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

"If there's anything that this outbreak has taught me, it's that I'm often wrong," says Dr. Daniel Bausch.

He's talking about Ebola. He's one of the world's leading experts on the virus — an infectious disease specialist at Tulane University and a senior consultant to the World Health Organization.

And as he makes clear, he's still got a lot to learn.

The virus came roaring back into headlines this past week. A Scottish nurse who survived Ebola is back in isolation in London, being "treated for Ebola," according to the Royal Free Hospital. The hospital says the patient's "condition has deteriorated and she is now critically ill."

And two new research papers found that the virus can live in a male survivor's semen for up to nine months, and that one man passed it to his sexual partner months after he was released from the Ebola ward.

"If you look back at the classic teaching about Ebola and survivors, it was that once you get better from this disease, even though it may take a while to recover, you made a full recovery and that kind of was the end of it," says Bausch.

And now, with an estimated 17,000 survivors, researchers are discovering all kinds of twists and turns. The semen study is particularly puzzling to Ilhem Messaoudi.

"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?"

There hasn't been much research — in animals or humans — about what happens after survival. What we do know is mostly from past outbreaks of the virus, in particular, two studies looking at past survivors of the disease and comparing their health to Ebola-free friends and family.

Research on 19 survivors of a 1995 outbreak in Kikwit in the Democratic Republic of the Congo found that most had joint pain and vision problems after the virus. One lost sight. Studies from the 1970s and 1980s had, like recent research, found the virus persisting in the semen and eyes of survivors.

Researchers following 49 survivors of a 2007 Ebola outbreak in Uganda found that — even two years after the illness — they had eye problems like inflammation and blurred vision as well as joint pain, difficulty sleeping, difficulty swallowing and even hearing loss, memory loss and confusion.

A third study examining 105 survivors of the 2014-15 outbreak in Guinea found that about 90 percent had chronic joint pain and 98 percent had poor appetites or an aversion to food. They also reported difficulty with short-term memory, headaches, sleeplessness, insomnia, dizziness, abdominal pain, constipation, sexual dysfunction, and decreased libido and exercise tolerance.

Bausch says, aside from arthritis and eye inflammation, it's still unclear which issues are directly related to the Ebola virus and which could be caused by the physical and emotional toll on the body. But something is going on.

"It's clear that there is a post-Ebola syndrome," he says.

Individual cases have opened a window into where the virus goes, and what it's capable of — even after a survivor's body has eliminated it from the bloodstream.

One well-reported example is Dr. Ian Crozier, who survived Ebola contracted in Sierra Leone, only to have one of his normally blue eyes turn green. Though the rest of his body, including his tears, was Ebola-free, his eye was teeming with the virus. The infection almost blinded him.

In a few other cases, Ebola hid out in the uterus. Most women who were pregnant when they got the virus miscarried. But, Bausch says, "a few women have survived with pregnancies intact." When they went into labor, the babies were stillborn and often anatomically abnormal. For months, the recovered mothers had carried babies stricken with Ebola.

How could healthy survivors who tested negative for Ebola still harbor the virus? As Messaoudi explains, it's because the immune system, which is capable of wiping out the virus in the bloodstream, doesn't reach every nook and cranny of the body.

"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?"

Bausch says these questions are important scientifically but not necessarily in terms of disease control. For example, there's a small possibility that the arthritis that so many survivors report is from the virus itself, sitting inside joint spaces. But that would not pose a public health risk.

"Because how do you get infected from someone's joint space? You don't," he says.

But there are some potentially worrisome sites where the virus holds on, like in semen.

As data on survivors trickles in, Bausch says, "There is a sense across WHO and U.N. systems that we need to have renewed efforts in terms of not only caring for survivors but recognizing that there are still transmission issues that may relate to survivors. And that's a tough thing for people to take on, both in terms of the logistics, but also just emotionally."

"The whole thought over the course of this outbreak and previous Ebola outbreaks is: You get down to zero cases, and then you count 42 days, and then you say it's over," he says.

Cases where Ebola lingers in the semen, eyes or even uterus of survivors push the outbreak's finish line farther away.

"We've always known that it wasn't completely over," says Bausch. There's always the possibility that whatever first seeded this outbreak, likely a fruit bat, is still out there. "So, we've always known that there was the potential for reintroduction from the wild. But I think more recently and with these data coming in, we're understanding that there's also this potential for reintroduction from persistent virus production in humans, most notably from sexual transmission" — even though experts still think sexual transmission is rare.

Meanwhile, he says all the evidence points to survivors clearing their systems of Ebola virus over time. But, says Bausch, it's probably not the day that they walk out of the Ebola treatment unit.

To see just how long the virus might linger, the U.S. National Institute of Allergy and Infectious Diseases and the Ministry of Health of Liberia have launched a five-year project to follow 1,500 survivors of the latest outbreak along with 6,000 of their close contacts. They'll monitor health issues, organ and eye function, and possibly bodily fluid content. It will be the largest controlled study of Ebola survivors to date.

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