By Kate Kelland
LONDON (Reuters) - The case of Pauline Cafferkey, the first person known to have recovered from Ebola and then suffer an apparently life-threatening relapse, is taking scientists into uncharted territory.
The Scottish nurse's critically ill situation, described as "staggering" by one British virologist, signals just how complex and formidable a foe the Ebola virus may turn out to be now that scientists have the chance to study its survivors.
Previous studies and preliminary data from research in survivors of the vast West African outbreak have detected Ebola virus in semen, breast milk, vaginal secretions, spinal fluid and fluids around the eyes.
But scientific literature has never documented an Ebola relapse case before, meaning Cafferkey's is likely to generate great fear and anxiety for the 17,000 or so other Ebola survivors across West Africa.
"This is totally unprecedented. We've never seen this, and there's so much uncertainty," said Jeremy Farrar, a specialist in infectious diseases and director of the Wellcome Trust.
"Is this a one off? A very rare event? Or is this going to be quite common? The honest answer is we don't know."
Frustration about the lack of scientific knowledge is clear. Until researchers can study in detail and in large numbers of people the virus's long-term effects, each survivor, be they healthy or sickly, will be able to teach virologists more.
"The closer we look at the Ebola virus, the more complicated it becomes," Derek Gatherer, a virus expert at Britain's Lancaster University, said when asked to comment on the relapse.
Ilhem Messaoudi, a biomedical sciences expert at the University of California, Riverside in the United States, noted that until recently, most Ebola outbreaks have been relatively small, in remote villages, and had such high death rates that there were barely any follow-up studies.
"So long-term health consequences and adverse outcomes that persist for months or years ... are incredibly understudied," he said.
"NOT OVER WHEN WE THINK IT'S OVER"
Doctors at the London Royal Free hospital where Cafferkey is in a high level isolation unit say she is "critically ill" and is being "treated for Ebola."
Her condition has deteriorated since she was readmitted to the hospital last week with what doctors described then as "an unusual late complication."
"We know Ebola can linger for many months after visible symptoms have cleared ... But this is frankly staggering," said Jonathan Ball, a professor of molecular virology at Britain's University of Nottingham.
While Cafferkey's doctors have one critical case, experts said her condition should galvanize efforts to ensure large scale follow-up studies of thousands of people in Sierra Leone, Liberia and Guinea known to have been infected with Ebola and to have been able to banish it from their bloodstream.
"The uncertainty is very difficult to communicate, but it absolutely underlines why research is so critical," Farrar said.
"There are so many unanswered questions, all with really profound implications - for the epidemic, for the survivors and their families, and for the next inevitable outbreak of Ebola."
Preliminary data published this week has already forced a re-think on how long male survivors should be advised to abstain from sex or use condoms, with a study showing traces of Ebola can be found in semen of some men at least nine months after they first became ill.
"Even if you don't have the virus in your bloodstream it can be hiding out," said Messaoudi. "And we need to be aware of that because it's setting up the stage for potentially new outbreaks."
For now, he said, the key message amid all the unknowns is "it's not over when we think it's over."