Endemic HBV among hospital in-patients in Bangladesh, including evidence of occult infection.

Fazle Rabbi Chowdhury,Mohammad Robed Amin,Bikash Chandra Das,M Rokibul Hasan,Tanjila Rahman,M Azim Ansari,Anna L Mcnaughton,Mamun Al-Mahtab,K M Shahidul Islam,M A Faiz,Lovely Barai,Philippa C Matthews,Mariateresa De Cesare,Susanna Dunachie,Katie Jeffery,Mili Rani Saha,Jolynne Mokaya,Monique I Andersson,Barbara Kronsteiner

doi:10.1099/jgv.0.001628

Abstract

Bangladesh is one of the top-ten most heavily burdened countries for viral hepatitis, with hepatitis B (HBV) infections responsible for the majority of cases. Recombinant and occult HBV infections (OBI) have been reported previously in the region. We investigated an adult fever cohort (n=201) recruited in Dhaka, to determine the prevalence of HBV and OBI. A target-enrichment deep sequencing pipeline was applied to samples with HBV DNA >3.0 log10 IU ml−1. HBV infection was present in 16/201 (8 %), among whom 3/16 (19 %) were defined as OBI (HBsAg-negative but detectable HBV DNA). Whole genome deep sequences (WGS) were obtained for four cases, identifying genotypes A, C and D. One OBI case had sufficient DNA for sequencing, revealing multiple polymorphisms in the surface gene that may contribute to the occult phenotype. We identified mutations associated with nucleos(t)ide analogue resistance in 3/4 samples sequenced, although the clinical significance in this cohort is unknown. The high prevalence of HBV in this setting illustrates the importance of opportunistic clinical screening and DNA testing of transfusion products to minimise OBI transmission. WGS can inform understanding of diverse disease phenotypes, supporting progress towards international targets for HBV elimination.

Highlights

Estimates suggest that approximately a third of the world’s population has been exposed to hepatitis B virus (HBV), with chronic HBV infection (CHB) affecting more than 260 million individuals worldwide, leading to 800 000 deaths annually [1]
We looked for evidence of dual infections in the mapping of reads to HBV genotypes A-I and consensus sequences were further checked for evidence of recombination by bootscan analysis using RDP4 [31]
Active HBV infection was confirmed in 16/201 individuals (7.9 %), comprising 10/16 who were positive for both HBV surface antigen (HBsAg) and HBV DNA (62.5 %), 3/16 positive for HBsAg with undetectable HBV DNA (18.8 %), and 3/16 with occult HBV infections (OBI) based on testing positive for HBV DNA with negative HBsAg (18.8 %) (Fig. S1, available in the online version of this article)

Summary

Introduction

Estimates suggest that approximately a third of the world’s population has been exposed to hepatitis B virus (HBV), with chronic HBV infection (CHB) affecting more than 260 million individuals worldwide, leading to 800 000 deaths annually [1]. In combination with the large population, this HBV prevalence puts Bangladesh in the top-ten highest-burdened countries for viral hepatitis worldwide [6], with the perinatal incidence of new infections among the highest in South Asia [7].

Methods

Results

Conclusion