reported in the USA; the annual average was 71 (Henderson and Coleman 1971; Peters and LeDuc 1990; Calisher 1994).

Snowshoe Hare virus (California group, Orthobunyavirus, Bunyaviridae)

Snowshoe Hare virus (SSHV) is very closely related to LaCrosse and TAHV viruses. Genetic reassortment among these three agents was demonstrated. Prototype strain ‘Snowshoe hare original’ was isolated from the blood of Lepus americanus, in Montana, USA in 1959 (Burgdorfer et al. 1961). In Europe, it was first isolated from Ochlerotatus communis in North European Russia in 1986 (Lvov et al. 1989a, b; Butenko et al. 1991; Vanlandingham et al. 2002). Distribution outside Europe is northern USA, Canada, and Asian Russia. Distribution in Europe was shown in Fig. 3.

The vectors are Aedes cinereus, Aedes vexans, Ochlerotatus communis, Ochlerotatus punctor, Ochlerotatus cataphylla, Culiseta inornata, and Culiseta impatiens.

Vertebrate hosts are snowshoe hare Lepus americanus, Clethrionomys rutilus, and Dicrostonyx torquatus (lemming). Experimental viremia is in Citellus lateralis, Citellus columbianus, Eutamias amoenus, and Microtus pennsylvanicus.

Natural foci are tundra and taiga biomes.

In animal disease, equine encephalitis accompanied with fever, ataxia, and circling was described in Canada; the horses have usually recovered within 1 week (Lynch et al. 1985; Heath et al. 1989).

Human disease is fever, headache, vomiting, and sometimes CNS affection.

Inkoo virus (California group, Orthobunyavirus, Bunyaviridae)

Inkoo virus (INKV) is a subtype of California encephalitis virus, closely related to Jamestown Canyon virus, and less to TAHV and SSHV (Calisher 1983; Vapalahti et al. 1996). It was first isolated (prototype strain KN-3641) from Ochlerotatus communis/punctor mosquitoes collected in Inkoo commune, South Finland in 1964 (Brummer-Korvenkontio 1969, 1974; Brummer-Korvenkontio et al. 1973). Distribution in Europe was shown in Fig. 4. The virus is obviously restricted to northern Europe, including Russia (Lvov et al. 1989a, b, 1996; Butenko et al. 1991; Vanlandingham et al. 2002).
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Fig. 4

Geographic distribution of moboviruses in Europe. Explanation: black points, the virus isolation; white circles and hachures, specific antibodies detected

Vectors are Ochlerotatus communis (principal vector), Ochlerotatus punctor, and Ochlerotatus hexodontus (Brummer-Korvenkontio et al. 1973; Traavik et al. 1978, 1985; Francy et al. 1989). Vertebrate host is Lepus timidus.

Natural foci are open farmland with water pools at northern latitudes.

Animal disease is unknown. Human cases are sporadic, not well characterized. Several cases (influenza-like, febrile illness) have been reported in Northwest, North, and Central Russia (Kolobukhina 1989a, b, 1990; Lvov et al. 1989a, b, 1996). The closely related Jamestown Canyon virus is the agent of CNS infections among adults in North America.

Batai virus (Bunyamwera group, Orthobunyavirus, Bunyaviridae); synonyms Čalovo and Chittoor viruses

Batai virus (BATV) was originally isolated (prototype strain AMM-2222) by B. Elisberg from Culex gelidus collected at Kuala Lumpur (Malaysia) in 1955 (Karabatsos 1985). Antigenically identical ‘Čalovo’ virus (strain 184) was then isolated from Anopheles maculipennis s.l. mosquitoes collected near Čalovo, South Slovakia in 1960 (Bárdoš and Čupková 1962) and strain ‘Olyka’ of BATV also from Anopheles maculipennis in West Ukraine in 1973 (Vinograd et al. 1973; Gaidamovich et al. 1973). Other strains of BATV are ‘Chittoor’ IG-20217 (Anopheles barbirostris, India in 1957) and Sar MS-50 (Aedes curtipes, Sarawak in 1962). Closely related to BATV are the African ‘Beliefe’ (UGMP-6830, nonregistered) and Ilesha viruses and less closely related (distinguishable by neutralization) are the American Northway, Cache Valley, and Tensaw viruses (Hunt and Calisher 1979; Dunn et al. 1994). Outside Europe, BATV occurs in Malaysia, Thailand, Cambodia, India, Sri Lanka, Sarawak (Borneo), Japan, Asian Russia (Irkutsk, Far East), Sudan, Cameroon, Nigeria, Uganda, and Central Africa (as Ilesha virus in the latter four countries). Distribution in Europe was shown in Fig. 5.
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Fig. 5

Geographic distribution of moboviruses in Europe. Explanation: black points, the virus isolation; white circles and hachures, specific antibodies detected

Principal vectors in Europe are zoophilic mosquitoes Anopheles maculipennis s.l. (experimental hibernation of the virus; Aspöck and Kunz 1970a; Beletskaya and Alekseev 1988) and Anopheles claviger, Coquillettidia richiardii and less often Ochlerotatus punctor and Ochlerotatus communis (Bárdoš and Čupková 1962; Smetana et al. 1967; Aspöck and Kunz 1968; Aspöck 1968; Aspöck et al. 1970; Brudnjak et al. 1970; Vinograd et al. 1973, 1980, 1981; Traavik et al. 1985; Francy et al. 1989).

Vertebrate hosts are domestic pig, horse, and ruminants (Geevarghese et al. 1994; Yanase et al. 2006). BATV was also isolated from several bird species (Corvus corone, Fulica atra, Perdix perdix; Vinograd and Obukhova 1975). Persistent avian infection was established experimentally, and the application of cortisone reactivated viremia 6 months postinfection (Vinograd and Roghochiy 1978).

Natural foci of BATV infection occur in agroecosystems (in and around villages, farms); principally domestic animal—zoophilic mosquito cycle.

BATV could be pathogenic to mammals: ‘Chittoor’ strain caused a mild illness among sheep and goats in Uttar Pradesh, 1961 (Pavri and Singh 1969), and the closely related North American Cache Valley virus outbreaks of stillbirths and congenital abnormalities (arthrogryposis and hydranencephaly—‘AGH syndrome’) in sheep and other ruminants (Chung et al. 1990; Edwards 1994; de la Concha-Bermejillo 2003). European veterinary data are missing but the research seems to be desirable, i.e., monitoring of stillbirths and congenital abnormalities among domestic ruminants.

In humans, seroconversion data have indicated an association of BATV with influenza-like illness accompanied by malaise, myalgia, and anorexia in South Moravia, Czechland (Bárdoš et al. 1969; Sluka 1969). Febrile illness caused by BATV was also observed in two patients in Thailand (Smith et al. 1969; Woodall 1969). BATV was also isolated from the blood of four febrile patients in Sudan (Nashed et al. 1993), and antigenically similar Ilesha virus was described as the cause of at least seven human cases of febrile illness with rash or even hemorrhagic fever including one fatal case in Africa (Woodall 1969; Peters and LeDuc 1990; J. M. Morvan personal communication). In addition, Ngari bunyavirus, causing outbreaks of hemorrhagic fever in East Africa, was demonstrated to be a reassortant of BATV and Bunyamwera virus (Gerrard et al. 2004; Briese et al. 2006; Yanase et al. 2006). Further research on pathogenic role of BATV in humans is necessary.

Exotic mosquito-borne human pathogenic viruses in Europe

Chikungunya, dengue, and yellow fever viruses sometimes produce outbreaks even in Europe that are caused by the import and presence of competent vectors of the particular disease, i.e., Aedes aegypti in the past (yellow fever, dengue), and Aedes albopictus recently (chikungunya) in Europe. A number of mobovirus infections are imported by viremic immigrants, tourists, and travellers returning from (sub)tropical countries (Gubler 1996; Fontenille et al. 2007). In general, mosquito-borne virus importation to Europe is possible via:
  1. 1.

    Viremic travelers

     
  2. 2.

    Trade in domestic, pet, and zoo (infected) vertebrates

     
  3. 3.

    Introduction of infected mosquitoes (including larvae, pupae, eggs—Aedes albopictus, etc.) on planes, ships, cars (international traffic and trade, e.g., tires)

     
  4. 4.

    Infected migratory birds (WNV)

     

Chikungunya virus (Alphavirus, Togaviridae)

Vectors of Chikungunya virus (CHIKV) are anthropophilic mosquitoes Aedes albopictus and Aedes aegypti, while different Aedes spp. in tropical sylvatic foci where other primates serve as its vertebrate hosts. Human disease involves the classic triad of clinical symptoms: fever, arthralgia, and maculopapular rash on the face, limbs, and trunk. Arthralgia persists in some patients for weeks or years (Powers and Logue 2007; Pialoux et al. 2007). In 2006–2007, tens of Chikungunya fever cases were reported among tourists returning from the islands of the Indian Ocean (Réunion, etc.) and Indian subcontinent to many European countries e.g. France, UK, Germany, Italy, Belgium, Switzerland, Czechland, Norway, and Spain (Fontenille et al. 2007; Powers and Logue 2007).

Chikungunya virus in a foreigner coming from India has established an Italian focus in Ravenna province (Castiglione di Cervia) with a following outbreak in July to September 2007 (166 patients). The virus was detected in local Aedes albopictus mosquitoes (Rezza et al. 2007). The enhanced risk of CHIKV for Europe has appeared with the introduction of the Aedes albopictus mosquito vector into Italy and other Mediterranean countries—Spain, Portugal, France, Albania, Croatia, South Serbia, Greece, and Turkey (Mitchell 1995; Knudsen et al. 1996; Gratz 2004; Fontenille et al. 2007).

Dengue virus (Flavivirus, Flaviviridae)

Four serotypes of Dengue virus (DENV 1–4) comprise a separate Dengue antigenic complex of flaviviruses (Calisher et al. 1989). The prototype strain of DENV-1 is Sabin strain (human blood in Hawaii, 1944). Dengue viruses occur in tropical regions of Southeast Asia, Australia, Pacific islands, India, Sri Lanka, Caribbean, Central and South America, and Africa (Solomon and Mallewa 2001).

Vectors of all four DENV species are anthropophilic Aedes aegypti (TOT) and Aedes albopictus (TOT, VT; Rosen 1987). There is no vertebrate host for DENV except for man, and wild primates in Southeast Asia. Foci of Dengue are synanthropic (urban, rural) and sylvatic in Southeast Asia.

Animal disease is unknown, although DENV is pathogenic to monkeys. Many thousands of dengue fever cases are in the tropics and subtropics over the world each year, with fever (approximately 5 days), intense headache, retrobulbar pain, myalgia, arthralgia, stiff neck, and rash. Sometimes, severe dengue hemorrhagic fever (petechial hemorrhages in the skin and internal organs) occurs with shock syndrome and is often fatal (Solomon and Mallewa 2001; Teichmann et al. 2004).

Several tens of human cases are introduced each year from tropical regions, as reported by many European countries (Teichmann et al. 2004). However, Dengue-1 and Dengue-2 viruses caused a huge outbreak in Greece in 1927–1928 (Theiler et al. 1960; Theiler and Downs 1973); 650,000 persons out of 704,000 inhabitants of Athens and Pireus contracted the disease between August and September 1928, and 1,061 died of dengue hemorrhagic fever (Papaevangelou and Halstead 1977; Halstead and Papaevangelou 1980). The virus (retrospectively both DENV-1 and DENV-2 by serology), however, was not isolated. Eritja et al. (2005) report that dengue occurred in Spain in the past—first probable outbreak, with a very low mortality (therefore certainly not yellow fever), occurred in Cádiz in 1778. A risk for Europe has appeared with the introduction of the vector Aedes albopictus mosquito in Mediterranean countries—see CHIKV.

Yellow fever virus (Flavivirus, Flaviviridae)

Yellow fever occurred in Europe in Portugal and Spain (Eritja et al. 2005) in the eighteenth and nineteenth centuries (since 1701; the largest outbreaks were in 1741 and 1802–1821, with a total of about 100,000 victims), later in Italy, France (Saint Nazaire in the 1860’s), and in England (Swansea in 1865). These outbreaks were generated by infected Aedes aegypti mosquitoes introduced on sailboats. Nowadays, the import of yellow fever human cases from the tropics is sporadic in European countries (e.g., Germany).

In addition, imported cases of West Nile fever have been identified in Europe. For instance, in 1984, Syria→Russia—one patient (WNV isolated); in 1998, Senegal→France—one patient (fever); in 2002, USA (Atlanta)→France—one patient; in 2002, USA (NY)→Czechland—one patient (with encephalitis; Hubálek et al. 2006); in 2003, Israel→Denmark—one patient (fever); and in 2003, Canada→Denmark—one patient (encephalitis).

Mosquito-borne viruses not pathogenic to man in Europe

Lednice and Usutu viruses are both associated with wild birds and occur in central Europe, although they are of African origin. There is no proved human case of clinical infection with either Lednice virus (highly improbable) or Usutu virus. However, with the latter virus, the human disease cannot be excluded.

Lednice virus (Turlock group, Bunyavirus, Bunyaviridae)

This is a member of M’Poko antigenic complex of the Turlock serogroup. Prototype strain 6118 was isolated from Culex modestus collected near Lednice, South Moravia (Czechland) in 1963 (Málková et al. 1972). Additional six isolations were made at the same locality in 1972 (Málková et al. 1965, 1986). The virus was originally classified as Yaba-1 virus, known to occur in Africa. Although Lednice virus (LEDV) is antigenically very closely related to African Yaba-1 and M’Poko viruses, the three viruses form M’Poko antigenic complex and can be differentiated by plaque-reduction neutralization (Calisher et al. 1984). Distribution is South Moravia in Czechland; antibodies were also detected in birds of Romania (Draganescu et al. 1981).

The only known vector is Culex modestus (Danielová 1984).

Vertebrate hosts are birds, largely of the order Anseriformes. Antibodies have been detected in Cygnus olor, Anser anser, and Anas platyrhynchos, less often in Fulica atra, Larus ridibundus, and domestic waterfowl bred at fishponds of the endemic area. However, viremia in birds is generally low and of short duration (Danielová and Málková 1976; Málková and Danielová 1977, 1978; Málková et al. 1979, 1986), while neither viremia nor antibodies have been detected in mammals. Natural foci are situated in littoral reedbelts in fishpond and wetland ecosystems (an avian-mosquito cycle).

Disease in vertebrates is unknown but quite improbable in mammals including man. No antibodies were detected by hemagglutination inhibition test in 581 inhabitants of the endemic area (Kolman 1974; Kolman et al. 1979).

Usutu virus (Japanese encephalitis group, Flavivirus, Flaviviridae)

The virus was first isolated (prototype strain SA Ar 1776) from Culex univittatus in South Africa in 1959 (Karabatsos 1985). Distribution in Europe was shown in Fig. 6. Usutu virus (USUV) appeared in Vienna in 2001 killing hundreds of wild birds (predominantly blackbirds, Turdus merula), and then it spread also to neighboring Hungary (Weissenböck et al. 2002, 2003, 2007; Chvala et al. 2007; Bakonyi et al. 2007). Antibodies to USUV were also reported in sentinel chickens in England (Buckley et al. 2006), Switzerland, North Italy (Weissenböck et al. 2007), and in a Fulica atra and a Larus ridibundus in Czechland and Poland, respectively (Hubálek et al., unpublished results).
https://static-content.springer.com/image/art%3A10.1007%2Fs00436-008-1064-7/MediaObjects/436_2008_1064_Fig6_HTML.gif
Fig. 6

Geographic distribution of moboviruses in Europe. Explanation: black points, the virus isolation; white circles and hachures, specific antibodies detected

The vectors in Africa are largely ornithophilic mosquitoes Culex spp. (Culex univittatus, Culex perfuscus), Coquillettidia aurites, and Mansonia africana. In Austria, RNA of USUV was detected in Culex pipiens, Culex hortensis, Culex territans, Culiseta annulata, Aedes vexans, and Aedes rossicus, although the virus has not been isolated (Weissenböck et al. 2007).

Vertebrate hosts are birds. USUV is pathogenic for certain passeriform birds and raptors (Weissenböck et al. 2002, 2003, 2007). Very little is known about the medical importance of USUV; human cases have not been described in Europe nor elsewhere.

Eco-epidemiological factors in the natural history of mosquito-borne viruses

Moboviruses and their circulation in natural foci can be influenced by great number of factors, affecting primarily their vectors—mosquitoes. For instance, major factors are land use and climate. Favorable ecological factors for moboviruses (not only those imported) are, in general:
  1. 1.

    Abundance of wild vertebrates and vectors

     
  2. 2.

    Intense summer precipitations, floods

     
  3. 3.

    Higher summer temperatures and drought

     
  4. 4.

    Appropriate habitats, e.g., humid building basements (Bucharest, Volgograd—WNV)

     
  5. 5.

    Contact transmission among wild birds (e.g., WNV)

     
Climate effects under global warming scenario on moboviruses may cause:
  1. 1.

    Higher virus replication rate in vector mosquitoes at elevated ambient temperature, with a shortened extrinsic incubation period (Lundström et al. 1990b)

     
  2. 2.

    Increased vector populations

     
  3. 3.

    Expanding range of vectors—northwards (e.g., Culex modestus)

     
  4. 4.

    But higher mortality rate of the vector population

     

Introduction and establishment of Aedes albopictus in Europe

The Asian mosquito species Aedes albopictus, vector of several dangerous moboviruses (e.g., DENV, CHIKV), has been introduced in Europe, most often by import of used tires from Asia, America, or Africa. Up to now, it has been observed in Albania (since 1975), Bosnia and Hercegovina, Croatia, Serbia and Montenegro, Slovenia, Greece, Italy, Switzerland, South France, Spain, Portugal, Belgium, and the Netherlands (Mitchell 1995; Knudsen et al. 1996; Gratz 2004; Eritja et al. 2005; Benedict et al. 2007; Scholte and Schaffner 2007; Straetemans 2008). In Albania and Italy (Romi 2001), it has been already established. The risk of infection of these European populations through infected immigrants, tourists, and travelers returning from tropical destinations is growing. In fact, one outbreak of chikungunya in Italy already happened (see above).The lower limits for persistence of Aedes albopictus populations are (i) the winter mean air temperature 0°C, (ii) mean annual air temperature 11°C, (iii) mean air temperature in July 20°C (optimum, 25–30°C), and (iv) annual precipitation of 500 mm, with sufficient rainfall in summer (Mitchell 1995; Knudsen et al. 1996; Kobayashi et al. 2002; Eritja et al. 2005; Medlock et al. 2006).

Epidemiological surveillance of mosquito-borne viruses

An approach combining epidemiology with ecology, consisting of:
  1. 1.

    Routine diagnosis of human disease

     
  2. 2.

    Reporting incidence of human disease

     
  3. 3.

    Increased awareness for imported mobovirus infections (Gubler 1996)

     
  4. 4.

    Monitoring animal disease (if it exists)

     
  5. 5.

    Monitoring mosquito vector populations

     
  6. 6.

    Testing mosquito vector infection rates

     
  7. 7.

    Domestic+wild vertebrate serosurveys

     
  8. 8.

    Monitoring ecological factors

     

Conclusions

Ten moboviruses have occurred in Europe since the twentieth century, but some of them are rather ephemeral in their European occurrence (CHIKV, DENV). In particular European countries, following moboviruses have been recorded [in brackets—antibodies only detected]:
Albania

[WNV, TAHV]

Austria

BATV, TAHV, USUV [SINV, WNV]

Belarus

WNV [SINV]

Bosnia

[BATV, TAHV]

Bulgaria

[SINV, WNV]

Croatia

BATV [WNV, TAHV]

Czechland

WNV, BATV, TAHV, LEDV [SINV, USUV]

Estonia

SINV, TAHV, INKV [WNV]

Finland

SINV, INKV [BATV, TAHV]

France (including Corsica)

WNV, TAHV

Germany

TAHV, USUV [BATV]

Great Britain

[TAHV, SINV, WNV, USUV]

Greece

[DENV, WNV, TAHV]

Hungary

SINV, WNV, TAHV, USUV [BATV]

Iceland and Faeroe Islands

[TAHV]

Italy (including Sicily, Sardinia)

SINV, WNV, TAHV [BATV]

Lithuania

[TAHV]

Moldova

WNV, BATV, TAHV [SINV]

Norway

SINV, BATV, TAHV

Poland

SINV [WNV, USUV, TAHV]

Portugal

WNV [SINV, BATV, TAHV]

Romania

TAHV [SINV, WNV, LEDV]

Russia (Eur.)

SINV, WNV, BATV, TAHV, SSHV, INKV

Serbia (including Kosovo and Montenegro)

BATV, TAHV [SINV, WNV]

Slovakia

SINV, WNV, BATV, TAHV

Slovenia

TAHV

Spain

WNV [SINV, TAHV]

Sweden

SINV, BATV, INKV

Switzerland

USUV

Turkey (Eur.)

[WNV]

Ukraine (including Crimea)

WNV, BATV, TAHV [SINV]

No moboviruses have been reported from Belgium, Denmark, Ireland (Eire), Latvia, Luxembourg, Macedonia, and the Netherlands. However, the absence of any mobovirus in these countries is improbable, being a matter of insufficient investigations.

Recognized vertebrate hosts (i.e., those vertebrates from which particular agents have been isolated) of ‘European’ moboviruses are (in parentheses—viremia was demonstrated experimentally, but no isolations have been reported from the field): (1) insectivores—TAHV; (2) bats—SINV, WNV, TAHV; (3) rodents—SINV, WNV, BATV, TAHV, SSHV; (4) lagomorphs—TAHV, SSHV; (5) carnivores—BATV, TAHV; (6) equids—WNV (BATV); (7) artiodactyls—WNV, BATV (TAHV); (8) primates—SINV, CHIKV, WNV, DENV, BATV, TAHV; (9) birds—SINV, WNV, DUSUV, BATV, LEDV (INKV); and (10) amphibians—SINV, WNV.

Out of the ten moboviruses reported in Europe to date, five are autochthonous and cause (at least occasionally) human disease (Sindbis, West Nile, Ťahyňa, Inkoo, and Batai viruses); two are exotic, being occasionally imported to Europe (chikungunya, dengue, plus yellow fever viruses), and two are associated with birds and are probably not pathogenic to humans (Lednice and Usutu viruses). In general, three groups of mobovirus diseases can be recognized according to main clinical symptoms produced: (i) febrile illness—usually with a rapid onset, fever, sweating, headache, nausea, weakness, myalgia, arthralgia, sometimes polyarthritis, and rash; (ii) the CNS affection—meningitis, meningoencephalitis, or encephalomyelitis with pareses, paralysis, and other sequelae; and (iii) hemorrhagic disease. Mobovirus outbreaks are strictly determined by the presence and/or import of particular competent vectors of the disease. Ecological variables (including weather and climate conditions) affect mosquito-borne viruses; considerably, the main factors are abundance of mosquito vectors and their vertebrate hosts, intense summer precipitations or floods, summer temperatures and drought, and presence of appropriate habitats, e.g., wetlands, small water pools, or humid building basements. A surveillance for moboviruses and the diseases they cause in Europe is recommendable, because these diseases may often pass unnoticed or misdiagnosed in free-living vertebrates but also in domestic animals and even in humans.

Acknowledgement

The review was supported by the Grant Agency of the Czech Academy of Sciences (IAA 600930611).

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© Springer-Verlag 2008