Identifying the Environmental Conditions Favouring West Nile Virus Outbreaks in Europe

March Identifying the Environmental Conditions Favouring West Nile Virus Outbreaks in Europe Matteo Marcantonio 0 1 Annapaola Rizzoli 0 1 Markus Metz 0 1 Roberto Ros 0 1 Giovanni Marini 0 1 Elizabeth Chadwick 0 1 Markus Neteler 0 1 0 1 Department of Biodiversity and Molecular Ecology, Research and Innovation Centre, Fondazione Edmund Mach , San Michele all'Adige , Italy , 2 School of Bioscience, Cardiff University , Cardiff, Wales , United Kingdom 1 Academic Editor: Sebastien Gourbiere, Universite de Perpignan Via Domitia , FRANCE West Nile Virus (WNV) is a globally important mosquito borne virus, with significant implications for human and animal health. The emergence and spread of new lineages, and increased pathogenicity, is the cause of escalating public health concern. Pinpointing the environmental conditions that favour WNV circulation and transmission to humans is challenging, due both to the complexity of its biological cycle, and the under-diagnosis and reporting of epidemiological data. Here, we used remote sensing and GIS to enable collation of multiple types of environmental data over a continental spatial scale, in order to model annual West Nile Fever (WNF) incidence across Europe and neighbouring countries. Multimodel selection and inference were used to gain a consensus from multiple linear mixed models. Climate and landscape were key predictors of WNF outbreaks (specifically, high precipitation in late winter/early spring, high summer temperatures, summer drought, occurrence of irrigated croplands and highly fragmented forests). Identification of the environmental conditions associated with WNF outbreaks is key to enabling public health bodies to properly focus surveillance and mitigation of West Nile virus impact, but more work needs to be done to enable accurate predictions of WNF risk. - Funding: This work was funded by the 7th Framework Programme: European West Nile collaborative research project (Grant agreement no. 261391; http://www.eurowestnile.org/) and by the Autonomous Province of Trento (Italy), Research funds for Grandi Progetti, Project LExEM (Laboratory of excellence for epidemiology and modeling, http:// www.lexem.eu/). The funders had no role in study West Nile virus (WNV) is a multi-host mosquito borne virus belonging to the Japanese encephalitis (JE) antigenic complex (genus Flavivirus, family Flaviridae) [1]. Although the majority (*80%) of human WNV infections are sub-clinical and can pass unnoticed, some 20% of patients experience flu-like symptoms known as West Nile fever (WNF), while approximately 1% develop a severe, and potentially fatal, neuro-invasive disease [2]. While clinical trials for human vaccines are underway [3] prevention currently depends on organized, sustained vector (mosquito) control campaigns and risk communication [48]. design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Sporadic cases of WNV have been documented in Europe and Africa since it was first identified in Uganda in 1937 [9], but until the 1990s it was considered a low risk for humans and domestic animals. Since then however, WNV has spread rapidly across all populated continents and it is now the most widespread arthropod borne virus in the world [10,11]. In Europe, human cases of WNF have been notified in almost all Eastern, Central, and Southern European countries [12] with hotspots in Italy since 2008 [13], Greece since 2010 [14] and continuous transmission in Russia and Romania since 1996 [15]. The number of WNF cases and the impacts on public health are, so far, limited in Europe relative to other vector borne infection (in 2013, 783 cases of WNF were reported by ECDC in Europe and neighbouring countries, as compared to 45,854 Lyme borreliosis reported by the World Health Organization between 2010 and 2013). However, both escalating case load and increased pathogenicity (e.g. substitution of the NY99 genotype with the more pathogenic WN02 in the USA [16]) are contributing to increased risk. Financial costs associated with the prevention of virus transmission to humans through blood and tissue transplantation are mounting (Blood safety regulation; see [17]). WNV is maintained in enzootic cycles involving several species of birds, and mosquitoes belonging principally to the Culex pipiens complex [7,1821]. Humans and horses are accidental and dead end hosts since they do not develop a viraemic titre sufficient to infect mosquitoes and amplify the transmission cycle [21]. In Europe, the common house mosquito, Cx. pipiens (Linnaeus, 1758), is considered the principal bridge vector of WNV between birds and mammals (horses and humans), although at least 60 other mosquito species can be found infected with the virus [7,20,21,22]. Culex pipiens occurs in two biological forms, Cx. pipiens pipiens and Cx. pipiens molestus, which can hybridize. Both behaviour and host preference vary between forms, with major implications for risk of transmission to humans depending on their relative abundance [23,24]. WNV ecology in the Old World is complex and several aspects of the WNV transmission cycle are as yet poorly quantified. The co-circulation of at least five lineages with variable pathogenicity and the overlap of new introductions with endemic circulation, render the quantification of the parameters necessary to develop transmission models challenging [10,25,26]. Although favourable environmental conditions for virus transmission seem to occur extensively in the Old World and a widespread circulation of the virus has been demonstrated by serological screening of wildlife and sentinel animals, clinical emergence in humans tends to be unpredictable, sporadic and clustered [12]. The occurrence of spatially and temporally localised hot-spots in emergence is likely to reflect the coincidence of circulating virus strain with favourable environmental (biotic and abiotic) conditions which modulate the interaction between virus, mosquito, and hosts, consequently leading to locally altered pathogen amplification, transmission and disease risks [27,28]. Variation in land use, climate, habitat structure, animal community, human socio-economic status or behaviour can all significantly affect the risk of infectionfor example, via impacts on the spatial and temporal distribution of the competent reservoir host assemblages and their immune status, as well as on the local abundance and genetic population structure of mosquito vectors and their vectorial capacity [2933]. At the same time, the availability of simultaneous information on the infection pattern in vectors and birds is lacking at a wide spatial scale, while the cost of integrated surveillance, and the economic and social disparities which affect several EU countries, limit the capacity of high-level institutions to collect detailed and standardised ecological and epidemiological dat (...truncated)