**1. Introduction**

West Nile virus (WNV) is an arthropod-borne flavivirus transmitted by the bites of infected mosquitoes mostly belonging to the *Culex* genus [1]. WNV is maintained in an enzootic bird-mosquito cycle but can be transmitted through mosquito bites to dead-end hosts, such as humans or equids and occasionally cause neuro-invasive disease that can be lethal in these hosts [2]. In Europe, WNV outbreaks occur during the summer and fall seasons (July–October) when *Culex* mosquitoes are abundant.

According to phylogenetic analysis, eight di fferent WNV lineages have been described [3]. WNV lineages 1 and 2 are the most widespread and caused most of the major epidemics encountered so far [4]. WNV lineage 1 was first reported in Europe in the 1960s when seropositive animals (horses and cattle) or viral isolates (mosquitoes and humans) were identified in France, Portugal, and Cyprus [5,6]. After more than 30 years without experiencing WNV outbreaks, North African, Western, and Eastern European countries reported again the emergence of WNV lineage 1 strains belonging to the Western-Mediterranean clade (in North Africa and Western Europe such as in Morocco in 1996, Italy in 1998, and in France in 2000) [7–9] and the Eastern-European clade (Eastern Europe during the 1996 Romanian outbreak and Russia in 1999) [10] a ffecting mainly equids and or/humans respectively. In France, after the 2000 WNV outbreaks in the Camargue area, sporadic cases of West Nile fever (WNF) occurred in departments bordering the Mediterranean coast in the 2000s (Var in 2003, Bouches-Du-Rhône, Gard and Hérault in the Camargue area in 2004, and Eastern Pyrenees in 2006) [11,12]. WNF has been mainly reported in France in horses, while human cases have been less frequently observed (seven cases in Var in 2003) [13].

Most European WNV outbreaks before 2010 had been caused by WNV lineage 1 strains. Unexpectedly, recent increase in WNV transmission and outbreaks, noticeable in Europe since 2010, has been associated with the introduction and spread of WNV lineage 2 strains [14–16]. A first WNV lineage 2 strain was initially detected in Hungary in 2004 [17] and subsequently spread to the eastern part of Austria in 2008 [15,18], to the Balkan peninsula, including Greece in 2010 [19], Serbia, Croatia, and Bulgaria in 2012 [20,21], further East to Italy in 2011 [22], and more recently it reached Spain in 2017 [23] and Germany in 2018 [24,25]. Another WNV lineage 2 strain, first detected in 2004 in Rostov Oblast in Southern Russia [26], has also been occasionally reported in Europe, in Romania [27] in 2010, in Italy in 2014 [28], and in Greece in 2018 [29].

After WNV reemergence in the Camargue area in 2000, a multidisciplinary WNV monitoring system has been implemented in France since 2001 including clinical surveillance in wild birds, horses, and humans, and records of mosquito abundance and diversity during the transmission season. Such clinical surveillance is implemented in departments from the Mediterranean area during the WNV at-risk period from 1 June until the end of November [11].

Here we report recent French WNV outbreaks (2015–2019) in humans, equids, and the wild avifauna in the Mediterranean area and describe the emergence of WNV lineage 2 in France in 2018 and the changing patterns of infection in humans and horses following this emergence.
