Global collaborations are creating critical breakthroughs in infectious diseases, such as dengue and COVID-19.
This was a recurring theme at EPI Research Day 2024, the flagship event of the University of Florida’s Emerging Pathogens Institute. The event highlights EPI’s distinct approach to the scientific process, said EPI Director J. Glenn Morris, M.D.
“EPI is strongly focused on team science – investigators from multiple disciplines coming together to tackle a common issue,” Morris said. “It’s not a solo investigator tucked away in a lab. Moving science forward requires a team with a diversity of expertise and skill sets, and creating those teams is EPI’s core strength.”
The one-day research symposium brought together more than 350 attendees from across UF, the National Institutes of Health, the U.S. Department of Agriculture, the Florida Department of Health and other universities.
More than 135 posters showcased a diversity of infectious disease research, from studying the gut microbiome of infants to tracking how climate conditions influenced the course of the Black Death. Much of the research on display was the work of UF students, postdoctoral researchers and other early-career scholars.
“A critical role EPI plays at the university is training the next generation, instilling in them the value of team science and introducing them to a wide variety of disciplines,” Morris said.
Keynote presentations by world-renowned scientists from Yale and Johns Hopkins Universities underscored the need for global partnerships to advance infectious disease research.
“We don’t want to become insular,” Morris said. “Science is a global process. It’s critical that we be a part of that.”
Global health equity benefits all
When EPI Research Day keynote speaker Albert Ko, M.D., was a student, models of human infectious disease focused primarily on the interaction between a pathogen and a patient. Over time, however, epidemiologists, including Ko, have increasingly recognized the important role other factors play in public health. These factors include societal changes, demographics, the physical environment, ecology, climate and even political will.
In his address, Ko, the Raj and Indra Nooyi Professor of Public Health at the Yale School of Public Health, described how two factors – rapid urbanization and social inequity – are driving the emergence of new public health threats.
By 2037, most people will live in cities, and over the next 20 years, the number living in urban informal settlements, formerly known as slums, will rise to 2 billion, Ko said. Communities with inadequate housing, and significant health threats and little to no access to services are often meters away from wealthier enclaves.
He saw firsthand the connections between poverty and disease during a 15-year effort to treat and contain leptospirosis in some of Brazil’s poorest neighborhoods. Leptospirosis is a potentially life-threatening illness that spreads through the urine of infected animals and is the most common zoonotic infection globally.
In Pau da Lima, a community in the Northeast Brazilian city of Salvador, Ko and his colleagues found that people’s risk of leptospirosis fell 10% with each extra dollar in per capita income. Incidence of the disease was highest in the area’s lowest point – the valley with the poorest land quality and the place where the most vulnerable people lived.
“We would tell patients to avoid rats and open sewers,” said Ko, a collaborating researcher at the Brazilian Ministry of Health’s Oswaldo Cruz Foundation (Fiocruz). “But when the sewer runs through the middle of your front yard and rats infest your neighborhood due to a lack of sanitation and garbage collection, that’s not a solution.”
Following his mentor Lee Riley’s imperative to use science to correct injustice, Ko created a Fiocruz-Yale program that has trained more than 350 Brazilians, as well as 120 American students and fellows, to help urban informal communities solve their own health problems. With the introduction of closed sewers, rapid diagnostic tests and early warning systems, leptospirosis fatalities dropped fivefold over about a decade.
Ko also pointed to the program as an example of how global health equity benefits everyone: The lessons learned from fighting leptospirosis later provided the foundation for combatting the Zika virus in Salvador and helped inform how Yale and the state of Connecticut responded to the COVID-19 pandemic.
As advances in science and technology yield societal benefits, researchers must ensure their work is not unintentionally perpetuating social inequity, Ko contended – not just the inequities between the Global North and South, but those found within our communities.
“In order to be equitable, global health has to be a two-way street,” he said. “This is a key moment in our field to think about whether our incentives are aligned with the global health outcomes we want to achieve.”
Leadership and training are key components to making global health equity a reality, Ko said.
“We look to institutes like EPI to help lead us into the future of addressing the social inequities that drive disease.”
‘Very close’ to a safe, effective dengue vaccine
Keynote speaker Anna Durbin, M.D., a professor of international health at Johns Hopkins Bloomberg School of Public Health, said researchers are tantalizingly close to rolling out a safe, effective vaccine for dengue.
Dengue is considered the most important mosquito-borne virus globally because it causes more infections, more cases of severe disease and likely more deaths than any other arbovirus, Durbin said. More than 60% of the world’s population is at risk for the disease, and dengue outbreaks can swiftly overwhelm healthcare systems. Dengue is spreading worldwide, and in the U.S., the disease occurs in Florida, Texas and Puerto Rico. Children are often the most vulnerable to severe dengue infections, which can become life-threatening within hours.
Dengue spreads through the bite of infected Aedes mosquitoes. It is not a single virus, but rather a group of four distinct viruses, or serotypes. After a dengue infection, a person has lifelong or long-lived protection against symptomatic disease caused by that particular serotype, but not the other three, Durbin said. The risk of severe or live-threatening dengue is highest after infection with a second, different serotype.
This has presented a formidable challenge to developing a dengue vaccine: To be safe and effective, the vaccine needs to produce a strong immune response to all four serotypes.
“If a vaccine does not combat all four serotypes, we could be predisposing people to more severe infection,” said Durbin, an expert in experimental vaccines who also serves as the director of the Johns Hopkins Center for Immunization Research.
Two candidate vaccines, Dengvaxia and TAK-003, fail to protect effectively against all four dengue viruses and require multiple doses, an obstacle to vaccine uptake, Durbin said.
However, a single-dose vaccine known as TV003, developed with funding by the National Institutes of Health, shows more promise. All four dengue virus serotypes introduced by TV003 are able to infect and replicate in recipients, and the vaccine was 88% successful at preventing severe dengue for more than three years, Durbin said.
“This one provided what we felt to be the most balanced immunogenicity and safety profile. It’s very encouraging,” said Durbin, who conducted the early clinical work on the four viruses that comprise TV003. “We’re very, very close.”
If TV003’s five-year clinical trial data, available this July, continue to show it is safe and effective, Durbin predicts high demand for the vaccine and its eventual adoption as a routine childhood vaccination. The NIH is partnering with manufacturers in multiple countries to help ensure the vaccine will be accessible to people who need it most, Durbin said.
She attributes the success of TV003 to the NIH’s investment and the collaborative efforts of researchers from multiple disciplines. These are the types of collaborations Durbin said she sees at the EPI.
“Science used to be a Mom-and-Pop shop where one investigator did everything. Now you have people with expertise in various fields – virology, immunology, epidemiology, bioinformatics – working together on a particular pathogen. It’s fantastic.”
Written by: Natalie van Hoose