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Yellow fever in Italy: an Infectious Thoughts interview


Despite a relatively low incidence of yellow fever in recent decades following effective vaccination campaigns, outbreaks of this disease have recently returned in numerous regions worldwide. In recent research, a team of Italian researchers has evaluated the risk of autochthonous yellow fever transmission in the Lazio region of central Italy. In this Infectious Thoughts interview, we hear more about the threat of yellow fever and recurrent arbovirus outbreaks in the Mediterranean region, as well as the role of reduced vaccination coverage and thriving vectors in the resurgence of these diseases and what lessons can be learned for dengue surveillance and control.

Interview responses by Manica Mattia, Guzzetta Giorgio, Filipponi Federico, Solimini Angelo, Caputo Beniamino, della Torre Alessandra, Rosà Roberto, Merler Stefano.

Despite a relatively low incidence of yellow fever in recent decades following effective vaccination campaigns, outbreaks of this disease have recently returned in numerous regions worldwide. Based on your experience, what are some of the main reasons for this?

The main factors that impact the epidemiology and transmission of a vector-borne pathogen as the yellow fever virus are not easily disentangled. One of the main concerns is a reduced vaccination coverage in previously endemic countries. In our opinion another concern is that the vectors of yellow fever virus have shown to be able to thrive under a wide range of conditions and that the efforts to put under control their abundance are costly, require strong commitments both from public health authorities and citizens and are only partially effective. It could have happened that without the immediate threat of virus circulation, the focus on vector control may be relaxed or less effective eventually creating high-risk conditions for the further spreading of yellow fever after some initial cases.

Your research focuses on risk of yellow fever outbreaks in Lazio, Italy. What are some of the main drivers of these autochthonous cases?

Although Europe has been theater of several yellow fever epidemics in past centuries, in the last decades, no cases of yellow fever have been reported, with the exception of the 2012 outbreak in the tropical Madeira island (Portugal). Indeed, today the probability of importing yellow fever infected cases from ongoing outbreaks is estimated to be low. However, our analysis suggests that in the case of introduction of an infected host, there is a seasonal window when all conditions for the successful transmission to secondary cases are met. The main driver of this is the high vector density of an exotic mosquito vector species, Aedes albopictus, now fully established in most European Mediterranean areas after a rapid global invasion process.

What consequences does the successful establishment of Aedes albopictus in Mediterranean regions have in terms of yellow fever and other mosquito-borne diseases such as dengue fever, given the recent cases in Spain and France? The most worrying consequence resulting from Aedes albopictus establishment is that there is an actual risk of arbovirus recurrent outbreaks the Mediterranean region, as highlighted by the two large chikungunya outbreaks recorded in Italy (2007 in Emilia Romagna region and 2017 in Lazio region) and by chikungunya and dengue cases recorded multiple times in Spain, France and Croatia over the last decade.

What were the main advantages of your model and methodologies in evaluating the risk of yellow fever transmission in Italy?

Up to now, our approach has been extensively used to evaluate the transmission risk and to characterize the transmission dynamic of mosquito-borne pathogens (see among others Guzzetta et al, 2016* and Manica et al 2017**). The main strength of our model is that it has been calibrated on entomological surveillance data quantifying the local abundance of mosquito and its biting rate; a further strength is the incorporation of stochasticity in disease dynamics.

* Guzzetta G., Montarsi F., Baldacchino F., Metz M., Capelli G., Rizzoli A., Pugliese A., Rosà R., Poletti P. and Merler S. 2016. Potential risk of dengue and chikungunya outbreaks in northern Italy based on a population model of Aedes albopictus (Diptera: Culicidae). PLoS Neglected Tropical Diseases 10(6):e0004762.

** Manica M., Guzzetta G., Poletti P., Filipponi F., Solimini A., Caputo B., della Torre A., Rosà R., Merler S. 2017. Transmission dynamics of the ongoing chikungunya outbreak in Central Italy: from coastal areas to the metropolitan city of Rome, summer 2017. Eurosurveillance 22(44):pii=17-00685.

What are the main policy implications of your research?

Given the severe medical consequence of yellow fever, and the not completely negligible transmission risk, the main health policies that may be advocated based on our results are the rising of the awareness of the risk among physicians and public health authorities in order to implement rapid and effective system to detect imported tropical infections and prevent the spreading of the viruses into non-endemic countries, as well as a large-scale implementation of vector monitoring and surveillance activities which can lead to improvements in risk assessment and outbreak preparedness, and, possibly, of larval control interventions aimed to reduce Aedes albopictus abundance.

How can these approaches and conclusions be transferred to monitoring other diseases such as dengue fever?

Our models can be applied also to several other arbovirus disease including dengue and chikungunya fever: we found similar conclusions related to the risk of transmission for yellow fever and dengue. One of the main parameters varying in the model is the competence of the mosquito to host the multiplication of the virus and to transmit it to new host. Indeed, the risk of outbreaks of chikungunya virus was predicted (and shown by the recurrent autochthonous cases in Europe) as this virus is better adapted to transmission by Aedes albopictus.

What are some of the key ways in which researchers, funders and organisations working on the control of flaviruses and their vectors could improve collaboration to raise awareness and accelerate the prevention and control of these diseases in European regions and worldwide?

A unified commitment from all is needed. One first step in this direction is the recent EU funded project Aedes Invasive Mosquito COST ACTION CA17108 which brings together researchers, public health officers, public and private stakeholders from all over Europe to fill the present gaps in surveillance and control of invasive vectors of exotic arboviruses. Successful control strategies to reduce the nuisance created by these species, as well as the risk of arbovirus transmission, require strong commitment and large public awareness and involvement, as well as customized best-practices to reduce their abundance and public health threat.

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