Origin of HAV strains responsible for 2016–2017 outbreak among MSM: Viral phylodynamics in Lazio region

In Europe HAV infection occurs mainly among specific risk groups, such as consumers of specific food. Sexual transmission of HAV has been demonstrated, particularly among Men-Who-Have-Sex-With-Men (MSM), causing MSM-specific outbreaksin Europe. Here we report a molecular epidemiologic and phylodynamic analysis on HAV sequences in Lazio (central Italy)to identify genetic background and the phylogenetic relations, and test the HAV infection dynamics during a large outbreak through phylodynamic model.Among all HAV sequences found during 2013–2018 in Lazio, low genetic diversity was observed in HAV population in 2016 and 2017, along with high frequenciesVRD_521_2016and RIVM-HAV16-090, suggesting a large expansion event of viral population. The initial expansion of both VRD_521_2016 and RIVM-HAV16-090 clusters dated back to 2012 (95% HPD:2006–2015). During the2016-2017outbreak in Lazio region, the R(e) peaked around mid-2016, with a value of 1.73 (95% HPD: 1.03–2.37), consistent with incidence trend of AHA cases in Lazio between 2016 and mid-2017. This study showed the magnitude of HAV outbreak in Lazio during 2016–2017, demonstrating the epidemic continuity to MSM-specific outbreak in Europe. The HAV dataset is available on interactive phylodynamic platform https://nextstrain.org to real-time update of future outbreaks.