Population density and water balance influence the global occurrence of hepatitis E epidemics

In developing countries, the waterborne transmission of hepatitis E virus (HEV), caused by HEV genotypes 1 (HEV-1) and 2 (HEV-2), leads to the onset of large recurrent outbreaks. HEV infections are of particular concern among pregnant women, due to very high mortality rates (up to 70%). Unfortunately, good understanding of the factors that trigger the occurrence of HEV epidemics is currently lacking; therefore, anticipating the onset of an outbreak is yet not possible. In order to map the geographical regions at higher risk of HEV epidemics and the conditions most favorable for the transmission of the virus, we compiled a dataset of HEV waterborne outbreaks and used it to obtain models of geographical suitability for HEV across the planet. The main three variables that best predict the geographical distribution of HEV outbreaks at global scale are population density, annual potential evapotranspiration and precipitation seasonality. At a regional scale, the temporal occurrence of HEV outbreaks in the Ganges watershed is negatively correlated with the discharge of the river (r = -0.77). Combined, our findings suggest that ultimately, population density and water balance are main parameters influencing the occurrence of HEV-1 and HEV-2 outbreaks. This study expands the current understanding of the combination of factors shaping the biogeography and seasonality of waterborne viral pathogens such as HEV-1 and HEV-2, and contributes to developing novel concepts for the prediction and control of human waterborne viruses in the near future.