A nurse who contracted Ebola while in Sierra Leone as an aid worker in December 2014 has been readmitted to hospital in London following an “unusual late complication” from the original infection.
Dr Nathalie MacDermott, Clinical Research Fellow, Imperial College London, said:
“To reiterate what others have commented, just because virus has been detected in bodily fluids it does not mean it is infectious to others. The test used detects viral genetic material which can be identified even if the virus is not alive/active. While we have seen cases of transmission in semen, with fairly good evidence to support this form of transmission, there is no conclusive evidence of consistent transmission of virus from survivors. Actually the evidence points against this as there have been so few known potential cases of transmission from survivors compared with the evolving number of survivors who appear to demonstrate virus persistence in bodily fluid in West Africa.
“There is evolving evidence from West Africa of viral persistence in certain bodily fluids from immune-privileged sites (i.e. areas of the body where the immune system finds it more difficult to penetrate such as the eye, the scrotum etc.). There was limited evidence previously as there were few survivors from previous epidemics, although there has always been some evidence of viral persistence in semen up to 3 months after survival. We now understand this persistence to be much longer and studies are ongoing in Liberia and Sierra Leone.
“At present we only know of one case of viral persistence in ocular fluid in this current epidemic, which is Dr Ian Crozier, a US doctor who was treated at Emory Hospital in Atlanta. There are cases of acute eye inflammation in West African survivors which may have viral persistence but it has not been possible to test them yet.
“As we study more and more survivors we are identifying potential chronic problems, with viral persistence being a feature of this.
“So far we have only got definite transmission history to other people through semen – the last case of Ebola in Liberia in March was a case of viral transmission from a survivor through sexual intercourse (male to female). The case in Liberia in June was also likely sexually transmitted and was definitely transmitted from a survivor but the details remain somewhat vague. There have been possible cases in Sierra Leone also, although the evidence is outstanding for this.
“There have also been reports of transmission to infants through breast milk of asymptomatic mothers and also in utero transmission in women who were never symptomatic. At the moment this is all anecdotal, but there is evolving suggestion of transmission through breast milk from asymptomatic mothers and also in utero from women with minimal or no symptoms themselves (in these cases the infants usually are stillborn or perhaps die in the first few days of life).”
Prof. Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:
“It isn’t clear yet where Ebolavirus has been detected in this case. We know that Ebolavirus can persist for a long time in certain parts of the body like the eye long after the virus has disappeared from the blood, and many individuals who have recovered from the more serious symptoms of infection continue to have some health problems like fatigues, pain and visual defects.
“The key issue is whether or not these individuals pose a risk to others, and with Ebola transmission is associated with symptoms such as diarrhoea, vomiting and bleeding. There is little, if any, evidence that the virus can transmit once these major symptoms have disappeared. There have been reports of possible sexual transmission – we know that the virus can hang around in the semen of recovered men – but these have not be proven conclusively.
“The tests that are used to detect virus detect the virus genetic material – its so-called genome – and detecting virus genome doesn’t mean that infectious virus is present.”
Dr Ed Wright, Senior Lecturer, University of Westminster, said:
“The news that Ebola virus has been detected in Pauline Cafferkey, a British nurse who was infected last year while helping treat patients in West Africa, is not a complete surprise given what we are learning about long-term persistence of the virus in West African individuals. Following the development of symptoms a patient is most infectious in the advanced stages of disease, when they are shedding millions of virus particles in bodily fluids, primarily vomit and diarrhoea. If the patient is able to mount a strong immune response that controls virus replication they can ultimately reduce the level of virus in their blood to a level beyond detection, effectively zero for clinical purposes. Once the test has been repeated and comes back as negative for a second time the person is considered to have cleared the infection and is now no longer infectious. However, there is a growing body of evidence to suggest the virus can persist in certain bodily fluids – breast milk and semen identified so far – for up to 6 months following infection without the person showing the characteristic symptoms. It is important to note that the level of virus found in these fluids is several orders of magnitude lower than that found during the initial, acute, phase of infection. Given the restricted locations where the virus has been found and the low amounts within these fluids people who may harbour the virus once recovered pose negligible risk to the general public as the virus could only be transmitted by close, intimate contact.”
Dr Derek Gatherer, Lecturer, Lancaster University, said:
“The news that Pauline Cafferkey has experienced further symptoms – in medical jargon, sequelae – since her recovery from Ebola, is unfortunate but unsurprising. The British Medical Journal recently reported that around half of the 13,000 survivors of the recent epidemic have persistent joint pain, often serious enough to be partially disabling. Others have reported visual problems and some have even gone blind. Other common sequelae include headaches, muscle pain, sleeplessness and abdominal pain. The causes of these post-recovery symptoms are still unclear, but are possibly associated with the damage done to the immune system in the fight against the virus. The eye symptoms may have something to do with the fact that virus can sometimes be persistently detected at a low level in tears – in one study virus particles were found in the eye fluid of a survivor 9 weeks after the viraemia – the presence of virus in the blood – had ended. It is now clear that we still have a lot to learn about Ebola’s long-term effects. We don’t know the details of Pauline Cafferkey’s case, which are of course subject to medical confidentiality, but it has been reported that some virus has been detected again in her body, and that is why she has been returned to the isolation ward. This is purely to minimise risk, and there is no danger to the general public.”
Prof. David Evans, Professor of Virology, University of St. Andrews, said:
“Persistent Ebola virus infections have rarely been reported previously. The majority of patients are considered non-infectious once symptoms and viremia (virus in the blood) disappear. However, eye infections have been detected 9 weeks after clearance of viremia and virus is detectable in seminal fluid at least 14 weeks after the onset of symptoms in some patients. Sexual transmission of Ebola has also been documented weeks after clearance of symptoms in convalescent patients. In other RNA viruses, such as poliovirus, there are rare cases of persistent infection lasting for several years in patients with compromised immune responses. It is therefore likely that RNA viruses can persist in some patients long after symptoms disappear, but that these individuals are rarely detected. This may reflect a lack of surveillance but also suggests that these individuals are not routinely the source of new infections.”
Dr Ben Neuman, Lecturer in Virology, University of Reading, said:
“Over the past few years, there has been mounting evidence of the mental and physical health problems in Ebola survivors that can last for years after the virus is cleared from the bloodstream. The newly discovered twist on this post-Ebola syndrome is that in some cases the health problems, often including damage to the eyes and joints, is actually caused by live Ebola virus growing in bodily fluids in some of the less accessible compartments of the body. Ebola can persist for weeks or even months in breast milk, semen and the fluid inside the eyeball.
“This is only the second case of reactivated Ebola, the other being the survivor whose eye changed from blue to green due to an ongoing infection, so it is difficult to be certain of the outcome at this stage. The likelihood of spreading Ebola depends on how much of the virus is present in the blood, and if her body was able to control the virus once, chances are she can do it twice.
“My heart goes out to nurse Cafferkey – she has acted bravely and responsibly throughout her battle with Ebola, and she deserves a break. Thanks to hard work by volunteers like her, we now have some potential treatment options for Ebola patients, and I am sure she will have the best care available.”
Prof. John Edmunds, Dean of Faculty of Epidemiology & Population Health, London School of Hygiene and Tropical Medicine (LSHTM), said:
“The Ebola virus can occasionally persist for some months in certain tissues within survivors. The risk of transmission from these individuals appears to be very low. However, with so many survivors in West Africa now, there is a risk that further outbreaks can be triggered, which is why authorities have to remain very vigilant.”
Prof. Julian Hiscox, Professor of Infection and Global Health, University of Liverpool, said:
“We know that Ebola virus can shelter in the body in what are called immune privileged sites such as the eye, central nervous system and testes. Due to the sheer scale of this outbreak compared to previous ones we are going to see aspects of Ebola virus infection that we have not observed before. I think the persistence of the virus in asymptomatic individuals is a potential reservoir of the virus. We know that infectious virus is present in semen for a number of months. It’s why men who have had Ebola and recovered are advised to abstain or wear condoms. ”
All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/?s=ebola&cat
Dr Nathalie MacDermott: I am writing the paediatric Ebola survivor guidelines for the WHO, I have no other conflicts of interest to declare
Prof. Jonathan Ball: No conflicts of interest although I am doing Ebola research
Dr Ed Wright: No conflicts of interest
Dr Derek Gatherer: I have an Early Career Small Grant (ECSG) from Lancaster University to study Ebola and have been participating in the National Institute for Biological Standards and Controls (NIBSC) project on Ebola diagnostics.
Prof. David Evans: No competing interests
Dr Ben Neuman: No conflicts of interest
Prof. John Edmunds: No conflict of interest that is relevant to this
Prof. Julian Hiscox: My laboratory studies the evolution and biology of Ebola virus.