This infectious disease expert helped build Uganda’s research infrastructure

September/October 2023 | Volume 22 Number 5

Photo courtesy of Jerrold Ellner Jerrold Ellner, MD, has worked in Uganda doing research on infectious diseases including HIV and TB since the late 1980s.

“If you wait for everything to be in place before you start your research, you’ll run out of time. Sometimes you just have to say, ‘let’s go with what we have.’”

Dr. Jerold Ellner's decades-long career as an immunologist and HIV researcher taught him this valuable lesson. Today he shares this advice with the young global health and infectious disease researchers he trains as part of the Fogarty-funded Training of Ugandans in Basic and Translational Research on TB and Emerging Infectious Diseases program.

Ellner’s own career began in 1972 with a fellowship from the National Institute of Allergy and Infectious Diseases (NIAID). A few years later, he took a faculty position at Case Western Reserve University. He crossed paths there with Dr. Frederick Robbins, working then as a university professor. In the early days of the HIV epidemic, Robbins—who’d won the 1954 Nobel prize (with Drs. John Enders and Thomas Weller) for isolating and cultivating polio viruses in tissue cultures—believed a similar approach might be useful to study HIV in Africa. Robbins needed help to create a new program in Uganda and tapped Ellner as co-principal investigator on a grant from NIAID’s program, International Collaboration for AIDS Research (ICAR).

Building infrastructure

Ellner made his first trip to Uganda in 1987, not quite a year after the election of President Yoweri Museveni. “It was a difficult time,” said Ellner. The overthrow of Idi Amin, a brutal military dictator who acted as president from 1971 through 1979, led to the 1980 return of Milton Obote, an oppressive leader who had preceded Amin. A coup ended Obote’s second five-year regime, yet it was the National Resistance Movement led by Museveni (who remains in office to this day) that gained control of the country. “Kampala was unstable… automatic weapon-fire at night in the street,” said Ellner. “And there was no research infrastructure: no vehicles, no refrigerators, no computers.”

Ellner, an MD who studied immunology, got help from Dr. Brooks Jackson setting up a quality control clinical laboratory, in Uganda in the late 1980s. "We had funding from the World AIDS Foundation and USAID to buy equipment. We established a first-rate laboratory, probably the best in sub-Saharan Africa at the time.” Over the years, both the lab and the research program evolved, offering unique opportunities to countless Ugandan scientists along the way. “At least a hundred individuals from Uganda have trained at Case Western and have since become leaders,” said Ellner. That list includes Dr. Harriet Mayanja-Kizza, former dean of medicine, and Dr. Moses Joloba, dean of biomedical science at Makerere University.

The partnership recently celebrated its 35th year. Case Western Reserve University remains involved as does Rutgers-New Jersey Medical School where Ellner is currently a professor, and Johns Hopkins where Jackson was Chair of the Department of Pathology before becoming Dean of the University of Minnesota School of Medicine.

Success combatting HIV in Uganda

“We were the first American university—first non-Ugandan university—to come with funding and set up research in the country. Now every major academic university is there,” said Ellner. “In the late 80s, early 90s, many countries in Africa either were not aware of their AIDS problem or were not discussing it. In Uganda, though, Museveni was saying, ‘We have a problem and I’d like anyone who can to come and help.”

When Ellner started in Uganda, the seroprevalence of HIV in the antenatal clinic where he worked was over 20%. “It was a scary time. We didn’t know the epidemiology of HIV or how it might change, much like the early days of COVID-19.” Extraordinarily, prevalence of the virus began to decrease in Uganda, due to behavioral messaging (such as promoting use of condoms), although other factors that stemmed the epidemic remain unclear. The country soon became a magnet for AIDS funding. “Uganda had embraced expatriate influence and had an interest in science and was working to control the epidemic—it would be a model for other countries,” explained Ellner.

Scientific contributions, past & future

Assessing his past achievements, Ellner believes some of the original studies remain significant. “In one study we showed that TB accelerated the course of HIV, increased viral replication and mutations. We also performed one of the first large studies of preventive therapies for TB in HIV, which was published in the New England Journal of Medicine in 1997.” It showed short-term impact using preventive therapy, an important observation at the time.

Ellner contributed to the first AIDS vaccine trial in sub-Saharan Africa. “Pasteur Merieux provided the vaccine; NIH provided the funding,” he said. The experimental vaccine developed by the French pharmaceutical company didn’t produce an ideal level of immune response, so Pasteur Merieux abandoned the project. But, Ellner noted, the team did complete a proof-of-concept vaccine trial for HIV in Africa, a remarkable achievement. And the trial led to the development of a cytotoxic T-lymphocyte lab at the Joint Clinical Research Centre in Kampala.

Research engagement across continents

Ellner’s current research involves applying TB discoveries made in Brazil, where he also works, to Uganda. His studies have shown that when certain, easily transmitted strains infect experimental mice (that have been altered to present disease symptoms similar to humans), this leads to the development of granulomas (much like human TB). Meanwhile, certain less easily transmitted strains lead to diffuse pneumonitis, inflammation, and more frequent death (in mice). “The TB strain causing infection may have a lot to do with clinical manifestations and pathology," he said. "We’re currently testing this in Uganda to determine whether the type of strain may determine whether you have cavities or not, the amount of consequent lung damage, and the duration of inflammation.”

Another area of Ellner’s research is based on the observation that lifetime risk of developing TB symptoms (following infection) ranges from 2% to 5%. “If we're considering preventive therapy, we need to identify the people at greatest risk of progression (since treatment can lead to severe, even fatal liver damage),” he said. His long-term plan is to develop a diagnostic biomarker (to show progression risk) along with targeted preventive therapy. In Brazil, a Rutgers team led by Dr. Padmini Salgame discovered a transcriptional signature—a profile of genes expressed in immune cells following a TB infection—linked to higher risk. “People with that signature had a 20% risk of developing symptoms, rather than just a 2% to 5% risk. And not just risk in the next four to six months but risk over four to six years.” In Uganda, Ellner’s conducting human trials to see whether this signature accurately predicts progression.

Wisdom gleaned from global experience

“Our current Fogarty training grant brings Ugandans to the U.S. for intensive instruction and coursework in basic and translational technology. Then they return to Uganda and usually get a PhD from Makerere University.” The goal is to develop a cadre of scientists doing bench-based research. He recently introduced data science into this program.

Though many aspects of research are now done on-site, the final data is commonly analyzed in the U.S. “The country would benefit from building capacity to analyze its own clinical data, particularly since a lot of this research impacts public policy.” If everything were done in-country, then U.S. involvement could be refocused on capacity building and transferring the capacity for cutting edge research to Ugandans, Ellner added.

“Working in Uganda, I vacillated between thinking everything is possible, and nothing is possible. That vacillation is a sign of enormous growth—if everything is easy, someone else can do it.”