United Kingdom - Scottish nurse treated for Ebola 'complication' - full recovery from Ebola , discharged

[Emily]

Excellent points, foxp3. I agree 100%. In the future, I think virology and immunology will become more integrated, but for now they are not. I did read about some of the world's top virologists opening up to considering host factors at a conference recently, so fingers crossed this progresses.

 

[Ruby Murray]

My first post here but I am refugee from the old FluWiki site.

I'm very disappointed (not to say surprised) that her extraordinary medical history was not flagged up when she presented unwell at an OOH primary care centre. And that she visited a school shortly before being admitted 2 days later.

I have also been wondering about the plasma/antiviral treatment and whether her immunity was different to an untreated survivor. Could it be possible that Will Pooley's infection was with a mutated strain that was less virulent (as I understand he did not become very unwell)?

 

[Emily]

Welcome to flutrackers, Ruby! I think one of the concerns about experimental immune treatments was that they could make things worse, but another factor here could be age or individual immune genetics. I think Pooley was about 10 years younger than Ms. Caferkey. I think both she and the doctor who later had an eye complication both wondered if their age set them up for worse infections, since the nurses who recovered much more easily were younger. Age was considered a possible risk factor in other ebola outbreaks.

 

[Pathfinder]

How Pauline Cafferkey's Ebola relapse tears up everything doctors thought they knew
...
Sarah Boseley Health editor
Friday 16 October 2015 12.05 EDT Last modified on Friday 16 October 2015 17.25 EDT
...
The UK has a world-class health service. Cafferkey?s family were angry that the possibility that her symptoms were linked to Ebola was not immediately picked up, but even though she did not have the usual fever and vomiting, within days the virus had been identified once more and she had been flown to specialised care.

But a resurgence of illness that did not look like classic Ebola in survivors in countries with fragile or collapsed health systems, such as Sierra Leone, Liberia and Guinea or ? for that matter ? DRC or Uganda, which have had outbreaks in the past, would not have been recognised. It is entirely possible that people have died from Ebola complications unnoticed, months after their initial recovery, and more could still die.
...
Earlier this year there was another clue, this time from studies of macaque monkeys, that the virus might re-emerge from one of its hiding places and wreak more damage.

?On two occasions two of the animals appeared to have recovered from the virus and then they had a relapse which involved the brain. It was really debilitating for them,? said Ball. ?It probably would have been a life-threatening illness but because it was an animal they put them to sleep ? that?s what the protocol states.

?And when they looked at those animals, basically looking for any changes in the body, they didn?t see any changes in the organs that you?d associate with Ebola virus. The spleen and the liver and things like that were all fine, there were no traces of Ebola, but the brain was very heavily involved, as was the eye.?

When Cafferkey fell ill last week, it did not look like Ebola. ?We?ve been reassured and there?s absolutely no reason to doubt it ? that she wasn?t presenting with symptoms that would pose a risk to other people,? said Ball. ?She wasn?t presenting with classic Ebola symptoms.?
...

http://www.theguardian.com/world/20...tears-up-everything-doctors-thought-they-knew

 

[Emily]

Earlier this year there was another clue, this time from studies of macaque monkeys, that the virus might re-emerge from one of its hiding places and wreak more damage.

?On two occasions two of the animals appeared to have recovered from the virus and then they had a relapse which involved the brain. It was really debilitating for them,? said Ball. ?It probably would have been a life-threatening illness but because it was an animal they put them to sleep ? that?s what the protocol states.

There were clues much earlier than those studies.

http://jid.oxfordjournals.org/conten...nt_2/S323.full

Viral Pathogenesis - Supplement Articles:

• Thomas Larsen,
• Edward L. Stevens,
• Kelly J. Davis,
• Joan B. Geisbert,
• Kathleen M. Daddario-DiCaprio,
• Peter B. Jahrling,
• Lisa E. Hensley,
• and Thomas W. Geisbert

Pathologic Findings Associated with Delayed Death in Nonhuman Primates Experimentally Infected with Zaire Ebola Virus J Infect Dis. (2007) 196 (Supplement 2): S323-S328 doi:10.1086/520589

Interestingly, rhesus macaques that have died from untreated EHF typically do not show detectable lesions or evidence of viral replication in the parenchymal tissue of the brain, eye, lung, pancreas, or thyroid [3, 4]. However, we report here our findings of viral infection and tissue injury in these organs in macaques that have had death significantly delayed as a result of various experimental therapies....
...

Notable discrepancies in pathologic findings between historical control animals and the treated animals experiencing delayed death were observed in several tissues. In historical control animals infected with ZEBOV, brain, endocrine pancreas, thyroid, eye, and pulmonary parenchyma are typically devoid of viral antigens or pathology. In contrast, the subject animals in this study exhibited lesions and/or viral antigens in many of these tissues. In addition, some animals experiencing delayed death also had diminished or no evidence of disease or viral antigens in major target tissues, compared with that in control animals.
....

That was presented in 2006 - so why the surprise now?

The data presented here demonstrate an interesting phenomenon of altered tissue tropism in ZEBOV-challenged macaques that survive beyond the normal course of disease. It is not clear why ZEBOV replicated so effectively in tissues that were not usually affected. In the 6 animals in this study, exposure to a variety of host mediators during the course of the prolonged illness may have changed the phenotype of some cells, making them more susceptible to ZEBOV. Alternatively, it is possible that ZEBOV can replicate in these cells and tissues but that replication and spread occurs more slowly than in more-preferred cells and tissues; thus, an increase in the duration of the disease course gives the virus time to gain a foothold in these secondary target organs.

These were the experimental treatments studied:

These therapies included (1) recombinant nematode anticoagulant protein c2, a drug that blocks the factor VIIa/tissue factor pathway of blood coagulation [5]; (2) recombinant human activated protein C, which is licensed for the treatment of cases of severe sepsis in humans at high risk of death [6]; (3) human monoclonal antibody KZ52, which is reactive with ZEBOV glycoprotein [7]; and (4) recombinant human interferon-β1a (Serono).

The result was a slower death from treatment with different tissues infected.

How the leap to optimism for ZMapp happened is a mystery to me. Maybe someone can point to the research on that.

http://www.pnas.org/content/111/48/17182.full

ETA:
I have found the primate study with good success with ZMapp. For now I am NOT aware of ZMapp survivors with complications.

 

[alert]

I look at what happened to Dr. Crozier's eye as a result of Ebola virus replication there long after it was cleared from the rest of his body and I imagine that if the same thing happened if this patient's spinal cord or the meninges of her brain, it might present like this and be life-threatening.

That's what it looks like is going on, at least to me.

 

[sharon sanders]

Welcome Ruby!

 

[Emily]

http://www.nytimes.com/2015/10/15/w...back-in-hospital-and-critically-ill.html?_r=0

[h=1]Ebola Survivor From Scotland Is Critically Ill[/h] By SHERI FINKOCT. 14, 2015
...


While virus was not found in Dr. Crozier?s blood or cerebrospinal fluid, a scan of his brain indicated that he had suffered from encephalitis, Dr. Bausch said. In West Africa, patients as ill as Dr. Crozier or Ms. Cafferkey might not have survived ?to experience these later manifestations,? he surmised.
One possibility is that late complications could be an unanticipated consequence of experimental treatments that include antibodies, like ZMapp, that help remove the virus from the patient?s blood, but are not thought to be capable of crossing from the bloodstream into the brain.
By decreasing the amount of virus in the blood, ?you perhaps blunt the immune system,? Dr. Bausch said. ?It?s all speculation, but it?s scientifically sound speculation.?

 

[Pathfinder]

So It Turns Out There's A Lot We Don't Know About Ebola

OCTOBER 17, 2015 7:03 AM ET

...
"It's an explosive virus. It replicates like crazy ... and it destroys everything in its path," says Messaoudi, a viral immunologist and professor of biomedical sciences at the University of California, Riverside, who is studying how the virus works in the human body. "So, how is it just hanging out in the testes for like nine months?"
...
"The immune system is a little heavy-handed at times," she says. Inflammation caused by the immune system's activity could cause serious damage in places like the eyes, brain, placenta, fetus, testes, joint spaces and central nervous system. Messaoudi likens members of the immune system to the Navy SEALs. "They are trained killers," she says, "so if you drop them in the wrong place and they misread their orders, it could lead to really big damage."

So, for the most part, the immune system stays away from those sites, making them great spots for viruses to hide out. (That's what other viruses do, like hepatitis B, and herpes viruses, including chicken pox, which hides in neurons for years and has the potential to re-emerge as shingles.)

But those viruses are different from Ebola, says Messaoudi. "Acute viruses like influenza, Ebola, yellow fever, West Nile [virus] ? they infect, they replicate, and they're cleared. That's just how we've always thought of them. I've never heard of a yellow fever reservoir or a West Nile reservoir. Maybe they exist, and we just don't know about it."

Messaoudi says one of the most confusing things about the Ebola virus is its size. It's a "no-frills virus" with a tiny genome, she says. Viruses that can hide in immune-privileged places and live for years usually have a lot more genes that allow them to quietly survive.

But Ebola is managing to scrape by in some corners of survivors' bodies, and those places are, by nature, hard to get to. "It presents a huge challenge, because how do we get enough antivirals into these sites?" says Messaoudi. Getting to fluid in the spine requires a spinal tap. Patients with the virus inside their eye might need a fine needle to go straight into the space between the iris and the cornea. "So how do we eradicate those reservoirs?" she asks. "And why do some people end up developing these reservoirs and other people don't?"
...

http://www.npr.org/sections/goatsan...rns-out-theres-a-lot-we-dont-know-about-ebola

 

[Pathfinder]

Update on Pauline Cafferkey

19 October 2015
Updated: 3pm

We are able to announce that Pauline Cafferkey?s condition has improved to serious but stable.

https://www.royalfree.nhs.uk/news-media/news/update-on-pauline-cafferkey/

 

[alert]

http://www.theguardian.com/world/201...-free-hospital


Ebola nurse Pauline Cafferkey nearly died from meningitis, doctors say



Doctors say British nurse has long recovery ahead of her after suffering meningitis brought on by lingering Ebola infection

[snip]

Because of her history, they then tested her blood and found “very low levels of the virus, the sort of levels you would see in patients that were about to recover”.

Every step that followed from that was precautionary.

?We didn?t know what the trajectory was ? if the virus in the blood was heralding the fact that something was going to happen or was it just what we would call incidental because we have never seen anything like this before, we were not sure what was going to happen whether this was going to turn into full blown Ebola virus and let?s be absolutely clear about this, it did not,? said Jacobs.

 

[Pathfinder]

Pauline Cafferkey has improved

21 October 2015

Doctors at the Royal Free Hospital have confirmed that Pauline Cafferkey’s condition improved significantly.

At a press conference today Dr Michael Jacobs said that she is unwell with viral meningitis caused by her original Ebola infection.

Pauline was first admitted to the high level isolation unit (HLIU) at the Royal Free Hospital in December 2014 after contracting the disease while working in Sierra Leone. She was discharged in January this year after making a recovery.

On 8 October 2015 she was re-admitted to the HLIU after developing late complications from her Ebola infection.

Dr Jacobs said: “I am really pleased she has made a significant improvement. She is inside the tent, she is still in bed, but she is talking freely within the tent. She has got a long recovery ahead of her and she will be with us for quite a while.”

After careful consideration Pauline decided she would take the experimental drug GS-5734, which is an anti-viral drug.

Dr Jacobs added: “I am hopeful Pauline will make a full recovery – maybe it will be with the help of this anti-viral drug, maybe it will be down to her own immune system. Over time I anticipate that the virus will be eradicated from her completely.”

ENDS

https://www.royalfree.nhs.uk/news-me...t-improvement/

 

[Emily]

http://www.firstwordpharma.com/node/1324709

Gilead discloses development of experimental Ebola drug GS-5734

(Ref: The Wall Street Journal, The Guardian, Business Insider, NBC News, StreetInsider, Gilead Sciences) October 21st, 2015
By: Joe Barber
...

Gilead, which disclosed that it shipped doses of GS-5734 to the Royal Free Hospital in London last week following a request for compassionate access to the drug, noted that in animal studies, GS-5734 was associated with 100 percent survival in monkeys treated with the medicine three days after exposure to the Ebola virus.
Mike Jacobs, an infectious diseases consultant at Royal Free Hospital, noted that the nurse, who was initially diagnosed with Ebola in December last year, had not been re-infected with the disease since her prior treatment, but that instead, the virus persisted in her brain despite treatment, leading to viral meningitis. "The virus re-emerged around the brain and around the spinal column to cause meningitis," Jacobs explained, adding "she developed some serious neurological complications."...

Her treatments for the initial infection are reported as:

http://www.webmd.com/news/20150126/pauline-cafferkey-ebola-recovers

By Peter Russell
WebMD Health News
Reviewed by Brunilda Nazario, MD


Jan. 26, 2015
...
Both health care workers were treated by Michael Jacobs, PhD, an infectious diseases consultant at the Royal Free. Pooley received the experimental drug ZMapp. Cafferkey was reportedly treated with an alternative antiviral drug called ZMabb, because supplies of ZMapp had run out.

Those who received ZMapp and survived are not reporting chronic or relapsing illness as far as I know.

Ms. Cafferkey is also reported to have had serum antibodies and an antiviral drug as part of here initial infection treatment:
http://www.theguardian.com/world/20...s-run-out-doctors-turn-alternative-treatments

 

[Pathfinder]

Pauline Cafferkey discharged

12 November 2015

We are pleased to announce that Pauline Cafferkey was discharged from the care of the Royal Free Hospital on 11 November and has been transferred to Queen Elizabeth University Hospital in Glasgow.

We are delighted that Pauline has made a full recovery from Ebola and is now well enough to return to Scotland. We would like to wish her well for the future.

Pauline Cafferkey said: “I am forever thankful for the amazing care I have received at the Royal Free Hospital. For a second time staff across many departments of the hospital have worked incredibly hard to help me recover and I will always be grateful to them and the NHS.

“I am looking forward to returning to Scotland and to seeing my family and friends again.”

ENDS

https://www.royalfree.nhs.uk/news-me...ey-discharged/