# First Report of Hepatitisis E Virus in Shellfish in Southeast Italy
## 1 Introduction  
Hepatitis E virus (HEV) represents one of the principal causative agents of hepatitis globally [1] and it is considered an emergent issue in industrialized regions, where transmission by contaminated food plays a key role [2]. HEV is a hepatotropic, single-stranded positive-sense RNA virus with a genome of approximately 7.2 kb, belonging to the _Hepuridze_ family, genus _Ortholepepvirus_, _Ortholepepvirus_ A species [3, 4]. Five of the eight genotypes of _Ortholepepvirus_ A (HEV-1, 2, 3, 4, and 7) infect humans [4]. HEV can exist in two forms: non-enveloped or \"quasi-enveloped\" [3]. All HEV genotypes belong to a single serotype [5]. The human viruses HEV-1 and HEV-2 genotypes are highly endemic in developing regions, including various regions of Africa, Asia, the Middle East, and Mexico, and are diffused through contaminated water. These viruses are accountable for a great number of outbreaks and cause severe hepatitis during pregnancy [6]. By contrast, genotypes 3 and 4 are revealed in both animals and humans and are the principal causes of hepatitis E in humans in several developed countries [7]. The World Health Organisation (WHO) has estimated that 20 million persons worldwide are newly infected with HEV annually, with 3.3 million developing acute hepatitis E and 70,000 dying of HEV-related causes [8]. Over the last decade, HEV infection has been reported to cause more than 21,000 cases of hepatitis E, with 28 deaths, in the European Union (EU), where food-borne transmission seems to be the major path of infection [9]. These data do not reflect the real number of infected people in the EU because HEV infection is not required to be reported to public health authorities in all member states of the EU, and the surveillance systems differ among countries. In Italy, the number of individuals infected with HEV increased during the years 2007-2018, as well as doubling from 2018 to 2019, although not all regional laboratories are able to specifically differentiate HEV from other hepatitis viruses. Moreover, a peak of cases wasreached in 2019 when the number of cases doubled compared to the previous year [10]. In European countries, HEV genotype 3 is the most prevalent HEV genotype infecting humans, with relatively few patients being infected with genotype 4. These genotypes are thought to be transmitted through foods, especially the consumption of undercooked or raw pig, wild boar, and deer meat [9]. Domestic swine appear to represent the principal source of zoonotic HEV transmission in Europe and are considered the main viral reservoir [9; 11]. The European Food Safety Authority has estimated that HEV can be transmitted to humans by the consumption of foods composed of meat from an infected animal and by foodstuffs fouled with HEV [9]. For the latter, virus shedding by feces (animal and human) represents an important public health risk. Indeed, environmental contamination, including contamination of organic fertilizers and water, can provide a source for HEV contamination of other foods, including shellfish, soft fruits, and leafy green vegetables [12]. In the feeding process, by filtering from their marine environment, shellfish can concentrate viral particles, becoming a potential source of human infection [13]. Although the consumption of raw shellfish, liver sausage, and wild boar meat was recognized as a hazard factor for locally acquired HEV infection in Italy [5], only a small number of surveys to date have evaluated the presence of HEV in shellfish for human consumption [13; 14; 15; 16; 17]. The Apulia region of southeast Italy, with an 860 km coastline [18], is a major source of shellfish for consumption throughout Italy. Shellfish are usually consumed in the undercooked or raw state in the Apulia region. To our knowledge, however, no survey to date has assessed the attendance of HEV in mussels sold at retail in the Apulia region.