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Genomic Revolutions in Blood Donation Screening and Safety: The natural history of occult hepatitis B virus infections and their risk for blood transfusion.


   Nuffield Department of Medicine

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  Dr Heli Harvala, Dr Monique Andersson  No more applications being accepted  Funded PhD Project (UK Students Only)

Oxford United Kingdom Bioinformatics Epidemiology Genomics Microbiology Pathology Virology

About the Project

A project in this area will investigate the occurrence and natural history of occult Hepatitis B Virus (HBV) infections, the markers associated with transmission of HBV in blood and organ recipients and the development of additional methods to identify infectious donations and exclude them from the blood supply. A major focus of work will be towards the characterisation of serological and patient/donor markers that delineate active from quiescent infections. These might include investigation of the potential value of ultra-sensitive HBsAg testing, anti-HBc antibody titres, HBV genotype and T cell reactivity to defined epitopes encodes in the core and surface antigen genes of HBV. As donors born in areas of endemic HBV represent the bulk of donors with OBI, an ability to differentiate between active and inactive infections will enable reinstatement of a large proportion of BAME donors and minimise loss of donations with rare blood groups. 

Appointed students will work under the supervision of Dr Monique Andersson (University of Oxford) and Dr Heli Harvala (NHS Blood and Transplant and University College London).

Training Opportunities offered in the studentship.

·      Standard HBV diagnostics, sample handling, PCR, serological assays.

·      Next generation sequencing methods and associated bioinformatics analysis of read data.

·      Detection methods of T cell immune reactivity to HBV

·      Participation in the clinical investigation of donors with occult HBV and its natural history.

·      Shared working with other PhD/MPhil students in the wider programme investigating a range of other aspects of transfusion-related microbiology

·      Programmes of presentations, seminars and attendance at national and international scientific meeting to present research findings

·      Working within a combined University / NHSBT environment, the latter providing knowledge of how a large scale, healthcare-based service provider works and delivers to patients and the donor community. 

Background information. Work in the Research Unit will be focussed in several areas critical for supporting and strengthening screening capabilities for transfusion transmitted infections by NHS Blood and Transplant services

·      Technology – Developing and evaluation of new technologies in virus genome detection and associated bioinformatics in blood and organ donations.

·      Viromics - Application of next generation sequencing for microbial and viral characterisation in investigations of transmission and pathogenicity

·      Safety - Targeted investigations of identified transmission risks, such as hepatitis B virus, arboviruses and other emerging pathogens

The Research Unit will comprise a large team of clinical and laboratory scientists in Oxford and in University College London, along with support and administrative staff and resource development. This infrastructure will support a final roster of nine PhD students working in Oxford, UCL and Public Health England. 


Funding Notes

Funding is provided for payment of PhD registration fees for Oxford University or UCL (£9200 / year) and tax-free stipend of £18,000 / year.

References

López-Labrador FX, Brown JR, Fischer N, Harvala H, Van Boheemen S, Cinek O, et al. Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part I: Wet lab procedure. J Clin Virol. 2021;134:104691.
Harvala H, Reynolds C, Gibney Z, Derrick J, Ijaz S, Davison KL, et al. Hepatitis B infections among blood donors in England between 2009 and 2018: Is an occult hepatitis B infection a risk for blood safety? Transfusion. 2021;61(8):2402-13.
Bonsall D, Golubchik T, de Cesare M, Limbada M, Kosloff B, MacIntyre-Cockett G, et al. A Comprehensive Genomics Solution for HIV Surveillance and Clinical Monitoring in Low-Income Settings. J Clin Microbiol. 2020;58(10).
Lythgoe KA, Hall M, Ferretti L, de Cesare M, MacIntyre-Cockett G, Trebes A, et al. SARS-CoV-2 within-host diversity and transmission. Science. 2021;372(6539):eabg0821.
Bonsall D, Gregory WF, Ip CL, Donfield S, Iles J, Ansari MA, et al. Evaluation of Viremia Frequencies of a Novel Human Pegivirus by Using Bioinformatic Screening and PCR. Emerg Infect Dis. 2016;22(4):671-8.
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