FREETOWN, Sierra Leone — "Have courage to buckle up," said the doctor, before he injected blood into the veins of Kadiatu Fofanah, a young woman in the throes of Ebola. It had been a week since Fofanah had doubled over, feverish and vomiting. "I was fading. I was so pale, I thought I would die," Fofanah recalls.
When her Ebola test came back positive, the doctor explained that a transfusion of blood from an Ebola survivor might save her. Fearing for her life, she accepted the experimental therapy. "Two days later I could walk," she says. "Five days later they took a blood sample and told me I was free from Ebola, and I was jubilated."
Fofanah, along with 34 other Ebola patients, received blood in the past month as part of a controlled clinical trial at the military hospital in Freetown. Although the study is ongoing and the results not yet analyzed, a grin flashes across the face of a doctor leading the trial, Col. Foday Sahr, as he says that 80 percent of the recipients have lived. Proper comparisons with the control arm of the study are not yet available, but the number bodes well in light of the grim survival rate from the disease until now in West Africa (below 50 percent). Sahr says his only regret is that the trial did not begin sooner.
"Hats off to Foday Sahr and his team, who did this trial against all the odds," says Calum Semple, a clinician scientist at the University of Liverpool who is involved in an upcoming, far-better-funded study to test convalescent plasma from Ebola survivors — their blood minus their red blood cells — in Sierra Leone.
Proponents of research on survivor blood drew inspiration from a 20-year-old report claiming that seven of eight patients lived after being injected with survivor blood during an Ebola outbreak in the Democratic Republic of Congo. The key ingredient is likely antibody proteins that are slowly produced by the immune system to block the Ebola virus in the weeks following an infection.
Plasma contains antibodies as well. And because red blood cells are returned to the donor, plasma can be donated more frequently than blood and stored for longer. "It's important to find out if [plasma] works, because in a future outbreak, you couldn't rely on whole blood, but you could build up a bank of plasma quickly," Semple says.
In about a week, the convalescent-plasma trials will start in Sierra Leone and Guinea. In the two countries, 284 people have been diagnosed with Ebola since Feb. 1. A matching study began in Liberia in December, but it's stalled because case numbers have dropped dramatically. The plasma trials include clinician scientists from institutions in Europe, the U.S. and the three affected countries, and each study aims to enroll over 100 people. However, if the outbreak tapers off before researchers reach that number, strong conclusions may still be drawn because results from the three trials can be combined.
With the trials coming a year after the start of the outbreak in Guinea, blood treatments will not make much of a dent in the overall death toll, which stands at 9,253. However, the results could prove vital in future Ebola outbreaks. Blood treatment doesn't come with the hurdles involved in developing and buying pharmaceuticals. "This is something that can be owned by the countries themselves," says Johan van Griensven, an infectious disease specialist at the Institute of Tropical Medicine in Belgium and co-investigator in the plasma trial in Guinea.
At a meeting held by the World Health Organization on Sept. 5, representatives from Guinea, Sierra Leone and Liberia pushed for tests on whole blood and blood plasma. "The countries really liked the blood option more than the drugs because there is no manufacturer behind it and no international regulatory approvals required," says David Wood, a virologist at the WHO.
Yet few international donors prioritized blood trials above other experimental treatments. For example, the U.S. government decided against studies on blood in favor of those on pharmaceutical drugs and vaccines, citing evidence of their efficacy in laboratory studies. Thus far the U.S. has committed more than $240 million to ongoing research on those therapies. In December, the World Bank granted $200,000 to the Sierra Leonean trial on whole blood. More recently, several donors committed more than $3.3 million to the three multi-institutional convalescent plasma studies.
About 20 percent of the plasma budget will be spent on medical equipment, refrigerators and infrastructure that will continue to bolster blood-transfusion services after Ebola has passed. It's an added benefit not lost on Sierra Leone's medical community. At the country's blood-bank headquarters in Freetown, a single rusted refrigerator stores donor blood and a lab technician enters data into an outdated computer. In the eastern region of the country, the main blood bank suffers from unreliable electricity. The director points to a handwritten log of the days when the refrigerator went down and stored blood went bad.
Semple understands the frustrations over the pace of research. After an influenza pandemic killed more than 18,000 people around the world between 2009 to 2010 — with virtually no clinical trials conducted — he and his colleagues formed a consortium to figure out how to perform quality science during a fast-moving crisis. The group, called ISARIC (International Severe Acute Respiratory and Emerging Infection Consortium), developed protocols for testing generic treatments for unspecified outbreaks that could include anything from swine flu to drug-resistant malaria. When Ebola hit, the consortium's members tweaked the protocols to suit convalescent plasma and West Africa. "That took a couple of months," Semple says. To him, that speed is a success compared with the year or more it typically takes to launch clinical trials.
Semple and two members of his team from the U.S. arrived in Freetown last week. Paperwork covers the dining-room table in their temporary quarters. A machine to analyze blood chemistry rests beside the television. It's one of several pieces of equipment shipped here for the plasma study, and it will help the researchers learn exactly how the transfusions affect patients.
Until recently, blood-chemistry measurements seemed frivolous. As Ebola pummeled hospitals, many doctors, aid workers and health officials felt they had no time for data collection because they were overwhelmed just trying to keep patients alive — never mind documenting their biology.
However, this evidence provides clues on how to curb deaths in the future, and Semple wishes international aid agencies had devoted resources to science sooner. "[NGOs] want to get in and save lives, and they feel great when they do, and that's wonderful," he says. "But if you want to make a difference on a large scale, you need to do clinical research."
Sahr agrees with the sentiment. But there is little time for complaints. He will soon be involved with three trials — blood, convalescent plasma and an antiviral drug from the North American-based pharmaceutical company Tekmira. "Better late than never," he says. "We'll learn what we can, and at least we'll have a place to start if there is an outbreak in the future."