A Promising New Approach Against a Forgotten Killer

Matt Kelly, M.D., remembers his first visits to Botswana more than a decade ago as if they happened yesterday. The pediatric wards at Princess Marina Hospital, located in the capital city of Gaborone, overflowed with infants and young children. Extra cots lined hallways to make space for parents cradling sick boys and girls, many of them struggling to breathe.

Kelly, then a global health fellow with the Children’s Hospital of Philadelphia, was witnessing a seasonal spike in pneumonia. While typically treatable with antibiotics, the respiratory infection remains a leading cause of death among children, killing more than 700,000 children under five annually. That’s more deaths than AIDS, malaria and measles combined, according to the World Health Organization, which has led some to call pneumonia the “forgotten killer” of children.  

The vast majority of pneumonia deaths occur in low- and middle-income countries, where access to medicines and vaccines is uneven, especially in rural areas. Undernourishment and exposure to air pollution, such as smoke from indoor cookstoves, also increase the risk of infection.

“On any given day, we would have 30 to 40 kids with pneumonia on the wards,” says Kelly, an associate professor of pediatrics and global health at the Duke Global Health Institute and the Duke School of Medicine. “I was blown away by the burden of pneumonia in Botswana when its deaths are preventable.”

But Kelly and his collaborators may have found a promising natural weapon that could eventually help countries like Botswana do more to protect children from pneumonia. In 2021, he and a team of researchers found that a high presence of a naturally occurring bacterium called Corynebacterium in the upper respiratory system appears to prevent pneumonia-causing bacteria from colonizing. The researchers are now testing whether strains of Corynebacterium could be used as a nasal probiotic to prevent respiratory infections.

“In order for pneumococcus and other bacteria that commonly cause pneumonia to cause an infection in the lungs, they must first colonize the upper respiratory tract,” Kelly explains. “If these bacteria are blocked from colonizing, then they don’t have the potential to cause an infection.”

The research began in 2016, when Kelly’s team started collecting nasal swabs from infants in Botswana every few months. They were hoping to find naturally occurring microbes that offered children some protection against bacteria that cause pneumonia, and that turned out to be the case with Corynebacterium. Infants who had high natural levels of the bacteria were less likely to become colonized by the most common bacteria causing pneumonia in children.

Strains of Corynebacterium are now being analyzed at the Wake Forest University School of Medicine’s Department of Microbiology and Immunology. If doses of the bacterium prove effective in preventing pneumonia infections in animal models, the next step would be to test the treatment in humans, a process that could take several years.

Using naturally occurring bacteria to treat infection isn’t new, Kelly notes. People with C. difficile colitis, an infection in the large intestine, are often treated with a dose of healthy bacteria to refuel their microbiome. Many commercially available probiotics promote the growth of healthy bacteria in the gut.

“There’s a lot of interest in how we can use the microbiome to prevent or treat infections,” Kelly says, noting vaccines and antibiotics don’t prevent or treat all infections. They’re also susceptible to immune evasion or antimicrobial resistance.

In places like Botswana, antibiotics also many not be widely available or accessible where people need them. Many children who develop pneumonia live in rural regions, hours away from treatment.

“If you look at what predisposes kids to pneumonia, it’s exposures that are tied to socioeconomics,” Kelly says. “We know from places that have sufficient resources to provide advanced medical care that a child dying from pneumonia should be a rare event.”

Kelly hopes research on healthy bacteria could be one step toward making that happen. He aspires to build on his current work by launching a program at Duke that tests nasal probiotics to prevent respiratory infections among children and adults.

“We’re not there yet, but in the coming decades we will see a lot of new treatments focused on changing the microbiome to promote health,” he says. “If we can identify ways to safely change a child’s microbiome, then we can use those methods to reduce the risk of them getting infections.”