Investigation of human adenovirus in paediatric haematology patients
Research type
Research Study
Full title
The investigation and molecular typing of adenovirus in paediatric bone marrow transplant patients by whole genome sequencing and immunohistochemistry
IRAS ID
238376
Contact name
Emma A Davies
Contact email
Sponsor organisation
Manchester University NHS Foundation Trust
Duration of Study in the UK
1 years, 6 months, 28 days
Research summary
Summary of Research
Adenoviruses are commonly found in the faeces of patients following bone marrow transplant causing little or no symptoms. In a small number of patients the virus infection gets out of control and spreads through the body causing organs to fail. Death can occur in >80% of patients where the virus spreads as the available treatments rarely work or are so toxic they make patients sicker. Research into why the virus spreads in only a small number of patients has focussed almost entirely on patient factors (such as transplant type) but the possibility the virus is different has not been explored. At the moment treatment is only started once the virus has spread from the faeces into the blood as the risk of harm to patients from the available drugs is high when the chance of spread is low. We believe that an improved understanding of the genetics of the adenoviruses that spread to cause more severe disease could lead to screening tests which would predict the risk of spread and allow clinicians to start treatment once adenovirus is detected in faeces in those at highest risk. Starting treatment early would mean shorter courses of treatment would be needed therefore reducing toxic effects and potentially improving patient outcomes. To achieve this this study aims to analyse the entire DNA sequence of adenoviruses from the general population and bone marrow transplant patients both with and without spread through the body to look for differences in their DNA using samples in long term storage from routine hospital visits. We would also like to visualise differences in the local gut immune system for adenovirus to see if those where the virus has spread have no adenovirus specific immune response in the gut.
Summary of Results
Adenoviruses are commonly found in the faeces of patients following bone marrow transplant causing little or no symptoms. In a small number of patients the virus infection gets out of control and spreads through the body causing organs to fail. Death can occur in >80% of patients where the virus spreads as the available treatments rarely work or are so toxic they make patients sicker. Research into why the virus spreads in only a small number of patients has focussed almost entirely on patient factors (such as transplant type) but the possibility the virus is different has not been explored. At the moment treatment is only started once the virus has spread from the faeces into the blood as the risk of harm to patients from the available drugs is high when the chance of spread is low.We believe that an improved understanding of the genetics of the adenoviruses that spread to cause more severe disease could lead to screening tests which would predict the risk of spread and allow clinicians to start treatment once adenovirus is detected in faeces in those at highest risk. Starting treatment early would mean shorter courses of treatment would be needed therefore reducing toxic effects and potentially improving patient outcomes. To achieve this this study aims to analyse the entire DNA sequence of adenoviruses from the general population and bone marrow transplant patients both with and without spread through the body to look for differences in their DNA using samples in long term storage from routine hospital visits. Whole genome sequencing of Adenoviruses is possible from blood, faeces and respiratory tract samples with high sucess rate and generation of high quality data. The method developed here is reproducible and can provide results within 72 hours which could be useful in managing infections in hospital. There appears no genetic differences between viruses isolated from those in the community and paediatric bone marrow transplant patients. There also appears to be no genetic difference between those bone marrow transplant patients who have virus in their blood and those who don't. This suggests routine whole genome sequencing of adenoviruses is not helpful in knowing when to start treatment in bone marrow transplant patients to improve outcomes.
REC name
HSC REC A
REC reference
18/NI/0170
Date of REC Opinion
11 Sep 2018
REC opinion
Favourable Opinion