Emerging Arboviruses in Europe

Abstract

Viruses transmitted by arthropods (arboviruses) pose a global public health threat. Sporadic cases or outbreaks caused by West Nile virus, Crimean–Congo haemorrhagic fever virus, tick-borne encephalitis virus, and phleboviruses are often reported in Europe. Recently, they expanded their distribution in geographic areas where they had never been observed before, while tropical viruses, like Dengue, Chikungunya, and Zika, started to cause autochthonous cases and outbreaks following the return of viraemic travellers from endemic countries. The primary or secondary vectors of these viruses are established in Europe, and the incidence of arboviral diseases is expected to increase due to several anthropogenic and/or environmental factors (mainly climate change, which affects the survival and amplification of the arthropod vectors). This is an update on the emerging arboviruses in Europe, associated challenges, and future perspectives.

1. Introduction

Arboviruses (arthropod-borne viruses) are a group of viruses transmitted to humans primarily by the bites of infected arthropods, mainly mosquitoes, ticks, and sandflies. Most arboviruses are RNA viruses (

Table 1. Main characteristics of emerging arboviruses in Europe (new introduction, increasing incidence, geographic expansion).

Vector	Virus	Family	Genus	Genome	Vector
Mosquitoes	West Nile	Flaviviridae	Flavivirus	RNA, linear	Culex spp.
	Usutu	Flaviviridae	Flavivirus	RNA, linear	Culex spp.
	Dengue	Flaviviridae	Flavivirus	RNA, linear	Aedes aegypti, Aedes albopictus
	Zika	Flaviviridae	Flavivirus	RNA, linear
	Chikungunya	Togaviridae	Alphavirus	RNA, linear
Ticks	Tick-borne encephalitis	Flaviviridae	Flavivirus	RNA, linear	Ixodes spp.
	Crimean–Congo haemorrhagic fever	Nairoviridae	Orthonairovirus	RNA, linear, 3-segmented	Hyalomma marginatum
Sandflies	Toscana and other phleboviruses	Phenuiviridae	Phlebovirus	RNA, linear, 3-segmented	Phlebotomus spp.

). They are maintained in nature in a transmission cycle between arthropod vectors and vertebrate hosts [1]. Most human infections are asymptomatic; when symptomatic, they present as a flu-like illness with or without rash, while in severe cases they present as neuroinvasive disease or haemorrhagic fever. According to the World Health Organization (WHO), arboviruses constitute a major public health issue, especially those transmitted by Aedes species mosquitoes (Dengue, Zika, and Chikungunya viruses) [2]. On 31 March 2022, the WHO launched the Arbovirus Initiative, with six pillars aiming to (1) monitor risk and anticipate outbreaks, (2) reduce local epidemic risk, (3) strengthen vector control, (4) prevent and prepare for pandemics, (5) enhance innovation and new approaches, and (6) build a Coalition of Partners [2].

Until recently, the most common arboviruses in Europe were tick-borne encephalitis virus (TBEV), Crimean–Congo haemorrhagic fever virus (CCHFV), West Nile virus WNV), and phleboviruses [mainly Toscana virus (TOSV)]. The situation changed during recent years, as autochthonous cases of Dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV) infections were reported in several European countries, while WNV, TBEV, CCHFV, and TOSV expanded their distribution in geographic areas where they had never been observed before. The European Centre for Disease Prevention and Control (ECDC) warns about the emerging threat of mosquito-borne diseases, as A. aegypti, the principal vector of DENV, CHIKV, ZIKV, and yellow fever virus, is already established in the western shores of the Black Sea, in the Madeira Islands, and recently in Cyprus, while the populations of Aedes albopictus, which serves as secondary vector of DENV, CHIKV and ZIKV, are already established in 13 EU/EEA countries, mainly in southern Europe, spreading further to the north, east, and west of the continent [3,4]. Media alarms about the emergence of tropical diseases in Europe, as rising temperatures linked to climate change cause illnesses brought by travellers returning from endemic regions.

In some circumstances, especially for the Aedes-transmitted viruses, even one introduction can lead to the autochthonous transmission of vector-borne diseases and lead to outbreaks under favourable climatic (temperature, humidity, and precipitation levels) and entomological conditions. This happened in 2007 in Italy, when more than 200 chikungunya cases (one fatal) were diagnosed following the return of a viraemic traveller from India [5]. The outbreak took place in summer (July–September), when the already established A. albopictus mosquitoes are active. This is not the case in tick-transmitted viruses, as it takes some time (even years) for the virus to infect the local tick populations following its introduction in a region. Migratory birds and infected imported wildlife and livestock also play a role in virus spread in new regions [6,7,8].

Global warming has been implicated in the expansion of arboviral diseases in Europe [9]. However, the consequences of climate change may vary across viruses, since its effect is combined with several other anthropogenic and ecological factors [10]. The availability of good-quality data is essential to reduce uncertainty when assessing the drivers of disease emergence [11].

The main emerging mosquito-, tick-, and sandfly-transmitted viruses in Europe are shown in Table 1. All these virus families are included in the updated WHO R&D (Research and Development) Blueprint for Epidemics prioritization list of pathogens with an epidemic or pandemic potential [12]. The competent vectors for these viruses are already present in Europe, with a tendency to expand their distribution, while the climatic conditions are becoming more suitable for their survival, especially in southern Europe [4,13].

2. Mosquito-Transmitted Viruses

2.1. West Nile Fever Virus

WNV was first identified in 1937 in Uganda, while its association with neurological disease was described in 1956 [14,15]. The virus is transmitted to humans by the bites of infected mosquitoes, mainly of the Culex species [16]. The Culex pipiens mosquito, the main vector of WNV, is native to Europe and is present throughout the EU/EEA [4]. Additional routes of transmission include blood transfusion, organ transplantation, the placenta, and breastfeeding, suggesting that preventive safety measures have to be implemented during epidemic seasons [17].

Approximately 80% of infections are asymptomatic, while 20% present as relatively mild disease (West Nile fever) with or without rash and/or lymphadenopathy; less than 1% of cases present as neuroinvasive disease (WNND), mainly encephalitis, but also meningitis and acute flaccid paralysis [18,19]. The infection of the nervous system occurs when the virus crosses the blood–brain barrier as a result of an inadequate immune response and failure to clear the virus in the periphery [20]. Immunocompromised persons and the elderly are most vulnerable to WNND; however, pediatric cases in immunocompromised children and organ recipients have been also reported [21]. Although WNV vaccines are available for use in equines, neither a vaccine nor a specific antiviral therapy has been licensed or approved for human use [22].

In Europe, a large outbreak of neurological cases caused by WNV lineage 1 occurred in 1996 in the southern plain and Danube Valley of Romania and in the capital city of Bucharest [23]. Until recently, WNV infections in Europe were caused by strains clustering into lineage 1, while lineage 2 was considered to be endemic only in Sub-Saharan Africa. In 2004, WNV lineage 2 was detected in a goshawk in Hungary [24], followed by few human cases in Austria and Hungary, while in 2010 an outbreak with 262 human cases caused by this lineage occurred in Greece; the first cases were detected around the Axios River delta, one of the major wetlands in the Mediterranean area [25]. Since then, WNV lineage 2 is the main cause of WNV infections in Europe. A “WNV record year” in Europe was 2018, when 1548 locally acquired human cases (166 fatal) were reported from eleven EU Member States (mostly from Italy, Greece, and Romania); although WNV infections are usually reported from July to October, in 2018, an early disease onset (May), combined with an unusually late date of onset (December), was observed [26]. An expansion of cases to new areas in Europe was seen in the following years [27]. A re-emergence of WNV lineage 1 occurred in 2021 in the Veneto region of northern Italy (Po River Valley), which caused a large outbreak in the following year [28]. In general, the presence of wetlands, water bodies (serving as breeding sites of WNV vectors), and locations under migratory bird routes, together with permissive summer temperatures, are among the environmental predictors of risk for WNV infections in new regions in Europe [29,30]. An early initiation of WNV activity was seen in 2024 in Mediterranean countries (occurring in the 23rd, 27th, and 28th weeks in Spain, Italy, and Greece, respectively) [31], probably related to the extremely high temperatures throughout the year. As of 2 October 2024, 18 countries in Europe have reported 1202 locally acquired human cases of WNV infection, most of them from Italy (422), followed by Greece (202) [32].

A recent phylogeography study showed that among the six genetic lineages of the virus detected in Europe, WNV-2a predominates, accounting for 73% of European sequences, and it has evolved into two major clusters, both originating from Central Europe [33]. It was shown that among several ecological, climatic, and anthropogenic factors affecting the emergence and spread of WNV, agricultural land use (crops and livestock) is positively associated with WNV spread direction and velocity, while the roles of the presence of wetlands and migratory bird flyways are also significant [33].

2.2. Usutu Virus

USUV was first identified in 1959 in Swaziland from Culex neavei mosquitoes [34]. The virus co-circulates with WNV in Europe, and although USUV appears to be more pathogenic for some bird species than WNV, it rarely causes disease in humans [35]. The first detection of USUV in Europe was in 2001 during a blackbird epizootic in Austria, but a retrospective study identified the virus in 1996 in Italy (Tuscany) [36,37]. Since then, USUV has been often detected in birds and mosquitoes in several European countries, while human cases, some of them with neuroinvasive forms, have been identified (mainly in Italy), especially in immunocompromised and elderly patients with co-morbidities [38,39,40,41,42]. Most cases are asymptomatic (detected during blood donation) or present as mild febrile illness; however, meningoencephalitis and atypical neurological forms of the disease have been reported [43,44]. There are two reports of fatal cases [45,46]; however, in one of them, a co-infection with a bacterial pathogen was hypothesized [46]. Vaccines and specific drugs are not available.

The public and animal health impact of USUV in the EU/EEA is considered limited; therefore, human USUV infection is not a mandatory notifiable disease [47]. From 2012 to 2021, eight EU/EEA countries reported USUV infection in humans (105 cases, including 12 with neurological symptoms) [48]. In Greece, the virus was detected in C. pipiens mosquitoes collected in 2020 and 2022, and in 2024 it was isolated from an asymptomatic blood donor [49] (and unpublished data). The spatial and temporal co-circulation of WNV and USUV presents challenges for surveillance and control programs [50].

USUV sequences cluster into eight lineages (three African and five European), and all, except the African 1 lineage, circulate in Europe [51]. By investigating the evolution and spatial spread of the virus in Europe, it was shown that Italy acts as donor of USUV to neighbouring countries [52].

2.3. Dengue Virus

DENV was first isolated in 1943 during a large outbreak in Japan [53]. The virus is transmitted to humans by the bites of infected Aedes mosquitoes (with Aedes aegypti as the primary vector and Aedes albopictus as the secondary vector), by organ transplantation, and by blood transfusion [54,55]. Human-to-mosquito transmission can occur up to 2 days before the symptoms’ onset, and up to 2 days after fever resolution [56]. There are four serotypes of the virus (DENV-1, -2, -3, -4) and two types of the disease: dengue fever, a mild disease with a favourable outcome, and severe dengue (<5% of cases), which involves thrombocytopenia and shock and occurs mostly among children under 15 years old in areas where various serotypes are circulating and re-infections with heterotypic serotypes are common [56,57]. Early diagnosis and proper medical care greatly lower the fatality rates of severe dengue [56].

The antibody-dependent enhancement (ADE) of viral replication, leading to excessive cytokine expression, is usually the reason for the severe form of the disease. It was found that DENV is evolving to escape host immunity and that both the patient’s antibody level and antigenic variation between infecting strains may affect disease risk [58].

Two dengue vaccines have been authorised by the European Medicines Agency (EMA) for use in the EU: Dengvaxia, a live recombinant tetravalent vaccine developed by Sanofi Pasteur, and Qdenga, a live-attenuated tetravalent vaccine developed by Takeda [59]. A pre-vaccination screening is required for the Dengvaxia vaccine, and only the persons with a previous DENV infection can receive it [59].

Dengue is widely distributed in tropical and subtropical areas of Asia, Africa, and South and Central America, where an increase in cases has been observed over the last 50 years. More than 6 million dengue cases and over 6000 dengue-related deaths were reported in 2023 from 92 countries, and that number has increased dramatically since the beginning of 2024, with over 13 million dengue cases and over 8500 dengue-related deaths reported globally [60].

From 2010 up to 18 October 2024, 564 autochthonous dengue cases were reported in mainland Europe, where A. albopictus is present: 239 cases from France (82 in 2024), 291 from Italy (199 in 2024), 24 from Spain (8 in 2024), and 10 from Croatia (all in 2010) [61]. It has to be mentioned that 2168 dengue cases (1080 of them confirmed) occurred during the explosive outbreak of 2012–2013 in the autonomous province of Madeira, Portugal, where A. aegypti is present; 81 travellers from Madeira returning to the mainland of Europe were diagnosed with dengue [62]. Phylogeographic analysis showed that the most probable origin of the strain (DENV-1) was Venezuela [63,64].

It is of interest that A. aegypti was previously established in southern Europe and caused dengue outbreaks in Greece during the late summers of 1927 and 1928, with more than 1 million cases and more than 1000 fatalities [65]. It disappeared in the early 1900s, but it is currently present in Madeira, in the western shores of the Black Sea, and in Cyprus, while the secondary vector, A. albopictus, is well established in a large part of Europe, mainly in the Mediterranean countries [4]. It has been suggested that the adaptation of viruses to this abundant mosquito vector species cannot be excluded, which could increase the risk for dengue and other arboviral outbreaks in Europe [66]. Viraemic travellers returning from endemic countries can transmit the virus in areas where competent vectors are present (especially during the season when the vectors are active) and initiate the further spread of the disease.

2.4. Chikungunya Virus

CHIKV was first isolated in 1953 from a febrile patient in Tanzania [67]. As for DENV, CHIKV is mainly transmitted by the bites of infected A. aegypti mosquitoes, and potentially by A. albopictus. As mentioned above, A. albopictus is established in many regions of Europe, and A. aegypti is established on the eastern shores of the Black Sea, in Madeira, and it was recently detected in Cyprus [4]. It was shown that a mutation in the viral envelope protein 1 (Ala226Val) plays a role in the efficient transmission of CHIKV by A. albopictus [68,69,70]. However, a recent study showed that A. albopictus presents similar vector competence for strains with and without this specific mutation [71]. This was seen in Europe in 2017, when unrelated chikungunya outbreaks occurred in France and Italy; a virus with the mutation introduced from Central Africa caused the outbreak in South France [72], while a virus without the mutation introduced from India/Pakistan was the cause of the outbreak in Italy [73,74].

The disease is characterized by abrupt fever, rash, and polyarthralgia which can last up to 5 years. The prolonged symptomatology of the joints, despite the robust host immune response, is due to the persistence of viral particles in synovial fluid [75]. A live, attenuated vaccine, developed by Valneva Austria GmbH, is approved by the FDA for adults >18 years old who are at high risk of exposure to the virus [76].

Since the first documented autochthonous vector-borne CHIKV outbreak in Italy in 2007 [5], five additional outbreaks occurred in Europe (Italy and South France), with more than 700 cases; the biggest outbreak occurred again in Italy (in the Lazio and Calabria regions), with 270 confirmed cases [77]. It seems that A. albopictus is an efficient vector of CHIKV (and DENV), as has been previously shown experimentally [78,79], suggesting that outbreaks may occur in areas where it is established.

2.5. Zika Virus

ZIKV was first isolated in 1947 from a captive, sentinel rhesus monkey during surveillance studies on yellow fever in the Zika forest in Uganda, while infection in humans was first reported in 1954 in Nigeria [80,81]. Like DENV and CHIKV, it is mainly transmitted by A. aegypti and potentially by A. albopictus. Sexual transmission can also occur, as well as through blood transfusion and organ transplantation [82,83,84,85]. Since 2007, when the virus left Africa and southeast Asia, causing an outbreak in Micronesia, it continues to be responsible for several outbreaks in the Pacific, with patients presenting mild symptoms, mainly fever, headache, joint pain, conjunctivitis, and maculopapular rash, usually lasting for 2–7 days [86]. However, the hallmark year in ZIKV history was 2015, when it spread to Brazil (and then to additional countries in Central and South America) and caused thousands of cases, with microcephaly and other congenital nervous system malformations (congenital Zika virus syndrome) in newborns (through perinatal transmission from infected mothers to their fetus), with 10% fatality [87]. ZIKV is also associated with Guillain–Barré syndrome in adults [88]. From February to November 2016, the WHO declared a public health emergency of international concern regarding microcephaly and other neurological disorders caused by ZIKV [87]. No vaccines or drugs are yet available for ZIKV infections.

In Europe, the first autochthonous vector-borne cases of ZIKV infection were reported in 2019 in southern France [89]. No additional cases have been reported so far. Although the potential vector A. albopictus is present, the risk for ZIKV infections in continental Europe is currently considered low, since its vectorial competence is lower than that of A. aegypti; however, if the virus were to be introduced by a viraemic traveller during the months when temperatures and vector abundance are high, autochthonous transmission in the European parts of the EU/EEA is possible [90]. In addition, since A. aegypti has started to (re-)emerge in Europe, awareness and entomological surveillance are needed.

3. Tick-Transmitted Viruses

3.1. Crimean–Congo Haemorrhagic Fever Virus

CCHFV (species Orthonairovirus haemorrhagiae) is maintained in nature through a silent tick–vertebrate–tick enzootic cycle. It is transmitted to humans through the bites of infected ticks, mainly of the Hyalomma genus (in Europe, H. marginatum and H. lusitanicum) or by direct contact with the blood or tissues of viraemic patients or livestock [91]. CCHFV infections range from asymptomatic or mild febrile illness to severe disease with haemorrhagic manifestations, multiorgan failure and shock, with a case fatality up to 30% among hospitalised patients [92].

The disease (CCHF) was first identified among soldiers in 1944 in the Crimean Peninsula, while the virus was first isolated in 1956 in the Congo, resulting in the current name of the virus and the disease [93,94]. CCHF is the most widespread tick-transmitted viral haemorrhagic fever; it is estimated that globally 10,000 to 15,000 infections (500 of them fatal) occur every year [91]. Due to the potential for a severe course of the disease, the transmission from person to person, and the increased risk for outbreaks, in the absence of specific drugs and licensed vaccines, CCHFV is classified as risk group 4 pathogen, requiring laboratories with biosafety level 4 facilities and strict biocontainment measures for patients.

CCHF is endemic in over 30 countries in Africa, Asia, and Europe (south of the 50th parallel north) [95]. Until recently, the CCHF endemic areas in Europe were the Balkans and Russia [96,97,98,99,100,101]. However, two autochthonous CCHF cases were reported in 2016 in Spain [102], while one additional case in 2013 was diagnosed retrospectively in 2020 [103]. From 2013 up to 28 August 2024, 61 CCHF cases were reported in the EU/EEA, and 14 of them had a fatal outcome [104]. It is of interest that 18 of the 61 cases were reported in the Iberian peninsula (17 in Spain and 1 in Portugal) [104]. Additional cases were reported in non-EU/EEA countries (Albania, North Macedonia, European Russia) [101,105]. The virus is often detected first in ticks and later in humans. As an example, in Spain, CCHFV was first detected in 2010 in H. lusitanicum ticks collected from red deer, while the first human cases were diagnosed in 2016 [102,106]. It is of interest that CCHFV was detected for the first time in H. marginatum ticks collected from 2022 to 2023 in southern France, near the Spanish border [107]. No CCHF cases have been reported in France so far.

Wild and domestic animals serve as asymptomatic reservoirs of CCHFV, and they present a short viremia (during this time they are capable of transmitting the virus to ticks and humans) [108]. Seroprevalence in animals is a good indicator for the circulation of the virus in a region [109]. As an example, a cross-sectional study in red deer in the Iberian Peninsula showed that the highest CCHFV seroprevalence occurred near the borders of regions where most of the primary human cases occurred [110]. The detection of various CCHFV genotypes in Europe suggests multiple virus introductions, most probably by migratory birds.

It has to be mentioned that CCHFV genotype V has recently been classified as a new species in the Orthonairovirus genus (Orthonairovirus parahaemorrhagiae) under the name Aigai virus (AIGV) [111]. AIGV was originally isolated from Rhipicephalus bursa ticks collected from goats in Greece [112]. The virus has been detected in ticks in several Balkan countries and Turkey, with a few mild cases in humans [113,114,115,116,117,118]. It has been suggested that AIGV is less pathogenic than CCHFV, but further studies are needed to show the level of its pathogenicity [119,120,121,122].

3.2. Tick-Borne Encepahlitis Virus

TBEV circulates in nature between ticks, animals, and humans. The most important hosts and reservoirs of the virus are small mammals, such as rodents, insectivores, and carnivores [123]. TBEV is transmitted to humans by bites from infected ticks of the Ixodes genus or by the consumption of unpasteurized milk or dairy products from viraemic animals [124]. The disease (TBE) was first recognized as a distinct entity in 1931 by an Austrian clinician [125], while the causative virus was isolated from ticks and patients in 1937 during a Russian Far East expedition [126].

TBEV strains cluster into three major subtypes: the European (transmitted by Ixodes ricinus), the Far Eastern, and the Siberian (the latter two transmitted by Ixodes persulcatus), which are divided into several lineages and clusters [127]. The European and Siberian subtypes are associated with milder disease (fatality rates of 0.5–2% and 1–3%, respectively), while the Far Eastern subtype is associated with more severe disease (fatality rate of up to 35%) [128]. The most prevalent subtype in Europe is the European one; however, all three subtypes are present and overlap in eastern and northern Europe [129,130].

Most infections are usually asymptomatic or result in mild febrile illness; in some cases (20–30% of the cases caused by the European subtype), the disease is biphasic, starting with a febrile illness, and, after the resolution of the fever, followed by second phase with symptoms from the central nervous system (meningitis, encephalitis, myelitis). This phase is often associated with long-lasting sequelae; the elderly are at higher risk of developing encephalitis and sequelae [128,131]. There are no antivirals targeting TBEV; however, licensed vaccines are available, and they are based on inactivated whole virions of TBEV strains of the European or Far-Eastern subtype [123]. Published vaccine effectiveness studies demonstrate a high effectiveness of the commercially available TBE vaccines in Europe (FSME-IMMUN^® and Encepur^®) [132].

The seroprevalence in wild and domestic mammals can serve as an indirect indicator of virus circulation in a region. For example, a 63.5% TBEV seroprevalence was detected in European bison in Poland, with the highest rates observed in the areas with the highest incidence of human cases reported in the country [133].

TBE is the most prevalent tick-borne viral disease in Europe; it is endemic in forested northern, central, and eastern parts of the continent, with the highest incidence in the Baltic and Central European countries [134]. A study on spatiotemporal spread of TBE in the EU/EEA from 2012 to 2020 showed that 19 countries reported 24,629 autochthonous cases, with the highest notification rates recorded in Lithuania, Latvia, and Estonia (16.2, 9.5, and 7.5 cases/100,000 population, respectively) [135]. The number of human TBE cases in all endemic regions of Europe has increased by almost 400% in the last 30 years, with the expansion of risk areas and identification of new foci [128,136,137].

4. Sand Fly-Transmitted Viruses

Toscana Virus and Other Phleboviruses

Several sand fly-transmitted virus species are included in the Phlebovirus genus; however, only a few of them have been associated with disease in humans, such as Sandfly Sicilian and Naples viruses (SFSV and SFNV) and Toscana virus (TOSV), while several others have been detected in sand flies with unknown pathogenicity. Phleboviruses usually cause a mild febrile illness in humans, also known as a three-day fever, while TOSV has the neurotropic potential to cause meningitis, meningoencephalitis, and encephalitis [138]. Additional neuroinvasive forms of TOSV infection include Guillain–Barré syndrome, hydrocephalus, myositis, fasciitis, polymyeloradiculopathy, deafness, and facial paralysis, while rare fatal TOSV cases have also been reported [139,140]. SFSV and SFNV were isolated from sick soldiers during World War II in Italy (Sicily and Naples) and Egypt, while TOSV was initially isolated in 1971 from Phlebotomus perniciosus in Central Italy [141]; the neuroinvasiveness of the virus was confirmed by isolation from the cerebrospinal fluid of a female patient with aseptic meningitis in Central Italy [142].

Phleboviral infections are endemic in Mediterranean countries, where cases occur every year, mainly in the summer when phlebotomine sand flies are active [143,144,145]. For example, a major outbreak of febrile syndrome occurred in 2002 among the Greek Army forces in Cyprus, and a Sicilian-like virus, Cyprus virus, was isolated from the blood of a patient [145]. During a study conducted between 2016 and 2021 in southern Tuscany in Italy, 331 TOSV neuroinvasive cases were confirmed [146].

Currently, three TOSV lineages are known: A, B, and C. Lineage A is present in Italy, France, Turkey, Tunisia, and Algeria, lineage B in Portugal, Spain, France, Morocco, Croatia, and Turkey, and lineage C in Croatia and Greece (reviewed in [139]). A severe encephalitis case caused by TOSV lineage C was reported in Greece; the patient was hospitalised in the intensive care unit, where she underwent mechanical ventilation and sedation [147]. Several additional phleboviruses have been identified through the molecular screening of sand flies, and further studies are needed to gain insight into their pathogenicity (reviewed in [138]).

5. Challenges

Arboviral diseases are a growing public health threat worldwide. The first step to combat them effectively is to include them in the differential diagnosis of febrile cases, especially when neurological symptoms or thrombocytopenia are present. Then, prompt identification of the pathogen is essential, not only for the patient’s life, but also for public health, since arboviruses usually cause clusters of cases or even large outbreaks. The challenge is greater in the case of emerging arboviruses, as early detection can prevent the further spread and establishment of the virus in a region. Therefore, awareness and preparedness are needed [148]. The travel history and previous vaccination of the patients are very important pieces of information, which, combined with knowledge on global epidemiology, can lead the differential diagnosis of the disease. In most cases, a syndromic approach has to be followed, based on clinical and demographic data combined with surrogated indicators [149]. Since most of the diagnostic assays of emerging arboviruses are not included in routine testing in the hospitals, and commercial kits for emerging pathogens are often lacking, reference laboratories have to be well prepared for the diagnostics of several virus families and genera and evaluate their methods through external quality assessment (EQA) programs. Advances in technology (e.g., the application of metagenomics) enable the rapid identification of etiological agents and can contribute to the prompt identification of “disease X” pathogens [150]. International organizations (e.g., WHO, ECDC, PAHO), networks (e.g., EVD-LabNet), and collaborative projects (e.g., the European VEO, MOOD, DURABLE) are of great value for sharing knowledge, expertise, protocols, reagents, and for organising EQAs and surveys to assess the need for diagnostic capacities and capabilities among participants [151,152,153].

An additional challenge is to understand the complex enzootic/zoonotic transmission cycles of arboviruses (which involve the viruses and their vectors and hosts) and their dynamic ecology and evolution [154,155,156,157,158,159,160,161]. These data can be used mainly for modelling strategies to predict and prevent arboviral emergence [157]. In an effort to explore the vector competence for three major arboviruses which recently emerged in Europe (CHIKV, DENV and ZIKV), eight A. albopictus populations from Europe were analysed for their competence; it was shown that southern European A. albopictus were susceptible to all three viruses, with the highest vector competence for CHIKV, and a prediction risk map was constructed [162]. In another study, a dataset of more than 1300 georeferenced TBEV detections in ticks and mammals, except for humans, was used to estimate the probability of TBEV presence in Europe [163]. However, although a lot of knowledge has been gained in recent years, it is still difficult to design accurate risk maps which could be used for prevention and control strategies.

Currently, active and passive surveillance efforts are being implemented for several arboviral infections in Europe (e.g., for WNV, CCHFV, TBEV), and the data collected from the ECDC and European Food Safety Authority (EFSA) from human and animal cases and surveillance activities are analysed and published in the annual European Union One Health Zoonoses Report [47,164]. Still, the challenge of evaluating the interactions amongst the three intercontinental threats—climate change, biodiversity loss, and infectious diseases—remains significant and needs further consideration for planetary health [165]. Therefore, the ECDC, EFSA, EMA, European Environmental Agency (EEA), and European Chemicals Agency (ECHA) are committed to increasing their collaboration to support the One Health agenda in the European Union [166]. In addition, the recently launched WHO Global Arbovirus Initiative is expected to strengthen the coordination, communication, capacity-building, research, preparedness, and response to arboviral diseases [11].

6. Future Perspectives

It is expected that arboviral diseases will continue to pose a growing public and veterinary health threat globally. Europe, especially the southern part, is included in the vulnerable regions. A plethora of factors interact and affect the survival and amplification of arthropods and their reservoir hosts and influence the life cycle, adaptation, and evolution of arboviruses, while globalization and increased transportation and trade facilitate their geographical spread. Local and global climatic phenomena (e.g., El Niño) and climate change, as well as regional factors, such as land use, vector control, human behaviour, and public health capacities, are among the drivers of arbovirus emergence [10,167]. Migratory birds also play a critical role in introducing arboviruses (e.g., WNV, USUV, and, to a lesser extent, CCHFV) to new regions; therefore, continued monitoring of mosquito and tick populations in the field is needed for risk assessment [168,169].

Viraemic travellers returning from endemic regions pose a risk of possibly introducing an arboviral disease in non-endemic regions [170]. This risk was present during the dengue outbreak in Madeira in 2012–2013, when 81 travellers returned to the mainland of Europe, where the population was susceptible and A. albopictus was established [62]. As mentioned above, the chikungunya outbreak in Italy in 2007 was initiated by a viraemic traveller returning from India [5]. Knowledge of the global epidemiology of arboviral diseases and awareness of the clinicians are essential for prompt detection of index cases in order to apply prevention and control measures. Furthermore, mosquito surveillance at European seaports and airports is helpful to monitor for the incursion of A. aegypti.

Climate and environmental factors are the most important drivers of arboviral diseases, as they have a direct impact on the life cycle of arthropods. A systematic assessment of the climate sensitivity of important human and domestic animal pathogens in Europe showed that up to two thirds of high h-index human and domestic animal pathogens that occur in Europe are associated with climate drivers, and that the vector-borne pathogens are among the most likely to be affected by climate change [171]. Numerous modelling approaches have been used to examine the effects of climate change upon arboviral diseases in Europe [9,172,173,174]. A computational model, developed to quantify the daily abundance of Aedes mosquitoes based on temperature and precipitation records, showed that the ecological niche of A. albopictus could contribute to the occurrence of chikungunya outbreaks and clusters of dengue autochthonous cases in mediterranean Europe (mainly in Italy, southern France, and Spain) [175]. Especially for dengue, it was empirically shown that the interdependence of host population susceptibility and climate drives the disease dynamics in a nonlinear and complex, yet predictable, way [176]. Therefore, monitoring forecasts of meteorological conditions can facilitate the detection of epidemic precursors of vector-borne disease outbreaks and serve as an early warning system for risk reduction [9].

In conclusion, to tackle emerging arboviral diseases, there is a need for awareness and preparedness for prevention and rapid detection, as well as vector monitoring and control strategies. Along with that, as the WHO emphasizes, there is a need for strengthening global R&D efforts through collaborative and efficient research roadmaps and for the integration of research into outbreak and pandemic response [12].