revealed that hares were preferred as hosts, with 60% of sand flies positive for hare blood, followed by humans with 30% and cats with 10%, whereas no dog blood was identified. This can explain the high transmission frequency of leishmaniasis in the green park where high population densities of hares are present (see above). Since blood feeding behaviour plays a significant role in the transmission and maintenance of vector-borne pathogens in natural systems, analyses of blood feeding preferences will therefore help to improve our understanding of the role of a particular host or reservoir in urban foci, leading to more effective control strategies.

Using an ex vivo model of infection in murine bone marrow-derived cells, the ex vivo virulence of the *L. infantum* isolates from *Phlebotomus perniciosus* captured in this area of Madrid was evaluated, showing that *L. infantum* isolates captured from this endemic area exhibited high virulence in terms of infection index, cytokine production and enzymatic activities involved in the pathogenesis of visceral leishmaniosis (Domínguez-Bernal et al. 2014).

In summary, this exceptional scenario is likely to be a cause of the urbanisation of leishmaniasis due to the coexistence of periurban and sylvatic transmission cycles involving different, domestic and sylvatic, reservoir species for sand fly vectors. These findings show the complexity of the eco-epidemiological factors that drive *Leishmania* transmission and, therefore, have important implications for Public Health in terms of taking effective measures to control the situation as soon as possible.

Martín-Martín I, Molina R, Ro-houšová I, Drahota J, Volf P and Jiménez M (2014). High levels of anti-*Phlebotomus perniciosus* saliva antibodies in different vertebrate hosts from the re-emerging leishmanio-sis focus in Madrid, Spain. *Vet. Parasitol.* 2014. Doi: 10.1016/j.vetpar.2014.02.045.

Molina R, Jiménez MI, Cruz I, Iriso A, Martín-Martín I, Sevillano O, Melero S and Bernal J (2012). The hare (*Lepus granatensis*) as potential sylvatic reservoir of *Leishmania infantum* in Spain. *Vet Parasitol.* 2012; 190:268-271.

Domínguez-Bernal G, Jiménez M, Molina R, Ordóñez-Gutiérrez L, Martínez-Rodrigo A, Mas A, Cutuli MT and Carrión J (2014). Characterisation of the ex vivo virulence of *Leishmania infantum* isolates from *Phlebotomus perniciosus* from an outbreak of human leishmaniosis in Madrid, Spain. *Parasites & Vectors* 2014, 7:499. Doi: 10.1186/s13071-014-0499-1.

## 7. Autochthonous canine leishmaniasis in Hungary

Tánczos et al. (2012) questioned the status of Hungary as a *Leishmania*-free country where only imported cases of *Leishmania* infections in humans and canines had been described before. When a first case of autochthonous canine leishmaniasis was diagnosed in a pug dog in 2007, an investigation of the other dogs from the kennel was initiated to assess the prevalence of *Leishmania*. During the study another dog developed clinical symptoms of leishmaniasis. In
total six out of 20 dogs were found positive by
testing for antibodies or by PCR analysis, but
only the two dogs mentioned showed clinical
signs. None of the dogs was reported to have
been abroad and no sand flies could be collec-
ted in and around the kennels so the source
of infection is not clear. Possible routes of
transmission resulting in autochthonous *Leish-
mania* infections are discussed by the authors
considering (i) the natural occurrence of two
*Phlebotomus* species in Hungary that may serve
as potential vectors for the pathogen, and
(ii) the risk posed by infected asymptomatic
dogs. The likely increase in numbers of dogs
travelling to or coming from endemic areas
together with a generally high percentage of
asymptomatic dogs and the lack in knowledge of
local veterinarians may have consequences for
the epidemiology of *Leishmania* and the distri-
bution of the disease in Hungary.

This study presents an example that, with the
spread of this zoonotic disease northwards
from southern Europe, *Leishmania* poses a se-
vere threat for human and canine health in cen-
tral and northern European countries.

Tánczos B, Balogh N, Király L, Biksi I, Szeredi L, Gyurkovsky M, Scalone A, Fiorentino E, Gramiccia M and Farkas R (2012). First record of autochthonous canine leishmaniasis in Hungary. *Vector Borne Zoonotic Dis*. 2012 Jul; 12(7):588-94. Doi: 10.1089/vbz.2011.0906. Epub 2012 May.

8. Isolation of (novel) sand fly-borne viruses

In countries around the Mediterranean ba-
sin, phlebotomine sand flies are involved in
the transmission of several arthropod-borne
viruses that belong to the genus *Phlebovirus*
within the *Bunyaviridae* family, i.e. Tosca-
na virus (TOSV; species *Sandfly fever* Naples
virus), Arbia virus (species *Salehebad* virus)
and *Sandfly fever Sicilian* virus. In southern
European countries Toscana virus constitutes a
threat for Public Health as it is one of the
major viral pathogens causing central nervous
system infections in humans. Findings of new
sand fly-borne phleboviruses from Mediterranean
countries indicated that the viral diversity
in the genus *Phlebovirus* is higher than ini-
tially expected. In Tunisia, the recent iso-
lation of Punique virus (PUNV; species *Sandfly
fever Naples* virus) raised the question of
its role in human infections and as a poten-
tial pathogen. The EDENext study by Sakhria et
al. (2013) demonstrated the co-circulation of
two related sand fly-borne phleboviruses, TOSV
and PUNV, both belonging to the same species,
*Sandfly fever* *Naples* virus. Serum samples from humans living in endemic areas for visceral leishmaniasis in northern Tunisia were tested by micro-neutralisation assay for neutralising antibodies which allowed these closely related viruses to be differentiated. With seroprevalence rates of 41% for TOSV and 9% for PUNV found in the samples it was demonstrated that PUNV is capable of infecting humans but at a low rate, and that TOSV seems to be responsible for the majority of human infections by sand fly-borne phleboviruses in northern Tunisia. Therefore it should always be considered by physicians for patients with meningitis or unexplained fever.

TOSV was initially discovered in central Italy but it was not until 15 years later that its role as causative agent in human neuro-invasive disease was noticed. TOSV circulates in several European countries, for example Italy, Portugal, Spain, France, Croatia and Turkey, and is now recognised as the leading cause of aseptic meningitis during the warm season. Bichaud et al. (2014) reported the first detection of TOSV from *P. perniciosus* in Corsica demonstrating the presence of the virus on the island. TOSV poses a risk to the Public Health of locals and tourists and therefore always needs to be considered by physicians when patients present with aseptic meningitis and febrile illness during the warm season.

The EDENext publication by Remoli et al. (2014) described the isolation of a novel *Phlebovirus*, named Fermo virus, placed in the species *Sandfly fever Naples* virus. The importance of this finding lies in the virus' ability to fill an ecological niche and to co-infect the same vector which in consequence may lead to the emergence of virus reassortants (with mixed gene segments) exhibiting different degrees of pathogenicity. Further studies need to focus on the distribution of Fermo virus and on its ability to cause infection and disease in humans.

A new phlebovirus, Adana virus, was isolated from a pool of *Phlebotomus* spp. in the province of Adana, in the Mediterranean region of Turkey. Genetic analysis based on complete coding of genomic sequences indicated that Adana virus belongs to the *Salehabad* virus species of the genus *Phlebovirus* in the family *Bunyaviridae*.

Bichaud L, Izri A, de Lambalerie X, Moureau G and Charrel RN (2014). First detection of Toscana virus in Corsica, France. *Clin Microbiol Infect.* 2014 Feb; 20(2):0101-4. Doi: 10.1111/1469-0691.12347. Epub 2013 Aug 30.

Remoli ME, Marchi A, Bucci P, Argentini C, Bongiorno G, Maroli M, Gradoni L, Gramiccia M and Ciufolini MG (2014). Viral isolates of a novel putative phlebovirus in the Marche Region of Italy. *Am J Trop Med Hyg.* 2014 Apr; 90(4):760-3. Doi: 10.4269/ajt-mh.13-0457. Epub 2014 Feb 17.

Sakhria S, Bichaud L, Mensi M, Salez N, Dachraoui K, Thirion L, Cherni S, Chelbi I, De Lambalerie X, Zhioua E, and Charrel RN (2013). Co-circulation of Toscana virus and Punique virus in northern Tunisia: a microneutralisation-based seroprevalence study. *PLoS Negl Trop Dis.* 2013 Sep 12; 7(9):e2429. Doi: 10.1371/journal.pntd.0002429. eCollection.
Adana virus is the third virus of the Salehabad virus species for which the complete sequence has been determined. To understand the epidemiology of Adana virus, a seroprevalence study using microneutralization assay was performed to detect the presence of specific antibodies in human and domestic animal sera collected in Adana as well as Mersin province, located 147km west of Adana. The results demonstrate that the virus is present in both provinces. The significance of this Adana virus as a possible public health problem in exposed human populations deserves further studies (Alkan et al. 2015).

Alkan C, Alwassouf S, Piorkowski G, Bichaud L, Tezcan S, Dincer E, Ergunay K, Ozbel Y, Alten B, de Lamballerie X and Charrel RN (2015). Isolation, genetic characterization, and seroprevalence of Adana virus, a novel phlebovirus belonging to the Salehabad virus complex, in Turkey. *J Virol* 89:4080-4091. DOI:10.1128/JVI.03027-14.

## 9. Geographic spread of sand fly-borne phleboviruses

Sand fly-borne phleboviruses are widely distributed in the Mediterranean basin, North Africa, the Indian subcontinent, the Middle East and central Asia. Except for Toscana virus, the leading cause of aseptic meningitis in endemic regions, phleboviruses are inadequately considered by physicians and are frequently underestimated. However, climate changes, environmental conditions and anthropogenic factors, such as increased trade and travel of humans and animals, have a considerable impact on the distribution of vectors. This, together with the virus' propensity for mutations, reassortment and recombinations of its three-segmented genome increases the risk for virus introduction and makes it probable that phleboviruses will extend their geographic range. Most studies document the distribution of sand fly-borne phleboviruses in Western Europe, while data for Eastern Europe, the Middle East and Africa are very limited. The EDENext review by Alkan et al. (2013) summarises the geographic spread of sand fly-borne phleboviruses with a focus on understudied regions and discusses possible countermeasures and the need to conduct studies aimed at developing new antiviral drugs and vaccines. In terms of Public Health, their potential as emerging pathogens should raise our awareness and highlight the need to understand not only the complex nature of sand fly-borne viruses and but also the biological significance of possible interactions between *Leishmania* parasites and phleboviruses.

Alkan C, Bichaud L, de Lamballerie X, Alten B, Gould EA and Charrel RN (2013). Sand fly-borne phleboviruses of Eurasia and Africa: epidemiology, genetic diversity, geographic range, control measures. *Antiviral Res.* 2013 Oct; 100(1):54-74. DOI: 10.1016/j.antiviral.2013.07.005. Epub 2013 Jul 19.
## Interview: Maria Antoniou

<figure><img src="image_26.png" /></figure>

Cyprus-born Maria Antoniou is assistant professor of parasitology at the University of Crete's Medical School and is head of the microbiology laboratory of the Medical Department and of the University Hospital in Heraklion, Crete. Maria spent a decade at London University's Imperial College of Science, Technology and Medicine, completing a BSc (ARCS) in zoology, MSc (DIC) in nematology and a PhD in parasitology-nematology, before a sabbatical studying leishmaniasis at INSERM (France's national institute for health and medical research). Her current research includes the protozoan parasites *Leishmania* and *Toxoplasma* and the epidemiology of zoonoses using GIS technology. This includes the epidemiology of leishmaniasis in Greece and Cyprus, isolating the parasite from patients, dogs and sand flies, the study of the geographical distribution of *Leishmania* strains and their vectors, and studies relating to the biology of the *Leishmania* parasite and its resistance to drugs.

**What did EDEN and EDENext mean for your institute and your students?**

**Maria Antoniou (University of Crete, Greece):** "EDEN and EDENext have been very important for us because they gave us a chance; first of all, to have money in order to do research and, secondly, to have the students involved with some salary too. There were about six students who worked with EDEN and EDENext money. The money gave us the opportunity to do the research, to collect samples from all over Greece and Cyprus regarding sand flies and sera from dogs for Leishmania production and from humans, from patients. And this material will be used as we go on to do work with other things like drug resistance of Leishmania and in collaborations for analysis of the sand flies. And also the students had the chance to go to conferences and to PhD meetings and were able to learn how to participate in big groups and how to tackle collaborations and so on. They will be the future scientists on these subjects for Greece and for Cyprus. Some of the students who finished their PhDs on EDEN money are now working in Cyprus for the government and are still helping the EDENext project because they were so excited and happy about all of this. Without any money they collect samples for us and I go to Cyprus to collaborate. One of the PhDs, through work carried out in Cyprus, was able to detect Leishmania donovani in Cyprus, which is the first detection in Europe; this is the introduction of a very virulent strain in Europe and so important work that has only been done because of this collaboration."

**It is a good base for the future?**

**Maria:** "Yes, good relations for the future are very important, not only for our lab but also for the students who go independent and get a job somewhere else. They know that these people do this and I can talk to them, I can ask them for advice and have collaborations with them for future work and I can provide them with materials through their lab to carry out their analysis on important questions which arise through this work."

**These collaborations are very important?**

**Maria:** "It was a great experience to collaborate with so many people from so many different fields and I think this is important for the professors as well as for the students. For example, now we have people who are experts in GIS which is something we did not have before, beyond an expert in Athens who collaborated with our lab. Now I have two students who can do very quick work with GIS, not just mapping but also statistical analysis. Also I have had the chance to send students to different labs for collaborations and people came to our lab for collaborations, which is bond-building for science but also for personal bond-building, which is very important...We have very, very good relationships which we are still building and we hope to be able to carry on working together. This networking is important. It was a very important stepping stone in the EDEN project, not just for EDEN people, but for the policies of the European Union, on how to fund projects. You can sit in your lab and just do research but discussing with people brings out ideas!"
Jordi Figuerola¹

¹Department of Wetland Ecology, EBD-CSIC, Sevilla, Spain

# Understanding the effect of a zoonotic virus on transmission

## INTRODUCTION

West Nile fever (WNF) is a zoonotic viral disease principally maintained in a zoonotic cycle between mosquitoes and birds (Reiter 2010). Although humans and horses are not competent hosts, they may become infected by West Nile virus (WNV). Most infections are of short duration and asymptomatic but in a few cases the virus causes neural disease, even leading to death (Rizzoli et al. 2015). Over past decades the incidence of WNF in horses and humans in Europe has increased (Rizzoli et al. 2015). In this paper I summarise some of the research conducted by EDEN and EDENext research teams aimed at understanding its transmission dynamics in Europe.

WNV outbreaks in Europe used to be of short duration and small scale (Rizzoli et al. 2015) and for this reason the traditional view for many years has been that migratory birds introduced the virus each spring from its endemic areas in Africa. One of the main results of our research has been to demonstrate that WNV circulation in some regions in Europe does not depend on introductions from Africa. Indeed, the virus can be considered endemic at least in Austria (Bakonyi et al. 2013), Italy (Engler et al. 2013), Romania (Dinu et al. 2015) and Spain (Figuerola et al. 2007, 2008). In all these areas, virus, seroconversions and/or cases of disease in birds, horses or humans have been recorded in the same areas over successive years. In addition, the analyses of the sequences of WNV lineage 1 detected in the western Mediterranean suggest that all the outbreaks occurring between 1996 and 2010 may be explained by a single introduction from Africa and posterior dispersal through Europe (Sotelo et al. 2011). The two original, independent, introductions of WNV lineage 2 in Europe, one in Austria and the other in Russia, and subsequent expansion through Central and Eastern Europe underline the importance of WNV dispersal within Europe (Rudolf et al. 2013, Kolodziejek et al. 2014, Dinu et al. 2015).

The persistence of WNV in temperate climates during the winter may occur through overwintering mosquitoes or through long-term infection in birds (Reisen 2013). Research in Romania and the Czech Republic has confirmed the presence of WNV in pools of overwintering mosquitoes (Reiter 2010). Studies are now under way to estimate the survival of female mosquitoes overwintering in anthropogenic areas. Furthermore, ticks provide an alternative vector for WNV, with the potential to act as long-term virus vectors and infect a wide spectrum of vertebrate hosts through the various tick developmental stages (Kolodziejek et al. 2013).

## MONITORING SEROPREVALENCE IN VERTEBRATE HOSTS

Analyses of the seroprevalence data of WNV neutralizing antibodies in a high number of different avian species has shown that WNV seroprevalence was higher in migratory birds and in larger species (see Figure 1) even after controlling for differences in the age of individuals (Figuerola et al. 2008, Lopez et al. 2008); mosquitoes may find it easier to detect larger birds. A higher WNV-induced mortality in small avian species does not seem a likely explanation for such differences in seroprevalence (Figuerola et al. 2008). Given the large interspecific differences in seroprevalence rates, it seems advisable to focus WNV vigilance programmes on larger avian species, because the detection of WNV circulation would require the analyses of a smaller number of individuals, a smaller sampling effort and lower laboratory costs (Figuerola et al. 2008). The use of sentinel captive birds (chickens or pigeons) may help to detect and characterise the seasons of the year with higher WNV circulation (Fall et al. 2013). Capture-recapture serological analyses also provide an effective approach for demonstrating local circulation of WNV in free-living
# the ecology of West Nile
 transmission in Europe

<figure><img src="image_27.png" /><figcaption>Figure 1. Prevalence of WNV neutralizing antibodies in different avian species. The prevalence of antibodies was higher in migratory species (open circles) than in resident species (filled circles). Antibody prevalence also increased with the body mass of species. (Based on the dataset analysed by Figuerola et al. 2008).</figcaption></figure>

ving wild birds (Figuerola et al. 2007). In this case, the birds provide spatially integrated monitoring of WNV circulation, while information from sentinel birds is restricted to the surroundings of cages. In particular, the common coot (*Fulica atra*) proved a good wild candidate for WNV surveillance in Europe given the high seroprevalence rate of WNV reported by different studies (Figuerola et al. 2007, Hubalek et al. 2008), and its low host competence (Komar et al. 2003).

## ENVIRONMENTAL FACTORS RELATED TO WNV INCIDENCE

Analyses of the spatial and temporal distribution of WNV outbreaks or of the seroprevalence rate in different vertebrate species may provide information on the environmental factors associated with higher WNV circulation. The analyses of WNV seroprevalence in horses across Tunisia suggested that

## REFERENCES

Alcaide M, Rico C, Ruiz S, Soriguer R, Muñoz J, Figuerola J (2009). Disentangling vector-borne transmission networks: a universal DNA barcoding method to identify vertebrate hosts from arthropods bloodmeals. *PLoS One* 4: e7092.

Bakonyi T, Ferenczi E, Erdélyi K, Kutasi O, Csörgő T, Seidel B, et al. (2013). Explosive spread of a neuroinvasive lineage 2 West Nile virus in central Europe, 2008/2009. *Veterinary Microbiology* 165:61-70.

Bargaoui R, Lecollinet S, Lancelot R (2015). Mapping the serological prevalence rate of West Nile fever in equids, Tunisia. *Transboundary Emerging Diseases* 62: 55-66.

Dinu S, Cotar AI, Panculecu-Gatej I-R, Falcuta E, Prioteasa FL, Sirbu A, Oprisan G, Badescu D, Reiter P, Ceianu CS (2015). West Nile virus circulation in south-eastern Romania in 2011-2013. *Eurosurveillance*, in press.

Engler O et al. (2013). European surveillance for West Nile virus in Mosquito populations. *International Journal of Environmental Research and Public Health* 10: 4869-4895.

Fall AG, DIAITE A, Seck MT, Bouyer J, Lefrançois T, Vachiéry N, Aprelon R, Faye O, Konaté L, Lancelot R (2013). West Nile virus transmission in sentinel chickens and potential mosquito vectors, Senegal River Delta, 2008-2009. *International Journal of Environmental Research and Public Health* 10: 4718-4727.

Figuerola J, Soriguer R, Rojo G, Tejedor C, Jiménez-Clavero MA (2007). Seroconversion in wild birds and local circulation of West Nile virus, Spain. *Emerging Infectious Diseases* 13: 1915-1917.

Figuerola J, Jiménez-Clavero M, López G, Rubio C, Soriguer R, Gómez-Tejedor C, Tenorio A (2008). Size matters: West Nile Virus neutralizing antibodies in resident and migratory birds in Spain. *Veterinary Microbiology* 39-46.
infection risk was higher closer to wetlands, and was also related to night-time temperature and vegetation cover (Bargaoui et al. 2015). In Europe, WNV outbreaks between 2002 and 2013 were more frequent near wetland areas, in hot and wet summers and positively related to human population size (Tran et al. 2014). WNV amplification may occur in wetlands, where mosquitoes and birds are abundant, but this does not have Public Health significance when people are absent and therefore not exposed to the virus. In the end, it may be that human distribution and human presence in areas of WNV circulation are an important determinant of WNV incidence.

Recent reanalyses of WNV infection cases in humans in Europe have identified landscape and, in particular, the presence of areas characterised by a mixture of forest, human habitation, farmland and transitional habitat as an important factor related to WNV incidence (Marcantonio et al. 2015). Vector population size is also affected by environmental conditions. It has been observed that the abundance of *Culex pipiens* in south-west Spain initially increased with summer temperatures. However, mosquito abundance decreased in hotter summers (Roiz et al. 2014). Climate change may have an effect on the abundance of vectors and pathogens, but the direction of this effect depends on the balance between positive and negative effects. For example, the relationship between temperature and *Cx. pipiens* abundance in south-west Spain was not linear, and winter rainfall was also associated with its abundance. As a result, no net change in *Cx. pipiens* abundance is expected in this area given the projected increases in temperature and decreases in rainfall over the next century. However, forecasting the impact of climate change on WNV transmission risk based only on vector abundance is not straightforward. Firstly, the relationship between WNV transmission risk and environmental conditions may not be linear, nor stationary (Roiz et al. 2014). Secondly, climate may have conflicting effects on different components of WNV transmission, i.e. vector abundance and vector survival (Reiter 2008). Consequently the net effect on transmission risk is difficult to estimate.

## ECOLOGY OF WNV TRANSMISSION

WNV surveillance of mosquitoes and birds has demonstrated that WNV is silently circulating in many areas in Europe without resulting in clinical cases in horses and humans. Different processes are involved in the genesis of WNV transmission to humans or horses. After WNV introduction into an area by infected birds, the virus must be amplified through an enzootic cycle involving competent species of vectors and vertebrate hosts. Not all species of vertebrates are competent hosts, and host competence differs widely between avian species (Komar et al. 2003). Consequently, amplification of WNV will be affected by the abundance and vectorial competence of the different mosquito species present, but also by the feeding behaviour of these mosquitoes. We can expect a larger circulation of WNV when and where competent mosquito species are abundant and mainly feeding on competent vertebrate hosts (Kilpatrick et al. 2006, Muñoz et al. 2012). Finally, the spillover of WNV from these usually unnoticed avian-mosquito cycles into humans and horses may involve a different vector species acting as an epidemiological bridge between infected birds and human/horse hosts. The environmental factors affecting the amplification and spillover phase may differ spatially and temporally (Kilpatrick et al. 2006, Muñoz et al. 2012) thereby affecting WNV transmission risk.

The development of universal primers for the sequencing of the COI gene in vertebrates has provided a powerful tool for the study of trophic interactions in haematophagous invertebrates (Alcaide et al. 2009). The recovered sequence can be compared with those stored in GenBank or in the Barcode of Life system to identify the mosquito's host. Several genera of mosquitoes are competent vectors for WNV, though species of the genera *Culex* are the most important vectors present in Europe (Engler et al. 2013). Based on their feeding behaviour in south-west Spain, *Cx. perexiguus*, *Cx. modestus* and *Cx. pipiens* were considered the main species involved in the avian-mosquito WNV cycle because these species were abundant, feed mainly on birds and are highly competent WNV vectors (see Figure 2). *Cx. perexiguus* was also important for WNV transmission to horses while WNV transmission risk in the studied area was very low and mainly due to *Cx. pipiens* and *Cx. theireli*. *Cx. perexiguus* seems a very important species for the amplification of WNV in southern Spain. This is a highly ornithophilic species (78% of blood meals had an avian origin) and high vectorial competence (Muñoz et al. 2012). The detection of WNV and Usutu virus in this species has further confirmed its importance for avian Flavivirus transmission (Vazquez et al. 2011). However, this species is not abundant near areas of human habitat, and does not usually feed on humans (0% of blood meals). Therefore, it probably plays a minor role as a bridge vector for the transmission of WNV to humans in south-west Spain (Muñoz et al. 2012, and unpublished information).

The analyses of blood meal origin in different mosquito species and localities confirmed that different species of mosquitoes had different intrinsic feeding preferences (i.e. mosquitoes can be classified as ornithophilic, mammophilic or herpetophilic).
<figure><img src="image_28.png" /><figcaption>Figure 2. Estimated risk of WNV transmission by different mosquito species in different localities. Transmission risk is calculated as the product of vector abundance, vector competence, fraction of mosquito females feeding on competent hosts (birds) and the fraction of mosquito females feeding in the group of interest (birds, horses or humans). Filled circles indicate the cases where WNV has been detected in the mosquito pools. The figure has been redrawn from Muñoz et al. (2012) original data, updated with new virus detection information and the risk values calculated considering that chickens are not competent hosts for WNV.</figcaption></figure>

However, there are important differences in blood meal origin between localities. Muñoz et al. (2012) have estimated that the probability of finding blood of avian origin in a blood-fed female mosquito is explained by mosquito species (49-65% of explained variation) and locality (30-50%). Given that not all vertebrates are competent hosts for WNV, this results in important differences between localities in the potential for 1) WNV amplification through mosquito-mediated bird to bird transmission and 2) risk of transmission to humans through mosquito-mediated bird to human transmission (Kilpatrick et al. 2006, Muñoz et al. 2012). Unfortunately, no information is currently available on the causes of this local variation in blood meal composition. Differences in vertebrate abundance might explain most of these differences, but ornithophilic and mammophilic species may respond differently to changes in vertebrate community composition. However, very little is known on the functional response of mosquitoes to changes in vertebrate availability, although it is important to highlight that human effects on landscape have important effects on biodiversity distribution.

Recently, an important debate has opened up on the potential role that biodiversity may have in reducing the risk of zoonotic diseases (Randolph and

Hubalek Z, Halouska J, Juricová Z, Sikutová S, Rudolf I, Honza M, Janková J, Chytil J, Marec F, Sitko J (2008). Serologic survey of birds for West Nile Flavivirus in southern Moravia (Czech Republic). *Vector-Borne and Zoonotic Diseases* 8: 659-666.

Kilpatrick AM, Daszak P, Jones MJ, Marra PP, Kramer LD (2006). Host heterogeneity dominates West Nile virus transmission. *Proceedings of the Royal Society B: Biological Sciences* 273:2327-2333.

Kolodziejek J, Marinov M, Kiss BJ, Alexe V, Nowotny N (2014). The complete sequence of a West Nile virus lineage 2 strain detected in a *Hyalomma marginatum marginatum* tick collected from a Song Thrush (*Turdus philomelos*) in Eastern Romania in 2013 revealed closest genetic relationship to strain Volgograd 2007. *PLoS One* 9: e109.

Komar N, Langevin S, Hinten S, Nemeth N, Edwards E, Hettler D et al. (2003). Experimental infection of North American birds with the New York 1999 strain of West Nile virus. *Emerg Infect Dis.* 9: 311-22.

Lopez G, Jimenez-Clavero MA, Tejedor CG, Soriguer R, Figuerola J (2008). Prevalence of West Nile virus neutralizing antibodies in Spain is related to the behavior of migratory birds. *Vector Borne Zoonotic Dis.* 8, 615-621.

Marcantonio M, Rizzoli A, Metz M, Rosa R, Marini G, Chadwick E, Neteler M (2015). Identifying the environmental conditions favouring West Nile virus outbreaks in Europe. *PLoS One* 10: e0121158.

Muñoz J, Ruiz S, Soriguer R, Alcaide M, Viana DS, Roiz D, Vázquez A, Figuerola J (2012). Feeding patterns of potential West Nile virus vectors in south-west Spain. *PLoS One* 7: e39.

Randolph SE and Dobson AD (2012). Pangloss revisited: a critique of the dilution effect and the biodiversity-buffers-disease paradigm. *Parasitology* 139: 847-863.

Reisen, WK (2013). Ecology of West Nile virus in North America. *Viruses* 5: 2079-2105.

Reiter, P (2008). Climate change and mosquito-borne disease: knowing the horse before hitting the cart. *Rev. Sci. Tech. Off. Int. Epiz.* 27: 383-398.

Reiter, P (2010). West Nile virus in Europe: understanding the present to gauge the future. *Eurosurveillance* 15.

Rizzoli A, Jimenez-Clavero MA, Barzon J, Cordioli P, Figuerola J, Koraka P, Martina B, Pardigon N, Sanders N, Ulbert S, Tenorio A (2015). The challenge of West Nile virus in Europe: knowledge
Dobson 2012). Although some models support the likelihood of the dilution mechanisms (Roche et al. 2011), it is important to note that the conclusions of these models strongly depend on the assumptions made on the interactions between vectors and hosts. Consequently, until more basic information is available on the interactions between vector and vertebrate distribution and abundance it is difficult to determine if the dilution effect is a general effect of biodiversity or a particular case that may only happen for some pathogens under some environmental conditions. Indeed, understanding the effects of this biodiversity on virus transmission and the impact of anthropogenic habitat transformations may greatly enhance our capacity to predict and manage the risk of WNV outbreaks in the future.

## ACKNOWLEDGEMENT

We would like to thank all the researchers who worked in the EDEN and EDENext mosquito-borne diseases teams. We thank the following institutions:

Agence Nationale de Sécurité Sanitaire de l'alimentation, de l'environnement et du travail, France

Consejo Superior de Investigaciones Científicas, Spain

Danube Delta National Institute for Research and Development, Romania

Institut Pasteur, France

Institute of Public Health, Albania

Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, Czech Republic

National Institute of Research and Development for Microbiology and Immunology 'Cantacuzino', Romania

Szent Istvan University, Faculty of Veterinary Science, Hungary

Università degli Studi di Roma La Sapienza, Italy

University of Veterinary Medicine Vienna, Austria

University of Zurich, Switzerland

gaps and research priorities. *Eurosurveillance*, in press.

Roche B, Rohani P, Dobson AP, Guégan J-F (2013). The impact of community organization on vector-borne pathogens. *The American Naturalist* 181: 1-11.

Roiz D, Ruiz S, Soriguer R, Figuerola J (2014). Climatic effects on mosquito abundance in Mediterranean wetlands. *Parasites & Vectors* 7: 333.

Rudolf I, Bakonyi T, Sebesta O, Mendel J, Pesko J, Betasova L, Blazejova H, Venclikova K, Strakova P, Nowotny N, Hubalek Z (2014). West Nile virus Lineage 2 isolated from *Culex modestus* mosquitoes in the Czech Republic, 2013: expansion of the European WNV endemic area to the north? *Eurosurveillance* 19: 31.

Sotelo E, Fernandez-Pinero J, Llorente F, Vázquez A, Moreno A, Agüero M, Cordioli P, Tenorio A, Jimenez-Clavero MA (2011). Phylogenetic relationships of Western Mediterranean West Nile virus strains (1996-2010) using full-length genome sequences: single or multiple introductions? *Journal of General Virology* 92: 2512-2522.

Tran A, Sudre B, Paz S, Rossi M, Desbrosse A, Chevalier V, Semenza JC (2014). Environmental predictors of West Nile fever risk in Europe. *International Journal of Health Geographics* 13: 26.

Vázquez A, Ruiz S, Herrero L, Moreno J, Molero F, Magallanes A, Sánchez-Seco MP, Figuerola J, Tenorio A (2011). West Nile and Usutu viruses in mosquitoes in Spain, 2008–2009. *American Journal of Tropical Medicine and Hygiene* 85: 178–181.
EDENext's Public Health Telegrams (PUBLICise Health) were established to inform interested individuals and institutions about research results on vector-borne diseases with direct or indirect impact on Public Health issues. Edited and produced by EDENext's Public Health team, each issue concentrates on the work of one of the project's five specialist groups. Here we present an updated version of the issue dedicated to the work of the team examining mosquito-borne diseases, first published in March 2014

1. New adhesive traps to monitor urban mosquitoes with a case study to assess efficacy of insecticide control strategies

An Italian research team has assessed the po-
tential of three adhesive traps for passive
monitoring of urban mosquito adult abundance
and seasonal dynamics, and for assessing the
efficacy of commonly used control measures.
They note that urban mosquitoes in temperate
regions may have a high nuisance value and are
associated with the risk of arbovirus transmis-
sion. In highly infested urban areas in Italy,
for example, this leads to calendar-based lar-
vicide treatments of street catch basins - the
main non-removable urban breeding site - and/
or insecticide ground spraying. The planning
of these interventions, as well as the evalua-
tion of their effectiveness, rarely benefits
from adequate monitoring of mosquito abundance
and dynamics. Therefore the team designed two
novel adhesive traps to monitor *Aedes albopic-
tus* and *Culex pipiens* adults visiting and/or
emerging from catch basins in order to eva-
luate the efficacy of insecticide-based control
strategies. The mosquito emerging trap (MET)
was used to assess the efficacy of larvicide
treatments. The catch basin trap (CBT) was
used together with the sticky trap (ST, com-
monly used to collect ovipositing / resting
females) to monitor adult abundance on the
campus of the University of Rome 'Sapienza',
where catch basins had been treated with insect
growth regulators (IGR) bi-monthly and low-vo-
lume insecticide spraying was carried out be-
fore sunset, and in a nearby control area.
Their results from MET showed that, although
all monitored diflubenzuron-treated catch ba-
sins were repeatedly visited by Ae. albopictus
and Cx. pipiens, adult emergence was inhibited
in most basins. Results obtained by ST and
CBT showed a significant lower adult abundance
in the treated area than in the untreated one
after the second adulticide spraying, which
was carried out during the major phase of Ae.
albopictus population expansion in Rome. They
conclude that all three adhesive traps have
potential for passive monitoring of urban mos-
quito adult abundance and seasonal dynamics,
and in assessing the efficacy of control mea-
sures.

Caputo B, Ienco A, Manica M, Petrarca V, Rosà R and della Torre A (2015). New adhesive traps to monitor urban mosquitoes with a case study to assess the efficacy of insecticide control strategies in temperate areas. *Parasites & Vectors* 2015, **8**: 134. Doi:10.1186/s13071-015-0734-4

2. West Nile virus in Europe: knowledge gaps and research priorities

A joint initiative from European experts on West Nile virus (WNV) has seen them analyse 118 scientific papers published between 2004 and 2014 to provide the state of the art on knowledge on WNV. Their work highlights the existing knowledge and research gaps that need to be addressed as a high priority in Europe and neighbouring countries. Noting the continual spread of WNV both in Europe and other regions, they point out that the high genetic diversity of the virus, with remarkable phenotypic variation, and its endemic circulation in several countries, requires an intensification of the integrated and multidisciplinary research efforts built under the 7th Framework Programme. It is important, they say, to better clarify several aspects of WNV circulation in Europe, including its ecology, genomic diversity, pathogenicity, transmissibility, diagnosis and control options, under different environmental and socio-economic scenarios. They add that identifying WNV endemic areas, as well as infection-free areas, is becoming necessary for the development of human vaccines and therapeutics, and for the application of blood and organ safety regulations.

Rizzoli A, Jiménez-Clavero MA, Barzon L, Cordioli P, Figuerola J, Koraka P, Martina B, Moreno A, Nowotny N, Pardigon N, Sanders N, Ulbert S and Tenorio A (2015). The challenge of West Nile virus in Europe: knowledge gaps and research priorities. *EuroSurveill.* 2015;20(20):pii=21135

3. The effects of climate change on mosquito
abundance in Mediterranean wetlands

Noting that the impact of climate change on
vector-borne diseases is highly controversial,
distribution and abundance, and as a result
may alter disease risk. The team analysed the
relationship between environmental variables
estimated by remote sensing and spatial dis-
tribution (presence, abundance and diversity)
of seven mosquito species which are vectors of
West Nile and other pathogens (Usutu, avian
malaria and dirofilariasis) in the Doñana Natu-
ral Park, Spain. They sampled 972,346 female
mosquitoes, the most abundant species being
Culex theileri, Ochlerotatus caspius, Culex
modestus, Culex perexiguus, Culex pipiens,
Anopheles atroparvus and Ochlerotatus detri-
tus. Their results suggest that: (1) hydroppe-
riod, inundation surface and NDVI are strongly
related to the spatial distribution of mosqui-
toes; (2) the spatial scales used to measure
these variables affects the quantification of
these relationships, the larger scale being
more informative; (3) these relationships are
species-specific; (4) hydroperiod is negatively
related to mosquito presence and richness; (5)
Culex abundance is positively related to hy-
droperiod; (6) NDVI is positively related to
mosquito diversity, presence and abundance,
except in the case of the two salt marsh spe-
cies (Oc. caspius and Oc. detritus); and (7)
inundation surfaces positively condition the
abundance and richness of most species except
the salt marsh mosquitoes. They conclude that
while environmental conditions affect the dis-
tribution and abundance of mosquitoes, other
factors such as human modification of lands-
capes may give rise to significant changes in
mosquito populations and consequently disease
risk.

Roiz D, Ruiz S, Soriguer R and
Figuerola J (2015). Landscape
Effects on the Presence, Abun-
dance and Diversity of Mosqui-
toes in Mediterranean Wetlands.
PLoS ONE 10(6): e0128112. Doi:
10.1371/journal.pone.0128112
# Ecology and eco-epidemiology of
**Culicoides**-borne diseases:

## what have we learnt and where do we go
from here?

Kate R. Searle<fnref n="1" />, Alberto Allepuz<fnref n="2" />, Sebastian Napp<fnref n="3" />,
Steven White<fnref n="1" />, Simon Carpenter<fnref n="4" />, Miguel Miranda<fnref n="5" />,
Claire Garros<fnref n="6" />,<fnref n="7" />, Rene Bødker<fnref n="8" />, Assane Gueye Fall<fnref n="9" />,
Bethan V. Purse<fnref n="1" /> and Catherine Cêtre-Sossah<fnref n="6" />,<fnref n="7" />

## INTRODUCTION

*Culicoides* biting midges are abundant haematophagous flies capable of acting as vectors for arthropod-borne viruses of veterinary and medical importance. The past two decades have witnessed dramatic changes in the epidemiology of *Culicoides*-borne viruses, including the emergence of exotic viruses in northern temperate regions, increases in global disease incidence and enhanced virus diversity in tropical zones. The drivers of these changes may include altered climate, land use, trade and animal husbandry practices. During this time, several new *Culicoides* species and new wild reservoir hosts have been implicated in disease transmission, highlighting the dynamic nature of pathogen-vector-host interactions and the importance of understanding how the wider natural and agricultural environment influences these processes. Throughout EDENext, the *Culicoides* group has sought to enhance the evidence base for ef-

fective disease policy and management by engaging in a wide range of empirical and model-based research activities. Here, we summarise the main findings of the *Culicoides* group in relation to vector behaviour, life history traits, population dynamics and phenology. We then discuss how this enhanced understanding has stimulated a suite of methods aimed at understanding the consequence of midge vector biology for *Culicoides*-borne disease spread and control across Europe. Finally, we identify the key knowledge gaps hindering further refinement of models and improved implementation of disease policy.

## VECTOR BEHAVIOUR, LIFE HISTORY TRAITS,
POPULATION DYNAMICS AND PHENOLOGY

In response to the recent emergence of bluetongue virus (BTV) and Schmallenberg virus (SBV), researchers within EDENext have studied the behaviour, life history, phenology and population dynamics of *Culicoides* species across Europe and North Africa.

The EDENext *Culicoides* group collaborated with international colleagues outside the project to provide a comprehensive review of the biometrics of *Culicoides* in relation to the transmission of *Culicoides*-borne diseases (Purse et al. 2015). This review focused on potential vector species worldwide and key elements of vectorial capacity, and assessed the sensitivity of *Culicoides* life cycles to abiotic and biotic factors. It also considered the implications for designing control measures and understanding

<footnote n="1">¹ NERC Centre for Ecology and Hydrology, UK</footnote>

<footnote n="2">² Centre de Recerca en Sanitat Animal (CReSA) -
Institut de Recerca i Tecnologia Agroalimentàries
(IRTA) / Autonomous University of Barcelona, Spain</footnote>

<footnote n="3">³ Centre de Recerca en Sanitat Animal (CReSA) -
Institut de Recerca i Tecnologia Agroalimentàries
(IRTA), Spain</footnote>

<footnote n="4">⁴ The Pirbright Institute, UK</footnote>

<footnote n="5">⁵ University of the Balearic Islands, Spain</footnote>

<footnote n="6">⁶ CIRAD, Montpellier, France</footnote>

<footnote n="7">⁷ INRA, Montpellier, France</footnote>

<footnote n="8">⁸ National Veterinary Institute, Danish Technical
University, Denmark</footnote>

<footnote n="9">⁹ Institut Sénégalais de Recherches Agricoles,
Sénégal</footnote>
the impacts of environmental change in different ecological contexts. Finally, critical geographical, biological and taxonomic knowledge gaps were prioritised. These knowledge gaps, along with others identified within the EDENext *Culicoides* group, are discussed in the conclusions of this article.

A critical aspect of providing an evidence base for informing disease management and policy involves assessing how aspects of *Culicoides* vector capacity vary across Europe and North Africa. The EDENext *Culicoides* group assessed vector competence for several *Culicoides* vectors and viruses, for instance investigating the competence of *C. imicola* with three BTV serotypes (BTV-8, BTV-4 and BTV-1). The EDENext *Culicoides* group developed standardised methods for comparative estimates of vector susceptibility to infection and onward transmission potential. One aspect of this work involved significant advances in feeding techniques for North-Western Palaearctic species (*C. imicola*, Obsoletus group species) thereby targeting key potential vectors of orbiviruses. Our group developed novel methods using the Hemotek feeder to improve comparison between sites and countries, allowing the first multi-country comparison of feeding rates in *Culicoides*. These methodological advances were transferred to Senegal and applied to *C. oxystoma*, an important Afrotropical vector species. Importantly, these methodological advances in feeding methods allowed crucial vector competence assessments, standardised across countries, which can be used in disease transmission studies, bionomics and genomics experiments, thereby comprising a vital prerequisite for understanding of *Culicoides*-borne arboviruses.

To investigate existing prevalence of key *Culicoides*-borne arboviruses across our study region, the EDENext *Culicoides* group screened field collected individual *Culicoides* from virus epidemic areas. In Denmark, 200 pools of *Culicoides* (comprising 10 to 50 individuals) were screened for BTV and 300 for SBV in 2012, demonstrating high prevalence between July to September across the whole country (Rasmussen et al. 2014). Similarly, in France pools of 50 *Culicoides* were screened for SBV across the national entomological surveillance network in 2011; and in Senegal seroprevalence was assessed for nine serotypes of African Horse Sickness (AHSV), demonstrating seroprevalence of 65% for AHSV-9 and 60% for AHSV-2 based on serosurveys of donkeys in 2008 (Fall et al. 2015).

Key life history parameters were also empirically assessed for *Culicoides* vector species. Parallel studies in France, Spain and the UK investigated how fecundity, oogenesis and survival within vector species varied in relation to environmental parameters. Understanding how these life history traits vary by species and environment is a key component to building population and epidemiological models capable of predicting how orbiviruses may spread across landscapes in diverse geographic regions.

<figure><img src="image_29.png" /><figcaption>Night trapping in Denmark.
© Carsten Kirkeby, Danish Technical University</figcaption></figure>

The *Culicoides* group also combined *Culicoides* surveillance data from the UK and Spain to develop two modelling frameworks for predicting the maximum abundance and seasonal abundance of five key *Culicoides* vector taxa (*Culicoides obsoletus* complex, *C. pulicaris*, *C. imicola*, *C. impunctatus*, *C. newsteadii*) for sites across Western Europe. The first method estimated the effect of environmental covariates (wild and domestic host densities, meteorological variables and land cover) on the maximum abundance of *Culicoides* at each site. This modelling framework was used to generate predictions at new sites across Western Europe falling into similar environmental spaces as those used to train the model. The second method estimated the seasonal abundance of *Culicoides* (*C. obsoletus* complex, *C. pulicaris*, *C. imicola*, *C. impunctatus*, *C. newsteadii*) using the surveillance datasets from the UK and Spain containing weekly trapping data from the UK and Spain for approximately 400 sites spanning multiple years from 2005 to 2010. This modelling methodology was used to generate predictions of seasonal activity at new locations across Western Europe, properly accounting for uncertainty in model fitting and parameter estimates using Bayesian methods. In western Senegal, the seasonal dynamics of *Culicoides* vector species were empirically assessed and modelled. The temporal dynamics of the four dominant species, including *C. imicola* and
C. oxystoma, were analysed over 12 months (July 2011-July 2012) using horse-baited and light traps. A cross-sectional study was also conducted with the national veterinary services in Senegal to model the spatial distribution of key vector species across 108 sites and 36 districts (Diarra et al. 2014).

In the UK, the EDENext *Culicoides* group used five years of *Culicoides* surveillance data from national surveillance activities to assess how the phenology of individual species varied geographically and seasonally (Searle et al. 2014). This work demonstrated significant inter-specific differences in *Culicoides* adult phenology, the most notable of which related to the seasonal activity of one species, *Culicoides scoticus*, being approximately eight weeks shorter than that of *Culicoides obsoletus*. The work also demonstrated important species-specific differences in the length of the seasonal vector-free period (SVFP), which were related to host density and local variation in landscape habitat. There was evidence that the current treatment of *Avaritia Culicoides* as a single group in surveillance work inhibits understanding of environmentally-driven spatial variation in species phenology and hinders the development of models for predicting the SVFP from environmental factors.

Importantly, the study demonstrated that active surveillance of haematophagous female *Culicoides* vector populations cannot currently be replaced using remote environmental models of abundance. This failure was most likely related to the diverse ecology of species conflated within this taxonomic grouping. It was found that the timing of the end of the season was the most difficult to forecast, and should perhaps be treated with more caution by policy makers than the beginning of the season, because it varies widely between species, years and locations in response to environmental heterogeneity. To rectify this concern, the study recommended that intensive trapping should take place across a range of climatic zones with species-level identification of *Culicoides* females wherever feasible to facilitate more accurate detection and understanding of the start of the vector-free period in temperate zones.

## SPATIO-TEMPORAL DYNAMICS OF VBD SPREAD AND CONTROL

Within EDENext, several group members studied the effect of direct control methods on *Culicoides*. Most of the common insecticidal products authorised in the EU for use in domestic animals are based on pyrethroids. The products are used topically as pour-on solutions, which provide efficacy for at least 4-8 weeks. Other insecticides are used for dipping or spraying. To date, few attempts have been conducted to apply chemical control of *Culicoides* spp. in an area-wide approach and there is currently no veterinary product on the European market authorised for the control of *Culicoides*.

Within EDENext, we conducted coordinated research at laboratory and field level for developing standardised control methods for *Culicoides*. The main aim of this work has been to provide an evidence base for the development of control practices that will reduce the rate of biting by *Culicoides* on animals. As a result of this work, our group has provided data on resistance to insecticides, such as permethrin and deltamethrin, for *C. obsoletus* and *C. imicola* from France, Spain, Senegal and South Africa (Venail et al. 2011, 2015a, b, c). Field evaluation of the efficacy of the ZeroFly® mosquito net (a commercial deltamethrine-impregnated net) was conducted in Senegal. This experiment demonstrated that the number of *Culicoides* captured (all species combined) was not significantly different between control and treatment nets showing that the impregnated net had no significant effect on the capture, instantaneous and delayed mortality rates of *Culicoides*. However, results did vary by *Culicoides* species, with larger bodied species suffering a greater negative impact than smaller species.

The group also assessed the impact of vector control using a UK data-driven *Culicoides* mechanistic population model to explore the impact of vector control on seasonal vector abundance. This mechanistic simulation population model for *Culicoides obsoletus* explicitly links environmental variation with life-history processes, such as development time, fecundity and mortality, and predicts the seasonal abundance of adults. Mechanistic vector dynamics are important as they affect disease seasonality and are affected by environmental variability. Building upon this model framework, the group investigated the efficiency of alternative timing and intensity of vector control; focusing on a control strategy that targets host-seeking adults that come into contact with insecticide, akin to the insecticide-treated nets used for the protection of sheep and cattle and evaluated by the CBD group in Del Rio et al. (2014).
This work demonstrated that for significantly high control efficiencies (a combination of mortality rate of insects and the pro-
portion of the population that contact the treated hosts), we may eradicate the *Culicoides* population. However, for low control
efficiencies, there is only a small reduction of the average annual *Culicoides* abundance. Importantly, for intermediate control
efficiencies the average annual *Culicoides* abundance was markedly reduced but the peak autumn abundance was greatly
increased. This was because pre-adults were released from density-dependent competition due to the decrease in population
in the spring peak. As a consequence, although the control strategy had a desirable effect on the whole, the increase in peak
autumn abundance may have dramatic consequences for the reproductive value for a disease (*R*₀, the number of new disease
cases generated by one case) in this warmer period and the prevalence and seasonal persistence of midge-borne diseases.

This work also considered the seasonal timing of vector control. Here, the insecticide was present at a constant level for only a limited time in the year (50 days) and the starting day in the year at which the control window started was varied. When the control window was centred over the spring abundance peak (approximately 100th starting day), the spring peak was reduced. However, the knock-on effect was a markedly increased peak in autumn abundance. Furthermore, the mean abundance throughout the year also increased. This was in contrast to windows centred over the autumn peak, which markedly reduced the midge population in the control year but also reduced the subsequent spring population, because fewer individuals entered diapause.

In summary, vector control strategies with differing efficiencies and timing may either successfully reduce the vector population, or deleteriously increase the vector population. Control efforts should concentrate on reducing the autumn peak, as this will reduce the midge population at the peak, as well as on average through the year and in subsequent years. However, the precise timing is crucial for effective control, especially if the strategy is used year upon year, since late autumn control may increase subsequent late summer populations. Key knowledge gaps in predicting the outcome of vector control include the proportion of the adult population visiting the treated hosts in different ecological settings, the rate of decay of impact of nets or treatments on mortality as well as diapause triggers and levels of density dependent competition.

In other work, our group also considered the design of optimal prevention and control strategies for *Culicoides*-borne diseases. The independent or combined impact of vaccination and vector control on the reproductive value for a disease (*R*₀) will vary seasonally, geographically and between years with different meteorological conditions. EU Member States are presently not able to determine the necessary protective levels of vaccination cover, vector control efforts or movement restrictions based on objective calculations of *R*₀ or derived indicators for each country or ecosystem. Calculations of *R*₀ for within- and between-herd spread will allow stakeholders and Member States to adjust the intensity of preventive strategies as well as outbreak control measures to the predicted level of transmission in each country or ecosystem at various meteorological conditions.

Within EDENext, we have developed statistical and mechanistic simulation spread models simulating virus transmission within herds and between herds to facilitate the development of optimal prevention and control strategies. We developed a set of representative outbreak scenarios for various geographical areas, seasons and meteorology including average weather conditions and 90% extremes. This set of outbreak scenarios was used to run different spread models and formed the basis of the model comparison. We then identified spatial and temporal levels of vaccination and vector control that were necessary to keep R₀ below one, thereby preventing spread of the disease, which have been presented as guidelines for control of *Culicoides*-borne diseases in Europe.

Our group also assessed the effectiveness of alternative vaccination strategies on the potential spread of the Schmallenberg
virus (SBV) at the landscape scale in Scotland. Here a stochastic mathematical model of SBV spread was used to identify the
optimal method for deployment of a vaccine, under different regimes of current and changing temperatures, and in scenarios
where *Culicoides* show a marked or no preference for feeding on cattle over sheep. Targeting strategies for vaccination included
ad hoc strategies, where farmers could voluntarily take up vaccination, versus tactical strategies such as vaccination of only
cattle, only breeding replacement stock, or only in the south of the country to break the transmission chain and reduce overall
disease spread (Bessell et al. 2014). This analysis demonstrated that vaccine impact was optimised by targeting high risk areas
in the south of Scotland, or by vaccinating only cattle. Importantly, given the recent rise in average temperatures experienced in
the UK, the results demonstrated that at higher than average temperatures, and hence increased transmission potential, the re-
lative impact of vaccination was considerably enhanced. Vaccine impact was also enhanced if vectors fed preferentially on cattle.
These findings are of considerable importance when planning control strategies for SBV and also have important implications
for management of other arboviruses such as bluetongue virus. Critically, environmental determinants and feeding preferences
should be researched further to inform development of effective control strategies.

<figure><img src="image_30.png" /><figcaption>Trap</figcaption></figure>

In order to assess the effectiveness of alternative vaccination strategies in controlling the European bat
virus (EBV) outbreak in
2014 in France, we conducted a
parallel study in the Czech Republic. In this study, we investigated the effects of three different
vaccination strategies on the transmission of the European bat virus (EBV) in cattle. We compared three
vaccination strategies: one with no vector control (control group), one with vector control (vector control group), and
one with no vector control and followed by a second vaccination (second vaccination group).
<figure><img src="image_31.png" /><figcaption>Trapping in Denmark. © René B Bødker, Danish Technical University</figcaption></figure>

In other group work, we developed a spread model (Græsnøll et al. 2014) and used it to compare different preventive vaccination strategies for blue-tongue virus (BTV) in Denmark, determining that the most cost-effective vaccination strategy was to vaccinate cattle on pastures (Græsbøll et al. 2014). The group also undertook an intensive study in Denmark to quantify dispersal of vectors between farms (Kirkeby et al. 2013), a key parameter in *Culicoides*-borne disease spread models. In France, Pioz et al. (2014) investigated the effect of vaccination on the propagation of bluetongue virus based on data from the 2008 bluetongue virus serotype 1 of southwest France. The average estimated velocity across the country, despite restrictions on animal movements, was 5.4km/day, which is very similar to the velocity of spread of the bluetongue virus serotype 8 epizootic in France. In comparison to municipalities with no vaccine coverage, the velocity of BTV-1 spread decreased by 1.7km/day in vaccinated municipalities. Our findings emphasise the importance of vaccination in limiting disease spread across natural landscapes. Environmental factors, specifically those related to *Culicoides* abundance and activity, were found to be good predictors of the velocity of BTV-1 spread, indicating that these variables need to be adequately accounted for when evaluating the role of vaccination on bluetongue spread.

The CBD group also collaborated with the EMIDA VICE project to model the monthly mean abundance of *Culicoides* vectors across Western Europe. *Culicoides* surveillance data from Norway, Sweden, Denmark, Germany, Poland, Austria, Switzerland, France and Spain were used to generate the monthly outputs. These predictions were then used to generate monthly Europe-wide R₀ prediction. These outputs showed R₀ values exceeding ‘1’ for most of Europe for several months a year, suggesting that prevention and control of transmission can only be achieved when peak transmission intensity is reduced by more than 90%. As such, reductions in vector abundance or vector contact in the magnitude of 50% will only have limited impact in most areas during the peak transmission period in Europe. In

REFERENCES

Bessell et al. (2014). Impact of temperature, feeding preference and vaccination on Schmallenberg virus transmission in Scotland. *Scientific Reports* 4: 5746.

Del Rio R, Barceló C, Lucientes J, Miranda MA (2014). Detrimental effect of cypermethrin treated nets on *Culicoides* populations (Diptera: Ceratopogonidae) and non-targeted fauna in livestock farms. *Veterinary Parasitology* 199: 230–234.

Diarra M, Fall M, Fall AG, Diop A, Seck MT, Garros C, Balenghien T, Allène X, Rakotoarivony I, Lance-lot R, Mall I, Bakhoum MT, Dosum AM, Ndao M, Bouyer J and Guis H (2014). Seasonal dynamics of *Culicoides* (Diptera: Ceratopogonidae) biting midges, potential vectors of African horse sickness and bluetongue viruses in the Niayes area of Senegal. *Parasites & Vectors* 2014, 7:147 doi:10.1186/1756-3305-7-147.

Fall M, Diarra M, Fall AG, Balenghien T, Seck MT, Bouyer J, Garros C, Gimonneau G, Allène X, Mall I, Delécolle J-C, Rakotoarivony I, Bakhoum MT, Dosum AM, Ndao M, Konatè L, Faye O and Baldet T (2015). *Culicoides* (Diptera: Ceratopogonidae) midges, the vectors of African horse sickness virus – a host/vector contact study in the Niayes area of Senegal. *Parasites & Vectors* 8:39.

Græsbøll K, Enoe C, Bødker R, Christiansen LE (2014). Optimal vaccination strategies against vector-borne diseases. *Spatial and Spatio-temporal Epidemiology* 11, 153-62.

Kirkeby C, Bødker R, Stockmarr A, Lind P, Heegaard PMH (2013). Quantifying Dispersal of European *Culicoides* (Diptera: Ceratopogonidae) Vectors between Farms Using a Novel Mark-Release-Recapture Technique. *PLoS One*. Doi: 10.1371/journal.pone.0061269.

Pioz M, Guis H, Pleydell D, Gay E, Calavas D, Durand B, Ducrot C and Lancelot R (2014). Did Vaccination Slow the Spread of Bluetongue in France? *PLoS One*. 2014; 9(1): e85444. Doi: 10.1371/journal.pone.0085444.

Purse BV, Carpenter S, Venter GJ, Bellis G and Mullens BA (2015). Bionomics of Temperate and Tropical *Culicoides* Midges: Knowledge Gaps and Consequences for Transmission of *Culicoides*-Borne Viruses. *Annual Review of Entomology* 60:20.1–20.20.

Rasmussen LD, Kirkeby C, Bødker R, Kristensen B, Rasmussen TB, Belsham GJ and Bøtner A (2014). Rapid spread of Schmallenberg virus-infected biting midges (*Culicoides* spp.) across Denmark in 2012. *Transboundary Emerging Diseases* 61(1):12-6. Doi: 10.1111/tbed.12189.
conclusion, the reduction in transmission intensity needed for prevention and control of *Culicoides*-borne bluetongue virus and Schmallenberg virus in European ruminants is likely to be so high that for all practical purposes vaccination is currently the only practical solution.

## CONCLUSIONS

Research on *Culicoides* lags behind that on most other vector groups, primarily because of their minute size, the lack of colonies of primary vector species and, until recently, the relatively low impact of *Culicoides*-borne animal disease agents in developed countries.

Our work has identified techniques that can reduce *Culicoides* survival and their attack rates on livestock, however these techniques work best for species whose ecology has been well characterised. Moreover, because many regions have multiple potential vectors with widely varying ecologies and diverse habitats, many of these techniques will only be effective locally and are unlikely to control widespread outbreaks.

Long-term *Culicoides* surveillance using trapping is currently restricted to BTV-epidemic regions of Western Europe. This surveillance can track the seasonal abundance and distribution of *Culicoides* vectors aiding in the demarcation of seasonally vector free areas for relaxation of animal trade and movement restrictions. However, the current treatment of the *Avaritia Culicoides* as a single group inhibits understanding of environmentally driven spatial variation in species phenology and hinders the development of models for predicting seasonally vector free periods from environmental factors. As such, we recommend that *Culicoides* surveillance methods should be adapted to focus on concentrated assessments of species-specific abundance during the start and end of seasonal activity in temperate regions to facilitate refinement of ruminant movement restrictions, thereby reducing the impact of *Culicoides*-borne arboviruses.

There remain key knowledge gaps in relation to vectoral capacity parameters for *Culicoides*. These parameters have complex interactions that ultimately determine how diseases are spread. Improved mathematical models must be developed with empirically derived parameters from laboratory and natural environments, and confronted with empirical data from disease outbreaks to create robust and accurate models for predicting virus transmission and spread.

Finally, we know that the landscape context alters disease transmission and spread, particularly through its influence on the abundance and interactions of *Culicoides* vectors with wild and domestic hosts. For instance, short-range upwind flight of *Culicoides* has been shown to be critical in explaining epidemic spread, however an understanding of how short-range midge movements are modulated by landscape and topography is currently lacking. Similarly, recent work has implicated wild ruminant hosts as playing an important role in disease spread, however little is known about how the abundance of wild ruminants affects the behaviour and distribution of vectors.
ACKNOWLEDGEMENT

This work would not have been possible without the
dedication and commitment of all the researchers in-
volved in the *Culicoides*-borne disease group within
EDENext. We thank the following institutions:

Centre de Coopération Internationale en Recherche
Agronomique pour le Développement (CIRAD), France
Danish Technical University, Denmark

Entente Interdépartementale pour la Démoustication
du littoral méditerranéen, France

Institut Sénégalais de Recherches Agricoles, Sénégal
Institute for Food and Agricultural Research and Tech-
nology (IRTA), Spain

Natural Environment Research Council, United King-
dom

The Pirbright Institute, United Kingdom

Universitat de les Illes Balears, Spain

Searle et. al. 2014. Drivers of *Culicoides* phenology: how
important is species-specific variation in determining dis-
ease policy? *PLoS One*, November 11, 2014. Doi: 10.137.

Venail R, Mathieu B, Setier-Rio ML, Borba C, Alexandre M, Viudes G, Garros C, Allene X, Carpenter S, Baldet T (2011). Laboratory and Field-Based Tests of Deltamethrin Insecticides Against Adult *Culicoides* Biting Midges. *Journal of Medical Entomology*, Volume: 48, Issue: 2, Pages: 351-357. Doi: 10.1603/ME10178.

Venail R, Fall M, del Rio R, Talavera S, Labuschagne K, Balenghien T, Garros C, Cêtre-Sossah C, Miranda M, Pagès N, Venter G, Carpenter S and Baldet T (2015a). Insecticide susceptibility of *Culicoides* biting midges (Diptera: Ceratopogonidae): a multicentric study using a modified WHO standard assay, *Parasites & Vectors*, in review.

Venail R, Lhoir J, Rakotoarivony I, Allène X, Setier-Rio ML, Scheid B, Gardes L, Gosset A, Lancelot R, Gimonneau G, Garros C, Balenghien T, Carpenter S and Baldet T (2015b). Insecticide susceptibility of *Culicoides* biting midges (Diptera: Ceratopogonidae) in France, *PLoS One*, in review.

Venail R, Balenghien T, Carpenter S and Baldet T (2015c). Assessment of the efficiency of insecticide formulations against *Culicoides* biting midges (Diptera: Ceratopogonidae) using a novel approach. *Vet Parasitology*, in review.
PUBLICise Health Public Health
Telegram: *Culicoides*-borne
diseases

EDENext's Public Health Telegrams (PUBLICise Health) were established to inform interested individuals and institutions about research results on vector-borne diseases with direct or indirect impact on Public Health issues. Edited and produced by EDENext's Public Health team, each issue concentrates on the work of one of the project's five specialist groups. Here we present an updated version of the issue dedicated to the work of the team examining *Culicoides*-borne diseases, first published in August 2014.

1. The impact of biting midges
on human Public Health in Europe

The EDENext study by Carpenter et al. (2013) considers the impact of biting midges of the genus *Culicoides* on human health in Europe. Special focus is placed on their potential for transmitting human pathogenic arboviruses. To date, the only arboviruses identified as being primarily transmitted by *Culicoides* between humans are Oropouche virus (OROV) and the Iquitos virus (IQTV), although the latter has not yet been confirmed. These two members of the family *Orthobunyaviridae* cause major epidemics of febrile illness in human populations of South and Central America and the Caribbean. The authors describe factors promoting sustained outbreaks of OROV in Brazil from an entomological perspective and assess areas of the epidemiology of this arbovirus that are currently poorly understood, but may influence the risk of incursion into Europe. Additionally, evidence implicating *Culicoides* in the transmission of other zoonotic infections is examined and placed in context with the presence of other vector groups in Europe.

Carpenter S, Groschup MH, Garros C, Felippe-Bauer ML and Purse BV (2013). *Culicoides* biting midges, arboviruses and public health in Europe. *Antiviral Res.* 2013 Oct; 100(1):102-13. Doi: 10.1016/j.antiviral.2013.07.020. Epub 2013 Aug 8.

2. Leishmania vector competence
of biting midges

Leishmaniases are diseases caused by various
species of the trypanosomatid protozoa genus
*Leishmania*. They can cause various symptoms,
ranging from a cutaneous form that leads to
cutaneous ulcera at the bite site to a highly
pathogenic visceral form. Millions of human
cases are reported from Asia, Africa, South
and Central America as well southern Europe
every year. Female biting sand flies of the ge-
nus *Phlebotomus* in the Old World or *Lutzomyia*
in the New World are currently the only known
vectors of *Leishmania* sp. Recent observations
of Australian midges transmitting Leishmania
may indicate that biting midges might also play
a role as potential vectors. To investigate
this theory, Seblova et al. (2012) experimen-
tally infected the colonized biting midge spe-
cies *Culicoides nubeculosus* with two human pa-
thogenic *Leishmania* species (*L. infantum* and
major). An early stage of *Leishmania* develop-
ment was demonstrated in the midge mid-gut un-
til two days after feeding, but a subsequent
loss of parasites occurred indicating that
*C. nubeculosus* is unlikely to act as a compe-
tent vector.

Seblova V, Sadlova J, Carpenter
S and Volf P (2012). Develop-
ment of *Leishmania* parasites
in *Culicoides nubeculosus* (Dip-
tera: Ceratopogonidae) and im-
plications for screening vector
competence. *J Med Entomol.*
2012 Sep; 49(5):967-70.

**3. Culicoides biology and ecology in Senegal**

A major area of research in EDENext has been
in conducting the first systematic surveys of
*Culicoides* in Senegal using a wide range of
monitoring techniques. In addition to provi-
ding detailed phylogenetic analyses (Bakhoum
et al. 2013) both spatial and temporal surveys
of *Culicoides* on livestock were successful-
ly completed in a region where African horse
sickness virus is of high epidemiological im-
portance (Fall et al. 2015a; Fall et al. 2015b;
Fall et al. 2015c; Fall 2015d; Diarra et al.
2014; Diarra et al. 2015). These studies are
also of Public Health interest in providing
baseline data regarding *Culicoides* populations
and their overlap with human populations. In
some areas of central Africa, certain biting
midge species may act as a huge nuisance for
human populations and are able to transmit
human filarial nematodes. It is highly likely
that future studies will examine the impact of
*Culicoides* in transmission of human pathoge-
nic arboviruses within Africa following the
implementation of virus discovery via next-
generation sequencing and these studies pro-
vide a strong baseline for these approaches.

Bakhoum MT, Fall M, Fall AG, Bellis GA, Gottlieb Y, et al. (2013). First Record of *Culicoides oxystoma* Kieffer and Diversity of Species within the Schultzei Group of *Culicoides* Latreille (Diptera: Ceratopogonidae) Biting Midges in Senegal. *PLoS ONE* 8(12): e84316. Doi: 10.1371/journal.pone.0084316.

Fall M, Diarra M, Fall AG, Balenghien T, Seck MT, Bouyer J, Garros C, Gimonneau G, Allène X, Mall I, Delécolle J-C, Rakotoarivony I, Bakhoum MT, Dusom AM, Ndao M, Konaté L, Faye O and Thierry Baldet T (2015). *Culicoides* (Diptera: Ceratopogonidae) midges, the vectors of African horse sickness virus - a host/vector contact study in the Niayes area of Senegal. *Parasites & Vectors* 2015, 8:39. Doi: 10.1186/s13071-014-0624-1.
Fall M, Fall A, Seck MT, Bouyer J, Diarra M, Balenghien T, Garros C, Bakhoum MT, Faye O, Baldet T and Gimonneau G (2015). Circadian activity of *Culicoides oxystoma* (Diptera: Ceratopogonidae), potential vector of bluetongue and African horse sickness viruses in the Niayes area, Senegal. *Parasitology Research*, 2015, 1-8.

Fall M, Fall A, Seck M, Bouyer J, Diarra M, Lancelot R, Gimonneau G, Garros C, Bakhoum M, Faye O, Baldet T and Balenghien T (2015). Host preferences and circadian rhythm of *Culicoides* (Diptera: Ceratopogonidae), vectors of African horse sickness and bluetongue viruses in Senegal. *Acta Tropica*, 2015 *149*:239-245.

Fall, M (2015). Ecologie et lutte contre les *Culicoides* vecteurs de la peste équine et de la fièvre catarrhale ovine au Sénégal (PhD thesis). Université Cheikh Anta Diop de Dakar, école doctorale Sciences de la Vie, de la Santé et de l'Environnement, Faculté des Sciences et Techniques.

Diarra M, Fall M, Fall AG, Aliou Diop A, Seck MT, Garros C, Balenghien T, Allène X, Rakotoarivony I, Lancelot R, Mall I, Bakhoum MT, Dosum AM, Ndao M, Bouyer J and Guis H (2014). Seasonal dynamics of *Culicoides* (Diptera: Ceratopogonidae) biting midges, potential vectors of African horse sickness and bluetongue viruses in the Niayes area of Senegal. *Parasites & Vectors* 2014, 7:147. Doi: 10.1186/1756-3305-7-147.

Diarra M, Fall M, Lancelot L, Diop A, Fall A, Ahmadou D, Seck MT, Garros C, Allene X, Rakotoarivony I, Bakhoum MT, Bouyer J and Guis H (2015). Modelling the abundances of two major *Culicoides* (Diptera: Ceratopogonidae) species in the Niayes area of Senegal. *PLoS ONE*, 10, e0131021.
<figure><img src="image_32.png" /></figure>

EXAMPLES
OF EDEN AND
EDENEXT IMPACTS
Renaud Lancelot<fnref n="1" />,<fnref n="2" />, Neil Alexander<fnref n="3" />, Els Ducheyne<fnref n="3" />, Guy Hendrickx<fnref n="3" />, Heikki Henttonen<fnref n="4" />, David J. Rogers<fnref n="5" />, William Wint<fnref n="3" />

## INTRODUCTION

In this chapter we provide information regarding the impacts, in other words the consequences, of the implementation of EDEN and EDENext, both on the targeted scientific community and on the more general public, in other words citizens in countries where these projects conducted their activities.

## ACADEMIC IMPACT

For research projects, important impact indicators are the number and quality of articles published in international, peer-reviewed journals. In this respect, EDEN and EDENext have been quite successful, with 470 papers released as of mid-June 2015, and 100 more papers already submitted and awaiting publication. Moreover, the quality of these papers fully complies with international standards: indeed, their median impact factor<fnref n="1" /> is 3.1 (fig. 1), with an inter-quartile range of [2.4; 3.5], and outliers of up to more than 40 (Bhatt et al. 2013).

Though EDEN ran for a longer time than EDENext, these statistics noticeably improved from the former to the latter. For example, the number of papers rose from 207 to 263, and their median impact factor<fnref n="1" /> increased from 2.6 to 3.3: good progress.

The most used journals are shown in Figure 2a. While the two most popular journals (Parasites & Vectors and Vector-Borne and Zoonotic Diseases, totalling more than 16% of published papers) are specialised in the domain of vectors and vector-borne infections, this is not the case for many of the others. Indeed, journals from the PLoS family, as well as Eurosurveillance and Emerging Infectious Diseases, are more general in their scope, with a strong orientation towards Public Health in the case of the latter two. This is a first indication of the special effort made by scientists involved in EDEN and EDENext to have a positive impact on Public Health.

In this respect, the most important findings with an actual or potential effect on Public Health are outlined in the vector group sections of this book. Figure 3 presents a brief summary of the topics covered by EDEN and EDENext papers. These two panels were produced using the word cloud method employed by sociologists to summarise focus group discussions. It was used by the EDENext Public Health group for their work on hantavirus risk perception among high-risk populations (for example, forestry workers) (Dressel and Schülle 2014). Figure 3a emphasises that the transmission of vector-borne infections in animal and human populations

<figure><img src="image_33.png" /><figcaption>Figure 1. Distribution of impact factors for papers approved by EDEN and EDENext steering committees</figcaption></figure>

was mainly from African only. Figure 2a shows the TBEV impact factor in TBEV-endemic countries from 2008 to 2014.

V

Figur

sees the tick. Other data are from a rodent

<footnote n="1">¹ CIRAD, UMR CMAEE, Montpellier, France</footnote>

<footnote n="2">² INRA, UMR 1309 CMAEE, Montpellier, France</footnote>

<footnote n="3">³ Euro-Aegis, Zoersel, Belgium</footnote>

<footnote n="4">⁴ Natural Resources Institute Finland, Vantaa, Finland</footnote>

<footnote n="5">⁵ University of Oxford, Oxford, United Kingdom</footnote>

<footnote n="1">¹ Metric available on Thomson Reuters' Web of Science</footnote>
was addressed in many papers. Indeed, most vector-borne infections are zoonotic, in other words common to animals and humans. The most cited pathogens belong in this category: hantaviruses, tick-borne encephalitis virus (TBEV), West Nile virus and some *Leishmania* species (for example, *L. infantum*). Moreover, though many publications focused on European ecosystems, Africa is well represented too. For instance, Senegal is involved in 18 papers and Morocco in 12, though the latter country was only represented in EDEN.

Figure 3b shows the words that better differentiate EDEN and EDENext. In EDEN, major attention was paid to hantaviruses and TBEV. For the latter, major advances were made in understanding its epidemiology. For instance, a brilliant demonstration was made by the tick group, led by Sarah Randolph (University of Oxford), showing that climate change could not explain the upsurge of TBE in Baltic countries (Sumilo et al. 2007). Instead, this upsurge was largely a consequence of the socio-economic transition from communism to capitalism and associated environmental changes (Godfrey and Randolph 2011). However, many concerns arose at the same time regarding the emergence of tick-borne pathogens, such as Crimean-Congo haemorrhagic fever virus (Randolph and Rogers 2010), and several *Anaplasma*, *Babesia*, *Bartonella*, *Borrelia*, or *Rickettsia* species (among many others

<figure><img src="image_34.png" /><figcaption>Figure 2. Top 10 journals used by EDEN and EDENext authors</figcaption></figure>

see, for example, Carpi et al. 2011). Therefore, when preparing EDENext, it was decided to place an emphasis on these emerging tick-borne pathogens. The research consortium was then altered to reflect this new orientation.

Other changes in the research scope explain the different word cloud patterns between EDEN and EDENext. Regarding rodent-borne pathogens, the acquired knowledge was capitalised upon and disseminated in high-profile journals (Goeijenbier et al. 2013, Vaheri et al. 2013). In addition, the rodent group wanted to further explore the range of pathogens transmitted by rodents and less emphasis was put on hantaviruses.
Also, at the end of EDEN, we decided to stop research on the risk of malaria re-emergence in the Mediterranean Basin. Indeed, this (rather small) EDEN sub-project was quite productive, with 33 papers. The main conclusion was that though the *Anopheles* vectors are still there (so-called ‘anophelism without malaria’) the risk of malaria re-emergence is low, provided that Public Health efforts are maintained for the quick detection of autochthonous malaria cases and the adoption of appropriate measures to break the cycle in humans (epidemiological surveys and treatment of cases) and vector populations.

Some changes were also implemented in the Phlebotomine sand fly group, reorienting researches on the *Leishmania* transmission mechanisms – particularly the role of sand fly saliva (11 papers on this topic), and extending the scope of pathogens to Phleboviruses. The group was very productive, with (i) 65 publications on sand flies, *Leishmania* transmission and implications for Public Health – see, for example, Antoniou et al. 2013, Gramiccia et al. 2013, Ntais et al. 2013, and (ii) 11 publications on Phleboviruses – see, for example, Alkan et al. 2013 for a review.

Finally, a new vector group was added in EDENext: *Culicoides* biting midges, responsible for the transmission of bluetongue and African horse sickness viruses, as well as the newly emerged Schmallenberg virus. Though this group did not benefit from the 'EDEN-momentum' effect, its scientific productivity was impressive in both quality and quantity, producing 36 publications, including six for work implemented in Senegal. Moreover, many of these papers had a high impact factor, and two of them even fell into the outstanding category (Hartemink et al. 2014, Purse et al. 2015).

NETWORKING AND EXPERTISE

Improved networking is another major impact of EDEN and EDENext. We have clear evidence of this positive impact, at different levels. The first one is provided by examining the network of institutions linked by common scientific publications (Figure 4). The network looks very compact with a highly skewed distribution of degrees (number of links connecting a given institution to others).

<figure><img src="image_35.png" /><figcaption>Figure 3. Word clouds for EDEN and EDENext publications</figcaption></figure>

<figure><img src="image_36.png" /></figure>

This distribution of degrees is characteristic of a scale-free network, which is known to provide an optimal pattern for knowledge transfer (Lin and Li 2010). Therefore, institutions at the heart of the network (coloured dots in Figure 5) are in a very good position to transfer knowledge and skills to their partners in the network.

More evidence is provided by the observed changes in network indices (number of institutions, number of links, degrees, closeness, betweenness) between EDEN and EDENext (Figure 6). All these indices show a sharp increase: networking was more intense after 10 years of projects, with an obvious snowball effect aggregating many more research and Public Health institutions than those which actually received funds from the Commission in the framework of EDEN and EDENext. For instance,

<figure><img src="image_37.png" /></figure>

<footnote n="2">² http://vec</footnote>

<footnote n="3">³ De</footnote>
eed,
eles
ublic
purposes to
make public
ations on
health in the
era of the
epidemic from
pions,
even

344 institutions were involved in the network presented in Figure 4, while only 58 institutions were funded in EDENext.

Beyond research, this network was formalised and utilised to provide expertise at the European level. A 'European Network for Arthropod Vector Surveillance for Human Public Health' (VBORNET) was set up and funded by the European Centre for Disease Prevention and Control (ECDC, Stockholm), bringing together 400 medical entomologists and Public Health specialists in vector-borne infections. It was coordinated by AVIA-GIS (Belgium) during its existence between 2009 and 2014. The network was used to collect, validate and map data regarding the present distribution of main vector species of Public Health interest. Thus, maps were produced for five invasive mosquito species (Figure 6), seven endemic mosquito species, six tick species, and 10 Phlebotomine sand fly species. They are available on the ECDC website<fnref n="2" />.

<figure><img src="image_38.png" /></figure>

Figure 4. The EDENext network of research institutions according to their affiliations in joint publications (April 2015). Institutions are represented by dots (they are not all EDENext beneficiaries). Line segments show the links between two institutions co-signing an EDENext paper. The degree is the number of links connecting a given institution to others. Institutions with the highest degrees are labelled and represented by coloured dots. The histogram on the bottom left of the network shows the distribution of degrees.

<figure><img src="image_39.png" /></figure>

Definitions 3:

Closeness: an important insti-
tution (node) is typically 'close'
to, and can communicate qui-
ckly with, the other nodes in
the network. Betweenness: an
important node lies on a high
proportion of paths between
other nodes in the network.

Figure 5. Changes in institution network indices between EDEN (reference situation) and EDENext

REFERENCES

Alkan C, Bichaud L, De Lamballerie X, Alten B, Gould E and Charrel R (2013). Sandfly-borne phleboviruses of Eurasia and Africa: epidemiology, genetic diversity, geographic range, control measures. *Antiviral Research*, 100(1):54–74.

Antoniou M, Gramiccia M, Molina A, Dvorak V and Volf P (2013). The role of indigenous phlebotomine sandflies and mammals in the spreading of leishmaniasis agents in the Mediterranean region. *Eurosurveillance*, 18(30):pii:20540.

Bhatt S, Gething P, Brady O, Messina J, Farlow A, Moyes C, Drake J, Brownstein J, Hoen A, Sankoh O, Myers M, George D, Jaenisch T, Wint G, Simmons C, Scott T, Farrar J and Hay S (2013). The global distribution and burden of dengue. *Nature*, 496(7446):504–507.

Braks M, Medlock J, Hubalek Z, Hjertqvist M, Per-
rin Y, Lancelot R, Ducheyne E, Hendrickx G, Stroo
A, Heyman P and Sprong H (2014). Vector-borne
disease intelligence: Strategies to deal with di-
sease burden and threats. *Frontiers in Public
Health*, 2(280).

Carpi G, Gagnacci F, Wittekindt N, Zhao F, Qi J, Tomsho L, Drautz D, Rizzoli A and Schuster S (2011). Metagenomic profile of the bacterial communities associated with *Ixodes ricinus* ticks. *PLoS ONE*, 6(10):e25604.

Diarra M (2015). Modélisation de la dynamique
temporelle et de la distribution spatiale des Cu-
licoides (Diptera: Ceratopogonidae) au Sénégal
[Modelling the dynamics and spatial distribu-
tion of Culicoides (Diptera: Ceratopogonidae) in
Senegal]. PhD thesis, Université Gaston Berger
de Saint-Louis du Sénégal, Ecole Doctorale des
Sciences et des Technologies, UFR de Sciences
Appliquées et de Technologie. 152 p.

Diouf N (2013). Potentiel rôle épidémiologique du Delta du fleuve Sénégal et impact des arboviroses dans la population équine : cas de la fièvre West Nile et de la peste équine [Potential epidemiological role of the Senegal River Delta and arthropod-borne-virus impacts within the horse population: case of West Nile fever (WNF) and African horse sickness (AHS)]. PhD thesis, Université Cheikh Anta Diop de Dakar - Ecole Doctorale Sciences de la Vie, de la Santé et de l'environnement (ED-SEV) Ecole Inter-Etats des Sciences et Médecine Vétérinaires de Dakar. 188 p.

Dressel K and Schülle S (2014). Using word clouds for risk perception in the field of public health - the case of vector-borne diseases. GRF Davos Planet@Risk, 2(2):85–88.

<footnote n="2">² http://www.ecdc.europa.eu/en/healthtopics/vectors/vector-maps/Pages/vector-maps.aspx</footnote>

<footnote n="3">³ Definitions: https://sites.google.com/site/networkanalysiscourse/home</footnote>
<figure><img src="image_40.png" /><figcaption>Figure 6. Distribution maps of invasive mosquito species Aedes albopictus in Europe in June 2010 (left) and January 2015 (right)</figcaption></figure>

VBORNET has now been superseded by the 'European network for sharing data on the geographic distribution of arthropod vectors, transmitting human and animal disease agents' (VectorNet) – still coordinated by AVIA-GIS. VectorNet has a wider scope than VBORNET, encompassing medical and veterinary Public Health and economics in the same domain. It is being co-funded by ECDC and the European Food Safety Authority (EFSA) over a four-year period (2014-2018). Its geographical scope is wider, now including the whole Mediterranean Basin. It also includes vectors of veterinary importance, such as *Culicoides* biting midges.

Products of these networks are now routinely used by ECDC, EFSA and national Public Health or veterinary services to write review papers (see, for example, Braks et al. 2014, Medlock et al. 2013, Medlock et al. 2012), to feed risk analyses and, more generally, to provide information for better control of vector-borne epidemics and epizootics, with a clear 'One Health' perspective.

## CAPACITY BUILDING

During EDEN and EDENext, a PhD network was established and PhD meetings were organised during each annual general meeting. On average, each of these PhD meetings was attended by around 20-30 PhD students and post-docs. These young scientists thus had the opportunity to present and discuss their work with their peers, with the gracious support of senior scientists providing constructive criticism.

Moreover, training courses were organised each year, in particular on the basic and advanced uses of geographical information systems, and spatial epidemiology and species distribution modelling (face-to-face training courses plus distance learning). Also, several workshops were organised on mathematical modelling. Finally, each vector group organised training sessions for field data collections, morphological and genetic identification of vectors, diagnostic methods, etc. Overall, we estimate that around 100 PhD students were fully or partially supported by the project, including 28 who received an EDEN (13) or EDENext (15) number for their PhD dissertation (as of June 2015).

This capacity building aspect of impact is of special importance for developing countries. Thus, we made a special effort for Senegal: four PhDs have already been obtained (Diarra 2015, Diouf 2013, Fall 2013, Fall 2015), and another (Mame T. Bakhhoum) will be defended by the end of 2015. Among them, Maryam Diarra obtained the joint best poster award at the GERI 2015 International Conference (among more than one hundred competitors). Among these five Senegalese PhD students, two of them obtained a permanent position at ISRA (Dakar) after their PhD contract: Assane Fall as a medical entomologist, and Maryam Diarra as an epidemiologist. Moreover, another has already been hired by the Directorate of Veterinary Services (Nicolas Diouf). Similar successes were obtained in Morocco and Turkey.
## SOCIO-ECONOMIC IMPACT

This kind of impact is the most difficult to assess, because EDEN and EDENext were not designed to have a direct socio-economic impact. However, there were at least two areas where this impact is noticeable and might be evaluated:

* **Employment:** as indicated above, about 100 PhD positions were partially or totally supported by EDEN and EDENext, including 45 in the latter. Moreover, many post-doc positions were at least partially funded by the project (a minimum of 10 for EDENext). Finally, many of these PhD students and post-docs have found a permanent position with a direct link to their work in these projects. We'll give just two examples in cases where we could trace the information back:

- Four PhD students were hired within the framework of the EDEN modelling group: all of them now have a permanent position in universities or Public Health agencies, after a few post-doc positions in excellent teams. For example, Catherine Linard completed a brilliant PhD in Louvain University (Belgium), with several very good papers (Linard et al. 2007a, Linard et al. 2009a, Linard et al. 2009b, Linard et al. 2007b, Tersago et al. 2008, Tran et al. 2008). She is now hired at Namur University (Belgium) after a post-doc at the University of Oxford (Tatem and Linard 2011).

- In Senegal, out of four students who defended their PhD thesis between 2013 and 2015, three now have permanent positions, two at the national agronomic research institute (ISRA) and one at the Directorate of Veterinary Services.

* **Technologies with commercial potential:**

- Diagnostic tests, such as the competition ELISA for CCHFV antibodies, designed and developed by several EDENext beneficiaries with FLI (Germany) as a leader and IdVet (France) as an SME associated with the project (Mertens et al. 2015).

- Integrated information systems such as Vecmap™, a spatial decision support system for targeted vector surveillance and control, designed and developed by several EDEN and EDENext beneficiaries and MEDES (Toulouse, France), led by AVIA-GIS, and co-funded by the European Space Agency. Vecmap is now routinely used in research projects (Ducheyne et al. 2015) and expertise networks such as VectorNet.

## ACKNOWLEDGEMENT

*We would like to thank Emilie Chirouze, Nicole Iltis and Marie-Christine Lambert, CIRAD-DIST, Montpellier, France, for their invaluable help in the bibliometric analysis.*

Ducheyne E, Charlier J, Vercruysse J, Rinaldi L, Biggeri A, Demeler J, Brandt C, de Waal T, Selemetas N, Höglund J et al. (2015). Modelling the spatial distribution of *Fasciola hepatica* in dairy cattle in Europe. *Geospatial health*, 9(2):261–270.

Fall A (2013). *Ecology of arboviruses in Senegal: example of West Nile virus in the Senegal River Delta and the Ferlo*. Entomology, University Cheikh Anta Diop, Faculty of Science and Technology, Doctoral School: Life Sciences, Health and Environment, Dakar.

Fall M (2015). *Ecologie et lutte contre les Culioides vecteurs de la peste équine et de la fièvre catarrhale ovine au Sénégal*. PhD thesis, Université Cheikh Anta Diop de Dakar, école doctorale Sciences de la Vie, de la Santé et de l'Environnement, Faculté des Sciences et Techniques.

Godfrey E and Randolph S (2011). Economic downturn results in tick-borne disease upsurge. *Parasites & Vectors*, 4(1):35.

Goelijbenier M, Wagenaar J, Goris M, Martina B, Henttonen H, Vaheri A, Reusken C, Hartskeerl R, Osterhaus A and Van Gorp E (2013). Rodent-borne hemorrhagic fevers: under-reognized, widely spread and preventable - epidemiology, diagnostics and treatment. *Critical Reviews in Microbiology*, 39(1):26–42.

Gramiccia M, Scalone A, Di Muccio T, Orsini S, Fiorentino E and Gradoni L (2013). The burden of visceral leishmaniasis in Italy from 1982 to 2012: a retrospective analysis of the multi-anual epidemic that occurred from 1989 to 2009. *Eurosurveillance*, 18(29):pii=20535.

Hartemink N, Vanwambeke S, Purse B, Gilbert M and Van Dyck H (2014). Towards a resource-based habitat approach for spatial modelling of vector-borne disease risks. *Biological Reviews of the Cambridge Philosophical Society*.

Lin M and Li N (2010). Scale-free network provides an optimal pattern for knowledge transfer. *Physica A: Statistical Mechanics and its Applications*, 389(3):473–480.

Linard C, Lamarque P, Heyman P, Ducoffre G, Luyasu V, Tersago K, Vanwambeke S and Lambin E (2007a). Determinants of the geographic distribution of Puumala virus and Lyme borreliosis infections in Belgium. *International Journal of Health Geographics*, 6:15.

Linard et al., 2009a; Linard C, Ponçon N, Fontenille D and Lambin E (2009a). A multi-agent simulation to assess the risk of malaria re-emergence in southern France. *Ecological Modelling*, 220:160–174.

<figure><img src="image_41.png" /></figure>

<figure><img src="image_42.png" /></figure>

<figure><img src="image_43.png" /></figure>

<figure><img src="image_44.png" /></figure>
Linard C, Ponçon N, Fontenille D and Lambin E (2009b). Risk of malaria re-emergence in southern France: testing scenarios with a multiagent simulation model. *EcoHealth*, May 2009:1–13.

Linard C, Tersago K, Leirs H and Lambin E (2007b). Environmental conditions and Puumala virus transmission in Belgium. *International Journal of Health Geographics*, 6(1):1–15.

Medlock J, Hansford K, Bormane A, Derdakova M, Estrada-Pena A, George J-C, Golovljova I, Jaenson T, Jensen J-K, Jensen P, Kazimirova M, Oteo J, Papa A, Pfister K, Plantard O, Randolph S, Rizzoil A, Santos-Silva M, Sprong H, Vial L, Hendrickx G, Zeller H and Van Bortel W (2013). Driving forces for changes in geographical distribution of *Ixodes ricinus* ticks in Europe. *Parasites & Vectors*, 6(1):1.

Medlock JM, Hansford KM, Schaffner F, Versteirt V, Hendrickx G, Zeller H and Bortel WV (2012). A review of the invasive mosquitoes in Europe: ecology, public health risks, and control options. *Vector Borne Zoonotic Dis.*, 12(20):1–13.

Mertens M, Vatansever Z, Mrenoshki S, Krstevski K, Stefanovska J, Djadjovski I, Cvetkovikj I, Farkas R, Schuster I, Donnet F, Comtet L, Torido N, Ben Mechlia M, Balkema-Buschmann A, Mitrov D and Groschup M (2015). Circulation of Crimean-Congo hemorrhagic fever virus in the Former Yugoslav Republic of Macedonia revealed by screening of cattle sera using a novel enzyme-linked immunosorbent assay. *PLoS Neglected Tropical Diseases*, 9(3):e0003519.

Ntais P, Sifaki-Pistola D, Christodoulou V, Messaritakis I, Pratlong F, Poupalos G and Antoniou M (2013). Leishmaniases in Greece. *The American Journal of Tropical Medicine and Hygiene*, 89(5):906–915.

Purse B, Carpenter S, Venter G, Bellis G and Mullens B (2015). Bionomics of temperate and tropical *Culicoides* midges: knowledge gaps and consequences for transmission of *Culicoides*-borne viruses. *Annual Review of Entomology*, 60(1):373–392. PMID: 25386725.

Randolph S and Rogers D (2010). The arrival, establishment and spread of exotic diseases: patterns and predictions. *Nature Reviews Microbiology*, 8:361–371.

Sumilo D, Asokliene L, Bormane A, Vasilenko V, Golovljova I and Randolph S (2007). Climate change cannot explain the upsurge of tick-borne encephalitis in the Baltics. *PLoS ONE*, 2(6):e500.

Tatem A and Linard C (2011). Population mapping of poor countries. *Nature*, 474(7349):36.

Tersago K, Schreurs A, Linard C, Verhagen R, Van Dongen S and Leirs H (2008). Population, environmental, and community effects on local bank

vole (*Myodes glareolus*) Puumala virus infection in an area with low human incidence. *Vector-Borne and Zoonotic Diseases*, 8(2):235–244.

Tran A, Ponçon N, Toty C, Linard C, Guis H, Ferre J, Lo Seen D, Roger F, de La Rocque S, Fontenille D and Baldet T (2008). Using remote sensing to map larval and adult populations of *Anopheles hyrcanus* (Diptera: Culicidae) a potential malaria vector in Southern France. *International Journal of Health Geographics*, 7(1):1–9.

Vaheri A, Strandin T, Hepojoki J, Sironen T, Henttonen H, Mäkela S and Mustonen J (2013). Uncovering the mysteries of hantavirus infections. *Nature Reviews Microbiology*, 11(8):539–550.

<figure><img src="image_45.png" /></figure>

innovative research

Research data for free

Anonymised, citable, provenance records of all datasets, regardless of whether they conform to a particular standard or are part of a digital library
## Sharing scientific data:
1+1=3

Els Ducheyne<fnref n="1" />, William Wint<fnref n="2" />,
Neil Alexander<fnref n="2" /> and Guy Hendrickx<fnref n="1" />

### INTRODUCTION

"Should publicly funded data be publicly available?" According to the Science Ministers of the OECD, including most developed countries of the world, this should be the case. These Ministers signed a declaration which essentially states that all publicly funded archive data should be made publicly available (oecd.org 2004) and that there is a need for coordinated efforts at national and international level to broaden access to data from publicly funded research to the advancement of scientific research and

innovation. EDEN and EDENext are both examples of publicly funded projects which demonstrated that sharing data does indeed result in the advancement of research and technological innovation. Here we discuss why these two projects succeeded in bringing the data and scientists together, we describe the added value of some of the EDEN and EDENext legacy projects, and demonstrate that this does lead to new innovative products.

### WAYS TO ENABLE DATA SHARING

Researchers are often wary of data sharing, especially before publication. There are, however, a number of ways in which data can be shared without endangering publication rights. Firstly, data summaries rather than raw results can be provided, for example, for geo-referenced data administrative unit data rather than individual point information. Alternatively, a number of individual datasets can be used to produce a spatial distribution model, but only the model output is shared, rather than the training data that underpin it. An output model based on multiple datasets is likely to be better than one based on a single set of inputs, so all contributors benefit.

Another possibility is to set up a web-based archive, as exemplified by the EDEN and EDENext data sites. The technical justifications for a shared data platform, managed by data management specialists, are primarily standardisation, quality control, improved access and efficiency. One example of standardisation is typified by the diversity of human population datasets available. There are a number of authoritative sources of such data: UNPOP (Feeney 2015), Worldpop (worldpop.org.uk 2015), GRUMP (sedac.ciesin.columbia.edu 2015), Landscan (web.ornl.gov 2015), or even national censuses, all of which are updated on a regular basis. Each dataset will have slightly different numbers, different dates, different spatial and/or temporal resolutions, and consequently provide different denominators for calculation of variables such as disease incidence. If each project member uses a different denominator dataset, then individual results cannot be easily compared. Similar arguments apply to almost every kind of data: land use, satellite imagery and climate, to name but a few.

Two of the justifications for shared data platforms - quality control and improved access - are linked. Specialists are more able to find obscure sources of data and are more likely to be able to translate the sometimes arcane formats in which they are stored into something that non-specialists can deal with. During the processing needed to translate or standardise the acquired files, the specialist can also make sure the data are clean and any errors flagged or corrected. Finally, efficiency is a key factor: centralised preparation and sharing means the processing and acquisition need only be done once as opposed to each researcher doing the same thing themselves. This saves time and resources.

<footnote n="1">¹ Avia-GIS, Risschotlei 33, 2980 Zoerset, Belgium</footnote>

<footnote n="2">² Environmental Research Group Oxford,
Department of Zoology, University
of Oxford, United Kingdom</footnote>
A more indirect way of 'sharing' data is to provide annotated lists of links indicating where data can be found. It should be noted that there are many such lists, but EDENext data is one of the most comprehensive with more than 1,500 such links, and indeed the links are the site's most visited pages.

Other platforms for data sharing are the emerging data journals and data repositories. The principle behind these is that datasets - from as little as numbers underlying graphs or maps in a publication to model outputs and to full-blown data archives - are deposited in an online open access repository, along with descriptive metadata describing the data and the methods used to generate them. This is then assigned a digital object identifier (DOI) and a citable reference with assigned authorship, in the same way as a scientific journal publication. One of the major advantages of this new way to publish is that, though the metadata document is peer reviewed, it is much quicker to produce than a full publication, because only production methods and descriptions are required and so there is no need to analyse the data or present discussions and conclusions. Further, it is perfectly acceptable to publish non-validated or negative data (which is almost impossible to publish in a research paper) provided that the metadata document accurately describes the datasets and any limitations.

The advantages of these data publications are obvious: they are easier to produce than full publications; even incomplete datasets can be given a citable reference as a publication; when the data are used they must be acknowledged in the references (no more 'Smith unpublished' or 'Jones pers comm'); they can be included as publications in a CV; they can be published prior to analyses, and, indeed, even if the analyses fail; they do not preclude publishing full papers using the data; and, of course, they allow access to the data by other researchers. The impact factors of these journals are admittedly low, certainly at the moment as these journals are not yet widely known. However, with the launch of Nature's new Scientific Data (Avants et al. 2014) it seems likely that their profile (and associated impact) will now start to increase quite rapidly.

## SHARED DATA: OWNERSHIP, ACCESS AND SECURITY

An important element of data sharing at any level is that the data owners are confident that they know to whom their data is being given, and that they get due credit or acknowledgement. This relies on access to the data being managed or controlled in some way, most often by implementing some sort of user registration with user access permissions set for each dataset. This allows, for example, some datasets to be available to all registered users, whilst others are restricted to particular user groups. This arrangement is another argument for centralised data archives as potential users can be screened for access, or put directly in touch with data owners to request access. The data providers therefore retain ownership and control of their data and can, for example, decide whether direct competitors are to be given their data, and if so can negotiate the conditions under which such access is granted. Demonstrably retained ownership enhances trust in the system and promotes further sharing.

## WHY DID IT WORK FOR EDEN AND EDENEXT?

EDEN and EDENext both promoted scientific collaboration at a multi-disciplinary and cross-country level. The framework was ambitious, bringing together a wide variety of scientists from different disciplines and across Europe. What was even more ambitious was to convince them to share the data and to have a commercial company host this platform.

Sharing was not only via personal interaction and capacity building, but also on a more practical level: sharing of scientific data on a common platform now amounting to more than 2,000 datasets. At the onset of EDEN the idea of data sharing seemed frightening to some, idealistic to others, while at the end of EDENext it is accepted as normal.

Seeing other partners open up their historic databases collected for various scientific purposes, ranging from molecular research to spatial modelling, inspired others to do the same thing. Trust was built within the network creating an atmosphere where people were comfortable to discuss, share and publish together. Just looking at the number of papers published (388 submitted EDENext papers up to the end of June 2015, and 269 from EDEN) and the geographical range covered by field activities (see Figure 1), it is undeniable that actively sharing information means a higher output can be achieved.

THaving Euro-AEGIS, a European Economic Interest Grouping composed of two private companies, Avia-GIS (Zoersel, Belgium) and ERGO (Oxford, UK), hosting the platform seemed to benefit all too, although this may have seemed odd in the beginning.

<figure><img src="image_46.png" /></figure>
The data and analysis are based on the data described in the paper. The analysis was performed using R, a statistical programming language, and the R包 was used to create the maps.

<figure><img src="image_47.png" /><figcaption>Figure 1: Map showing field sites reported in published (a) EDEN and (b) EDENext publications (status January 2015). Key to Fig 1a: AFR: Africa Platform / BIODIV: Biodiversity group / HRRS: High resolution remote sensing group / LEI: Leishmaniasis group / MAL: Mosquito-borne diseases group - malaria / ROBO: Rodent-borne diseases group / TBD: Tick-borne diseases group / WNV: Mosquito-borne diseases group - West Nile virus. Key to 1b: ALL: All vectors included in study / CBD: Culicoides group / MBD: Mosquito group / MOD: Modelling group / PhBD: Phlebotomine group / RBD: Rodent group / TBD: Tick group</figcaption></figure>

EDEN and EDENext are registered trademarks of Euro-AEGIS. All other trademarks are the property of their owners.

Still as it turned out, the scientists could focus on research and not worry about where which data was stored and if it would remain up-to-date as these technical tasks were taken care of. In addition, Euro-AEGIS was not a competitor in terms of initiating publications and provided training in GIS and spatial modelling to help improve the content of publications. Finally, using this database provided a method to ensure that the data, collected with a lot of effort in the field or in the lab, remain available to all partners involved beyond the end of this or any other multinational and multidisciplinary project, and does not get lost in oblivion, which may even be the most important reason to build and maintain it.

EDEN and EDENext are registered trademarks of Euro-AEGIS. All other trademarks are the property of their owners.

## LEGACY OF EDEN AND EDENEXT: CREATING NEW DATA SHARING NETWORKS

In order to be prepared for the challenges posed by vector-borne diseases (VBD), the European Centre for Disease Prevention and Control (ECDC) commissioned in 2008 an assessment of the magnitude and importance of vector-borne diseases in Europe (VBORNE). The priority vector-borne diseases were identified using both qualitative and quantitative methods, indicating that dengue and chikungunya were the highest priority. At the same time, risk analyses (see Figure 2) and fact sheets about a large number of vector-borne diseases were generated. The study concluded that one important aspect of preparedness for vector-borne diseases was the mapping of existing disease vectors and the surveillance of the introduction, establishment and spread of new disease vectors (VBORNE 2008).
<table><thead><tr><th colspan="5">Scenarios</th><th rowspan="3">Frequency of scenario</th><th colspan="9">Risk assessment related to</th></tr><tr><th rowspan="2">Vertebrate host</th><th rowspan="2">Invertebrate vector</th><th rowspan="2">Pathogen</th><th rowspan="2">Human disease</th><th rowspan="2"></th><th colspan="3">Vertebrate Host</th><th colspan="3">Invertebrate Vector</th><th colspan="3">Pathogen</th></tr><tr><th>Intro</th><th>Establ</th><th>Spread</th><th>Intro</th><th>Establ</th><th>Spread</th><th>Intro</th><th>Establ</th><th>Spread</th></tr></thead><tbody><tr><td>1</td><td>1</td><td>1</td><td>0</td><td>M</td><td></td><td>0</td><td>0</td><td>1</td><td>0</td><td>0</td><td>1</td><td>0</td><td>0</td><td>1</td></tr><tr><td>1</td><td>1</td><td>1</td><td>1</td><td>H</td><td></td><td>0</td><td>0</td><td>1</td><td>0</td><td>0</td><td>1</td><td>0</td><td>0</td><td>1</td></tr><tr><td>1</td><td>1</td><td>0</td><td>0</td><td>L</td><td></td><td>0</td><td>0</td><td>1</td><td>0</td><td>0</td><td>1</td><td>1</td><td>1</td><td>1</td></tr><tr><td>1</td><td>0</td><td>1</td><td>0</td><td>H</td><td></td><td>0</td><td>0</td><td>1</td><td>0</td><td>0</td><td>1</td><td>0</td><td>0</td><td>1</td></tr><tr><td>1</td><td>0</td><td>1</td><td>1</td><td>N</td><td></td><td>0</td><td>0</td><td>1</td><td>0</td><td>0</td><td>1</td><td>0</td><td>0</td><td>1</td></tr><tr><td>1</td><td>0</td><td>0</td><td>0</td><td>H</td><td></td><td>0</td><td>0</td><td>1</td><td>1</td><td>1</td><td>1</td><td>1</td><td>1</td><td>1</td></tr><tr><td>0</td><td>1</td><td>1</td><td>0</td><td>L</td><td></td><td>1</td><td>1</td><td>1</td><td>0</td><td>0</td><td>1</td><td>0</td><td>0</td><td>1</td></tr><tr><td>0</td><td>1</td><td>1</td><td>1</td><td>L</td><td></td><td>1</td><td>1</td><td>1</td><td>0</td><td>0</td><td>1</td><td>0</td><td>0</td><td>1</td></tr><tr><td>0</td><td>1</td><td>0</td><td>0</td><td>L</td><td></td><td>1</td><td>1</td><td>1</td><td>0</td><td>0</td><td>1</td><td>1</td><td>1</td><td>1</td></tr><tr><td>0</td><td>0</td><td>1</td><td>0</td><td>L</td><td></td><td>1</td><td>1</td><td>1</td><td>1</td><td>1</td><td>1</td><td>0</td><td>0</td><td>1</td></tr><tr><td>0</td><td>0</td><td>1</td><td>1</td><td>L</td><td></td><td>1</td><td>1</td><td>1</td><td>1</td><td>1</td><td>1</td><td>0</td><td>0</td><td>1</td></tr><tr><td>0</td><td>0</td><td>0</td><td>0</td><td>H</td><td></td><td>1</td><td>1</td><td>1</td><td>1</td><td>1</td><td>1</td><td>1</td><td>1</td><td>1</td></tr></tbody></table>

H – High, M – Medium, L – Low, N – Nil, NA – Not applicable

<caption>Figure 2: Example of a risk analysis table developed as part of VBORNE.</caption>

In order to further gather the available knowledge about the chikungunya/dengue vector, the TigerMaps network was established alongside the VBORNE project, bringing together a large number of specialised European entomologists focusing on the invasive mosquito *Aedes albopictus*. TigerMaps outputs included for the first time a pan-European database (see Figure 3), harmonised at the administrative unit level, not only of confirmed establishment but also of the confirmed absence (or lack of knowledge of both) of the mosquito. All these aspects are important to the study of invasive behaviour (ECDC 2009).

The VBORNE and TigerMaps temporary networks formed a crucial second stepping-stone towards the development of a large pan-European network of VBD specialists: first VBORNET, recently followed by VectorNet. Essential elements of this process were:

* Recognition of the EDEN know-how by ECDC, the largest European Public Health institute, through the successful completion of VBORNE and TigerMaps.

* Opening-up to non-EDEN experts, hence breaking the 'them-and-us' resentment, and at the same time spreading the EDEN spirit.

* Generation of factual data for the common good: both for decision makers and scientists.

* Focusing first on the dynamics of invasive mosquitoes, justifying the need for regular input from a large group of experts spread over many countries.

* Stressing the need to have a precise knowledge of the distribution of resident vectors to assess the risk of introduction of exotic pathogens.

* Solving the administrative issues related to co-funding large networks by two large EU institutes: ECDC and European Food Safety Agency (EFSA).

VBORNET was the first major expansion of the EDEN network, which integrated more than 400 entomologists from all over Europe. They were asked to define where vectors of disease can or cannot be found, while the network coordinators made sure that the information was recorded, validated and archived in a standardised way and, most importantly, made available in a usable format to the scientific and Public Health communities. This resulted in quarterly map outputs (see Figure 4) at various administrative levels for a large number of potential mosquito, tick and Phlebotomine disease vectors prioritised by ECDC.
<figure><img src="image_48.png" /></figure>

<table><caption>Figure 3: Examples of entomological information systematically collected at the administrative unit level as part of the TigerMaps network. Entomological dataset fields related to the (a) occurrences of Aedes albopictus and (b) surveillance and control for Aedes albopictus and other mosquitoes in general</caption><thead><tr><th colspan="6">Data related to Aedes albopictus</th></tr><tr><th>Presence 2007</th><th>If yes, since</th><th>If no, estimated period of presence (before 2007)</th><th>Type of occurrence</th><th>Report of the nuisance</th><th>Source of information</th></tr></thead><tbody><tr><td>Yes/no/ no data</td><td>year</td><td>year/s</td><td>Homogenous/ isolated foci</td><td>complaints/ no complaints</td><td>Publication/newspaper/personal communication</td></tr></tbody></table><table><thead><tr><th colspan="3">Data related to other mosquitoes</th><th colspan="6">Data related to Aedes albopictus</th></tr><tr><th>Surveillance/ study</th><th>Regular surveillance active since</th><th>Control</th><th>Surveillance</th><th>Type of surveillance</th><th>Surveillance active since</th><th>Control</th><th>Type of control programme</th><th>Organisation of control programme</th></tr></thead><tbody><tr><td>yes (date)/no/ no data</td><td>year</td><td>yes/no/ no data</td><td>yes/no/ no data</td><td>active/ passive</td><td>year</td><td>yes/no</td><td>larval/ adults/ both</td><td>public/ private/ both</td></tr></tbody></table>

Sharing entomological data is no longer an issue for network contributors because all can benefit. Indeed, vectors do not stop at country borders and gaining access to the data is beneficial to all parties involved. The enhanced datasets generated by sharing have also provided a more robust input for spatial modelling to underpin a gap analysis to identify areas that should be a priority for extra fieldwork.

In parallel to promoting the establishment of longer-term VBD networks in Europe, ECDC also was inspired by EDEN's environmental data-sharing initiative and ensured the integration of most of its data into its European Environment and Epidemiology Network (E3) geoportal. To initiate this effort, ECDC sponsored the maintenance of the EDEN data website between the EDEN and EDENext projects and launched four dedicated proof of concept studies, showcasing a tick-borne disease (Lyme borreliosis), a mosquito-borne disease (dengue), a water-borne disease (leptospirosis) and a food-borne disease (salmonellosis), confirming the great value of such an archive within the broader concept of spatial epidemiology beyond vector-borne diseases alone (e3geoportal.ecdc.europa.eu 2015). Data from the E3 geoportal is currently being used by ECDC staff and consultants to develop risk analyses.

Finally, a further level of expansion through inter-institutional sharing was achieved when ECDC and EFSA put their institutes behind a further harmonisation of entomological and spatial databases linking Public Health and veterinary VBDs as an important step towards a One Health approach. VectorNet (ecdc.europa.eu 2015) has been set-up to not only expand to veterinary entomologists and include biting midges as an additional vector group, but also to increase the geographical range taking in territories at the fringe of Europe in the east and south. Data gaps that were earlier identified during VBORNET are now subject to targeted surveillance campaigns and will provide high-quality missing data to the current VBORNET and EFSA databases from presence/absence to abundance data to feed risk analysis studies for the introduction, establishment or spread of VBDs. To complete the circle, ECDC uses its E3 Geoportal to feed back the collected and quality assessed data to the entire community.
## Vector distribution

Vector Categories:

Ticks

<figure><img src="image_49.png" /></figure>

Vector Species:

Ixodes ricinus

<figure><img src="image_50.png" /></figure>

NUTS0:

Andorra

Anguila*

Armenia-Hayastan

Aruba*

Azerbaijan

Belarus

NUTS2:

Prov. Antwerpen

Prov. Limburg (B)

Prov. Oost-Vlaanderen

Prov. Vlaams-Brabant

Prov. West-Vlaanderen

NUTS1:

Région de Bruxelles-Capitale / Brussels Hoofdstede

Région Wallonne

Vlaams Gewest

NUTS3:

Arr. Antwerpen

Arr. Mechelen

Arr. Turnhout

D1: Is Ixodes ricinus present:

Indigenous

<figure><img src="image_51.png" /></figure>

D2: Environment: Only Present In Sheltered Environment, Specify:

D3: Date first confirmed record:

<figure><img src="image_52.png" /></figure>

NA

Don't Know

Date (ddmmyyyy):

<table><thead><tr><th colspan="7">July 2015</th></tr><tr><th>Sun</th><th>Mon</th><th>Tue</th><th>Wed</th><th>Thu</th><th>Fri</th><th>Sat</th></tr></thead><tbody><tr><td>28</td><td>29</td><td>30</td><td>1</td><td>2</td><td>3</td><td>4</td></tr><tr><td>5</td><td>6</td><td>7</td><td>8</td><td>9</td><td>10</td><td>11</td></tr><tr><td>12</td><td>13</td><td>14</td><td>15</td><td>16</td><td>17</td><td>18</td></tr><tr><td>19</td><td>20</td><td>21</td><td>22</td><td>23</td><td>24</td><td>25</td></tr><tr><td>26</td><td>27</td><td>28</td><td>29</td><td>30</td><td>31</td><td>1</td></tr><tr><td>2</td><td>3</td><td>4</td><td>5</td><td>6</td><td>7</td><td>8</td></tr></tbody><tfoot><tr><td colspan="7">July</td></tr><tr><td colspan="7">2015</td></tr></tfoot></table>

D5: Scientist providing information:

5.1.1 Surname (*): Janssen

5.1.2 First Name(s) (*): Peter

5.1.3 Title:

5.1.4 Position:

5.1.5 Phone Office:

5.1.6 Phone Mobile:

5.1.7 E-mail (*):

5.2.1 Organisational legal name (*): Province Antwerpen

5.2.2 Organisational short name:

5.2.3 Department/Faculty/Institute/Laboratory:

5.3.1 PO Box:

5.3.2 Postal Code:

5.3.3 Cedex:

5.3.4 Street name and number:

5.3.5 Town:

5.3.6 Country:

5.3.7 Internet homepage:

D6: Point data: Related GIS Point Data is available

D7: Published source:

Technical report to Institute of Public Health

D4: Date last confirmed record:

<figure><img src="image_53.png" /></figure>

NA

Don't Know

Date (ddmmyyyy):

<table><caption>Figure 4: VBORNET data entry questionnaire</caption><thead><tr><th colspan="7">July 2015</th></tr><tr><th>Sun</th><th>Mon</th><th>Tue</th><th>Wed</th><th>Thu</th><th>Fri</th><th>Sat</th></tr></thead><tbody><tr><td>28</td><td>29</td><td>30</td><td>1</td><td>2</td><td>3</td><td>4</td></tr><tr><td>5</td><td>6</td><td>7</td><td>8</td><td>9</td><td>10</td><td>11</td></tr><tr><td>12</td><td>13</td><td>14</td><td>15</td><td>16</td><td>17</td><td>18</td></tr><tr><td>19</td><td>20</td><td>21</td><td>22</td><td>23</td><td>24</td><td>25</td></tr><tr><td>26</td><td>27</td><td>28</td><td>29</td><td>30</td><td>31</td><td>1</td></tr><tr><td>2</td><td>3</td><td>4</td><td>5</td><td>6</td><td>7</td><td>8</td></tr></tbody><tfoot><tr><td colspan="7">July</td></tr><tr><td colspan="7">2015</td></tr></tfoot></table>
GOING TO OTHER CONTINENTS
AND DISEASES: IDAMS,
THE 3D CONSORTIUM AND VMERGE

EDEN and EDENext were not limited to Europe. A strong link with West Africa in general, and Senegal in particular, was established and preserved over the entire 10 years. While the previous section focused on Europe only, the spatial data archive is also of great added value in North and West Africa and the rest of the world.

IDAMS (idams.eu 2015) is an FP7 project surveying and mapping dengue and dengue vectors at a global scale. It is associated with two other FP7 projects, Denguetools (denguetools.net 2015), and DenFree (denfree.eu 2015), in a '3D consortium', whose members have access to EDENext spatial data archives, and which also provide resources to add substantial primarily climate and climate change related datasets to the archive. These EDENext-generated environmental data have been used in a number of high-impact publications (for example, Bhatt et al. 2013).

The extensive databases generated by EDEN/EDENext and VBORNET/ VectorNet, are also shared with other research groups. Several ECDC studies have requested access to EDENext and IDAMS generated covariate datasets and information from VBORNET has been integrated into broader global vector datasets for the main vectors of dengue: *Aedes albopictus* and *Aedes aegypti*. This worldwide database contains 22,104 records for *Ae. albopictus* and 19,969 records for *Ae. aegypti* and has been submitted to a data journal for publication. The data will be used to produce spatial models for the vectors' current distributions, and EDENext-hosted climate change ensembles will be used to produce projected distributions. Similar initiatives are also in progress, for example, for *Hyalomma* ticks transmitting Crimean-Congo haemorrhagic fever virus.

Finally, VMERGE (vmerge.eu), also funded under FP7, has the overall objective of addressing the risk of introduction, emergence and spread of both known and unknown VBDs associated with mosquitoes and *Culicoides*, with a focus on Rift Valley fever and bluetongue. The aim is to improve the limited understanding of these emerging diseases and their potential for spread throughout northern Africa and Europe and to enhance epidemiological surveillance strategies and tools for better disease detection.

The EDEN and EDENext legacy seems ensured for the future. The data archives are widely used, properly acknowledged and have given rise to scientific and technological innovation. The answer to the prime question of this paper, "Is sharing of public data providing added value for the scientific community?" is a clear and loud "Yes", and more importantly it is possible and it has been achieved. Data sharing is a continuing story for now and the future.

REFERENCES

Avants B et al. (2014). Home: Scientific Data. Nature.com. 2014. Web. 17 Feb. 2015.

Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GRW, Simmons CP, Scott TW, Farrar JJ and Hay SI (2013). The global distribution and burden of dengue. *Nature* 496(7446): 504-507.

Denfree.eu (2015). Denfree website. Web. 17 Feb. 2015.

Denguetools.net (2015). Denguetools website. Web. 17 Feb. 2015.

E3geoportal.ecdc.europa.eu (2015). Home page. Web. 17 Feb. 2015.

Ecdc.europa.eu (2015). VectorNet: A European Network For Sharing Data On The Geographic Distribution Of Arthropod Vectors, Transmitting Human And Animal Disease Agents. Web. 17 Feb. 2015.

Feeney G (2015). POPIN >> data. United Nations Organisations. Web 17 Feb 2015.

Idams.eu (2015). International Research Consortium on Dengue Risk Assessment, Management and Surveillance. Web. 17 Feb. 2015.

OECD.org (2015). Science, Technology And Innovation For The 21st Century. Meeting Of The OECD Committee For Scientific And Technological Policy At Ministerial Level, 29-30 January 2004 - Final Communique - OECD. Web 17 Feb 2015.

Sedac.ciesin.columbia.edu (2015). Population Count Grid, V1: Global Rural-Urban Mapping Project (GRUMP), V1 SEDAC. Web. 17 Feb. 2015.

TigerMaps, ECDC (2009). Technical report: Development of *Aedes albopictus* risk maps, Stockholm, May 2009, p 45.

VBORNE, ECDC (2008). Assessment of magnitude and importance of vector-borne diseases in Europe. Final report, incl. 17 factsheets, 19 reviews and 4 risk analyses (available from the authors of this paper upon request).

Vmerge.eu (2015). Vmerge-project – Emerging Viral Vector-Borne Diseases. Web. 17 Feb. 2015.

web.ORNL.gov (2015). Landscan Home. Web 17 Feb. 2015.

Worldpop.org.uk (2015). Worldpop – Latest Map, Web accessed 17 Feb 2015.
## ACKNOWLEDGEMENT

We would like to thank all those who have worked with the EDEN and EDENext data management teams led by Avia-Gis (Belgium) and Euro-Aegis (United Kingdom).

real

The number of infected humans is expected to increase linearly with time.

Theirobia pterygoides is the most common vector in Europe.

When the efficiency of the vector decreases, the number of infected humans increases, and the risk of transmission increases.

For the purpose of this report, the term "vector" is used to mean the vector as it is used in the field, not as it is in the laboratory.
## INTRODUCTION

Nienke Hartemink

Faculty of Veterinary Medicine,
Utrecht University, The Netherlands

The basic reproduction number, $R_0$, has a long history, especially in the field of vector-borne diseases. This paper provides a brief overview of the use of this concept in vector-borne disease epidemiology as well as new developments and recent applications, notably within the EDEN and EDENext framework. Furthermore, it describes a novel framework for the inclusion of landscape factors and animal movements in vector-borne disease risk assessments, which can be merged with more quantitative approaches in order to achieve a mechanistic and

realistic description of the spatial and temporal variation in vector-borne disease risk.

## $R_0$ FOR VECTOR-BORNE DISEASES

The basic reproduction number, $R_0$, is a key concept in the epidemiology of infectious diseases. It is defined as the expected number of secondary cases caused by one infectious individual introduced into a naïve population. It can be used as a measure of the potential success of invasion of a pathogen into a population; if the value of $R_0$ is higher than 1, an outbreak of the infectious agent is possible, whereas if $R_0$ is less than 1, the infection will die out (Anderson and May 1991, Diekmann and Heesterbeek 2000).

The theory underlying $R_0$ models for vector-borne diseases (hereafter VBDs) originated in the early 20th century, when Ronald Ross first developed a theoretical framework to describe the transmission of malaria. His work was extended by several others, including George MacDonald in the 1950s and 1960s and, by 1970, the foundations of the Ross-MacDonald theory were established (MacDonald 1957, Smith et al. 2012). The by now well-known Ross-MacDonald formula for the transmission of malaria is usually written as:

$$R_0 = \frac{ma^2bc}{(-\ln(p))r}$$

where *m* is the ratio of mosquitoes to humans, *a* the mosquito biting rate (on humans), *b* and *c* the pathogen transmission efficiencies, *p* the daily survival rate of mosquitoes, *r* the recovery rate in humans (i.e. the reciprocal of the infective period of the host) and *n* the duration of the extrinsic incubation period (EIP). Since the development of this Ross-Macdonald model for malaria, hundreds of models for mosquito-borne diseases have been derived and published, and most of them resemble the original models quite closely (Reiner et al. 2013). The Ross-MacDonald formula applies to situations where one vector species and one host species are involved in the disease transmission.

For those situations where multiple types of infected individuals are involved or where multiple transmission routes are possible, the $R_0$ value can be derived using the next-generation matrix approach (Diekmann and Heesterbeek 2000). The first step in this approach is to identify the different types-at-birth in the system, in other words to categorise individuals by their state at the moment they become infected. These types-at-birth differ in traits that affect their ability to produce secondary cases, such as infectivity, contacts, life history traits, possible transmission routes etc. For VBDs, there are at least two types-at-birth (host and vector), but often, there are more. For a system with *m* types-at-birth, the next-generation matrix (hereafter NGM) will be
Several R₀ maps have now been developed and published for VBDs, including maps for bluetongue virus (Racloz et al. 2008, Brugger and Rubel 2013), chagas disease (Cordovez et al. 2014) and tick-borne diseases such as Lyme disease (Wu et al. 2013) and Crimean-Congo haemorrhagic fever (CCHF) (Estrada-Peña et al. 2013).

Overview of approach

<figure><img src="image_54.png" /><figcaption>Figure 1. Example of the construction of an R₀ map for canine leishmaniasis (from Hartemink et al. 2011). Parameters of the R₀ formula can be tem-
perature-dependent (in this example, biting rate a, mortality rate and extrinsic incubation period depend on the temperature in July, left side of figure),
or constant (parameters in blue circles, right side of figure). Important parameters include the estimated vector abundance and host abundance (top).
Calculating the R₀ value for each pixel yields the R₀ map.</figcaption></figure>

IMPACT OF TEMPERATURE

R₀ maps can also reflect the temperature dependency of disease transmission. Several processes influencing transmission
dynamics are known to vary with temperature, and this can be taken into account by making the corresponding parameters in
the expression for R₀ temperature-dependent. Temperature can have opposing effects on different ingredients of R₀, a pheno-
menon that has been discussed by, amongst others, Rogers and Randolph (2006). Therefore, caution should be taken when
using models to predict the effect of climate change; for instance, models taking only the effect of temperature on the pathogen
development rate into account are just too simplistic (Reiter 2001, Reiter et al. 2004). Parameters that are known to be tempe-
ration-dependent for many VBD systems are i) the biting rate, ii) the rate of development of the pathogen in the vector (which
determines the length of the extrinsic incubation period or EIP) and iii) the mortality of the vector. Even parameters often assumed
to remain constant (such as the transmission efficiencies *b* and *c* in the expressions for R₀) are affected by temperature in one
or more vector species. For example, *Culicoides nubeculosus*, a midge that is normally refractory to the strains of bluetongue
virus circulating in Europe at the present time (i.e. *b*=0), is capable of transmitting bluetongue virus when its larvae or pupae are
kept at higher than normal temperatures, as is discussed in Rogers and Randolph (2006).
## LIMITATIONS OF R₀

While R₀ and the NGM approach offer a promising tool to assess the risk of establishment, by means of the per-generation growth rate of a starting epidemic, as well as a way to quantify the contributions of different ingredients or transmission routes to this growth rate, there are also some limitations. One of them is that it is not straightforward to include animal movements and landscape factors into the R₀ calculation. One of the assumptions underlying the R₀ concept is that there is local homogeneous mixing, that is, we consider a population where all individuals can get in contact with each other. An R₀ map thus gives local values of the expected number of infected individuals resulting from one infected individual in a naïve population present at that specific location. An R₀ map at 1km resolution assumes that there is homogeneous mixing within the 1km grid cell or pixel, but no substantial exchange of individuals between cells. Also the configuration of certain landscape factors, and its effect on how animals move though the landscape, cannot easily be incorporated in R₀ formulas, although some studies on metapopulations have looked at the effect of migration rates (for example, Jesse and Heesterbeek 2011).

## ROLE OF LANDSCAPE FACTORS, CONNECTIVITY AND FRAGMENTATION

Landscape, and elements characterising it, such as land use, land cover, composition and structure, have been suggested to have a considerable impact on the dynamics and therefore the occurrence of VBDs (Ostfeld, Glass and Keesing 2005, Lambin et al. 2010). Landscape, defined as all the visible features of an area of land (Oxford Dictionary), includes the physical elements of landforms (such as mountains, hills, water bodies such as rivers, lakes, ponds and the sea), living elements of land cover (including indigenous vegetation), human elements (including different forms of land use, buildings and structures) and transitory elements such as lighting and weather conditions (Human Geography Dictionary).

These landscape elements will affect the presence, spread and persistence of vector-borne and zoonotic diseases as they may influence the presence of vectors, reservoir hosts, susceptible hosts (including humans) and the pathogen, as well as their overlap in time and space. Land use will, among other things, affect the number of people present in an area and the way they use the landscape, which in turn affects their chances of getting in contact with the pathogen, via the vector or, for example, in the case of hantavirus, via contaminated soil. Land cover will, at least partly, determine the availability and quality of habitat of the different species which interact with the pathogen, i.e. the vectors and hosts. Many of these aspects had been covered in EDEN, as summarised in the paper by Lambin et al. (2010). In EDENext, the focus shifted, based on the notion that it is not just the landscape *composition*, but also the landscape *configuration* and *connectivity* that will affect the suitability of an area for a pathogen to establish, spread and/or persist. Habitat connectivity and habitat fragmentation are likely to have an effect on the dispersal of animals and thereby of the pathogens they carry.

Characterising and quantifying the level of connectivity of a habitat or landscape is not straightforward. Notwithstanding the importance of the concept of connectivity, there is no generally accepted and employed formal definition (Crooks and Sanjayan 2006) and many different measures for connectivity have been applied in various research fields. In the field of landscape ecology, it has long been recognised that habitat connectivity is determined by two different components (Bennett 1990, 2003). The structural component of connectivity is determined by the spatial arrangement of different types of habitats in the landscape. It refers to the mappable, spatial arrangement of habitats. The behavioural component of connectivity relates to the behavioural response of individuals and species to the physical structure of the landscape.

Consequently, even though living in the same landscape, species with contrasting behavioural responses (to habitat disturbance, for example) will experience different levels of connectivity (Bennett 2003). In the field of vector-borne disease epidemiology, this distinction between the structural and behavioural connectivity is often not made and landscapes are classified as well connected or fragmented mostly based on human perception of the landscape. Given the fact that the effect of landscape configuration on connectivity, population density and contact rates is species- and disease-system specific, and the fact that the way to measure connectivity is not well-defined (and in many cases probably overlooks the way that animals, including humans, actually use the landscape), it is not surprising that different studies on the effect of habitat connectivity and fragmentation on disease risk come up with different answers.
In EDENext, a modelling study looked into the effect of fragmentation on animal movement and tick-borne disease transmission by means of an agent-based model, which takes landscape-specific dispersal rates into account. This study predicts a positive effect of fragmentation level on disease risk (Li et al. 2012). Another study, using a multilevel statistical analysis to find landscape factors associated with the occurrence of hantavirus cases in humans, found a positive association with well-connected forest. It is clear that there is no straightforward relationship between landscape configuration and pathogen transmission; the relationship will be different for each disease system and will depend on the way the vector and host species use the landscape, their dispersal capacity, their habitat requirements and many other factors.

## RESOURCE-BASED HABITAT CONCEPT (RBHC)

In order to overcome the problem of not being able to include landscape factors and animal movements in our risk assessments, several members of the EDENext modelling team worked together to explore approaches used in other research fields to see whether these approaches would be applicable in the VBD context. It became clear that the research field of vector-borne disease risk modelling shares many goals and challenges with the field of conservation biology. In both fields, the aims include the mapping of organisms of interest and the study of environmental factors which help the prediction of presence, abundance or dynamics of focal species.

One particular concept, the resource-based habitat concept, has been explored in great detail and seems to be a promising framework to identify systematically the different ecological resources that are necessary for the completion of the transmission cycle and to relate these resources to (combinations of) landscape features and other environmental factors (Hartemink et al. 2014). The framework has been developed in the field of conservational biology, with special application to butterfly conservation, to help identify functional habitats from a mechanistic, biological viewpoint (Dennis, Shreeve and Van Dyck 2003, Vanreusel and Van Dyck 2007). The concept facilitates the study of functional habitats of the species involved in pathogen transmission (i.e. pathogen, vectors and hosts) by regarding the resources required by each of the species and linking them to specific environmental features at the landscape level.

Using the movement capacities of the animals involved, the potential functional habitat range (i.e. the delineated zones that correspond to the combined and integrated information on resources, utilities and scale of movement) can be determined for each species. Once the functional habitat of the vector and host species is determined, the functional habitat of the pathogen can be delineated, by looking at the areas when transmission can occur (i.e. where functional habitats of vector and host overlap and other (thermal) requirements of the pathogen are met).

## REFERENCES

Anderson RM and May RM (1991). *Infectious Diseases of Humans; Dynamics and Control*. Oxford University Press, Oxford.

Bennett AF (1990). *Habitat corridors: their role in wildlife management and conservation*. Dept. of Conservation and Environment, Victoria; Arthur Rylah Institute for Environmental Research, Melbourne, Australia; Heidelberg, Vic., Australia.

Bennett AF (2003). *Linkages in the landscape: the role of corridors and connectivity in wildlife conservation*. IUCN, Gland, Switzerland and Cambridge, UK.

Boender GJ, Hagenaars TJ, Bouma A, Nodelijk G, Elbers ARW, Jong MCM de and Boven M van (2007). Risk Maps for the Spread of Highly Pathogenic Avian Influenza in Poultry. *PLoS Computational Biology* 3, e71.

Boender GJ, Nodelijk G, Hagenaars TJ, Elbers AR and Jong MC de (2008). Local spread of classical swine fever upon virus introduction into The Netherlands: mapping of areas at high risk. *BMC Vet Res* 4, 9.

Brugger K and Rubel F (2013). Bluetooth Disease Risk Assessment Based on Observed and Projected Culicoides obsoletus spp. Vector Diseases. *PLoS ONE* 8.

Carpenter S, Mellor PS and Torr SJ (2008). Control techniques for *Culicoides* biting midges and their application in the UK and northwestern Palaearctic. *Medical and Veterinary Entomology* 22, 175–187.

Cordovez JM, Rendon LM, Gonzalez C and Guhl F (2014). Using the basic reproduction number to assess the effects of climate change in the risk of Chagas disease transmission in Colombia. *Acta Tropica* 129, 74–82.

Crooks KR and Sanjayan M (2006). *Connectivity Conservation*. Cambridge University Press, Cambridge.

Dennis RLH, Shreeve TG and Van Dyck H (2003). Towards a functional resource-based concept for habitat: a butterfly biology viewpoint. *Oikos* 102, 417–426.

Diekmann O, Heesterbeek H and Britton T (2013). *Mathematical Tools for Understanding Infectious Disease Dynamics*. Princeton University Press.

Diekmann O and Heesterbeek JAP (2000). *Mathematical epidemiology of infectious diseases: Model building, analysis and interpretation*. John Wiley & Sons, Ltd., New York.

Diekmann O, Heesterbeek JAP and Roberts MG (2010). The construction of next-generation ma-
In this way, the concept provides new insight into spatial and temporal variation in transmission opportunities and exposure that ultimately determine disease risks. Since application of the concept requires a systematic inventory of the resource required by each of the interacting species, it may also be a tool to identify knowledge gaps. An interesting advantage of the method is that it forces us to think about the spatial configuration of resources and how these influence disease risk, which may lead to novel control options; changing the spatial configuration of key resources across the landscape may decrease the overlap of functional habitat of vector and host, or may decrease the vector population, if essential resources for the vector are not placed within flight range distance.

An interesting example is a study in South America, where transmission of oropouche virus was decreased by removing rotten banana stumps or cacao husks, which are breeding sites for the main vector, *C. paraensis*, in the vicinity of houses (Hoch, Roberts and Pinheiro 1986). Removal of bluetongue-virus vector (*Culicoides* spp.) breeding sites has also been shown to be useful in reducing vector abundance in North America for *C. sonorensis* (Linley, Evans and Evans 1970; Mullens and Rodriguez 1989; Carpenter, Mellor and Torr 2008a), even though this has not always translated into reduction of bluetongue infection as

mechanism, and how this may be impacted by the movement of vectors and hosts.

While much is known about the movement and transmission of vector-borne diseases, there is still a great deal that is not well understood, and much of this is currently being investigated.

<figure><img src="image_55.png" /></figure>

**Figure 2:** Schematic overview of the application of the resource-based habitat approach to VBDs. In the first phase, ecological functions (orange boxes) and associated resources (green boxes) are identified for the pathogen and the (possibly multiple) vector and host species. Then, information on the movement capacities of the species involved and on the structure and composition of the landscape together, and in mutual dependence, determine the functional habitats of vector and host species. That is, the movement range determines the distance that should be considered when looking at the accessibility of the different resources, whereas the type of terrain may affect the movement range. Transmission opportunities, given the presence or introduction of the pathogen, are determined by the overlap of these functional habitats and by environmental conditions, such as thermal conditions. Figure published earlier in Hartemink, Vanwambeke et al. (2015).
that is, the
size of the
ecological
area as

The
ecological
area as

and
ecological
area as

measured by sero-conversion rate (Mayo et al. 2012). So, in summa-
ry, RBHC allows for the integration of landscape factors and animal
movements in epidemiological spatial risk assessments and hence
bridges the gap between existing mechanistic modelling approaches
that ignore landscape factors and dispersal and satellite image-based
approaches that are based on statistical inference only.

MERGING RBHC AND R₀:
INCORPORATING LANDSCAPE FACTORS
AND MOVEMENT RANGE
IN A QUANTITATIVE WAY

While RBHC may therefore offer promising scope to deal with spatial modelling of VBD risks, it is currently only a conceptual model that gives a qualitative risk assessment, but lacks the advantage of an integrating quantitative approach, such as R₀. The next step would be to take the RBHC framework to the next level, and make it a quantitative approach, by parameterizing it for a case study. This would allow us to take advantage of the properly weighted way in which the R₀ formula combines all the ingredients of the transmission cycle and the spatially explicit and biologically realistic way in which RBHC incorporates the functional use of the landscape.

ACKNOWLEDGEMENT

This work would not have been possible without the dedication and
commitment of all the researchers involved in the EDEN and EDENext
modelling teams. We thank the following institutions:

Université Catholique de Louvain, Belgium

Université Libre de Bruxelles, Belgium

University of Oxford, United Kingdom

University of Utrecht, The Netherlands

trices for compartmental epidemic models. *Journal of The Royal Society Interface* 7, 873–885.

Estrada-Peña A, Ruiz-Fons F, Acevedo P, Gortazar C and de la Fuente J (2013). Factors driving the circulation and possible expansion of Crimean-Congo haemorrhagic fever virus in the western Palearctic. *Journal of Applied Microbiology* 114, 278–286.

Hartemink NA, Cianci D and Reiter P (2015). R₀ for vector-borne diseases; impact of the assumption for the duration of the extrinsic incubation period. *Vector Borne Zoonotic Dis* 15, 215-217.

Hartemink NA, Davis SA, Reiter P, Hubálek Z and Heesterbeek JAP (2007). The importance of bird-to-bird transmission for the establishment of West Nile virus. *Vector Borne Zoonotic Dis* 7.

Hartemink NA, Purse BV, Meiswinkel R, Brown HE, Koeijer A de, Elbers ARW, Boender GJ, Rogers DJ and Heesterbeek JAP (2009). Mapping the basic reproduction number (R₀) for vector-borne diseases: A case study on bluetongue virus. *Epidemics* 1, 153–161.

Hartemink NA, Randolph SE, Davis SA and Heesterbeek JAP (2008). The basic reproduction number for complex disease systems: defining R0 for tick-borne infections. *The American Naturalist* 171, 743–754.

Hartemink NA, Vanwambeke SO, Heesterbeek H, Rogers D, Morley D, Pesson B, Davies C, Mahamdallie S and Ready P (2011). Integrated Mapping of Establishment Risk for Emerging Vector-Borne Infections: A Case Study of Canine Leishmaniasis in Southwest France. *PLoS ONE* 6, e20817.

Hartemink NA, Vanwambeke SO, Purse BV, Gilbert M and Van Dyck H (2015). Towards a resource-based habitat approach for spatial modelling of vector-borne disease risks. *Biological Reviews*, published online 21 Oct 2014. DOI: 10.1111/brv.12149

Hoch AL, Roberts DR and Pinheiro FD (1986). Breeding sites of *Culicoides paraensis* and options for control by environmental management. *Bulletin of the Pan American Health Organization* 20, 284–293.

Jesse M and Heesterbeek H (2011). Divide and conquer? Persistence of infectious agents in spatial metapopulations of hosts. *Journal of Theoretical Biology* 275, 12–20.

Lambin EF, Tran A, Vanwambeke SO, Linard C and Soti V (2010). Pathogenic landscapes: Interactions between land, people, disease vectors, and their animal hosts. *International Journal of Health Geographics* 9, 54.
Linley JR, Evans FD and Evans HT (1970). Seasonal emergence of *Culicoides furens* (Diptera: Ceratopogonidae) at Vero Beach, Florida. *Annals of the Entomological Society of America* 63, 1332-1339.

Li S, Hartemink N, Speybroeck N and Vanwambeke SO (2012). Consequences of Landscape Fragmentation on Lyme Disease Risk: A Cellular Automata Approach. *PLoS ONE* 7, e39612.

MacDonald G (1957). *The epidemiology and control of malaria*. Oxford University Press, London.

Mayo CE, Mullens BA, Gerry AC, Barker CM, Mertens PPC, Maan S, Maan N, Gardner IA, Guethrie AJ and MacLachlan NJ (2012). The combination of abundance and infection rates of *Culicoides sonorensis* estimates risk of subsequent bluetongue virus infection of sentinel cattle on California dairy farms. *Veterinary Parasitology* 187, 295-301.

Mullens BA and Rodriguez JL (1989). Response of *Culicoides variipennis* (Diptera: Ceratopogonidae) to water level fluctuations in experimental dairy wastewater ponds. *Journal of Medical Entomology* 26, 566-572.

Ostfeld RS, Glass GE and Keesing F (2005). Spatial epidemiology: an emerging (or re-emerging) discipline. *Trends in Ecology & Evolution* 20, 328-336.

Raclov Z, Venter G, Griot C and Stark KD (2008). Estimating the temporal and spatial risk of blue-tongue related to the incursion of infected vectors into Switzerland. *BMC Vet Res* 4, 42.

Reiner RC, Perkins TA, Barker CM, Niu T, Chaves LF, Ellis AM et al. (2013). A systematic review of mathematical models of mosquito-borne pathogen transmission: 1970–2010. *Journal of The Royal Society Interface* 10, 20120921.

Reiter P (2001). Climate change and mosquito-borne disease. *Environ Health Perspect* 109 Suppl 1, 141-161.

Reiter P, Thomas CJ, Atkinson PM, Hay SI, Randolph SE, Rogers DJ, Shanks GD, Snow RW and Spielman A (2004). Global warming and malaria: a call for accuracy. *The Lancet Infectious Diseases* 4, 323-324.

Rogers DJ and Randolph SE (2006). Climate change and vector-borne diseases. In *Advances in Parasitology* (eds S.I. Hay, A. Graham and D.J. Rogers), pp. 345-381. Academic Press.

Smith DL, Battle KE, Hay SI, Barker CM, Scott TW and McKenzie FE (2012). Ross, Macdonald, and a Theory for the Dynamics and Control of Mosquito-Transmitted Pathogens. *PLoS Pathog* 8, e1002588.

Vanreusel W and Van Dyck H (2007). When functional habitat does not match vegetation types: A resource-based approach to map butterfly habitat. *Biological Conservation* 135, 202-211.

Wu X, Duvvuri VR, Lou Y, Ogden NH, Pelcat Y and Wu J (2013). Developing a temperature-driven map of the basic reproductive number of the emerging tick vector of Lyme disease *Ixodes scapularis* in Canada. *Journal of Theoretical Biology* 319, 50-61.
## Interview: Guy Hendrickx

<figure><img src="image_56.png" /></figure>

### What role have the EDEN and EDENext PhD networks played?

Belgium-born Guy Hendrickx, DVM, PhD, graduated as a doctor in veterinary medicine in 1985 (Gent, Belgium) and has more than 25 years of experience in the field of spatial epidemiology, livestock geography and decision support systems. Between 1987 and 2000, he completed a series of long-term assignments in Africa working on FAO tsetse control projects. Back in Europe he created Avia-GIS in 2001 to help bridge the gap between research and decision making in the field of spatial decision support systems applied to animal and Public Health. He established Euro-AEGIS with ERGO (Oxford, UK) and, as one of his first European assignments, was requested by CI-RAD to build the EDEN consortium and write the EDEN project. In EDEN he was operational manager and secretary of the Steering Committee. He is particularly interested in developing multidisciplinary research networks with a focus on PhD networks. In 2012 his company won the first Janssen Open Kempense Innovation Award for the VECMAP™ software package which is now going to the market.

**Guy Hendrickx (Avia-GIS, Belgium):** "When we started talking about EDEN in 2002/2003, there was a huge gap in Europe of people working in the field. Especially because of the pressure on publications, there was more and more emphasis on lab work and having, as quickly as possible, results you could publish in the biggest possible journals. It was all about bioinformatics and anything like lab-type publications, genetics were very much high on the list. So, for a young student looking for a career, it was not very appealing to go the field and, like the presentation we saw this morning [GERI 2015], conducting two years of sampling sand flies and coming up with some graphs and linking this to a few factors was not very appealing.

"Given this framework, the fact that EDEN was such a large network, covering all of Europe, suddenly made the topic sexy in the sense that it became interesting for PhD students, especially because they were not working alone. When you are doing field work the one major constraint is time - it takes a lot of time - and you can be alone a lot or you may be lucky and be with a very nice team, but if you know that you are part of a group and you can meet every year or at least have a lot of contacts with other people doing similar things in other countries, it makes it very interesting because it gives it a kind of community feeling.

"It very quickly became obvious that we should actually install it [PhD network] in EDEN and in the first year meeting it got organised. Part of the reason it was organised so late in the EDEN project was the very complicated politics and, especially, because people were very reluctant regarding data sharing and working together, there were not many large

European projects like it. Before the submission, most of the time was put into how we as teams were positioning ourselves and most of the discussions and attention went into that. So at that time it was like, OK, the work will be done by PhD students but how this would be organised was not defined. In the steering committee meetings of the first year it became more clear and in organising the first annual meeting the idea came to us to organise, before the actual meeting, one or two days as a PhD meeting and that actually sealed it.

"PhD students got their specific time where they could discuss between themselves their results and the idea of having a PhD group became very concrete. Also, there was a PhD prize so each year we could give a prize to the best presentation from a PhD student. It was a significant prize so for the PhD students it was very attractive and at the PhD meetings during the annual meetings there was always plenty of time for presentations, not just 15 minutes, but at least 20 or 25 minutes with questions.

"It took a while before the seniors in EDEN understood the importance of it. I think, on purpose, we actually excluded the seniors from the first PhD meeting, with only PhD students there, to make them feel comfortable. All these studies were just starting so we didn't really need questions to scare them off. It was only at the second PhD meeting in the second year that the seniors were more involved.
Interview: **Guy Hendrickx**

It became a structure where it was more like a summer school, only in a fairly cold period of the year! There was a relaxed feeling and everybody knew it was possible to ask very precise or deep questions without anyone feeling personally threatened...It worked out fine.

"In EDENext it was very much embedded in the project, the PhD group was even more like a group than in EDEN. We have had at least 60 PhD students and that's a generation. It is really quite amazing in Europe. It means that over the past 10 years, EDEN and EDENext have put a stamp of quality on a whole generation of PhD students. There are several students from EDEN that have been working in EDENext and that is very nice. It has definitely created a group of people thinking in a certain way about research and, actually, they are still applying that."

<figure><img src="image_57.png" /></figure>
<figure><img src="image_58.png" /></figure>

SCIENTIFIC ADVANCES
FOR BETTER PUBLIC
HEALTH
Kerstin Dressel<fnref n="1" />, Matthias Niedrig<fnref n="2" /> and
Martin H. Groschup<fnref n="3" /> (EDENext Public Health
Group)

INTRODUCTION

Vector-borne infections comprise a major group of diseases with high impact on human and animal health. Arthropod vectors such as mosquitoes, ticks, midges and sand flies or mammals such as bank voles are responsible for the transmission of pathogens to humans, domestic animals and wildlife hosts. Environmental changes and the dramatic increase in global trade and travel have meant that several diseases are starting to emerge in Europe, causing increasing challenges for Public Health (PH). This is clearly shown by recent events such as dengue emergence in Madeira, Portugal, in 2012, the outbreak of human hantavirus infections with more than 2,800 cases in Germany the same year; and the spread of Crimean-Congo haemorrhagic fever (CCHF) in south-eastern Europe, particularly in Turkey. These events mean that the risks and the consequences triggered by vector-borne infections are just starting to surface in the public awareness.

A prominent role was assigned to Public Health within the EDENext Project, funded by the European FP7 programme. PH in this context can be defined as an approach that focuses on vector-borne diseases as an important risk with an increasing impact on human and animal health. Emphasis is therefore laid on an integrated health approach ('One-Health') as it recognises the interrelated nature of both human and animal health, and recognises the links between health and the environment. The Public Health group was included in EDENext to interface with all five vector-specific groups: ticks, rodents, sand flies, midges and mosquitoes.

The EDENext Public Health work plan was defined and developed as an integrated risk-based approach applied to vector-borne diseases - the first time this has been formally attempted. We have developed a shared definition that has been presented both as an EDENext White Paper (2013) and a risk governance framework for PH activities relating to vector-borne diseases (VBD) (Schmidt et al. 2013). The risk governance framework provides a systematic approach for the analysis, assessment and governance of emerging health risks that adopts the guidelines developed by the International Risk Governance Council (IRGC 2005, 2008). The framework incorporates the five IRGC elements: (i) pre-assessment, (ii) appraisal, (iii) characterisation and evaluation, (iv) management directives and (v) communication, and has adapted them to Public Health.

This paper takes two case studies - on CCHF virus and hantavirus, causing nephropathica epidemica (NE, also referred to as HFRS or FHSR) in humans - to show that it was possible within the large collaborative EDENext project to address all five of these different elements of risk governance. The first chapter defines the relevance and the shared understanding of PH within the project. Chapter 2 shows how this concept has been applied within EDENext. Chapter 3 considers the two disease case studies within this framework.

This paper also reports on our attempts to formally define the additional necessary components to PH activities in the VBD arena. Whereas quantitative risk assessment is always considered to be the primary focal point for decision-making, we will illustrate how concern assessment, particularly the risk perception of vector-borne infections by the general public living in endemic areas, is equally important when identifying appropriate measures to manage the risks to public and animal health. We will also elaborate on the health communication strategies required for PH authorities to raise professional and public awareness of these diseases, especially in endemic regions.

We emphasise that the focus in each of the following sections is on findings that were actually produced within the EDENext project, which shall be used as an illustration of the underlying assumptions and the idea of the framework that we have proposed.

<footnote n="1">¹sine-Institut GmbH, Munich, Germany</footnote>

<footnote n="2">²Robert Koch-Institut, Berlin, Germany</footnote>

<footnote n="3">³Friedrich Loeffler-Institut, Island of Riems, Germany</footnote>
A SHARED UNDERSTANDING OF PUBLIC HEALTH IN THE FIELD
OF VECTOR-BORNE DISEASES WITHIN EDENEXT

We have based our EDENext understanding of Public Health on the four main areas identified by Kaplan et al. (2009) and agreed on the following shared definition (see White Paper 2013, p. 5 & p. 11): "The term Public Health used in this EDENext White Paper refers to a holistic, interdisciplinary and multi-level approach. Public Health is concerned with questions of prevention, rather than cure and it is concerned with health at the level of the population rather than the individual. It is, moreover, concerned with the facilitation of health equity in the society through the mobilisation of political, social and economic resources. Hence, Public Health considers various determinants of health, such as the ecological environment, interdependence between animal and human health, political structures, socio-cultural patterns, economic, living and working conditions, social and community networks or individual lifestyle factors."

APPLICATION OF THE PH PERSPECTIVES IN EDENEXT RESEARCH

Research projects on vector-borne diseases are rarely (if ever) designed to concisely answer questions relevant to PH. Three major activities were therefore applied within the EDENext consortium to promote the relevance of PH to research scientists concerned with these diseases and its vectors: EDENext PH reviews, PH guidelines, and PH Telegrams.

APPRAISAL OF THE 'STATE OF THE ART' KNOWLEDGE
IN TERMS OF PH (EDENEXT PH REVIEWS)

Before starting new research projects addressing PH topics it was important to screen and critically review available literature on the PH relevance of vector-borne diseases. These meta-analyses were eventually published as PH reviews:

* The impact of Crimean-Congo hemorrhagic fever virus on public health by Mertens et al. (2013) *Antiviral Research* 98: 248-260.

* Hantavirus infections in Europe and their impact on public health by Vahari et al. (2013) *Rev Med Virol.* 23:35-49.

* *Culicoides* biting midges and public health by Carpenter et al. (2013) *Antiviral Research* 100, 102-13.

* Sandfly-borne phleboviruses of Eurasia and Africa: epidemiology, genetic diversity, geographic range, control measures by Alkan et al. *Antiviral Research* (2013) 100:54-74.

* *Ixodes ricinus* and its transmitted pathogens in urban and peri-urban areas in Europe, new hazards and relevance for public health by Rizzoli et al. (2014) *Frontiers in Public Health* 2:251.

* Arboviruses pathogenic for domestic and wild animals by Hubálek et al. (2014) *Adv. Virus Res.* 89:201-75.

* Hantavirus emergence in rodents, insectivores and bats: What comes next? by Schlegel, et al. (2014) in: *The Role of Animals in Emerging Viral Diseases* (ed. N. Johnson), Elsevier, Academic Press, pp. 235-292
## GUIDELINES FOR PH RESEARCH WITHIN EDENEXT (EDENEXT PH GUIDELINES)

The Public Health relevance of particular research activities (such as studies on the distribution and spread of known vector species in new areas, the vector competence of putative local arthropods for arboviruses, the impact of environmental changes on vector distributions, virus prevalence and variety in arthropod vectors etc.) is frequently not appreciated by scientists working on vector-borne diseases. In order to communicate the PH idea and to enhance applicability for users of the PH risk governance framework, specific 'Guidelines for Public Health-oriented Science in EDENext' were produced to specifically help project partners identify and elucidate the PH content of their research. These practically oriented guidelines encouraged researchers to address all PH relevant issues in the design phase of a study, with a range of topics including (i) identifying and characterising risk areas; (ii) understanding transmission of vector-borne infections, (iii) finding options for prevention, control and treatment; and iv) evaluation of the relevance of the results to PH activities.

## TRANSLATION OF EDENEXT RESEARCH RESULTS FOR THE LAY AUDIENCE AND STAKEHOLDERS/DECISION MAKERS (EDENEXT PH TELEGRAMS)

EDENext publications were systematically scanned by the PH work group for data relevant to protect human health, then summarised in lay language and accessible formats into so-called Public Health Telegrams on Vector-borne diseases - PUBLICise Health: 'RainboGram' on rodent-borne diseases, 'TiBoGram' on tick-borne diseases, 'MoBoGram' on mosquito-borne diseases, 'CuliBoGram' on Culicoides-borne diseases and, 'PhBD-Gram' on phlebotomine-borne diseases. These can be downloaded directly from the EDENext website (http://www.edenext.eu/publications/publicise-health-edenext-s-public-health-telegram) and updated versions are also presented in this book.

## THE EDENEXT PH RISK GOVERNANCE FRAMEWORK: CASE STUDIES ON CCHF AND HANTAVIRUSES

The Public Health risk governance framework developed within EDENext comprises the following five elements of the International Risk Governance Council (IRGC 2005, 2008): (i) pre-assessment, (ii) appraisal, (iii) characterisation and evaluation, (iv) management directives and (v) communication. We selected the IRGC framework rather than other existing risk analysis approaches (see Sedda et al. 2015) because it includes three often neglected components: a focus on pre-assessment, an emphasis on concern assessment (which explicitly takes social, cultural, political, financial and economic considerations into account), and it highlights the central importance of communication within the risk governance process (White Paper 2013, p. 12). The PH risk governance framework was then exemplified in two case studies: Crimean-Congo haemorrhagic fever (CCHF) and nephropathia epidemica (NE). Recently, hanta and CCHF viruses have received considerable scientific and public attention. NE case numbers are rising in several parts of Europe, for example in Germany, and recent outbreaks of CCHF in Turkey and Greece have raised awareness amongst physicians and led to improved detection, though formal risk assessments are still lacking or inadequate.

## EXAMPLES FOR THE PRE-ASSESSMENT PHASE IN PUBLIC HEALTH RISK GOVERNANCE: DIAGNOSTIC CAPACITY

According to the IRGC framework, the pre-assessment phase focuses on early warning and monitoring, risk screening and scientific conventions of risk and concern assessment. In our framework these include a number of components (for details see Schmidt et al. 2013): scientific tools and diagnostic (laboratory) capacities for addressing and specifying the dimensions of the emerging health risk, and the identification and evaluation of existing regulatory systems used to justify specific actions.
Two external quality assessment (EQA) studies on CCHF and NE gave a good overview of the capacity and molecular diagnostic performance of European laboratories (Escadafal et al. 2012; 2012a). Since there is no approved vaccine or specific treatment for CCHF, reliable surveillance and diagnosis is essential. Diagnostic techniques include virus culture, serology and, more recently, molecular methods. The international EQA of CCHF molecular diagnostics to assess the efficiency and accuracy of molecular diagnostic methods applied by expert laboratories was organised by the European Network for the Diagnostics of 'Imported' Viral Diseases (ENIVD). Uneven performances using the same method indicates that there is still a need to improve testing conditions and standardise protocols. The purpose of the second EQA study on NE diagnostics organised by ENIVD was to collect updated information on the efficiency and accuracy of NE serological methods applied by expert laboratories. All studies showed a need to improve the diagnostic profile of several laboratories.

The unsatisfactory diagnostic performance in both case studies is related to the rarity of the diseases and the absence of commercial diagnostic assays. The evaluation of the diagnostic performance through an external assessment with inactivated samples offers a unique opportunity to verify diagnostic procedures since most laboratories have not evaluated their assays. Participants can learn how the assay they used performs and whether it needs improvement. Regarding the laboratory capacity, we can presume there is a sufficient number for the diagnosis of these kinds of rare diseases.

## APPRAISAL: A FOCUS ON THE PUBLIC'S RISK PERCEPTION OF VECTOR-BORNE DISEASES IN ENDEMIC AREAS

PH agencies need to communicate risk effectively. The complexity of the diseases and the interdependence of international PH systems, involving governmental as well as non-governmental agencies and bodies, mean that only a participatory approach will be effective. This approach must involve key players in the field of PH and take into account public risk perceptions with regard to vector-borne diseases.

Our PH risk governance framework shows that quantitative scientific risk assessment alone is inadequate for effective decision-making and that social science-based concern assessment is as important. Concern assessment is defined as encompassing risk perceptions of the affected population in all groups at risk, as well as their social response to a particular risk. It also encompasses social, economic and trans-boundary effects of the health risk (for more details see White Paper 2013; Schmidt et al. 2013). We have therefore performed a risk perception study on two vector-borne diseases.

This qualitative study was based on in-depth interviews with Public Health authorities and relevant stakeholders, and used focus group interviews with the general public in endemic areas (Dressel 2014). The study was conducted in five European countries supported by the rodent and tick vector groups of EDENext. The study on rodent-borne NE was conducted in France, Finland and Germany; and the work on tick-borne CCHF was completed in the Republic of Macedonia and Turkey.

The focus group analysis covered risk awareness, risk knowledge, risk behaviour and coping strategies, as well as information behaviour and public expectations in times of enhanced risk. Results were categorised by respondents' age, sex, occupation, personal affectedness and region. Fifteen focus groups in total (three per country) with 8-10 attendees each were conducted in endemic areas of each country. One group in each country was composed of professionals such as forest rangers or lumberjacks or veterinarians affected by the particular disease. The setting of the focus group followed certain socio-demographic variables that are known to influence risk perception, information behaviour, coping strategies and knowledge such as sex, age or region. The following summarises the risk perceptions that we found (see also Schüle 2012, Dressel 2012, Dressel 2013, 2014, Dressel, Sekovska and Stefanovska 2014, 2014a, Dressel 2014a, 2014b).

## FINLAND (NE)

In Finland, where Simo Tuppurainen assisted in the risk perception and communication study, Puumala virus (PUUV) is widespread throughout most parts of the country, but is not generally considered a challenging risk, perhaps because it is a familiar one. We found, however, that rural people, who are most at risk, do accept the risk more than urban residents, who tend to take PUUV more seriously even though they have only occasional contact with voles (particularly through their summer cottages). We also
found that risk perception did not vary with gender but did with age: older people, who are more experienced with the disease, tend to be more concerned than younger ones

per
the
han

FRANCE (NE)

In France, where Gabriela Pfeifle assisted in the risk perception and communication study, there was a striking lack of knowledge with regard to NE/PUUV in all groups (including the occupational risk group) even in the two areas where it is endemic, and so it was considered much less important than other VBDs, in particular leptospirosis. A typical interview quote was: "Funny, or better scary, to see how many things exist I am not aware of," said a man in the 25-45 age range in an urban group. Nevertheless, people felt they had a right to be informed about the risk by public authorities. Occupational risk group attendees were not concerned about NE risk, and saw other risks as more important. Urban residents were more worried about environmental risks than rural people, who considered the risks from VBD generally as a normal part of the natural environment.

<figure><img src="image_59.png" /></figure>

Figur

GERMANY (NE)

In Germany, where Steffen Schüle assisted in the risk perception and communication study, NE is quite common in several areas. Knowing someone who is/was personally affected by a risk played the most important role in sensitising respondents to the risk at the micro level. In contrast, people who did not know affected people tended to underestimate the risk or were more careless about it. The ecological dimension (such as living close to a forest or having a garden) was mentioned on all levels as a potential risk factor. Older people tended to be more sensitive regarding the perception of their ecological environment and its risk, for example in their awareness of the changing mice population. Overall, focus groups reported that a lack of knowledge led to a feeling of insecurity and not knowing what do to and how to tackle NE/PUUV.

<figure><img src="image_60.png" /></figure>

REPUBLIC OF MACEDONIA (CCHF)

In the Republic of Macedonia, where Jovana Stefanovska and Blagica Sekovska assisted in the risk perception and communication study, only generic haemorrhagic fevers are detected and treated, and no specific CCHF diagnostic test is used. There are no specific health campaigns, which would raise CCHF awareness among general practitioners or the public. Participants of both rural and urban focus groups were generally aware that tick bites could cause disease, though CCHF itself was unknown. Risk perception for this particular disease was extraordinarily low, despite the fact that neighbouring countries (Albania, Bulgaria, and Greece) have reported cases.

Figur

TURKEY (CCHF)

Contrary to the Republic of Macedonia, in Turkey, where Ayca Bakalacs and Pinar Oktem assisted in the risk perception and communication study, the risk perception of CCHF was high in all groups. Those people who were most at risk were well aware of the fact that they have an increased CCHF exposure risk and they know about necessary protective measures. Women generally stated that they are afraid of being bitten by ticks and getting the disease when going to the fields and barns: "We have panic, we have fear. [...] We are frightened in the barn and in the fields," said a 36-year-old woman in a rural focus group. Men also expressed their awareness of the risk, but did not use emotional words to do so. This was particularly striking among young men, who sometimes did not consider themselves at risk at all. In contrast, older men were even able to define the actual timeframe and specific circumstances of higher CCHF risk situations.

For each focus group, a word cloud was generated about the first association of focus group attendees with regards to the particular risk posed by hantavirus or CCHF. To the authors' knowledge this is the first time this has been attempted in such studies. It was particularly illuminating as the word clouds from all focus groups in any one country accurately reflected their risk

<figure><img src="image_61.png" /></figure>

Figur
perception and, particularly, their knowledge of the disease. The following three illustrations show the differences between the three case studies on hantavirus.

<figure><img src="image_62.png" /><figcaption>Figure 1: Word cloud of all Finnish focus groups on hantavirus.</figcaption></figure>

<figure><img src="image_63.png" /><figcaption>Figure 2: Word cloud of all French focus groups on hantavirus.</figcaption></figure>

<figure><img src="image_64.png" /><figcaption>Figure 3: Word cloud of all German focus groups on hantavirus.</figcaption></figure>

REFERENCES

Alkan C, Bichaud L, de Lamballerie X, Alten B, Gould EA, Charrel RN (2013). Sandfly-borne phleboviruses of Eurasia and Africa: epidemiology, genetic diversity, geographic range, control measures. *Antiviral Research* 100:54-74.

Carpenter S, Groschup MH, Garros C, Bauer MLF, Purse B (2013). *Culicoides* biting midges and public health. *Antiviral Research* 100, 102-13.

Dressel KM, Vanwambeke SO, Wint W and Niedrig M (2015). EDENext models for public health: two cultures, one goal. Case study of hantavirus disease in Germany. Poster presentation at the international conference: *Impact of Environmental Change on Infectious Diseases* IECD 2015, Melia, Sitges, Spain, 23-25 March 2015.

Dressel K (2014a). 'Joining Forces – Wege aus der Krise' oral presentation – 37. *Kongress der Deutschen Gesellschaft für Soziologie*, Session: Modelling and Simulation, 10 October 2014, Trier, Germany.

Dressel K (2014b). 'From risk maps and risk alleviation in Public Health: examples for Hantavirus and CCHF infection', oral presentation at the *International Meeting of Emerging Diseases and Surveillance*, IMED 2014, 3 November 2014, Vienna, Austria.

Dressel K and Schüle S (2014). Using Word Clouds for Risk Perception in the Field of Public Health – the Case of Vector-Borne Diseases, *Planet Risk*, Vol 2, No. 1, 2014.

Dressel K (2013). Risk Perception of Vector-Borne Diseases in Europe: The Case of Hantavirus in Finland, France and Germany, oral presentation at the *Medical Biodefense Conference*, Munich, Germany, 25 October 2013.

Dressel K (2012). A New Concept of Risk Governance in the Field of Public Health – The Case of Hantavirus Disease in Germany, oral presentation at the session: Environmental Changes and Health Implications at the *International Risk and Disaster Conference*, Davos, Switzerland, 28 August 2012.

Dressel K and Sedda L (2013b). How to integrate risk perception findings in spatial and temporal risk models? The Hantavirus case. *2nd One Health Summit*, Davos, Switzerland, 20 November 2013.

Dressel K, Sekovska B and Stefanovska J (2014). Risk Management Strategies in Case of an Outbreak of CCHF. A Comparative EDENext Case Study in R. Macedonia and Turkey, oral presentation at the *International Days of Veterinary Medicine*, Ohrid, Macedonia, 5 September 2014.
ere
low
atchy
nta-
ion for

ON

the
pests
we
use
virus
to
make
the
fect
of
ding

JS

ge-
dge,
steps
case,
age-

PH
imple
n of
hen-
risk.
ured
et al.
by
heir
id
by
polic-
tics,
dent
ach

ES

tion
and/

or stakeholders and the general public. This guarantees that communication is an iterative process that can be adapted and changed as needed (White Paper, p. 21).

Meaningful risk communication (or health communication) strategies can only be established using consolidated knowledge of the risk perception held by the public and stakeholders, considering what they know and what they don't know. This is particularly relevant when health is concerned, as improving the public's risk awareness effectively reduces risk behaviour, the risk of infection and influences the effectiveness of PH interventions.

What people know about a disease usually reflects, at least to some degree, the actual spread of a particular disease in a particular region. Within the EDENext risk perception studies, we have included both countries that are widely affected by a specific VBD (NE in Finland and CCHF in Turkey) as well as countries where the disease risk is only very low (NE in France, CCHF in Macedonia), Germany was intermediate with some endemic regions and some areas with no disease. We found that health risk communication strategies need to be adapted to the specific regional situation. In addition, we found that the area of residence also plays an important role: the more rural the population, the more knowledgeable the population is about a particular disease which predominantly occurs in rural environments; the more urban the population the less familiar it is and the higher the concern is, especially regarding rural health risks. Similarly, age is a strong determining factor for risk awareness and risk knowledge. Gender also played a role in some cases, as we have seen in the case of CCHF in Turkey.

In countries with newly emerging diseases, sensitisation of the population is needed in terms of campaigns that will not provoke panic, but spread a solid knowledge to promote risk awareness of these diseases. This should also include dedicated information campaigns and training for people at occupational risk. In addition, general practitioners, who can be expected to be the first people to correctly recognise and diagnose the disease, should be informed. In countries with current health risks restricted to endemic areas, no widespread information campaign is necessary, but information campaigns should be targeted to the specific needs of the population in endemic areas. Case specific recommendations on targeted health communication strategies that take into account socio-cultural factors of risk perception of VBD were formulated for the five examined countries (Dressel 2014).

In an innovative and fruitful joint approach between EDENext modellers and the Public Health group, focus group participants in the risk perception study reviewed health risk communication material (risk maps) and their opinions were collected. The risk maps were then modified and adapted by the modellers in response to the needs and wishes expressed by people living in endemic areas (Dressel 2014a, 2014b). There is great potential for modelers to support risk communication strategies by providing model outputs that can be used by practitioners as well as for informing the general public (Vanwambeke, Tersago and Sedda 2013; Dressel and Sedda 2013; Niedrig and Dressel 2013; Dressel et al. 2014; Dressel et al. 2015).

Dressel K, Sekovska B and Stefanovska J (2014a). Risk Management Strategies in Case of an Outbreak of Crimean Congo Hemorrhagic Fever (CCHF) and Other Vector-Borne Diseases (VBD), a Comparative Case Study of R: Mace donia, Turkey and Germany. *Mac Vet Rev* 2014; Volume 37; Supplement 1; S. 25-26.

Dressel K, Vanwambeke SO, Sedda L, Wint W, Lancelot R, Tersago K and Niedrig M (2014). Joint EDENext Approach on Modelling and Public Health, oral presentation at the *EDENext Annual General Meeting*, Rovaniemi, Finland, 26 March 2014.

Dressel K (2014). Deliverable 16.1, Report of Public Risk Perception, EDENext project. Unpublished.

Dressel K, Groschup M, Mertens M, Niedrig M, Schmidt K, Schülé S (2012). *White Paper: Public Health and Vector-Borne Diseases. A New Concept for Risk Governance*. Published on EDE-Next website: www.edenext.eu.

Escadafal C, Öhlschläger S, Avši T, Papa-Konidari A, Vanhomwegen J, Wölfel R, Mirazimi A, Teichmann A, Donoso-Mantke O, Niedrig M (2012b). First international external quality assessment of molecular detection of Crimean-Congo hemorrhagic fever virus. *PLoS Neglected Tropical Diseases*, 6(6), e1706

Escadafal C, Avši -Županc T, Vapalahti O, Niklason B, Teichmann A, Niedrig M, Donoso-Mantke O (2012). Second External Quality Assurance Study for the Serological Diagnosis of Hanta-viruses in Europe. *PLoS Neglected Tropical Diseases*, 6(4):e1607

Hubálek Z, Rudolf I, Nowotny N (2014). Arboviruses pathogenic for domestic and wild animals. *Adv Virus Res.* 89:201-75.

International Risk Governance Council (2005). *White Paper on Risk Governance. Towards an Integrative Approach*, IRGC, Geneva.

International Risk Governance Council (2008). *An introduction to the IRGC Risk Governance Framework*, IRGC, Geneva.

Kaplan JP, Bond TC, Merson MH, Reddy KS, Rodriguez MH, Sewankambo NK and Wasserheit NK (2009). Towards a common definition of global health, *Lancet* 373, 1993-1995.

Mertens M, Schmidt K, Ozkul A, Groschup MH (2013). The impact of Crimean Congo hemorrhagic fever virus on public health. *Antiviral Research* 98: 248-260.

Niedrig M and Dressel K (2013). Improved Public Health by creating an interface between concern assessment and modeling. Oral presentation at the *2nd One Health Summit*, Davos, Switzerland, 20 November 2013.
## CONCLUSIONS

We have shown in this paper that the great challenge of introducing Public Health perspectives to vector-borne research scientists was not only taken up, but generated several valuable inputs with immediate impact for PH practice. The idea of a common understanding of a "holistic, interdisciplinary and multi-level approach" was taken seriously by the EDENext consortium and the inherent potential of such an approach became apparent in a wealth of publications, models and recommendations to decision makers. The EDENext Public Health risk governance framework has shown its potential and illustrated how each discipline involved, ranging from vector scientists, modellers and social scientists to human and animal epidemiologists, has contributed with its specific expertise to complete and integrate PH relevant knowledge. It is necessary to evaluate, to revise, to adapt and to improve the overall framework after every new or new emerging epidemic in order to pave the way for target-specific risk management and sensible health communication strategies, and to enhance preparedness for future epidemics in the field of One Health.

Rizzoli A, Silaghi C, Obiegala A, Rudolf I, Hubalek Z, Foldvari G, Plantard O, Vayssier-Taussat M, Bonnet S, Spitalska E, Kazirova M (2014). *Ixodes ricinus* and its transmitted pathogens in urban and peri-urban areas in Europe: new hazards and relevance for public health. *Frontiers in Public Health* 2:251

Schlegel M, Jacob J, Krüger DH, Rang A, Ulrich RG (2014). Hantavirus emergence in rodents, insectivores and bats: What comes next? In: *The Role of Animals in Emerging Viral Diseases* (ed. N. Johnson), Elsevier, Academic Press, Amsterdam, Boston, Heidelberg, London, New York, Oxford, Paris, San Diego, San Francisco, Singapore, Sydney, Tokyo, pp. 235-292.

Schmidt K, Dressel K, Niedrig M, Mertens M, Schüle S, Groschup M (2013). Public Health and Vector-Borne Diseases – A New Concept for Risk Governance. *Zoonosis and Public Health*, 2013, 60, S. 528-538.

Sedda L, Morley D, Braks MAH, de Simone L, Benz D, Rogers DH (2015, in print). *Risk assessment of vector-borne diseases for Public Health risk governance*.

Schüle S (2012). Public Risk Perception and Risk Communication from a Public Health Perspective, oral presentation at the EDENext annual meeting, Izmir, Turkey, 26 March 2012.

Vahari A, Henttonen H, Voutilainen L, Mustonen J, Sironen T, Vapalahti O (2013). Hantavirus infections in Europe and their impact on public health. *Rev Med Virol*, 23:35-49.

Vanwambeke S, Tersago K and Sedda L (2013). One Health as a tool to strengthen interactions between risk modelling and veterinary and human public health. Oral presentation at the 2nd *One Health Summit*, Davos, Switzerland, 20 November 2013.

## ACKNOWLEDGEMENT

We would like to thank all those who worked with and in the EDENext Public Health team. In particular, we thank the following institutions:

- Friedrich Loeffler-Institut, Germany

- Robert Koch-Institut, Germany

- sine-Institut GmbH, Germany
## Interview: Marieta Braks

<figure><img src="image_65.png" /></figure>

For you as a Public Health professional, what have been the outstanding achievements of EDEN and EDENext?

**Marieta Braks (National Institute for Public Health and the Environment (RIVM), Netherlands):** "One thing is that in the 10 years EDEN and EDENext have run, people who were not in it were very jealous. I know lots of Americans who are very jealous that you can run such a thing for 10 years with 30 institutions from 15 countries and manage to go through to the end. I think it has often been said that it cannot be done and this is proof that it can, especially [concerning] data sharing. This has been an enormous move because people said that people were not going to do it...I know a lot of people who have worked in this field but didn't find a community, they were very isolated. These projects have made a community of different vectors and different disciplines, from molecular biology and ecology to Public Health and modelling and that is quite an achievement. I know that it has sometimes been a struggle. I have seen a lot of different people who didn't understand each other and if you have 10 years, two times five years, together it proves that it takes that long to get over it, so you need that investment. And I think the next step is for EDENext to be even more applied to Public Health. It's still quite far from my daily usage."

How could it be closer to your daily professional life?

**Marieta Braks** studied biology at the University of Utrecht and obtained her PhD in entomology for research on the host-seeking behaviour of mosquitoes in the laboratory and in the field (Tanzania) from Wageningen University in 1999. Subsequently, she accepted a four-year post-doctoral position at the Florida Medical Entomology Laboratory UFL (USA) investigating the invasion ecology of yellow fever and Asian tiger mosquitoes in the USA and Brazil. She then worked at the Entomology Laboratory of the University of California at Riverside and the Department of Vector-borne Diseases of the California State Department of Public Health. In 2007, she returned to the Netherlands to work at the Centre for Zoonoses and Environmental Microbiology and has extensive experience in the surveillance and control of vectors and diseases at RIVM (National Institute for Public Health and the Environment). She joined the EDENext advisory committee in 2012.

**Marieta:** "If I can give an example. Only two days ago a physician asked me about tularaemia, which is a very complicated disease transmitted by different vectors, sometimes by water, sometimes by hare and maybe some others too. And it's different in every country. When I worked in California it was biting flies, it is ticks in Sweden, mosquitoes in other areas, by moles...it is very complicated. In Holland we have had a few incidents of tularaemia so a physician who is dealing with these patients said, 'You guys don't really know anything about ticks right?' Obviously I was a bit shocked by this but having been in Public Health I didn't go defensive and say we have been investigating for 20 years. Apparently, though, we didn't do anything for him.

"The problem with the work that we do is that it is not generalised. If you take measles it is the same in Poland, in California or in South Africa, so by now we have figured out how it is transmitted. The problem with tularaemia and all the other diseases is that it is very spatially and temporally variable so you feel that you don't progress because it breaks out somewhere else and the entomologist has to go out in the field again and you may do that for 50 years. So you have to do something...to explain that it is always different and it is not because it is our hobby or anything, but transmission cycles are temperature dependent, host dependent. It's an important message that we have shown across Europe, why we have to do it and that you cannot generalise as you can go hopelessly wrong.

"If you cannot explain this, for the physician it feels as though you are just asking for more money again. And that is what occurred to me last week when I talked to this physician. I thought, we know lots about ticks, we know about Lyme, but you cannot investigate tularaemia