The world’s largest outbreak of the Ebola virus has infected more than 28,000 people and killed more than 11,000 since March 2014 when the epidemic began spreading across West Africa. In July 2015 the World Health Organization announced a major development in the Ebola fight: preliminary results of an Ebola vaccine study in Guinea showed 100 percent effectiveness.
Part of the driving force behind the design and analysis of that vaccine trial is Ira Longini, Ph.D., a professor in the department of biostatistics at the UF College of Public Health and Health Professions and the College of Medicine. An expert in infectious disease modeling and statistics, Longini spent several months on assignment at WHO’s headquarters in Geneva, Switzerland, as researchers rushed to implement an Ebola vaccine trial.
“The research by Dr. Longini and colleagues signals an extraordinary breakthrough in the search for an effective Ebola vaccination,” said Michael G. Perri, Ph.D., dean of the College of Public Health and Health Professions. “The successful testing of a vaccine with the potential to alleviate suffering and save the lives of tens of thousands of people represents a monumental milestone in disease prevention and the advancement of public health.”
Longini has worked on the analysis of epidemics of influenza, HIV/AIDS, tuberculosis, cholera, dengue, malaria, rhinovirus, rotavirus, measles and other infectious disease. He frequently collaborates with the U.S. Department of Health and Human Services, WHO, the U.S. Centers for Disease Control and Prevention and other public health organizations on mathematical and statistical models for the control of a possible bioterrorist attack with an infectious agent such as smallpox, as well as natural infectious disease threats.
As the world grows smaller, warmer and wetter, governments need to have an organizational blueprint about how to best respond to infectious disease outbreaks. In a recent issue of the journal Science, Longini and biostatistician M. Elizabeth Halloran, M.D, D.Sc., of the Fred Hutchinson Cancer Research Center and the University of Washington, outlined how policymakers and health care workers can use epidemiological methods, statistics, mathematics and models of how well vaccination campaigns work to respond to new, unexpected outbreaks.
“Human connectivity is getting more and more complete. Through jet travel, we can move viruses very quickly,” said Longini, the director of the Center for Statistics and Quantitative Infectious Diseases at UF’s Emerging Pathogens Institute and the College of Public Health and Health Professions. “Viruses can get transported out of previously isolated populations in Africa or other parts of the world within days now instead of years.”
Longini and his colleagues published some of the first research modeling the current Ebola outbreak. In a paper published Sept. 2, 2014 in the journal PLOS Currents: Outbreaks, his team showed a 20 percent chance that an isolated case of Ebola would show up in the U.S. by the end of that month. On Sept. 30 the CDC confirmed the first case of Ebola diagnosed in the U.S. in a man who had traveled from Liberia to Dallas. He passed away Oct. 8.
In the effort to test the safety and efficacy of Ebola vaccines, scientists also had to test how to deploy the vaccinations. Groups with the CDC and the National Institutes of Health’s National Institute of Allergy and Infectious Disease designed two efficacy trials to administer vaccinations in Liberia and Sierra Leone, respectively, that were ultimately unsuccessful. The WHO team, with which Longini is involved, decided to use a ring vaccination design in Guinea.
With ring vaccination, people in contact with those who have contracted a virus, including family members, neighbors and co-workers, receive the vaccination. It is the same approach used in the eradication of small pox.
“The way it’s controlled is by isolating cases and quarantining close contacts of cases, as well as contacts of those contacts,” Longini said. “People who weren’t directly exposed to Ebola were vaccinated, and then monitored for safety and immune response.”
These kinds of trials are urgent for what seems like contradictory reasons: while researchers wanted to get vaccines to people who needed them, the researchers also needed to study which method of administering the vaccines was most effective.
“The trial had to be implemented very quickly,” Longini said. “First of all, people were dying of Ebola, and second, we couldn’t rely on transmission continuing forever.”
At the time of the WHO team’s preliminary reporting July 31, 2015 in the journal Lancet, more than 4,000 close contacts of nearly 100 patients infected with Ebola had participated in the trial. None of the vaccinated participants developed Ebola virus disease 10 days or more after receiving the vaccine. Based on these results, the trial stopped randomizing participants to allow for all people at risk to receive the vaccine immediately.
The trial is ongoing, as cases of Ebola remain in Guinea and Sierra Leone, Longini said. A meeting of the WHO in late October will decide when the trial will end. After the trial, the vaccine will have to be proven safe and efficacious in order to be licensed and no longer considered experimental.
So far, there appears to be no ill effect from the vaccine, and it has been cleared for use in children as young as six. Researchers are still studying its safety in women who are pregnant or breastfeeding, and people who have immunodeficiency, such as people with HIV. But neither pregnant women nor people with HIV who were inadvertently given the vaccine had ill effects.
Longini said one of the challenges of this trial — and something that will benefit the response to outbreaks of other infectious diseases in the future — was to design ways to manage data in an emergency situation. This will help others implement the ring vaccination method in the outbreak of infectious diseases such as Middle Eastern respiratory virus, coronavirus, dengue, chikungunya, cholera and even pandemic influenza.
“A tremendous amount of data and information will come out of this trial. It is the most detailed data set collected for Ebola transmission,” Longini said. “We were able to devise a dynamic way to analyze these types of trials where everything was moving in space and time. These constructs will be useful to evaluate other vaccines, and even other antivirals or antibacterials.”
By Morgan Sherburne