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

Abstract

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.

Figure 1

Outbreaks caused worldwide by hepatitis E virus (HEV-1 or HEV-2) due to the consumption or use of fecally-contaminated water included in the dataset compiled in this study. This map corresponds to outbreaks occurred from 1980–2017 affecting either population living in urban or rural settings, or in refugee camps.

Figure 2

Map of the general model of the ecological suitability for the occurrence of hepatitis E waterborne outbreaks obtained by the Maxent method. This model was obtained combining outbreak data, population density and environmental data. Purple circles represent the location of the outbreaks used to obtain the model. The maps were obtained using obtained using the MaxEnt software version 3.4.1 (Steven J. Phillips, Miroslav Dudík, Robert E. Schapire. Maxent software for modeling species niches and distributions. Available from http://biodiversityinformatics.amnh.org/open_source/maxent/).

Figure 3

Map showing the environmental model of the ecological suitability for the occurrence of HEV outbreaks obtained using MaxEnt. To obtain this model, we combined only outbreak and environmental data. Population density data was excluded to highlight the effect of environmental parameters. The maps were obtained using obtained using the MaxEnt software version 3.4.1 (Steven J. Phillips, Miroslav Dudík, Robert E. Schapire. Maxent software for modeling species niches and distributions. Available from http://biodiversityinformatics.amnh.org/open_source/maxent/).

Figure 4

(A) Map of the Ganges watershed with the RivDIS locations, the registered outbreaks included in the dataset and the river network. Maps^© www.thunderforest.com, Data^© www.osm.org/copyright. (B) The blue line represents the monthly average values of the flow of the Ganges River (m³/s) registered in RivDIS stations. Red dots stand for the number of outbreaks recorded from 1980 until 2017 in the watershed area. The variables are negatively correlated (r = −0.77, p = 0.004).