Dengue is an Aedes-borne viral disease, endemic in South America, Central America and the Caribbean, Southeast Asia, the Western Pacific and Sub-Saharan Africa.1 Globally, there are an estimated 100–400 million infections per year and almost half the world population is at risk of infection by DENV.1,2 The incidence has increased dramatically over the last years, with the highest number of dengue cases recorded in 2019.1

Dengue virus is transmitted primarily via the bite of female mosquitoes of Aedes aegypti and Aedes albopictus, which are also vectors of chikungunya, yellow fever, West Nile and Zika viruses,1,3,4 and of a total of 26 viruses – at least, experimentally.5Ae. albopictus is a highly invasive vector which has managed to spread throughout the world, beyond tropical and subtropical zones through international travel and trade and is now present in many areas in southern Europe, including Spain.6

Ae. albopictus can resist over winter,7,8 although its period of vector activity ranges from spring to autumn. The optimal climatic conditions for its establishment and expansion include temperatures>0°C, with annual averages>11°C and 500mm of precipitation, and summers with 25–30°C and rain. Ae. albopictus was first detected in Spain in 20049 and it is established in the regions of Catalonia, Valencia, Murcia, Andalusia, the Balearic Islands, Aragon and the Basque Country and more recently in Madrid and Extremadura.10

Many travelers return with viraemic infections to Europe and consequently transmission is possible when Ae. albopictus is present in their areas or residence. In the case of Spain viremic travel-related cases are reported every year and their number is projected to continue increasing in the near future.11

Profiling the spatial risk of autochthonous dengue is necessary in identifying areas with populations at risk and guiding the geographic strategy for prevention and control measures.12–14 Risk maps can combine information on the distribution of the vector, its potential expansion, as well as the occurrence of the disease to predict the risk of infection.2,14 Therefore, the aim of this work was to map the risk of autochthonous dengue cases in Spain based on the potential expansion of Ae. albopictus, the number of travelers from endemic countries and the number of cases declared to the Spanish National Network of Epidemiological Surveillance (RENAVE) in order to guide preparedness and response plans for detection and control of dengue in Spain.

In this work a risk assessment of autochthonous dengue occurrence in Spain, by municipality, has been carried out, taking into account environmental factors for the expansion of Ae. albopictus, the volume of travelers from endemic areas and the number of notified dengue cases.

The meteorological conditions make Spain and especially the eastern areas, a favorable area for the introduction, establishment and expansion of the vector. Different studies carried out in Europe indicate that the Mediterranean area as well as other locations in the north of our country are suitable for the mosquito.14,21,22 In fact, since the first detection of Ae. albopictus in Spain, occurred in 2004 in Catalonia,9 the vector has colonized other neighboring areas and is currently present in most locations in the Levantine coast, Balearic Islands and even in inland and northern areas.

Ae. albopictus species was usually associated with sporadic dengue cases or self-limited outbreaks, due to its limited competence related to its feeding behavior and the relative recent adaptation of flaviviruses to the vector (including dengue fever virus).23 However, since 2010, a few autochthonous outbreaks of dengue caused by Ae. albopictus occurred in Europe.24 In addition to the 2018 and 2019 outbreaks in Spain, outbreaks were also detected in France and Croatia. Nevertheless, it is important to highlight that, although the presence of the vector is necessary it is not sufficient for the occurrence of autochthonous cases. Other factors such as vector density, population density, environmental conditions and the regular presence of viremic people are necessary for such outbreaks to occur and for sustained transmission over time.

Globalization and international travel and trade, have increased the risk of introduction of imported diseases.6 As reported by the World Tourism Organization, Europe receives the highest number of visitors with more than 580 million visits per year with an average increase of 2.8% over the last 10 years.25 According to the statistics on border movements (FRONTUR) from the National Institute of Statistics, Spain received in 2018 more than 82 million of tourists, with almost 20% from countries outside Europe.26 Considering AENA's arrivals by plane, the annual average from 2014 to 2017 of travelers from endemic countries was 5.3 million. Based on the number of travelers from endemic countries arriving to Europe,6 indicated that southern Europe is a zone at risk of autochthonous dengue outbreaks, as it has been probed with the above mentioned outbreaks.

Other studies have also investigated the spatial distribution of Ae. albopictus and dengue in Europe and worldwide. Cunze et al. presented risk maps for the expansion of Ae. albopictus in Europe based on the suitability of the habitat and the environmental limiting factor for its establishment. Using a maximum entropy model with environmental conditions such as the ones used in our work, they found that Spain and in particular the Levantine coast had high suitability for the expansion of Ae. albopictus.21 Leta et al. employed species distribution models with environmental conditions and disease distribution to produce worldwide maps indicating the territories suitable for Ae. albopictus and Ae. aegypti. In these maps, Spain showed a relative low suitability for both species in a worldwide context.14 Liebig et al. a global model was built to predict the risk of indigenous dengue cases based on the arrivals of travelers from endemic countries. According to the findings of this study, Spain appears among the countries with high numbers of estimated imported cases, although below Italy and France.27

The first autochthonous cases of dengue in our country occurred in 2018 and were attributed to Ae. albopictus. The autochthonous cases had been in Andalusia, Murcia and Catalonia at the estimated time of transmission.28 In 2019, another autochthonous case was declared in Catalonia.29 These events seem to be consistent with our findings; the dengue risk map showed a medium risk in Murcia while municipalities in Catalonia characterized as high risk or very high risk. Early identification of areas at risk for the appearance of dengue cases can alert local authorities to stablish prevention and control measures, but also clinicians and public health authorities related to surveillance and alert and respond systems to develop more targeted plans by stratifying risk areas and prioritize actions. Among them, surveillance, prevention and control of vectors should be included as an important node on health interventions in the integrated management of vector–borne diseases. Such plans would not only mitigate the potential risk of dengue but also of other severe diseases transmitted by this invasive mosquito.

The findings of this study are subject to some limitations. Firstly, the centroid of the municipality was used instead of the exact coordinates of the mosquito trap. This may have affected the Ae. albopictus risk distribution risk model since environmental conditions can vary even within a municipality. Although this could be the case, the analysis and production of maps was conducted at the municipal level, minimizing possible environmental differences. The model used for the Ae. albopictus expansion risk map was based on current environmental conditions and did not take into account climate change which may affect both meteorological conditions and vector distribution. Mosquitoes have already been detected in areas in which they were not previously found. Other limitations concern the IDVZE calculation. The travelers’ information was analyzed at the provincial level, since the municipality was unknown and countries were defined as endemic as a whole, i.e. the entire territory was considered endemic without distinguishing endemic zones in the country and grading the risk accordingly.

The results of this analysis can guide public health measures for the surveillance and control of dengue and the proper allocation of resources, to prevent autochthonous dengue cases and outbreaks in our country, once travel restrictions will be eased.

This is the first work that provides a dengue risk assessment tool for Spain, based on a spatial approach. Several areas in the Mediterranean coast of Spain are at a higher risk of autochthonous dengue, based on environmental conditions, the expansion of Ae. albopictus, the number of imported cases of dengue and the number of travelers coming from endemic countries. The risk map can inform public health and local authorities in order to stratify risk and planning actions aimed at controlling the disease and guide the proper allocation of resources. Measures to mitigate the risk of local dengue transmission and prevent future dengue outbreaks should be prioritized for municipalities in these areas.

Beatriz Fernandez-Martinez: conceptualization; data curation; formal analysis; methodology; writing – review & editing.

Despina Pampaka: writing – original draft; writing – review & editing.

Pablo Suarez-Sanchez: formal analysis; methodology.

Josué Martinez de la Puente: writing – review & editing.

Jordi Figuerola: writing – review & editing.

Maria Jose Sierra: writing – review & editing.

Inmaculada León-Gomez: formal analysis; methodology; writing – review & editing.

Javu¡ier del Aguila: review & editing.

Diana Gómez Barroso: conceptualization; methodology; project administration; resources; supervision; writing – original draft; writing – review & editing.

This study was supported by project PI18/00850, funded by Instituto de Salud Carlos III and cofunded by European Union (ERDF7ESF, “Investing in your future”).

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.