Dried Blood Spot Testing for Blood Borne Virus Infection v1.0
Research type
Research Study
Full title
Dried Blood Spot Testing for Blood Borne Virus Infection:- Quantitative HCV PCR and whole genome sequencing.
IRAS ID
290445
Contact name
Paul Klapper
Contact email
Sponsor organisation
University of Manchester
Clinicaltrials.gov Identifier
NHS001875,
Duration of Study in the UK
2 years, 11 months, 10 days
Research summary
Summary of Research
Hepatitis C virus infection (HCV) is a major cause of liver inflammation (hepatitis), infection with this virus can cause liver failure and death many years after an initial infection. Yet hepatitis C infection can be cured if it is diagnosed and treated. In the United Kingdom the majority of infections (90%) are found in injecting drug users, who have proved difficult to test because of difficulty in drawing blood from their veins damaged through prolonged intravenous drug usage. Using a simple finger prick test (the dried blood spot test; DBS) which collects a spot of blood onto paper that is then dried and transported to the laboratory, diagnosis can now be easily made in individuals with poor veins. We aim to develop a method to precisely measure the amount of virus in these DBS samples to allow us to show how the amount changes in response to treatment. Also by examining the genetic make up of the virus, determine the optimum antiviral drug treatment for the individual infected and at the same time enable study how different strains of virus spread in the community as an aid to public health control of infection. Information gathered would also aid development of new methods of control of spread including vaccination. The simplicity of collection of DBS allows extension of diagnosis, monitoring and treatment outside the traditional healthcare environment and would have clear potential for use in healthcare resource poor regions throughout the world. This initial study will, within 2 years, demonstrate the feasibility of the approach which, if successful, will allow development of clinical trials to determine the feasibility and utility of the new techniques and their introduction into routine practice.
Summary of Results
Hepatitis C affects ~58 million people worldwide, with 1.5 million new infections each year, many among injecting drug users. Dried blood spots (DBS) are valuable for diagnosis in hard-to-reach and low-resource settings, but standard DBS cannot reliably measure viral load. The HemaXis™ DB 10 device enables volumetric DBS sampling, allowing HCV RNA quantitation. Using mock DBS samples (prepared by drying plasma mixed with whole blood) viral loads (i.e the concentration of virus) from DBS were found to be consistently lower than plasma (by around 2,344 IU/mL) however, the method showed high specificity (100%) and good sensitivity (85.6%), demonstrating strong potential to expand HCV diagnosis and management. We were also able to show that combining dried blood spots (DBS) with Oxford Nanopore sequencing (ONS) enables accurate, low-cost, and decentralised HCV genotyping and whole-genome sequencing. Using 127 mock DBS samples, the protocol achieved 96% concordance with the standard genotyping assay (Roche Cobas®) assay for partial genome sequencing and 100% agreement for whole-genome sequencing of genotype 1a, even detecting rare subtypes missed by standard methods. The approach offers a practical, real-time solution for HCV diagnostics and genomic epidemiology in hard-to-reach and resource-limited settings, with future work needed to expand whole genome sequencing to all HCV genotypes and perform quantitative DBS testing in a real world setting.
REC name
London - Central Research Ethics Committee
REC reference
21/PR/1245
Date of REC Opinion
9 Sep 2021
REC opinion
Favourable Opinion