Scientists have identified a 'molecular barcode' in the blood of patients with Ebola virus disease that can predict whether they are likely to survive or die from the viral infection.
A team at the University of Liverpool, in collaboration with Public Health England, Boston University and other international partners, used blood samples taken from infected and recovering patients during the 2013-2016 West Africa outbreak to identify gene products that act as strong predictors of patient outcome.
Funded by the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections and the United States Food and Drug Administration, the new research provides data on the underlying causes of Ebola virus infection and suggests that this type of blood analysis could be integrated into future outbreak responses as a diagnostic tool to help guide treatment strategies.
Since the Ebola outbreak in West Africa much research has been done to further understand the biology of the Ebola virus. In particular, the processes that lead to survival or a fatal infection are unknown, although the amount of virus present in the body (viral load) can be a key determinant.
However, while this premise worked well for predicting outcomes for people with extreme viral loads, it was less clear for people with mid-range counts, the majority of cases, where the outcome prediction was approximately equal between survival and a fatal infection.
The results of this new study, which are published in Genome Biology, identified a small number of genes whose expression accurately predicts patient survival, independent of viral load.
Blood samples collected by the European Mobile Laboratory in Guinea of Ebola patients who either went on to survive or die from the acute infection, were analysed using genomic techniques to identify and quantify messenger RNA (mRNA) expression. These results were compared to blood samples from a separate group of survivors who had recovered from infection and were now free of the Ebola virus.
The analysis also provided some fundamental information on the host response to Ebola virus infection in humans, and found that an immediate robust immune response didn't affect whether people went on to live or die from the infection. The data also points to the virus causing significant liver damage.
Professor Julian Hiscox, a virologist at the University of Liverpool's Institute of Infection and Global Health, said: "Our study provides a benchmark of Ebola virus infection in humans, and suggests that rapid analysis of a patient's response to infection in an outbreak could provide valuable predictive information on disease outcome."
Professor Miles Carroll, Director of Research at Public Health England, added: "This study helps us to further our understanding of the human response to Ebola virus infection. This understanding should enable more effective patient care resulting in improved clinical outcomes in future outbreaks."
Dr John Connor, Associate Professor of Microbiology, Boston University School of Medicine, added: "It is not just defining how much Ebola virus that is present in a patient that defines whether a patient will survive. How the patient fights the infection is also key. Defining common aspects of how the immune system responds in individuals that survive opens a new window for studying how to keep Ebola virus infection from being a fatal infection."
The paper 'Transcriptomic signatures differentiate survival from fatal outcomes in humans infected with Ebola virus' is published in the journal Genome Biology [DOI 10.1186/s13059-016-1137-3]
University of Liverpool
The University of Liverpool is one of the UK's leading research institutions with 81% of research rated world leading or internationally excellent. Liverpool is ranked in the top 1% of higher education institutions worldwide and is a member of the Russell Group. Visit http://www.
Public Health England
PHE exists to protect and improve the nation's health and wellbeing, and reduce health inequalities. It does this through advocacy, partnerships, world-class science, knowledge and intelligence, and the delivery of specialist public health services. PHE is an operationally autonomous executive agency of the UK Government's Department of Health. For more information on PHE visit http://www.
Boston University School of Medicine
Originally established in 1848 as the New England Female Medical College, and incorporated into Boston University in 1873, Boston University School of Medicine (BUSM) today is a leading academic medical center with an enrollment of more than 700 medical students and 950 students pursuing degrees in graduate medical sciences. BUSM faculty contribute to more than 668 active grants and contracts, with total anticipated awards valued at more than $693 million in amyloidosis, arthritis, cardiovascular disease, cancer, infectious diseases, pulmonary disease and dermatology, among other areas. The School's teaching affiliates include Boston Medical Center, its primary teaching hospital, the Boston VA Healthcare System, Kaiser Permanente in northern California, as well as Boston HealthNet, a network of 15 community health centers. For more information, please visit http://www.
National Institute for Health Research (NIHR)
The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. The NIHR is the research arm of the NHS. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website (http://www.
Food and Drug Administration (USA)
This work was funded by the FDA Medical Countermeasures Initiative (MCMi) under contract HHSF223201510104C. The views, opinions, and/or findings are those of the authors and not necessarily those of the FDA. Learn more about MCMi at: http://www.