Evidence that Rodents Are a Reservoir of Hepatitis E Virus for Humans in Nepal

Abstract

Hepatitis E virus (HEV) is an important cause of enterically transmitted hepatitis in developing countries. Sporadic autochthonous cases of hepatitis E have been reported recently in the UnitedStates and other industrialized countries. The source of HEV infection in these cases is unknown; zoonotic transmission has been suggested. Antibodies to HEV have been detected in many animals in areas where HEV is endemic and in domestic swine and rats in the United States. There is evidence supporting HEV transmission between swine and humans. Nevertheless, HEV has not been detected in wild rodents. We tested murid rodents and house shrews trapped in Nepal's Kathmandu Valley, where hepatitis E is hyperendemic, for HEV infection. The most commonly trapped species was Rattus rattus brunneusculus. Serum samples from 675 animals were tested for immunoglobulin G against HEV by enzyme-linked immunosorbent assay; 78 (12%) were positive, indicating acute or past infection. Antibody prevalence was higher among R. rattus brunneusculus and Bandicota bengalensis than in Suncus murinus. Forty-four specimens from 78 antibody-positive animals had sufficient residual volume for detection of HEV RNA (viremia) by reverse transcription-PCR. PCR amplification detected four animals (9%; three were R. rattus brunneusculus and one was B. bengalensis) with viremia. Phylogenetic analysis of the four genome sequences (405 bp in the capsid gene) recovered showed that they were identical, most closely related to two human isolates from Nepal (95 and 96% nucleotide homology, respectively), and distinct from HEV sequences isolated elsewhere. These data prove that certain peridomestic rodents acquire HEV in the wild and suggest that cross-species transmission occurs, with rodents serving as a virus reservoir for humans.Hepatitis E virus (HEV) is the most important cause of acute hepatitis in many developing countries of Asia, the Middle East, and Africa as well as in Mexico (29). In industrialized countries, autochthonous hepatitis E was thought to be absent. Yet recently, a few autochthonous hepatitis E cases from the United States and other industrialized countries have been reported (12,13,18,22,24,31,32,39).HEV transmission is thought to occur primarily by the fecaloral route; water-borne epidemics are characteristic (1,28,29). Therefore, the occurrence of isolated hepatitis E cases can be explained only by silent transmission of HEV among human or animal case contacts.The occurrence of autochthonous hepatitis E in industrialized countries has focused renewed attention on the question of whether hepatitis E is a zoonosis (29; M. Favorov, O. Nazarova, and H. S. Margolis, presented at the Second International Conference on Emerging Zoonoses, Strasbourg, France, 5 to 9 November 1998). Antibodies to HEV have been found in cows, sheep, goats, chickens, water buffaloes, swine, wild rats, mice, and monkeys from areas where hepatitis E is endemic and in domestic swine and rats in the United States (3,9,10,20,21,26,37). Successful transmission of human HEV...

Rare Detection of Occult Hepatitis B Virus Infection in Children of Mothers with Positive Hepatitis B Surface Antigen

“…It was reported that novel hemagglutinin-esterase gene of human torovirus had been cloned [18], but it was a result of cross contamination by another virus occurred at the inception of the process [19]. Similarly, hepatitis E virus was reported to be isolated from rodents [20], which turned out to be caused by cross-contamination [21]. Moreover, simian virus 40 was proposed to be associated with the development of non-Hodgkin lymphoma [22], but it was demonstrated to be associated with false-positive PCR results [23].…”

Phylogenetic analysis of global hepatitis E virus sequences: genetic diversity, subtypes and zoonosis

“…Groups 1 and 2 represented genotypes 1 and 2, while genotype 3 was further divided into five genetic groups: groups 3 (USA), 4 (Italy and swine New Zealand), 5 (Greece and Spain), 6 (Greece and UK) and 7 (Argentina and Austria), and genotype 4 into two groups: 8 and 9 (China and Taiwan). Diversity of genotypes 3 and 4 appears to relate to their zoonotic origin from a variety of animals in different parts of the world, whereas the relative conservation of genotypes 1 and 2 is consistent with their primary circulation in humans and less frequent isolation from animals [32].…”

No Evidence for Hepatitis E Virus Genotype 3 Susceptibility in Rats

“…However, the virus genome has not been detected, and the source of the infection was confirmed in few cases; thus far, it is not clear whether the anti-HEV IgG was induced by HEV or other HEV-like viruses. The detection of a partial genome of G1 HEV from wild rats in Nepal was reported in 2002 ( 4 ); however, this report was retracted in 2006 because the isolated strain was determined to be a result of laboratory contamination. Recently, Lack et al isolated strains of G3 HEV from a variety species of wild rats in the United States ( 5 ); this finding suggests that wild rats are hosts for G3 HEV.…”