Molecular epidemiology of hepatitis delta virus in the Western Pacific region

https://doi.org/10.1016/j.jcv.2014.05.021Get rights and content

Highlights

  • Patient isolates from four Pacific Islands were screened for hepatitis delta virus RNA.

  • 37% of patients with chronic hepatitis B from Kiribati were positive for HDV RNA.

  • Phylogenetic analysis revealed that the isolates were of genotype 1.

  • These isolates formed a distinct Pacific clade with a sample from Nauru.

  • The isolates are possibly related to strains of African origin.

Abstract

Background

Hepatitis delta virus (HDV) is a defective RNA virus requiring the presence of the hepatitis B virus (HBV) for the completion of its life cycle. Active replication of HDV can lead to severe hepatitis, and although present worldwide has an irregular geographical distribution, especially in the Asian Pacific region.

Objectives

The aim of this study was to determine the prevalence and molecular epidemiology of HDV isolates in Oceania following the 1998 evaluation of the hepatitis B vaccine program.

Study design

Sera collected from 184 hepatitis B surface antigen (HBsAg) positive Pacific Islanders living in Micronesia, Polynesia and Melanesia were tested for HDV RNA.

Results

Twenty of 54 patients with chronic hepatitis B (CHB) from Kiribati were positive for serum HDV RNA (37%), whilst sera from patients with CHB from Tonga (59), Fiji (42) and Vanuatu (29) were negative. The mean HDV RNA load for the 20 samples was 7.00 log10 copies/mL. Phylogenetic analysis revealed that the Kiribati HDV isolates were of genotype 1 and clustered with a previously published isolate from Nauru forming a distinct clade of Pacific HDV. All Micronesian isolates contained a serine at codon 202 of large hepatitis delta antigen (L-HDAg) demonstrating possible relatedness to strains of HDV-1 of African origin.

Conclusions

This study has confirmed endemic HDV infection in Micronesia and identified Kiribati as having amongst the highest prevalence for HDV viraemia in patients with CHB. Further investigations are ongoing into the origins of this unique HDV Pacific strain, and its inter-relationship with HBV.

Section snippets

Background

Infection with hepatitis delta virus (HDV) occurs in individuals by either super-infection in someone already infected with the hepatitis B virus (HBV) or by co-infection at the time of HBV transmission. Serological surveys have shown that infection with HDV is present worldwide [1] but has an irregular distribution, being endemic in the Mediterranean basin, parts of Africa, the Middle East and South America [2], [3]. The prevalence in Western Europe [4], Scandinavia [5] and Australia [6] is

Objectives

The objective of this study was to define the molecular epidemiology of HDV isolated from individuals who reside in the Western Pacific, providing a reference point for future epidemiological comparisons and investigations.

Serum samples

HBsAg-positive samples were collected from four Pacific Islands shown in Fig. 1. A total of 184 serum samples were analysed: 54 from Kiribati, 29 from Vanuatu, 42 from Fiji, and 59 from Tonga. The demographic details of these individuals have been previously reported [11]. Written approval for all the initial and current survey procedures was obtained from the Department of Health in each country and informed consent was obtained from each adult or the mother or guardian of each participant [11]

HDV screening and quantitative testing by real-time PCR

Testing for HDV RNA was carried out on samples from four Western Pacific Islands, Fiji and Vanuatu located in Melanesia, Tonga within Polynesia and Kiribati located in Micronesia (Fig. 1). Using the qualitative screening PCR assay of Casey et al. [33], HDV RNA was detected in 18 out of 54 patients (33.3%) from Kiribati, whereas no signal was detected in any of the 59 HBsAg positive samples from Tonga, the 42 samples from Fiji nor the 29 samples from Vanuatu.

The HDV quantitative real-time PCR

Discussion

Of the 350 million chronic carriers of HBV worldwide, more than 15 million have serological evidence of exposure to HDV [39]. Traditionally, the regions where HDV is endemic are central Africa, the Horn of Africa, the Amazon Basin, eastern and Mediterranean Europe, the Middle East, and parts of Asia. In 2007 Zuberi et al. reported a sero-prevalence of 26.8% HDV infection in HBsAg positive patients in Pakistan [40], whilst Braga et al. in 2012 reported 41.9% sero-prevalence in the Brazilian

Author contributions

MH, SB, QN, SL and KJ did the conception and design of the study. MH, ML, LY, RE, UD, SB, SL and KJ did acquisition of data, and analysis and interpretation of data. MH, ML, LY, SL and KJ did drafting the article or revising it critically for important intellectual content. MH, ML, LY, RE, UD, SB, QN, SL and KJ finally approved the version to be submitted.

Funding

This study was supported by the Molecular Research and Development division of the Victorian Infectious Diseases Reference Laboratory.

Competing interests

None declared.

Ethical approval

Written approval for all the initial and current survey procedures was obtained from the Department of Health in each country and informed consent was obtained from each adult or the mother or guardian of each participant.

Acknowledgements

Funding for the initial epidemiological study was provided by UNICEF through the contributions of the Governments of Australia through the Australian Agency for International Development and New Zealand through New Zealand Overseas Development Assistance, Ministry of Foreign Affairs and Trade. The Governments of Fiji, Kiribati, Tonga and Vanuatu contributed personnel and logistic support and the authors are grateful for this support. The authors would like to acknowledge Jenny Leydon from the

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