A University of Minnesota team helped test an Ebola vaccine in the midst of an epidemic.
On New Year’s Day 2015, Cavan Reilly (above) arrived in Monrovia, Liberia, to begin work on the first clinical trial in West Africa for an Ebola vaccine. Liberia and its neighboring countries, Guinea and Sierra Leone, were in the midst of an Ebola epidemic that would ultimately infect more than 28,000 people and claim more than 11,000 lives. It was into this scenario that Reilly had flown, and his family and friends were anxious about the risk of him contracting the highly contagious and deadly disease.
Reilly (B.S. ‘93) is the associate director of the Coordinating Centers for Biometric Research at the University of Minnesota’s School of Public Health (SPH). He was one of several members of a U of M team that included biostatisticians, epidemiologists, data management experts, and project managers who traveled to the region during the epidemic. And although Reilly had assured his loved ones he’d be perfectly safe in an office, supervising procedural details of the trial and talking with government officials, when he disembarked in Monrovia’s crowded airport, he realized he’d underestimated the risks.
“To try and get your baggage, you’re walking shoulder to shoulder with Liberians,” he says, sitting in a conference room at the U’s Biometric Research offices on University Avenue. Since Ebola is spread through direct contact with bodily fluids of an infected person, Reilly quickly realized that avoiding close contact with people who may have been infected was impossible. (The Centers for Disease Control and Prevention would later report that Liberia was not deemed Ebola-free during that particular outbreak until January 2016, although the number of new infections diminished sharply by late 2015.)
That Reilly and his U colleagues felt the need to travel to Liberia at such a dangerous time speaks to the complexities of setting up drug trials in developing nations. Biostatistics, a field that uses statistics to advance biomedical research, is employed in medicine and public health to determine not only the effectiveness of new drugs but also the causes and long-term outlook for different diseases. Reilly, who has a Ph.D. in statistics, says he was drawn to the field because it gives him an opportunity to merge his talent with numbers with his desire to have a positive impact on people’s health and wellbeing.
The U’s involvement in Liberia during those tests actually started in the fall of 2014, when Jim Neaton (B.A. ’69, M.S. ’70, Ph.D. ’84), a professor in the Division of Biostatistics, got a call from the National Institutes of Health (NIH) asking for help with vaccine and treatment trials. “People would say we are the go-to people to design and conduct studies,” says Neaton of his department, which is known throughout the world for their research on infectious diseases.
While statistics are often used to summarize data that’s already been gathered, biostatisticians set up rules before experiments are conducted. “A big part of my job is developing procedures prior to seeing the data,” Reilly explains. In other words, the process is key.
And that can get challenging when working in developing countries. “It’s not like doing research in the U.S., where we can recruit patients through clinics,” says Reilly. Liberia has no national identification system; houses don’t even have addresses. It’s also not uncommon for medical trials in the country to take place without control groups. Given these challenges, Reilly and Neaton said it was important to travel to Liberia to make sure the details were in order.
“I wanted to be able to look at the control and make sure nobody could tell the difference between the active and the placebo drug,” says Reilly. “And I wanted to see what the procedures were like . . . so I could speak to the integrity of the data.”
While the epidemic waned before the team—which included experts from the National Institute of Allergy and Infectious Diseases and the Liberian government—was able to get full enrollment for the study, members were able to establish the safety of two vaccines, including one which would ultimately be used in the mid-summer 2019 Ebola outbreak in the Democratic Republic of Congo.
The team’s most recent study, conducted in collaboration with NIH and the Liberian Ministry of Health, looked at the health status of Ebola survivors. Published last March in the New England Journal of Medicine, the study confirms that Ebola survivors suffer from a variety of ongoing health challenges. Not only do they experience increased urinary frequency, fatigue, headaches, and neurological and musculoskeletal problems when compared to close contacts who did not contract the disease, they also report higher rates of memory loss than people who were not infected. Genetic material from the Ebola virus was also found in the semen of some male survivors for more than three years, which could potentially result in the infection of their sex partners.
There was some better news: The study disproved the prevailing wisdom that Ebola survivors suffer from higher rates of uveitis, an inflammation of the eye that can lead to blindness. “I think we were the first study to really demonstrate that actually there’s just a lot of uveitis in West Africa,” says Reilly. He adds that the study findings also showed a need for follow-up care to help survivors cope with ongoing health problems associated with the disease. The results could also help improve response to other outbreaks, including the Ebola epidemic that was raging in the Democratic Republic of the Congo as of midsummer, with more than 2,000 people infected and two-thirds of those dying.
The team is currently conducting a vaccine trial in Liberia, Guinea, Sierra Leone, and Mali that focuses on vaccine safety, particularly in children. “This is a very poor part of the world,” says Neaton. “There is a tremendous burden of disease and it’s very good that the United States is bringing some research to this region."