Cytomegalovirus (CMV), a common congenital infection that occurs in approximately 1% of all U.S. births, is one of the leading causes of sensorineural hearing loss.1 While antiviral medications can stabilize hearing loss if administered shortly after birth, infants are not often screened for CMV. “Newborns who test positive for CMV and are treated with an antiviral medication for six weeks can have their hearing stabilized and, in a few cases, rescued,” says Daniel Choo, MD, director, pediatric otolaryngology-head and neck surgery, and professor, otolaryngology-head and neck surgery, University of Cincinnati (UC) Medical Center. Even infants who show no hearing loss at birth may be infected with CMV, which can lay dormant for years. Delayed manifestations of congenital CMV infection, particularly hearing loss, can occur months or years after birth2 making it difficult to connect the hearing loss with CMV. Consequently, “detecting children with CMV during the first three weeks of life, when diagnosis is more reliable, is key,” explains Dr. Choo.
UC Medical Center researchers are studying newborn hearing screening procedures to determine when it is cost-effective and most clinically appropriate to test for CMV. “It makes medical and fiscal sense to test babies for CMV if they don’t pass this initial hearing screen. At UC Medical Center, a baby who fails this first hearing test is sent to a pediatric audiologist, who performs a diagnostic hearing test (Auditory Brainstem Response test) and swabs the infant’s mouth to obtain saliva, where CMV is concentrated. If the results are positive for CMV, the baby’s family is given the option of undergoing treatment for six weeks with antiviral medication. In the past six months, several children with CMV have been identified as a result of following this protocol,” says Dr. Choo.
Adverse effects of older CMV treatments (intravenous ganciclovir) can be significant: 66% of patients experience bone marrow suppression; for them, the treatment is tapered or stopped.1 This complication led Dr. Choo to investigate an alternate delivery system that would avoid systemic toxicities and bone marrow suppression, such as injecting the antiviral solution into the cochlea and inner ear structure of guinea pigs. With another National Institutes of Health grant, Dr. Choo collaborated with Kevin Li, PhD, professor, UC College of Pharmacy, to determine if Dr. Li’s hydrogel could serve as a better drug-delivery vehicle. These biocompatible hydrogels, synthesized in Dr. Li’s laboratory, are liquid at room temperature and can be mixed with a drug. The gels are engineered such that they undergo a phase transition (to a gel-like consistency) in a body-temperature environment. This phase transition allows the gel to deliver drugs to the inner ear in a much more controlled fashion and potentially, in a more sustained manner. “This allowed us to deliver, very successfully, antivirals (ganciclovir and cidofovir) to the inner ear in an experimental animal (guinea pigs) model of CMV infection,” Dr. Choo says.
Currently, Dr. Choo says, for some families who have been uncomfortable not treating delayed-onset CMV hearing loss in their children, “we have tried to be proactive and offer our families treatment with valganciclovir (and oral antiviral medication). Our preliminary experience indicates that the children tolerate the oral antivirals surprisingly well.” In a collaboration just being developed, UC will be one of a several select sites studying if the use of valganciclovir will preserve or rescue hearing in children with CMV, whose only symptom is hearing loss.
“The key learning for otolaryngologists is that CMV hearing loss is one of the few causes of hearing loss in children that can be stabilized or stopped – if the condition is diagnosed early, within three weeks of birth, and treated appropriately,” Dr. Choo observes.
1. Schleiss MR. Congenital cytomegalovirus infection: update on management strategies. Curr Treat Options Neurol. 2008;10(3):186-192.
2. Fowler KB. Congenital cytomegalovirus infection: audiologic outcome. Clin Infect Dis. 2013;57(suppl 4):S182-S184.
Daniel Choo, MD
Director, Pediatric Otolaryngology-Head and Neck Surgery
Professor, Otolaryngology-Head and Neck Surgery
University of Cincinnati Medical Center
University of Cincinnati College of Medicine/UC Health