Evaluating the risk for Usutu virus circulation in Europe: comparison of environmental niche models and epidemiological models.

BACKGROUND: Usutu virus (USUV) is a mosquito-borne flavivirus, reported in many countries of Africa and Europe, with an increasing spatial distribution and host range. Recent outbreaks leading to regional declines of European common blackbird (Turdus merula) populations and a rising number of human cases emphasize the need for increased awareness and spatial risk assessment. METHODS: Modelling approaches in ecology and epidemiology differ substantially in their algorithms, potentially resulting in diverging model outputs. Therefore, we implemented a parallel approach incorporating two commonly applied modelling techniques: (1) Maxent, a correlation-based environmental niche model and (2) a mechanistic epidemiological susceptible-exposed-infected-removed (SEIR) model. Across Europe, surveillance data of USUV-positive birds from 2003 to 2016 was acquired to train the environmental niche model and to serve as test cases for the SEIR model. The SEIR model is mainly driven by daily mean temperature and calculates the basic reproduction number R0. The environmental niche model was run with long-term bio-climatic variables derived from the same source in order to estimate climatic suitability. RESULTS: Large areas across Europe are currently suitable for USUV transmission. Both models show patterns of high risk for USUV in parts of France, in the Pannonian Basin as well as northern Italy. The environmental niche model depicts the current situation better, but with USUV still being in an invasive stage there is a chance for under-estimation of risk. Areas where transmission occurred are mostly predicted correctly by the SEIR model, but it mostly fails to resolve the temporal dynamics of USUV events. High R0 values predicted by the SEIR model in areas without evidence for real-life transmission suggest that it may tend towards over-estimation of risk. CONCLUSIONS: The results from our parallel-model approach highlight that relying on a single model for assessing vector-borne disease risk may lead to incomplete conclusions. Utilizing different modelling approaches is thus crucial for risk-assessment of under-studied emerging pathogens like USUV.

Distribution of Usutu Virus in Germany and Its Effect on Breeding Bird Populations.

Usutu virus (USUV) is an emerging mosquitoborne flavivirus with an increasing number of reports from several countries in Europe, where USUV infection has caused high avian mortality rates. However, 20 years after the first observed outbreak of USUV in Europe, there is still no reliable assessment of the large-scale impact of USUV outbreaks on bird populations. In this study, we identified the areas suitable for USUV circulation in Germany and analyzed the effects of USUV on breeding bird populations. We calculated the USUV-associated additional decline of common blackbird (Turdus merula) populations as 15.7% inside USUV-suitable areas but found no significant effect for the other 14 common bird species investigated. Our results show that the emergence of USUV is a further threat for birds in Europe and that the large-scale impact on population levels, at least for common blackbirds, must be considered.

Spatiotemporally Explicit Epidemic Model for West Nile Virus Outbreak in Germany: An Inversely Calibrated Approach.

Since the first autochthonous transmission of West Nile Virus was detected in Germany (WNV) in 2018, it has become endemic in several parts of the country and is continuing to spread due to the attainment of a suitable environment for vector occurrence and pathogen transmission. Increasing temperature associated with a changing climate has been identified as a potential driver of mosquito-borne disease in temperate regions. This scenario justifies the need for the development of a spatially and temporarily explicit model that describes the dynamics of WNV transmission in Germany. In this study, we developed a process-based mechanistic epidemic model driven by environmental and epidemiological data. Functional traits of mosquitoes and birds of interest were used to parameterize our compartmental model appropriately. Air temperature, precipitation, and relative humidity were the key climatic forcings used to replicate the fundamental niche responsible for supporting mosquito population and infection transmission risks in the study area. An inverse calibration method was used to optimize our parameter selection. Our model was able to generate spatially and temporally explicit basic reproductive number (R0) maps showing dynamics of the WNV occurrences across Germany, which was strongly associated with the deviation from daily means of climatic forcings, signaling the impact of a changing climate in vector-borne disease dynamics. Epidemiological data for human infections sourced from Robert Koch Institute and animal cases collected from the Animal Diseases Information System (TSIS) of the Friedrich-Loeffler-Institute were used to validate model-simulated transmission rates. From our results, it was evident that West Nile Virus is likely to spread towards the western parts of Germany with the rapid attainment of environmental suitability for vector mosquitoes and amplifying host birds, especially short-distance migratory birds. Locations with high risk of WNV outbreak (Baden-Württemberg, Bavaria, Berlin, Brandenburg, Hamburg, North Rhine-Westphalia, Rhineland-Palatinate, Saarland, Saxony-Anhalt and Saxony) were shown on R0 maps. This study presents a path for developing an early warning system for vector-borne diseases driven by climate change.

Predicting ectotherm disease vector spread--benefits from multidisciplinary approaches and directions forward.

The occurrence of ectotherm disease vectors outside of their previous distribution area and the emergence of vector-borne diseases can be increasingly observed at a global scale and are accompanied by a growing number of studies which investigate the vast range of determining factors and their causal links. Consequently, a broad span of scientific disciplines is involved in tackling these complex phenomena. First, we evaluate the citation behaviour of relevant scientific literature in order to clarify the question "do scientists consider results of other disciplines to extend their expertise?" We then highlight emerging tools and concepts useful for risk assessment. Correlative models (regression-based, machine-learning and profile techniques), mechanistic models (basic reproduction number R0) and methods of spatial regression, interaction and interpolation are described. We discuss further steps towards multidisciplinary approaches regarding new tools and emerging concepts to combine existing approaches such as Bayesian geostatistical modelling, mechanistic models which avoid the need for parameter fitting, joined correlative and mechanistic models, multi-criteria decision analysis and geographic profiling. We take the quality of both occurrence data for vector, host and disease cases, and data of the predictor variables into consideration as both determine the accuracy of risk area identification. Finally, we underline the importance of multidisciplinary research approaches. Even if the establishment of communication networks between scientific disciplines and the share of specific methods is time consuming, it promises new insights for the surveillance and control of vector-borne diseases worldwide.

Chikungunya Beyond the Tropics: Where and When Do We Expect Disease Transmission in Europe?

Chikungunya virus disease (chikungunya) is a mosquito-borne infectious disease reported in at least 50 countries, mostly in the tropics. It has spread around the globe within the last two decades, with local outbreaks in Europe. The vector mosquito Aedes albopictus (Diptera, Culicidae) has already widely established itself in southern Europe and is spreading towards central parts of the continent. Public health authorities and policymakers need to be informed about where and when a chikungunya transmission is likely to take place. Here, we adapted a previously published global ecological niche model (ENM) by including only non-tropical chikungunya occurrence records and selecting bioclimatic variables that can reflect the temperate and sub-tropical conditions in Europe with greater accuracy. Additionally, we applied an epidemiological model to capture the temporal outbreak risk of chikungunya in six selected European cities. Overall, the non-tropical ENM captures all the previous outbreaks in Europe, whereas the global ENM had underestimated the risk. Highly suitable areas are more widespread than previously assumed. They are found in coastal areas of the Mediterranean Sea, in the western part of the Iberian Peninsula, and in Atlantic coastal areas of France. Under a worst-case scenario, even large areas of western Germany and the Benelux states are considered potential areas of transmission. For the six selected European cities, June-September (the 22th-38th week) is the most vulnerable time period, with the maximum continuous duration of a possible transmission period lasting up to 93 days (Ravenna, Italy).

Deriving risk maps from epidemiological models of vector borne diseases: State-of-the-art and suggestions for best practice.

Epidemiological models (EMs) are widely used to predict the temporal outbreak risk of vector-borne diseases (VBDs). EMs typically use the basic reproduction number (R0), a threshold quantity, to indicate risk. To provide an overall view of the risk, these model outputs can be transformed into spatial risk maps, using various aggregation methods (e.g. average R0 over time, cumulative number of days with R0 > 1). However, there is no standardized methodology available for this. Depending on the specific aggregation methods used, the yielded spatial risk maps may have considerably different interpretations. Additionally, the method used to visualize the aggregated data also affects the perceived spatial patterns. In this review, we compare commonly used aggregation and visualization methods and discuss the respective interpretation of risk maps. Research publications using epidemiological modelling methods were drawn from Web of Science. Only publications containing maps of R0 transformed from EMs were considered for the analysis. An example EM was applied to illustrate how aggregation and visualization methods affect the final presentations of risk maps. Risk maps can be generated to show duration, intensity and spatio-temporal dynamics of potential outbreak risk of VBDs. We show that 1) different temporal aggregation methods lead to different interpretations; 2) similar spatial patterns do not necessarily bear the same meaning; 3) visualization methods considerably affect how results are perceived, and thus should be applied with caution. We recommend mapping both intensity and duration of the VBD outbreak risk, using small time-steps to show spatio-temporal dynamics when possible.

Do we know how mosquito disease vectors will respond to climate change?

Mosquito-borne diseases are on the rise globally. Besides invasion processes and the increasing connectivity between distant regions through the trade of goods and human mobility, climate change is seen as an important driver for changing the likelihood of occurrence of vectors and diseases, respectively. Ectothermic insects respond directly to thermal conditions and thus we can expect them to follow climatic trends. However, a variety of species and different stages in their life cycles need to be considered. Here, we review the current literature in this field and disentangle the state of knowledge and the challenges and open questions for future research. The integration of diurnal temperature ranges in prospective experimental studies will strongly improve the knowledge of mosquitoes' ecology and mosquito-borne disease transmission for temperate regions in particular. In addition, invasive mosquitoes are known to rapidly adapt to the climatic conditions, but the underlying processes are not yet fully understood.

Mosquito-Borne Diseases: Advances in Modelling Climate-Change Impacts.

Vector-borne diseases are on the rise globally. As the consequences of climate change are becoming evident, climate-based models of disease risk are of growing importance. Here, we review the current state-of-the-art in both mechanistic and correlative disease modelling, the data driving these models, the vectors and diseases covered, and climate models applied to assess future risk. We find that modelling techniques have advanced considerably, especially in terms of using ensembles of climate models and scenarios. Effects of extreme events, precipitation regimes, and seasonality on diseases are still poorly studied. Thorough validation of models is still a challenge and is complicated by a lack of field and laboratory data. On a larger scale, the main challenges today lie in cross-disciplinary and cross-sectoral transfer of data and methods.

Areas with High Hazard Potential for Autochthonous Transmission of Aedes albopictus-Associated Arboviruses in Germany.

The intensity and extent of transmission of arboviruses such as dengue, chikungunya, and Zika virus have increased markedly over the last decades. Autochthonous transmission of dengue and chikungunya by Aedes albopictus has been recorded in Southern Europe where the invasive mosquito was already established and viraemic travelers had imported the virus. Ae. albopictus populations are spreading northward into Germany. Here, we model the current and future climatically suitable regions for Ae. albopictus establishment in Germany, using climate data of spatially high resolution. To highlight areas where vectors and viraemic travellers are most likely to come into contact, reported dengue and chikungunya incidences are integrated at the county level. German cities with the highest likelihood of autochthonous transmission of Aedes albopictus-borne arboviruses are currently located in the western parts of the country: Freiburg im Breisgau, Speyer, and Karlsruhe, affecting about 0.5 million people. In addition, 8.8 million people live in regions considered to show elevated hazard potential assuming further spread of the mosquito: Baden-Württemberg (Upper Rhine, Lake Constance regions), southern parts of Hesse, and North Rhine-Westphalia (Lower Rhine). Overall, a more targeted and thus cost-efficient implementation of vector control measures and health surveillance will be supported by the detailed maps provided here.

Implementing cargo movement into climate based risk assessment of vector-borne diseases.

During the last decades the disease vector Aedes albopictus (Asian tiger mosquito) has rapidly spread around the globe. Global shipment of goods contributes to its permanent introduction. Invaded regions are facing novel and serious public health concerns, especially regarding the transmission of formerly non-endemic arboviruses such as dengue and chikungunya. The further development and potential spread to other regions depends largely on their climatic suitability. Here, we have developed a tool for identifying and prioritizing European areas at risk for the establishment of Aedes albopictus by taking into account, for the first time, the freight imports from this mosquito's endemic countries and the climate suitability at harbors and their surrounding regions. In a second step we consider the further transport of containers by train and inland waterways because these types of transport can be well controlled. We identify European regions at risk, where a huge amount of transported goods meet climatically suitable conditions for the disease vector. The current and future suitability of the climate for Aedes albopictus was modeled by a correlative niche model approach and the Regional Climate Model COSMO-CLM. This risk assessment combines impacts of globalization and global warming to improve effective and proactive interventions in disease vector surveillance and control actions.

First assessment for the presence of phlebotomine vectors in Bavaria, Southern Germany, by combined distribution modeling and field surveys.

Leishmaniasis is caused by protozoa of the genus Leishmania and transmitted by sand flies from mammalian reservoirs to humans. In recent years, a northward spread of L. infantum from highly endemic Mediterranean countries into previously non-endemic Central European areas has been suspected based on presumed sporadic cases of autochthonous leishmaniasis. Here, we investigated whether sand flies are prevalent in Bavaria in Southern Germany, a federal state in which autochthonous cases have previously been reported. Considering the present and future climatic conditions, we determined whether Bavaria is suitable for five sand fly species with assumed spreading tendencies towards Central Europe: Phlebotomus ariasi, P. neglectus, P. perfiliewi and P. perniciosus that are known vectors for Leishmania in Europe, and P. mascittii, a suspected but not proven vector. Within Bavaria we defined sampling regions based on their climatic suitability and their spatial distance to the sites of the autochthonous cases and/or to areas of reported sand fly detection in states adjacent to Bavaria. At 155 locations in 7 sampling regions, CDC light traps were placed during 38 nights in the summers of 2009 and 2010, resulting in 202 trap-nights. All traps were negative for sand flies. The results suggest that Bavaria is not yet endemic for sand flies, but do not exclude the possibility of sporadic cases of autochthonous human or zoonotic Leishmania infections. This study, which combined methodological approaches from different disciplines, serves as reference for future surveys and risk analyses of sand flies and leishmaniasis in so far non-endemic areas of Europe.

Low-temperature threshold for egg survival of a post-diapause and non-diapause European aedine strain, Aedes albopictus (Diptera: Culicidae).

BACKGROUND: The interplay between global warming and invasive arthropods in temperate zones is of utmost interest in terms of the potential expansions of vector-borne diseases. Up to now, investigations on the recent establishment of mosquito vectors have focused on temperatures during their phases of activity. However, cold temperatures may also act as a strong ecological constraint. Projected changes in winter climate indicate an increase of mean minimum temperatures of the coldest quarter, less frequent days with frost and a shorter frost-season in Europe at the end of the century. Nevertheless, single cold extremes are also expected to persist under warming scenarios, which have a strong impact on reproduction success. METHODS: Here, the temperature constraints of European Aedes albopictus eggs, which had passed through a diapause, compared to non-diapausing eggs were examined systematically under controlled laboratory conditions. Additionally, one tropical strain of Ae. albopictus and of Ae. aegypti was used in the comparison. RESULTS: The lower temperature threshold tolerated by the European eggs of Ae. albopictus which have undergone a diapause, was -10°C for long term exposures (12 and 24h) and -12°C for 1h exposure. Non-diapausing eggs of European Ae. albopictus were found to hatch after a -7°C cold treatment (8, 12 and 24h exposure). Both tropical aedine species only tolerated the long term treatment at -2°C. Neither Ae. albopictus nor Ae. aegypti eggs hatched after being exposed to -15°C. Survival was mainly influenced by temperature (F = 329.2, df = 1, p < 0.001), whereas the duration of the cold treatment only significantly influenced the hatching response at the thermal limits of survival (F = 5.6, df = 1, p = 0.031) but not at 0°C (F = 0.1, df = 1, p = 0.730). Hatching success after the cold treatment was significantly increased in European eggs, which have undergone a diapause compared to non-diapausing eggs (F = 14.7, df = 3, p < 0.001). These results illustrate rapid adaptation. CONCLUSIONS: Here, low temperature thresholds for aedine mosquito egg survival were detected. The compilation of risk maps for temperate regions can substantially be improved by considering areas where an establishment of a vector population is unlikely due to winter conditions.