Epidemiological and Evolutionary Analysis of West Nile Virus Lineage 2 in Italy

Abstract

West Nile virus (WNV) is a mosquito-borne virus potentially causing serious illness in humans and other animals. Since 2004, several studies have highlighted the progressive spread of WNV Lineage 2 (L2) in Europe, with Italy being one of the countries with the highest number of cases of West Nile disease reported. In this paper, we give an overview of the epidemiological and genetic features characterising the spread and evolution of WNV L2 in Italy, leveraging data obtained from national surveillance activities between 2011 and 2021, including 46 newly assembled genomes that were analysed under both phylogeographic and phylodynamic frameworks. In addition, to better understand the seasonal patterns of the virus, we used a machine learning model predicting areas at high-risk of WNV spread. Our results show a progressive increase in WNV L2 in Italy, clarifying the dynamics of interregional circulation, with no significant introductions from other countries in recent years. Moreover, the predicting model identified the presence of suitable conditions for the 2022 earlier and wider spread of WNV in Italy, underlining the importance of using quantitative models for early warning detection of WNV outbreaks. Taken together, these findings can be used as a reference to develop new strategies to mitigate the impact of the pathogen on human and other animal health in endemic areas and new regions.

Spatial and temporal dynamics of West Nile virus between Africa and Europe

“…Overall, while the evolutionary history of WNV L1 is characterised by a complex behaviour possibly due to the constant connections between different continents, WNV L2 shows only one main independent introduction from Southern African countries (cluster 4) to Europe (cluster 5). Once in Europe, the lineage began to spread all over the continent, founding favourable eco-climatic conditions, which allowed it to become endemic and a serious public health concern in numerous regions and countries 28 , 32 . Our phylogenetic and phylogeographic reconstructions also suggest a second introduction of minor importance from Southern African countries to Europe, supported by the existence of a separate cluster 2 within Clade 2d, which includes three European strains (Italy/2014, Romania/2014, Hungary/2017) closely related to the strains of CAR (1993) and South Africa (1958 and 1977) of cluster 1.…”

“…In fact, vectors play a crucial role in transmitting viruses during their blood meal 43 . Most human outbreaks worldwide have been caused by L1 strains despite the strong presence of L2 in Europe and some African countries 10 , 15 , 31 , 32 , 43 , and the existence of other local strains, such as L8 and KOUTV in Africa 44 , 45 , or the Rabensburg virus and L4 in Europe 46 , 47 . While WNV L1 and L2 seem to have a minor impact in Africa 10 , the introduction of these African strains in Europe have caused a significant number of severe WNV cases in humans and other animals 31 , 32 , 43 , showing that local strains could have the ability to adapt to new environments and ecological niches and therefore be transmitted and become established.…”

“…In Italy, sampling activities were carried out between 2001 and 2022 as part of the national surveillance plan coordinated by the Ministry of Health, the Istituto Superiore di Sanità (epidemiology and national reference laboratory, human), and the Istituto Zooprofilattico of Abruzzo and Molise (IZS-Teramo) (epidemiology and national reference laboratory, animal/entomology) ( https://westnile.izs.it/j6_wnd/home , https://www.epicentro.iss.it/westnile/ ) 32 . In Senegal, sampling activities were carried out by the Institut Pasteur de Dakar (IPD-Dakar) in collaboration with the Ministry of Health, within the framework of the mosquito-based arbovirus surveillance system and a sentinel syndromic surveillance network (4 S).…”

“…In addition, 10 WNV L1 and 10 WNV L2 whole genome sequences, obtained from samples collected in Senegal between 1985 and 2018, were shared by the IPD-Dakar of Senegal and added to the dataset. The final dataset also included 30 WNV L1 and 45 L2 whole genome sequences, obtained at IZS-Teramo between 2008 and 2022, which were downloaded from the Supplementary Materials of 32 and [Origin and evolution of West Nile virus lineage 1 in Italy].…”

“…Only genomes longer than 10 Kb were retained and quality-filtering was performed 32 , but no sequences were removed because they did not contain a percentage of ambiguous bases greater than 10%. A total of 229 WNV L1 and 298 WNV L2 genomes, 188 of which came from Italy (81 L1 and 97 L2) and 31 from Senegal (18 L1 and 13 L2), were selected for further analysis.…”