Chapter 20 : Waterborne Hepatitis

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This chapter addresses the biology and epidemiology of the waterborne viruses, hepatitis A virus (HAV) and hepatitis E virus (HEV), the value of diagnostic assays for each virus in different settings, and the current and future prospects for prevention and control of HAV and HEV infections. The HEV genome contains three open reading frames (ORFs), organized as 5’-ORF1-ORF3-ORF2-3’, with ORF3 and ORF2 largely overlapping. Acute infections with any of the hepatitis viruses, including HAV and HEV, cannot be distinguished on clinical characteristics or pathological examinations. Although the cyclical nature of HAV incidence suggests that caution should be exercised when interpreting the absolute disease incidence based on short-term trends, there can be no doubt that HAV vaccination in children is an effective public health measure, and it is hoped that other developed countries will implement similar policies in the near future. Although HAV (and potentially HEV) may be partly controlled with vaccines, there is evidence that some cases of waterborne hepatitis are due to as yet unidentified viral agents. A better understanding of HEV disease burden and appropriate use of the candidate vaccine in development will require enhanced efforts in surveillance and diagnosis of HEV, taking advantage of improved serological tests with appropriate use of confirmatory nucleic acid testing in countries where HEV is not endemic.

Citation: Anderson D. 2009. Waterborne Hepatitis, p 311-324. In Specter S, Hodinka R, Young S, Wiedbrauk D (ed), Clinical Virology Manual, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815974.ch20
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Genome replication and the encoded proteins of HAV (A) and HEV (B). Both viruses have positive-strand RNA genomes of around 7,500 nucleotides. HAV replication proceeds via transcription from the genome to give full-length negative- and then positive-strand RNA, which can either be assembled into the virus particle or used to translate further copies of a single, giant polyprotein which is processed by viral protease to yield the replicative proteins and capsid proteins. Assembly of five copies of each of the three capsid proteins (VP0, VP3, and PX) into pentamers and then 12 pentamers into capsids is required to form the antigenic sites of the virus. (B) Details of HEV replication are unknown, but it most likely produces a full-length negative-strand RNA and then full-length positive-strand RNA (new viral genomes and mRNA for the ORF1 polyprotein) as well as a single subgenomic messenger RNA which is used to translate the ORF2 (capsid) and ORF3 proteins. Processing of the ORF1 polyprotein yields the replicative proteins, but the precise locations of cleavage sites is unknown. Cleavage of full-length PORF2 results in assembly of VLPs from the truncated product, but it is not known whether the truncated or full-length PORF2 is normally involved in virus assembly. PORF3 is dispensable for replication in vitro but not in vivo.

Citation: Anderson D. 2009. Waterborne Hepatitis, p 311-324. In Specter S, Hodinka R, Young S, Wiedbrauk D (ed), Clinical Virology Manual, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815974.ch20
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Image of FIGURE 2

Serological and virological courses of infection with HAV or HEV. For HAV, the serological responses shown are typical of those detected with numerous commercially available assays. For HEV, the serological responses shown are those that probably occur in most patients, but the detection of these responses will vary widely depending on the assays used. High levels of HAV-specific IgG provide lifelong protection from reinfection, but HEV-specific IgG declines rapidly during the first 6 months and might not persist at protective levels for life. ALT, alanine aminotransferase.

Citation: Anderson D. 2009. Waterborne Hepatitis, p 311-324. In Specter S, Hodinka R, Young S, Wiedbrauk D (ed), Clinical Virology Manual, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815974.ch20
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HEV IgM reactivities of patients with acute hepatitis in Nepal. Samples from patients with symptoms consistent with acute hepatitis in the month of August 1997 were tested in a prototype HEV IgM ELISA based on the ORF2.1 antigen, at the Siddhi Polyclinic, Nepal. Results are shown as the sample-to-cutoff ratio (data from I. L. Shrestha and D. Anderson).

Citation: Anderson D. 2009. Waterborne Hepatitis, p 311-324. In Specter S, Hodinka R, Young S, Wiedbrauk D (ed), Clinical Virology Manual, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815974.ch20
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Representative test results obtained with the Assure HEV IgM RPOC test. A sample with no detectable HEV-specific IgM (S982) shows a single line (control, C), while samples with HEVspecific IgM (J89, J60, and J70) show both control and test (T) lines. (Reprinted from Anderson and Shrestha, 2009, with permission of the publisher.)

Citation: Anderson D. 2009. Waterborne Hepatitis, p 311-324. In Specter S, Hodinka R, Young S, Wiedbrauk D (ed), Clinical Virology Manual, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815974.ch20
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