Worldwide diversity of hepatitis A and E viruses in urban wastewater
Abstract
Abstract Hepatitis A and E viruses (HAV, HEV) are the main causes of enterically transmitted hepatitis. Many infections remain undiagnosed due to their mild clinical course or asymptomatic presentation, and limited testing. Yet, knowledge of circulating genotype diversity is needed to understand their epidemiology and guide interventions. Wastewater surveillance may complement clinical monitoring by capturing infections missed through routine diagnostics. We applied capture-based metagenomic sequencing to characterize HAV and HEV genetic diversity in wastewater from 62 cities across 38 countries (2017-2019), complemented with longitudinal sampling from five European cities (2020-2021). Rocahepevirus ratti (rat HEV) genotype C1 was detected in 70% of cities, extending its known geographic range by 12 countries. Rat HEV sequences clustered by city and country, though some lineages spanned multiple continents. Paslahepevirus balayani (human HEV), predominantly genotype 3, was most prevalent in European cities. HAV genotype distribution largely reflected regional endemicity, although some subgenotypes were detected in regions where they are rarely reported clinically. Faecal source analysis suggested that rat HEV detected in wastewater originates primarily from rodent contamination rather than human infection. These findings reveal the global distribution of HAV and HEV genotypes and the widespread occurrence of rat HEV, demonstrating the value of wastewater metagenomics for…
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