Campagnari Developing Novel Treatment for Ear Infections

The research centers around Moraxella catarrhalis, one of the most significant causes of bacterial middle ear disease and sinusitis in infants and children. It is funded by a five-year, $2 million grant from the National Institute on Deafness and Other Communication Disorders.

Approximately 80 percent of all children younger than 3 experience at least one ear infection, and many experience recurrent disease, which often results in hearing impairment, delayed speech and learning problems, says Campagnari, professor of microbiology and immunology and medicine.

Ear infections represent a major health care problem, resulting in three to four million doctor visits annually. They are the most common cause for surgery (for insertion of tympanostomy tubes) and antibiotic use in pediatric populations.

“These infections put considerable stress on health care systems worldwide, thus there is significant interest in identifying vaccine antigens to prevent middle ear disease and to develop novel antimicrobial treatments against ear infections,” Campagnari says.

Recent studies have suggested that once a child is colonized with M. catarrhalis there is a significant increase in the development of acute and recurrent ear infections. Therefore, preventing attachment and colonization of M. catarrhalis on respiratory mucosal surfaces could significantly reduce the incidence of these infections.

Campagnari’s laboratory has previously demonstrated that PilA, a primary component of a bacterial surface component termed the type IV pilus, is conserved on the surface of clinical isolates, constitutively expressed, and an important factor for adherence.

“The first goal of our research is to test our hypotheses that M. catarrhalis PilA is critical in the initial stages of colonization, involved in biofilm formation leading to persistence on mucosal surfaces and warrants evaluation as a potential vaccine antigen,” he says.

Novel therapeutic approaches designed to eradicate planktonic (free-living) and biofilm-associated (surface-attached) bacteria from the middle ear would not only significantly decrease the constant use of antibiotics in young children — they would also decrease the associated morbidity and the need to perform surgeries for chronic OM.

“The second goal of this research plan is to adapt PDT, a medical treatment for several types of cancer and dermatological issues, into an efficacious, noninvasive antibacterial therapy for the treatment and eradication of ear infections,” Campagnari says.

The antimicrobial PDT studies will be performed in collaboration with Gal Shafirstein, DSc, director of PDT Clinical Research at Roswell Park Comprehensive Cancer Center.

The project addresses a significant health care problem from both a basic and translational research approach, Campagnari says.

“Taken together, the data resulting from these studies will provide new insights essential for the design of clinical approaches to prevent persistent colonization with M. catarrhalis and to treat pediatric ear infections that are refractory to standard therapies,” he says.

Nicole R. Luke-Marshall, PhD, research assistant professor of microbiology and immunology, serves as the primary co-investigator on the award.

One of Campagnari’s longtime colleagues and collaborators, Luke-Marshall brings a unique blend of scientific expertise to the project, including extensive research experience in molecular biology, genetics, bacterial pathogenesis and analyses of bacterial biofilms.

“Dr. Luke-Marshall’s published expertise on the chinchilla model of colonization and antimicrobial photodynamic therapy will be essential to the overall success of this exciting translational research, which could change the paradigm for the treatment of otitis media in the unfortunate group of young children that are chronically afflicted with this disease,” Campagnari says.

For more than a decade, Timothy F. Murphy, MD, SUNY Distinguished Professor of medicine and senior associate dean for clinical and translational research, has studied how M. catarrhalis causes middle ear infections.

“The work by Dr. Campagnari and his group has enormous potential to prevent and treat what is a huge national and global problem. Better ways to prevent and treat ear infections are urgently needed,” he says.

Antibiotics alone are not the solution to treating ear infections — especially recurrent infections, Murphy notes. The best way to tackle the problem is through prevention.

“Vaccines are the single most cost-effective health care intervention ever invented,” he says. “Dr. Campagnari has identified a potential vaccine that could be used to prevent infections by one of the most important bacteria that cause ear infections.”

“He is proposing a completely novel approach to therapy,” Murphy adds. “This exciting research has the potential to completely change how ear infections are treated.”