Seroepidemiology and genetic characterization of hepatitis E virus in the northeast of china
Introduction
Hepatitis E, the major form of enterically transmitted non-A, non-B hepatitis, is caused by hepatitis E virus (HEV), a member of the Hepeviridae family. HEV has a 7.2-kb positive-sense RNA genome encoding three opening reading frames (ORFs) (Panda et al., 2007). Natural antibodies against HEV have been detected in numerous animal species (pigs, sheep, goats, cattle, horses, donkeys, deer, cats, rodents, and mongooses), suggesting the possibility of zoonotic spread of the virus (Favorov et al., 2000, Wang et al., 2002, Guthmann et al., 2004, Saad et al., 2007). However, HEV RNA has been detected only in pigs, sika deer and wild mongooses (Tei et al., 2003, Nakamura et al., 2006, Panda et al., 2007). Epidemics of hepatitis E associated with contaminated water supplies have occurred in several countries in the developing world and HEV is endemic in many other areas with inadequate sanitation (Worm et al., 2000, Schlauder and Mushahwar, 2001). Although hepatitis E usually is regarded as a travelers’ disease in industrialized countries, HEV infections also may occur sporadically in individuals who have no history of travel to areas of endemicity (Takahashi et al., 2002). Although a single serotype has been proposed, HEV isolates identified worldwide have been classified into four genotypes based on nucleotide sequence analyses. These include genotypes 1 (throughout Asia and Africa), 2 (Mexico, Nigeria and Chad), 3 (USA, Europe, Japan, South America and Australasia), and 4 (China, Japan, and Vietnam) (Schlauder and Mushahwar, 2001, Lu et al., 2006). Genotypes 1 and 2 have been isolated only from humans whilst genotypes 3 and 4 seem to be principally viruses of pigs, although they also cause sporadic cases of hepatitis E in humans. Such human cases are believed to be zoonotic in origin and presumably arise following transmission from pigs and, occasionally, deer via various routes, including the consumption of contaminated pig and deer meat.
One of the prototype sequences of genotype 1 HEV was derived from the causative agent of a large epidemic of hepatitis E in the Xinjiang Uighur autonomous region of (western) China in 1986 (Aye et al., 1992). Genotype 4 HEV is endemic in pigs in China (Wang et al., 2002) and sporadic human cases of hepatitis E throughout the country are causes by genotypes 1 and, perhaps more often, 4 (Li et al., 2002). However, there is little information regarding the epidemiology of HEV and which genotypes are prevalent specifically in the northeast of China. Therefore, we conducted a survey to ascertain the current epidemiology of HEV in humans and animals in the northeast of China and analyzed the relationship between human and animal HEV by comparison of nucleotide sequences of HEV isolated from both.
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Serum samples
Serum samples used in this study were collected from 22 farms in the northeast of China, including Heilongjiang, Jilin and Liaoning provinces (Fig. 1). 4600 pig serum samples were collected from farms (nos. 1–4, 8–12, 15–19), 1612 cattle serum samples from farms (nos. 5–7, 10, 12–14, 20–21), 1302 sheep serum samples from farms (nos. 5–7, 13–14, 20, 22). 985 human serum samples from individuals with frequent contact with swine, including pig farmers and slaughtermen, were collected from farms
Detection of anti-HEV in human and animals
Serum samples were collected from 22 farms in the Northeast of China (Heilongjiang, Jilin and Liaoning provinces). Among the human samples, other than those from patients with acute hepatitis E, 71 were positive for anti-HEV IgM, including 0.6% (6/985) of individuals with frequent contact with swine, none of individuals with infrequent contact with swine and 1.6% (65/3994) of the general population with very rare contact with swine. The overall prevalence of anti-HEV IgG was 31.6% (311/985) in
Discussion
Hepatitis E virus (HEV), the etiological agent of hepatitis E, is a hepevirus in the family Hepeviridae. Transmitted primarily by the fecal–oral route, the virus is found worldwide and can cause epidemics and sporadic cases (Panda et al., 2007). In industrialized countries, although anti-HEV has been detected in normal blood donors, sporadic cases of hepatitis E not associated with traveling to regions of high endemicity have been reported only rarely. Recently, anti-HEV antibodies have been
Acknowledgments
We thank the farm workers in the three provinces, China, who provided us with the serum samples. We also thank Mr. Baoshan Yan from Kinghawk Biopharmaceutical Company (Beijing, China) for his assistance in detection of HEV RNA using real-time fluorescent RT-PCR. This study was supported by the “863” project (grant: 2006AA02Z453) from the Ministry of Science and Technology, China.
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