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expert reaction to updates from the Royal Free Hospital on the condition of Ebola patient Pauline Cafferkey

The Royal Free Hospital has provided updates to the condition of Pauline Cafferkey, the British Nurse who was readmitted to hospital following infection with Ebola virus in 2014, saying that she is recovering well after developing meningitis caused by Ebola.

The SMC produced a Factsheet with background information of the Ebola virus as well as a Q&A on persistence of Ebola. All of our previous output on this subject can be seen here.

 

Prof. Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:

“It’s great news that Pauline, once again, seems to be winning the battle against  the virus.

“Many scientists suspected that the virus had hidden away in her brain and something happened that meant that she subsequently developed meningitis, I don’t think we really know what that trigger was.

“We also don’t know how many other survivors have experienced similar problems either in the current outbreak of in past outbreaks. This is not something that was on the radar and in those worse affected areas – Guinea, Liberia and Sierra Leone – we have no idea if survivors there have or will turn up with these sorts of complications, but it is obviously something that we and they need to be aware of.

“It just goes to show that even when the worse of the outbreak is over, the international community still need to support these nations.”

 

Dr Nathalie MacDermott, Clinical Research Fellow, Imperial College London, said:

“It is good to hear news of Ms Cafferkey’s improving condition. As said in the press conference this is an unprecedented situation, we have not before seen a re-emergence of the virus in the form of meningitis. It is possible some survivors in West Africa may have suffered from a similar situation but this has gone undiagnosed. Due to the poor health infrastructure in the affected West African nations it is unlikely that, if other survivors have been affected in a similar manner, they will have received the same level of care Ms Cafferkey has. It is important that those involved in caring for survivors of Ebola virus disease are aware of this possible complication and remain vigilant for it.

“Meningitis is a condition where a bacteria or virus causes inflammation of the tissues overlying the brain. This can be caused by many different viruses and bacteria. Ebola virus has been known to cause meningitis like symptoms in some patients when they are first infected with the virus. We have also been aware that the virus can persist in the cerebrospinal fluid (CSF, fluid surrounding the brain and spinal cord) of people who have recovered from their initial infection based on results from a few survivors in West Africa. The length of time the virus can persist for in the CSF is unclear, although Ms Cafferkey’s case sheds some light on this. It is now apparent that the Ebola virus can re-emerge at a later time to cause meningitis in those who have already survived their acute infection.

“This possibly occurs because a small number of particles of the virus have remained in the cerebrospinal fluid. The immune system keeps these in check by not allowing the virus to replicate as much as it would like, although it may be unable to completely clear the virus from the CSF as some particles may hide from the immune system. If the immune system is distracted or weakened the virus can gain a foothold again to replicate and increase the number of viral particles in the CSF, this causes irritation and inflammation of the meninges resulting in meningitis.”

 

Dr Ben Neuman, Lecturer in Virology, University of Reading, said:

“For Ebola to cause meningitis is completely unprecedented. However, knowing what they are dealing with should be very helpful for the doctors who are treating Nurse Cafferkey. We may not have seen Ebola meningitis before but doctors have vast experience of treating other kinds of viral meningitis.

“The biggest risk to Pauline’s health is that the immune response aimed at the virus will cause collateral damage to her brain – that is essentially what happens in viral meningitis. The treatment will be a combination of keeping Nurse Cafferkey comfortable and well hydrated, plus the administration of a new drug called GS-5734. There are very few details available for GS-5734 at the moment but it appears to be the same sort of drug as Favipiravir, the Japanese Ebola drug that was shown to protect people from the disease.

“Antibody treatments for Ebola are just too big to cross from the blood to the brain so the drug has to be something small. GS-5734 is – let’s hope it’s going to be the good break Pauline richly deserves.”

 

Dr Ed Wright, Senior Lecturer, University of Westminster, said:

“Welcome news from the staff of the Royal Free hospital treating Pauline Cafferkey for complications arising from her infection with Ebola virus at the turn of the year is that she is expected to make a full recovery. The cause of her readmission into hospital was meningitis – infection of her nervous system, brain and spinal cord, by Ebola virus that remained from her initial infection. The virus was able to hide away and replicate within these tissues as Pauline’s immune response was not able to penetrate these sites. This made treating the infection different to before as drugs were needed that could gain access to the brain. Drugs used in a handful of previous cases of Ebola virus disease, convalescent serum, ZMapp etc., are antibody-based so not suitable to treat infections of the brain. Therefore, the doctors use GS-5734, a small molecule that inhibits Ebola virus from replicating by disrupting the process that generates new copies of the viral genes. This in turn means no new virus particles can be made. This drug has previously been shown to be 100% protective in animals infected with Ebola virus.
“While complications arising from persistent Ebola virus infections are devastating for those who have already beaten the virus once, it is currently thought that only a very small percentage of people harbour the virus after the initial disease has resolved. In addition, evidence has been published recently that shows that even this persistent virus will be eventually cleared by the body’s own defences. With ~17,000 survivors from the outbreak in West Africa we are learning a lot about how to treat those infected and long term implications for survivors and there is no doubt a lot more we will learn in the coming months.”

 

Declared interests

Prof. Jonathan Ball: No conflicts of interest although I am doing Ebola research

Dr Nathalie MacDermott: I am doing research into Ebola virus disease at Imperial College London funded by the Wellcome Trust ISSF scheme and the Institute of Global Health Innovation. I have no other conflicts to declare.

Dr Ben Neuman: No conflicts of interest

Dr Ed Wright: None declared

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