What started as a weeklong trip to treat pediatric epilepsy patients in Africa nearly 20 years ago has evolved into a sophisticated data collection and public health program that is providing Yale researchers with answers about the mysterious source of a neurological disease killing children.
Steven Schiff, MD, Harvey and Kate Cushing Professor of Neurosurgery, is leading the Yale team partnering with Ugandan leaders and health care workers in the Jinja District of Uganda to change the lives of the local population.
“Dr. Benjamin Warf was working as the medical director of the pediatric neurosurgery hospital in eastern Uganda in 2007,” Schiff explains. “Because I was a pediatric epilepsy doctor at the time, he asked if I would like to join him for a week in Uganda to see if I could help their epilepsy team. Of course, I jumped at the chance.”
Surprisingly, Schiff didn’t see any epilepsy patients that week. He did, however, see several children a day who had survived a serious infection early in life.
“They were typically 2 to 3 months old, and after surviving their previous infections, they had large heads which were expanding under pressure,” Schiff says. “Dr. Warf didn’t know what was causing the infections despite culturing the cerebrospinal fluid of over 1,000 children. His team wasn’t able to grow anything in the lab. So, I asked him what the most important unsolved problem he was facing was, and he said, ‘Well, Steve, maybe you could help figure out what makes these kids sick.’”
After a lot of false starts and years of investigative work, answers started arriving in 2020.
“We created all sorts of infrastructure at multiple sites, and used the best techniques for collecting and transporting deep-frozen samples, and had tremendous partners in the Ugandan doctors we were working with,” Schiff says. “Through all of that work we discovered we were dealing with an unusual bacteria that was very difficult to get to grow in the lab and it was extremely dangerous to these infants.”
The team learned that the Ugandan children were suffering from hydrocephalus caused by a unique strain of what was previously thought to be a relatively harmless bacteria discovered in the 1950s. The Ugandan strain was a frequently lethal brain-seeking, or neurotropic, bacteria.
“This was the dominant cause of the biggest group of infants who needed hydrocephalus surgery in Uganda,” says Schiff. “We conducted a number of clinical trials to figure out when these children caught the bacteria including maternal and neonatal sepsis trials. We studied over 1,000 kids and discovered the risk of infection was rainfall dependent. The infections increased when the area experienced rainfall roughly two weeks before birth.”
Armed with the knowledge they were dealing with an environmentally driven disease, the team is now using a combination of hospital technology and field-work efforts to better understand why the number of infections rises following a significant rainfall.
“We’re using satellite measurements of rainfall, of surface water, of temperature, and of vegetation to characterize the environment,” Schiff explains. “We’ve also created a software system, with ethics approval from Uganda and Yale, that enable us to track and report every infant born with these conditions in real-time.”