Sept. 12, 2014 -- Peering into the small house in Liberia where Kent Brantly was bedridden and quarantined with Ebola, there was no doubt in Dr. Lance Plyler’s mind that his friend and colleague was going to die.
Brantly, a 33-year-old doctor just months out of his residency, had come to Liberia in October to serve on a 2-year medical mission. He had two young children.
“When I looked in the window, it just hit me like a ton of bricks,” says Plyler, an internal medicine specialist. He is the medical director of disaster response for Samaritan’s Purse, the missionary organization both men were working for in Africa.
Brantly was burning with a nearly 105-degree fever, his breathing was too fast and too shallow, and his blood oxygen was very low, says Plyler, who is also trained in palliative care for dying patients.
“I’ve been doing internal medicine for 25 years, so I’m not an alarmist. But … I was certain he had a couple of hours to live, at best.”
Plyler knew he had something that might save the young doctor’s life, or hasten his demise. It was up to him to make the decision. And he prayed.
Race Against Time
Just a week earlier, Plyler, who was Brantly’s boss, had received the bad news.
A scientist at the NIH reference lab that was testing Brantly’s blood samples for Ebola texted Plyler a coded message.
“We had a pseudonym for Kent so it wouldn’t raise alarm, but his name was Tamba Snell. The text read, ‘I am very sad to inform you that Tamba Snell is positive.’” Tamba is a common Liberian name.
“I’ll never forget it as long as I live, because it was my worst moment in Liberia,” Plyler says.
With the diagnosis confirmed, Plyler started a frantic search for something to help his friend and another American, Nancy Writebol, who had also caught the virus. He got on his phone and computer, making hour after hour of urgent inquiries, trying to find a way to save their lives. He contacted experts at the CDC, NIH, and the Public Health Agency of Canada. Through those experts, he learned about two promising experimental treatments, ZMapp and TKM-Ebola.
ZMapp, a cocktail of Ebola-fighting antibodies, intrigued Plyler more. He reached out to Larry Zeitlin, PhD, president of Mapp Biopharmaceuticals, one of the companies developing the treatment, to find out more about it.
Zeitlin warned him that the drug had never been tested in humans. But he did share promising research, which has since been published in the journal Nature -- the serum had saved all 18 macaque monkeys after they were experimentally infected with the deadly virus.
That gave Plyler hope that it might not be too late to try on his friends.
As luck would have it, there was one course of ZMapp treatment in Sierra Leone. Plyler isn’t sure why it was there. He’s heard that researchers were planning to test how stable the drug might be in the hot, humid climate of Africa, where it would most likely be used in clinics with only rudimentary facilities.
After he located the ZMapp, the next goal was getting it to Liberia. After another flurry of phone calls, he got the drug across the Guinean border. From there, it was transported to Foya, a border town in Liberia, where Samaritan’s Purse picked it up and flew it into the capital, Monrovia, the location of ELWA Hospital, where Brantly was medical director of the Samaritan’s Purse Ebola Consolidated Case Management Center.
The drug arrived in a Styrofoam cooler. It held one course of treatment consisting of three doses of the drug. All three doses were meant to be given to a single patient. Plyler had been given strict instructions not to split the doses.
That’s because the first dose just knocks down the virus. Without the final two doses, the infection can flare again.
“If you think of it like a boxing match, the initial dose just gives it the first big blow, but the viral load will rise again, so you have to give it again and then give it a third time,” he says.
And each dose was frozen.
“I was absolutely petrified when it arrived, because I had to make a decision if I was going to administer or not,” Plyler says.
After consulting with Brantly, who was in stable condition at the time, they decided to give the treatment to Writebol, who was in worse shape.
To start thawing the ZMapp, they placed a single 250-milliliter vial under her arm as she lay in bed. They hoped her body heat would safely speed the thawing process. Too much heat -- from a hot-water bath, for example -- could kill the precious antibodies.
That night, though, Brantly’s condition worsened.
When Plyler looked in on his friend on Thursday, July 31, he says he immediately grasped the urgency of the situation.
“I can’t describe to you the pressure. It was unbelievable,” he says.
He called Brantly’s wife, Amber, who is a nurse, and told her things looked dire.
“I told her, 'Amber, he’s in very bad condition. I’m very, very concerned.’ I never said he was dying because I was trying to be tactful, but she knew. And Kent knew he was dying. We never talked about it, but he’s a great doctor. He knew.”
Then, Plyler says, he prayed. “I said, ‘God, he cannot die.’”
He called others, including Franklin Graham, the president and CEO of Samaritan’s Purse, and asked them to pray.
He says he felt a calm sense of certainty and knew what he had to do. He had to split the doses.
He quickly grabbed another frozen vial of ZMapp. “I was trying like crazy to defrost it. I was putting it under my leg, sitting on it, and time was of the essence,” he says.
Then he remembered the vial they’d placed under Writebol’s arm earlier that day.
It takes some time to properly put on the necessary personal protective equipment required to safely approach a person who’s infected with Ebola, and Plyler wasn’t wearing any. So he quickly grabbed someone who was wearing the gear and sent them into Writebol’s house to retrieve the vial, which thankfully had thawed.
They placed it in a plastic bag and sprayed it with a chlorine solution. Then they rushed it back to Brantly’s house, where it was hung in an IV solution.
“I told Kent, ‘I’m going to give you the antibodies.’ And he just said ‘OK.'”
Then Plyler waited outside the window, watching as the antibodies dripped into Brantly’s arm. He stayed there through the night, watching for any change.
Prayers and Antibodies
About half an hour after the treatment started, Brantly began to shake uncontrollably, a sign known clinically as rigors.
“I’m certain that was the antibodies saturating and overwhelming the virus,” Plyler says.
After a while, the rigors subsided. Brantly’s temperature came down. His breathing became more regular. A rash that had spread across his torso became less intense. Within hours, Brantly got up and walked to the bathroom, which he had not done in a day and a half.
Plyler got out his cell phone and texted Lisa Hensley, PhD, a microbiologist and Ebola specialist at NIH who’d helped him find the ZMapp.
“I said, ‘Lisa, Kent is distinctly better. Is that possible from the antibodies?’” Plyler recalls. “And she said, ‘Yes, it’s possible, the macaques would get better within hours.’"
The next day, after more ZMapp had thawed, he gave Writebol her first dose. She would get two doses of ZMapp in Africa. He says she, too, responded well to the drug.
After being evacuated from Liberia, both patients would finish their final doses of ZMapp at Emory Hospital in Atlanta and recover. Emory had requested additional vials from Kentucky BioProcessing, the small biotech company that’s growing the antibodies in tobacco plants.
Plyler understands that scientists might be skeptical about Brantly’s rapid recovery. And he doesn’t discount the hard work of the 10 doctors and nurses who gave Writebol and Brantly round-the-clock supportive care while they were in Liberia. He knows that proper hydration and nutrition play a big part in whether Ebola-infected patients live or die.
“I’m a doctor. I know that was just one anecdotal experience,” he says. “We need to do a large number of studies to see if this can be reproduced in a large number of people. But that was the most powerful anecdotal experience I’ve ever had in my life.”
Asked what he thinks saved his friend, Plyler has a ready answer.
“I call it prayers and antibodies, in that order, that saved his life,” he says. “That’s how it went down.”