Seroepidemiology and genotyping of hepatitis E virus in Singapore reveal rise in number of cases and similarity of human strains to those detected in pig livers

Abstract

Hepatitis E virus (HEV) causes 20 million infections worldwide yearly, of which only about 3.3 million are symptomatic. In developed Asian countries, HEV strains detected in human sera and in food sources were genetically similar, suggesting that indigenous HEV infections may be largely food‐borne. To assess the burden of hepatitis E in Singapore, we performed a seroepidemiologic study of the infection. Additionally, we carried out HEV genotyping on archived, residual HEV IgM‐positive serum samples collected between 2014 and 2016 (n = 449), and on pig liver samples (n = 36) purchased from wet markets and supermarkets. Our study shows a rise in hepatitis E incidence (IgM) from 1.7 to 4.1 cases per 100,000 resident population from 2012 to 2016 and an increase in hepatitis E IgG positivity rate among residents from 14% in 2007 to 35% in 2016. Other findings also suggest the epidemiology of hepatitis E in Singapore has shifted, from it being mainly a disease imported from the Indian subcontinent, to one that is now increasingly prevalent in our resident population. Genotypes obtained from 143 human samples identified the majority to be genotype 3 (n = 121), 21 to be genotype 1 and one to be genotype 4. Further phylogenetic analyses suggest genotype 3a to be the cause of indigenous infections in residents, which showed genetic similarity to the genotype 3a strains detected in pig livers. This link between the strains in the majority of human samples and those in pig livers consumed by the public suggests a possible food‐borne route of HEV infection in Singapore.

A systematic review of the epidemiology of Hepatitis E virus infection in South – Eastern Asia

“…However, in Singapore, the situation was the reverse of what is observed in Cambodia. Here, IgG seroprevalence increased from 14% in 2007 to 35% in 2016 [ 58 ]. In addition to factors enumerated as influencing variation of seroprevalence between countries, cultural practices, eating habits, and whether a country is developed or developing [ 59 ] will affect seroprevalence within a particular country.…”

“…However, even in Singapore, a developed country with a high – income economy, the seroprevalence (of 10.5% – 22.3%) appeared relatively high [ 58 , 60 ]. This scenario goes to prove that the endemicity of HEV is no longer restricted to only developing countries, but even developed countries are no exception [ 51 ].…”

“…HEV – 1 is believed to be restricted to only developing countries, but here, in addition to HEV – 3 and HEV – 4, HEV – 1 was also reported in Singapore ( Figure 4 ). However, the study alluded to the fact that HEV – 1 might be imported into the country by travelers or non – residents [ 58 ]. Another striking observation also is that despite recorded HEV outbreak in Indonesia, HEV – 1 and HEV – 2 were not reported in the country.…”

Serological prevalence and molecular characterization of hepatitis E virus in imported pigs in Singapore (2000–2019)

“…In Singapore, hepatitis E is listed as one of the infectious diseases notifiable to the Ministry of Health. In recent years, there have been reports of increased hepatitis E incidence and increased HEV seroprevalence rates among immunocompromised individuals (Tan et al., 2013; Wong et al., 2019; Zhu et al., 2019). These studies hypothesized a possible food‐borne route of HEV infection in Singapore as the local cultural predilection among the non‐Muslim population is to eat pig liver semi‐cooked.…”

“…Hence, examining the prevalence of HEV in slaughterhouse pigs will provide an indication of its occurrence in the regional source farm. Additionally, a recent study by Wong et al (2019) had demonstrated the presence of G3 HEV in pig livers sold at local markets. Therefore, the aim of this study was to investigate the presence of HEV further upstream along the food supply chain through an examination of anti-HEV antibodies and HEV RNA in imported pig samples and post-slaughter livers collected from 2000 to 2019.…”