Cytomegalovirus: Screening, Treatment, and Prevention Strategies

Abstract

It’s a virus that can spread through even brief physical contact, and can have serious, long-lasting consequences in newborns. There is no vaccine currently available, and experts say that far too few people know that it can happen to their families.www.shutterstock.com.Cytomegalovirus, or CMV, is an extremely common but sometimes devastating infection that occurs in adults and children alike. And although most people will contract CMV and recover without even knowing they’ve had it, congenital CMV is the leading infectious cause of birth defects in the United States. It is also the single most common of any congenital infection. One of the most significant birth defects associated with congenital CMV is hearing loss. With June marking National Cytomegalovirus Awareness Month, The Hearing Journal spoke with experts about screening, treatment, and prevention strategies, as well as new developments in this rapidly changing area of medicine. EPIDEMIOLOGY The CDC says that more than half of adults in the United States will be infected with cytomegalovirus by the time they turn 40. Further, the agency reports, one in every three children will be infected before they reach their fifth birthday. Many people will be infected with the virus without ever knowing it. Infections may be completely asymptomatic or produce influenza-like symptoms so mild that the illness passes without the infected person giving it a second thought. However, the CDC explains, once the virus is inside a person’s body, it stays there for the rest of the person’s life. The virus, which is a type of herpes virus, can be reactivated in a person’s body years after infection, and people may also be reinfected later with another strain. “It’s believed that about 50% to 80% of adults in the United States will have contracted CMV before they’re 40 years of age,” says Angela Shoup, PhD, Executive Director of the Callier Center for Communication Disorders, Professor of Behavioral and Brain Sciences at the University of Texas at Dallas and Professor of Otolaryngology. “There are other prevalence rates, depending on the global location, that range from 45% to 100%. And you can contract it very easily. You can get it from any exposure to bodily fluids.” Some examples, Shoup explained, can include contracting the virus while changing a baby’s diaper, wiping off a pacifier after a toddler drops it, or even a simple kiss. Even symptomatic infections can be hard to identify. People experiencing symptoms of CMV infections generally experience mild, influenza-like symptoms, including fatigue, sore throat, and fever. CMV is most dangerous in those with weakened immune systems and when caught before birth. “Typically, once contracted, CMV will remain dormant for most of your life,” says Shoup. “But the problem we encounter, and are really cognizant of, is when cytomegalovirus is contracted by an adult who’s been immunocompromised. Patients with HIV can have severe sequelae from cytomegalovirus. Anybody who’s immunocompromised would be more at risk.” These sequelae can involve damage to the liver, lungs, esophagus, stomach, intestines, and eyes, according to the CDC. In newborn babies, CMV contracted in utero can lead to a wide range of issues, including jaundice, thrombocytopenia, microcephaly, being born small for gestational age, cognitive disability, lung and spleen problems, and hearing or vision loss. About one in every 200 babies born in the United States will have congenital CMV, and 20% of these babies will show symptoms, including the hearing loss that is widely associated with the virus. The mechanism by which CMV can cause hearing damage is not fully understood, Shoup says, but scientific literature on the subject indicates that the virus may impact hearing through more than one avenue. One mechanism could be that the virus causes damage to the cochlea at the cellular level, whereas another is inflammation that occurs in response to the infection. INCREASING AWARENESS Far too few people are familiar with CMV and its potential complications, experts say. The National CMV Foundation (NationalCMV.org) estimates that just 9% of women are aware of the virus. “Awareness for this condition is quite low,” says Albert Park, MD, chief of Pediatric Otolaryngology at the University of Utah. “We know all about COVID, and even Zika has hit the national consciousness. But, unfortunately, congenital CMV has not reached that sort of threshold. And yet, in terms of the public health implications of this condition, [cytomegalovirus] is certainly much more frequent than Zika.” At the same time, Park adds, most Americans are more familiar with congenital conditions like Down Syndrome and spina bifida, which are in fact less common than CMV. Park is one of a group of investigators who have worked to develop validated diagnostic tests for congenital CMV over the last two decades. In that time, he’s seen awareness of the virus increase steadily among health care providers. “Fifteen, twenty years ago, I rarely saw a child with congenital CMV,” says Park. Then, in 2012, Park diagnosed the virus in a child with hearing loss who turned out to be the granddaughter of a Utah lawmaker. The legislator had never heard of congenital CMV and used her influence to convene a group of experts who, Park says, would have otherwise never been able to align their overburdened schedules. That meeting led directly to the 2013 introduction of a hearing-targeted CMV screening program for newborns in the state of Utah. A full decade later, in February of 2023, Minnesota became the first state to introduce universal congenital CMV screening. “Before, I would maybe see a child once a year or every two years with this condition,” he says. “Now we’re seeing one or two a week.” Although various places around the world are beginning to adopt screening programs, universal screening is a long way off, Park says. The National CMV Foundation describes this lack of universal screening as an unmet need. The group’s website lists more than 100 clinical centers that have started some form of early testing or screening, but these are located in fewer than half of American states. In the meantime, however, Park and his colleagues have expanded their targeted screening program to include looking for symptoms like microcephaly or low birth weight. “We’re not there yet,” he adds. “We’re not doing universal screening. But at least this is a step forward.” TREATMENT AND PREVENTION Currently, there is no vaccine for CMV. But researchers are making progress, and one study of a vaccine candidate made by Moderna is expected to complete enrollment in October of this year. The study will evaluate whether a vaccine candidate effectively prevents CMV infection among young women. “After all, you can’t transmit CMV to your baby in utero if you don’t have it yourself,” says Mark R. Schleiss, MD, American Legion and Auxiliary Heart Research Foundation Professor at the University of Minnesota, who introduced the idea of legislation to create Minnesota’s universal screening program to lawmakers in 2015 and worked with parent advocates to get the legislation, known in Minnesota as the “Vivian Act,” to the governor’s desk for signature in 2021. “Everybody in the pharmaceutical industry, the National Institutes of Health and other interested parties in obstetrics, pediatrics and infectious diseases, is waiting with bated breath to see what the answer is going to be.” One challenge, Schleiss continues, is predicting which babies with congenital CMV will experience hearing loss. Often, hearing loss from congenital CMV occurs in the first few months of life, rather than presenting immediately at birth. What’s more, standard hearing tests in newborns might miss as many as half of infants who will eventually experience hearing loss related to the virus, Schleiss says. “If hearing loss occurs in the first few months of life and an intervention isn’t offered, that can have a permanent impact on a child’s speech and language development,” Schleiss explains. In these cases, parents and care providers may miss the opportunity to intervene until the child is a toddler, at which point they may already have speech and language delays. Doctors can prescribe antiviral medications like ganciclovir or valganciclovir to fight the infection, but these drugs have only a modest impact on hearing loss that has already occurred. “If you look critically at the data, the benefits of long-term antiviral therapy are very modest,” Schleiss says. Prescription of antivirals can be a thorny issue, he adds. “By screening more babies, and making the diagnosis more often, we have now seen what some people would say is a vast overprescription of valganciclovir.” Valganciclovir can be life-saving medicine for patients with some conditions, like advanced AIDS or leukemia. “But for the newborn baby who’s born with damage due to CMV infection they acquire before birth, it helps a little bit. That’s the best you can say.” This limitation, he says, is not fully understood, though Schleiss believes it has to do with the timing of the infection. In short, the virus may have already caused hearing damage before the baby is born. “Symptomatic babies who have multiple body systems involved, have been shown to benefit from antiviral treatment,” Shoup says. “Typically, though, it is off-label to provide antiviral treatment to infants who are otherwise asymptomatic but have hearing loss at birth.” Ethical issues may arise from the prescription of these antivirals as well, Schleiss adds, because offering such treatments may offer a “false sense of assurance” that children treated with drugs like valganciclovir will somehow have their disabilities or health issues attenuated or reversed, when in fact this is not the case. Antivirals also come with complications, like neutropenia, which Schleiss says occurs in about one-third of children, and a high cost-in some instances, $1,000 a month. Park attempted once to conduct an NIH-funded placebo-controlled study of valganciclovir in children with congenital CMV and isolated hearing loss, but the study could not enroll enough patients to move forward. Hearing aids and cochlear implants are other options for children with hearing loss from CMV. The hearing aids are generally prescribed based on results of hearing tests. Cochlear implantation is not used in a one-size-fits-all approach, however, and Park points out that there is some controversy about which children with CMV should undergo surgery. He describes the decision to provide a child with cochlear implants as a multidisciplinary process that requires input from multiple doctors and, of course, the child’s parents. There is also no currently accepted standard of care for congenital CMV, even though some professional organizations and researchers, including Park himself, have published guideline recommendations. The American Academy of Audiology released a position statement this past spring. “I work with audiology [specialists] to help the families determine whether hearing aids, if necessary, are the best approach, or maybe even cochlear implantation. There are some children who have such a high degree of hearing loss that hearing aids aren’t going to provide them with the functional hearing that they would need to evoke speech or language,” says Park. Children with congenital CMV must be watched closely over the long term, Park continues, because once a child has hearing damage from the infection, the chances that the damage will worsen over time increase greatly. “The time point is going to depend on the type and degree of hearing loss,” Shoup says of her own institution’s practices. “Once they meet cochlear implant criteria, they will transition over to the cochlear implant program.” Before then, however, she notes that clinicians will have already looked at other options as needed. “If we’ve identified that they do have hearing loss, we provide amplification and other treatment services as appropriate, and closely monitor children to change technologies or treatment options as required,” says Shoup. “And many of these kids will progress to cochlear implantation. Not all of them, but many.” The wishes of the family must also be taken into account. “There is a Deaf culture, of course, and there are certainly plenty of people out there who say, ‘We’re fine, thank you very much. We don’t consider this a disability like you do,” Schleiss says. “It’s more common to embrace that philosophy for genetic and familial forms of deafness. I think a child born with congenital CMV who’s got significant hearing loss born to hearing parents, by and large, those parents want to do everything they can to preserve that child’s hearing.” In terms of the future, Shoup says she hopes to see more data emerge on the role of antiviral treatments for children with congenital CMV, and to see interprofessional collaborative care to enhance patient and family support. Schleiss also says antiviral drugs will play a role in future care, with more effective and less toxic drugs possibly offering new options. In the meantime, Park says that progress in the creation of vaccines, much of which can be seen with the rapid development of COVID vaccines, may offer a preventive measure someday soon. “I’m certainly hopeful,” says Park. “I know that it’s been a long road. But the hope is that in the next five to 10 years, we’ll have something available, and that could be a game changer.”