Hepatitis E continues to be a significant global health challenge. In the EU/EEA region, the number of reported cases increased tenfold between 2005 and 2015. Sweden experienced a similar trend, with cases doubling between 2014 and 2017. Although there was a decline during the COVID-19 pandemic, the upward trend resumed this year. In the Region Västra Götaland, Sweden, approximately 16% of blood donors had anti-HEV antibodies, and about 5% had detectable HEV RNA. Yet, only 5-18 cases were reported annually between 2015 and 2024. This contrast highlights the significant underdiagnosis of hepatitis E in the region.
Rat hepatitis E virus (RHEV) has recently emerged as a growing public health concern. Initially believed to be confined to rodent populations, the first human case of RHEV was identified in Hong Kong in 2018. Since then, additional human cases have been reported in Canada and Europe. In 2017, RHEV was detected in effluent wastewater in Gothenburg using metagenomic techniques. However, the public health implications of RHEV in human infections were not considered at that time.
A recent study (One Health. 2024 Aug 22;19:100882) led by Dr. Hao Wang from the University of Gothenburg, in collaboration with researchers from Sahlgrenska University Hospital, examined the prevalence and genetic diversity of HEV and RHEV in weekly influent wastewater samples from the Rya wastewater treatment plant. The results revealed a high prevalence of both HEV and RHEV in wastewater samples, with RHEV concentrations being 1-4 log10 higher than HEV. Importantly, HEV subtype 3c/i dominated the wastewater samples, while HEV subtype 3f was more prevalent in clinical cases. Additionally, unreported HEV-3b and unclassified strains were identified in wastewater samples. Most RHEV strains were clustered within European genetic groups, none of which were genetically close to human RHEV cases reported to date.
These findings suggest a significant underestimation of hepatitis E infections in the region. The discrepancy in HEV subtypes between wastewater and clinical samples highlights either an underdiagnosis of HEV infections or variations in viral shedding patterns between HEV-3 subtypes. Prior research has shown that HEV-3f is dominant in Swedish wild boar and domestic pigs, while HEV-3c/i is found in water sources, including effluent wastewater, lakes, and tap water. This suggests that waterborne transmission may occur in addition to the well-established zoonotic transmission routes.
The prevalence of RHEV in wastewater is likely attributed to rodents inhabiting sewer systems, with household pets such as guinea pigs, hamsters, dogs, and cats potentially acting as additional reservoirs. These animals may contribute to the spread of both HEV and RHEV by shedding the viruses into wastewater. However, the role of pets in zoonotic transmission requires further investigation. Additionally, a proportion of hepatitis cases in Sweden remain unexplained, with no identified source of infection. Since current diagnostic methods do not detect RHEV, it is crucial to determine whether RHEV plays a role in these unexplained cases. The widespread presence and genetic diversity of RHEV in wastewater highlight the need for continued surveillance to assess its potential impact on human health.
Key references on this topic:
- Churqui, M.P., et al., High prevalence of hepatitis E and rat hepatitis E viruses in wastewater in Gothenburg, Sweden. One Health, 2024: p. 100882.
- Wang, H., et al., Hepatitis E virus genotype 3 strains and a plethora of other viruses detected in raw and still in tap water. Water Res, 2020. 168: p. 115141.
- Wang, H., et al., Hepatitis E virus strains infecting Swedish domestic pigs are unique for each pig farm and remain in the farm for at least 2 years. Transbound Emerg Dis, 2019. 66(3): p. 1314-1323.
- Wang, H., et al., Genetically similar hepatitis E virus strains infect both humans and wild boars in the Barcelona area, Spain, and Sweden. Transbound Emerg Dis, 2019. 66(2): p. 978-985.
