One of the four Precision Sequencing partners, the MRC-University of Glasgow Centre for Virus Research (CVR) is a research institute that uses high-throughput sequencing to gather information about viral genomes in order to identify and characterise viruses and understand virus-host interaction.
Dr Ana Da Silva Filipe, manager of the sequencing facility at the CVR, tells us about the role of the CVR in the treatment of a Scottish nurse who contracted Ebola while volunteering in Sierra Leone.
In 2014 an Ebola virus epidemic spread from central Africa into west Africa. Sierra Leone was one of the worst affected countries and as part of the humanitarian work, the Centre for Virus Research (CVR) sent volunteers to help set up and run clinical diagnostic field labs.
During this time a Scottish nurse, Pauline Cafferkey, was also volunteering in Sierra Leone. Pauline was providing direct care to patients with the disease and unfortunately became infected with Ebola.
It was established that Pauline had a very unique infection with the highest viral load ever recorded in an Ebola survivor. Pauline was initially treated at the high-level isolation unit at the Royal Free Hospital in London. Remarkably, after intense treatment, Pauline recovered and received the all clear to return home to Scotland. Several months later she began to feel unwell, suffering from severe headaches, neck pain and a high fever.
Following initial diagnostic tests, Ebola virus was once again detected, this time as a result of meningitis. Due to their experience, the CVR team was asked to get involved to sequence the genome of the virus.
“We processed and analysed samples extracted from the cerebrospinal fluid and blood. Through these we could confirm that the Ebola virus was circulating in the patient’s cerebrospinal fluid in vast amounts, when compared to the blood samples”, explained Dr Da Silva Filipe. “Typically, Ebola virus is detected in the blood and despite the known neurological complications associated to this viral infection, it was quite unique to detect Ebola virus RNA in a sample taken from the central nervous system, months after the initial infection. We wanted to determine if the virus was the same one as before, in order to assist the Royal Free team to select the most appropriate experimental therapy. To do this, we used high-throughput sequencing.”
From the data received, the CVR very quickly established that the virus was the same one that had caused the previous infection, and that the characteristics of the virus had hardly changed.
“One possibility to explain these observations was that the initial viral load was so high, that the virus somehow leaked in to Pauline’s central nervous system. We know this virus has the ability to hide in immune-protected areas and we think it concealed itself there and grew very slowly, undetected, until it reached high enough amounts to cause meningitis and leak back in to the blood stream,” said Dr Da Silva Filipe.
The data collected at the CVR suggested that the virus had not become resistant to the previous monoclonal antibody therapy and therefore this might remain a treatment option for Pauline.
All of this work was carried out in close collaboration with Public Health England, CVR Bioinformatics and the team of consultants assisting Pauline, including Dr Emma Thomson at the CVR. Due to the urgent nature of this case, the CVR team had to generate the data extremely quickly, informing Pauline’s consultants of the results of the sequencing less than 70 hours after receiving the samples.
“We frequently process clinical samples, typically characterised by low amounts of material, which can be challenging. Fortunately, the experience we have accumulated over the years means we are well prepared to respond to these challenging samples and equally well prepared to perform different types of analysis. In urgent situations such as this, we are able to implement a very fast response.”
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