Congenital cytomegalovirus infection : hearing prospects and antiviral strategies : dreamscapes of clarity

Korte inhoud:With a prevalence between 0.2% and 6.1% of all live births, congenital cytomegalovirus infection (cCMV) is the most common congenital infection worldwide. Accounting for 21% of the sensorineural hearing loss (SNHL) at birth and 25% of the SNHL by the age of four years, cCMV is an important cause of non-hereditary congenital and late-onset hearing loss. Once present, the hearing loss can deteriorate or improve over the years which requires long-term audiological follow-up. The prevalence and characteristics of cCMV-related hearing loss have already been described though risk factors for hearing loss remain unclear. By analysing data of the Flemish CMV registry, we found that children with petechiae at birth, periventricular cysts on MRI, or a seroconversion in the first trimester had a higher risk of congenital hearing loss. Moreover, children with a first trimester infection were also at higher risk to develop late-onset hearing loss. In contrast, children with a third trimester seroconversion had a limited risk to develop late-onset hearing loss which led to a targeted audiological follow-up program. We recommend to cease audiological follow-up if normal hearing is found at the age of one year in children with a third trimester seroconversion. Clinicians can use these novel findings to counsel parents about the risk of cCMV-related hearing loss. For decades, antiviral therapy with (val)ganciclovir has been offered to children with moderate to severe symptoms at birth. We performed a systematic review to assess the effect of (val)ganciclovir on hearing outcome but it was difficult to draw firm conclusions due to the low-quality design of the included studies and high heterogeneity between the included studies. Consequently, the effect of valganciclovir on long-term hearing outcome remains unclear and treatment duration (a six-week or six-month therapy) is still a matter of debate. Therefore, we performed a quasi-randomized trial investigating the effect of (val)ganciclovir on hearing outcome at the age of four years or older. To equate the risk of spontaneous hearing evolution, treated and untreated children were matched for known risk factors of spontaneous hearing evolution. In our study, (val)ganciclovir did not result in more hearing improvement or less hearing deterioration. In contrast, a six-week therapy prevented late-onset hearing loss. Comparing a six-week to a six-month therapy, we found no additional benefit of prolonging therapy to six months. These findings can aid in treatment decision making and hopefully initiate a critical revision by clinicians and researchers to consider a six-month therapy as a future research topic instead of a beneficial standard care. Systemic therapy with (val)ganciclovir is associated with side-effects. Fundamental and translational research might aid in optimization of the treatment protocol. Murine inner ear research was initiated at our centre to implement a murine model of cCMV-related hearing loss. This will enable us to investigate the feasibility of local drug delivery into the inner ear and learn more about the pathophysiology in the near future. This research project has gathered new insights into cCMV-related hearing prospects and antiviral strategies. To further explore risk factors for cCMV-related hearing loss, it would be interesting to investigate the importance of viral strain, viral load, host/viral genetic profile, and host inflammatory response. We believe that insights into the pathophysiology of cCMV-related hearing loss could aid in current understanding, estimation of hearing outcome, and targeted therapies. Although our studies were based on the largest database worldwide, a larger sample size is needed to tackle current limitations. Future studies investigating the effect of valganciclovir in asymptomatic children and investigating therapeutic effect on long-term neurological outcome are needed.

Jaar van publicatie:2024

Toegankelijkheid:Closed