Therapy Of Congenital Cytomegalovirus Infection Research Articles

Antiviral therapy for congenital cytomegalovirus infection in neonates and infants up to 12 months of age

Antiviral therapy for congenital cytomegalovirus infection in neonates and infants up to 12 months of age

1143. Late-Onset Hearing Loss and Antiviral Therapy for Congenital Cytomegalovirus Infection

BackgroundCongenital cytomegalovirus (CMV) is the leading non-genetic cause of sensorineural hearing loss (SNHL) in children. While SNHL is often present at birth, as many as 25% of congenital CMV-infected infants may develop late-onset hearing loss. Antiviral therapy improves hearing outcomes, but its effect on the occurrence of late-onset SNHL is not fully known. Thus, our objective was to describe the prevalence of late-onset SNHL among congenital CMV-infected children treated with antiviral therapy in the first month of age.MethodsFrom 2013 to present, infants with congenital CMV infection referred to Nationwide Children’s Hospital’s (NCH) NEO-ID Clinic, Columbus, OH underwent complete evaluation including hearing testing. Pertinent demographic, clinical, laboratory, and radiographic data were obtained and managed using REDCap electronic data capture tools. Infants who passed the newborn hearing screen and subsequently developed late-onset SNHL were identified and compared with respect to receipt of antiviral therapy in the neonatal period. Statistical analyses were performed using GraphPad Prism for macOS version 8.3.0.ResultsDuring the 6-year study period, 99 infants had congenital CMV infection and 69 (70%) of them passed the newborn hearing screen. 46 (46%) neonates received antiviral therapy (1, ganciclovir; 38, valganciclovir; 7, both) for clinically apparent congenital CMV infection. One (2%) child developed late-onset SNHL.This infant was born at 37 weeks’ gestation (birth weight, 2525 g) with microcephaly (head circumference, 31 cm) and cerebral calcifications and was diagnosed with congenital CMV infection at 8 days of age. Treatment with valganciclovir was initiated at 9 days of age, and he developed mild unilateral SNHL at 1 month of age while on treatment and subsequently right severe-profound SNHL and left mild-moderate SNHL. In comparison, among 23 infants with clinically inapparent disease who passed the newborn hearing screen and did not receive antiviral therapy, 5 (22%) subsequently developed SNHL (p=0.014).ConclusionInfants who received antiviral therapy for clinically apparent congenital CMV infection had significantly less late-onset SNHL than untreated infants, thus supporting a hearing protective effect of antiviral treatment.Disclosures All Authors: No reported disclosures

Evolution of awareness and knowledge of congenital cytomegalovirus infection among health care providers in France between 2011 and 2018.

Cytomegalovirus (CMV) is the most frequent cause of congenital viral infection. Approximately 1 % of newborns are congenitally infected and in up to 10 % of them the consequences are severe. Antenatal and postnatal treatments, although promising, are still under evaluation. Hygiene counseling to prevent CMV infection is important and should be systematic. To evaluate health care providers' awareness of CMV maternal and congenital infection in France. A questionnaire on CMV infection was sent in 2018 by e-mail to obstetricians, pediatricians, midwives and laboratory physicians, and members of medical or midwifery associations. We evaluated their knowledge concerning CMV epidemiology, transmission, symptoms in adults, newborns and long-term effects (scores from 0 to 30) and compared the results with those of our 2012 published study. Of the 597 respondents who completed the questionnaire, 91 % were unaware of the precise transmission route of CMV, 33 % wrongly thought thatin utero therapy for congenital CMV infection was a current standard of care in France, and less than half were familiar with the HAS (Haute Autorité de Santé) and CNGOF (Collège National des Gynécologues et Obstétriciens Français) recommendations. When respondents' knowledge of CMV was greater, patients were given more hygiene counseling. Between 2011 and 2018, knowledge improved among doctors and midwives concerning the route of transmission, the symptoms in adults, and the long-term effects of CMV infection. Knowledge is improving among healthcare providers, but gaps remain. To bridge these gaps, health care providers should improve their knowledge about congenital CMV by various means: medical reviews, continuing medical education, meetings, conferences, the Internet. Moreover, greater knowledge will allow for more effective counseling of pregnant women, as recommended by HCSP and CNGOF in France.

Experience using recombinant interferon-alpha with taurine therapy of congenital cytomegalovirus infection in children

Cytomegalovirus (CMV) belongs to the most frequent causes of intrauterine infection and can cause birth defects and severe manifestations of the disease fatal. In most cases the infection is latent, but there is a high risk of developing late manifestations. For the prevention of vertical transmission of CMV infection are needed early prenatal diagnosis of infection in a pregnant woman with the definition of the extent of its activity and conduct of antiviral therapy. When intravenous anti-CMV immunoglobulin observed rapid clinical efficacy. However, the titer of circulating antibodies in the child’s body is rapidly reduced, determines the duration of the protective effect of the drug to 4-5 weeks. Since the suppository form of interferon-α with taurine has been used successfully in obstetric practice, we have examined its effectiveness in the treatment of 11 outpatient children aged 1 month to 3 years with congenital CMV infection, 3 of them received specific immunoglobulin baby immediately after birth. The drug was administered rectally by prolonged scheme for 3 months 2 times a day every 12 hours within 10 days, followed by 1 suppository 2 times a day every other day (3 times a week). The therapy in all children experienced rapid resolution of symptoms CMV: normalization of the size of lymph nodes, liver and spleen, blood count, serum ALT, urinalysis, as well as the disappearance of CMV DNA in blood and IgM antibodies to CMV infection after treatment. During 12 months of follow-up episodes of reactivation of CMV infection in any of the observed child is not mentioned.

Perinatal HIV-infection in Sankt Petersburg and Modern Therapy Concomitant Viral Infections

The study included 338 HIV-infected children (B-23) and 350 children with perinatal contact HIV infection (R-75), consisting on the dispensary in the department of maternal and child the St. Petersburg City AIDS Center. In 32 persons (9.5%) diagnosed with secondary infections. In the structure of viral opportunistic infections (herpesvirus, SARS) amounted to 39.8%, bacterial (bronchitis, tonsillitis, pyoderma, tuberculosis) — 34.8%, fungal and parasitic (candidiasis of the oral mucosa, PCP) — 25.4 %. Combined therapy (causal, pathogenetic, symptomatic) SARS in children with B-23 and R-75, allows you to get in early (6th d. Treatment) regress the main symptoms of acute respiratory diseases. Modern therapy of congenital cytomegalovirus infection (VTSMI) in children with B-23 and R-75 of the first year of life with antitsitomegalovirusnogo immunoglobulin and preparation of human recombinant interferon alfa-2b in the form of rectal suppositories — VIFERON, causes persistent normalization of clinical and laboratory parameters.

Prenatal Therapy of Congenital Cytomegalovirus Infection

Prenatal Therapy of Congenital Cytomegalovirus Infection

Efficacy of prolonged valganciclovir therapy for congenital cytomegalovirus infection

We report prolonged valganciclovir (VGCV) treatment of a symptomatic cytomegalovirus infection case. Automated auditory brainstem evoked response performed at 5days of age revealed severe hearing impairment. Cranial magnetic resonance (MR) imaging at 11days of age showed abnormal findings. At 5weeks of age, VGCV was started. The viral load in blood cells, plasma, and urine decreased during the 6-week treatment. Because of improvement of hearing level and no adverse effects, VGCV was restarted for an additional 6weeks. Neither the patient's hearing impairment nor results of cranial MR imaging have become worse in 6months. It is crucial to gather information from as many cases as possible treated with VGCV to establish a standard protocol for VGCV treatment.

Fetal manifestations and poor outcomes of congenital cytomegalovirus infections: Possible candidates for intrauterine antiviral treatments

This retrospective study was performed to reveal the natural history of cytomegalovirus (CMV) infected fetuses during the perinatal period and to find prenatal findings associated with poor outcomes. 33 neonates with CMV infection, born after 30 weeks of gestation, were registered from a total of 12 414 infants between 1995 and 2003. Maternal and neonatal medical records were reviewed regarding fetal growth; abdominal signs including ascites and hepatosplenomegaly; cerebral signs including ventriculomegaly, microcephaly, and calcification; and fetal heart rate monitoring, for signs which may have been detected by the standard obstetric ultrasonography. Univariate and multivariate analyses were performed to test for any associations between these manifestations and poor outcomes such as death and neurological damages. Among the 33 infants, 6 died, 10 developed neurological damage including cerebral palsy (n = 8), epilepsy (n = 5), and hearing difficulties (n = 5), and the remaining 17 were normal. After adjusting for ganciclovir treatment and gender, death was 40-fold more likely associated with infants having abdominal signs (OR 40, 95%CI 4.6-930) than those without abdominal signs. Similarly, poor outcomes (death or neurological damage) were more likely associated with infants having either abdominal or cerebral signs (OR 39, 95%CI 3.8-1323). Fetal growth restriction and non-reassuring fetal heart rate patterns were not significantly associated with poor outcomes. The absence of abdominal signs guarantees the infant's survival. The presence of abdominal or cerebral signs is associated with poor outcomes, suggesting that these fetuses are possible candidates to receive in-utero therapy of congenital CMV infection.

Genotype analysis of measles outbreaks in the WHO European region 2005–2006

Cytomegalovirus (CMV) is the most frequent cause of congenital viral infection. Approximately 1 % of newborns are congenitally infected and in up to 10 % of them the consequences are severe. Antenatal and postnatal treatments, although promising, are still under evaluation. Hygiene counseling to prevent CMV infection is important and should be systematic.To evaluate health care providers’ awareness of CMV maternal and congenital infection in France.A questionnaire on CMV infection was sent in 2018 by e-mail to obstetricians, pediatricians, midwives and laboratory physicians, and members of medical or midwifery associations. We evaluated their knowledge concerning CMV epidemiology, transmission, symptoms in adults, newborns and long-term effects (scores from 0 to 30) and compared the results with those of our 2012 published study.Of the 597 respondents who completed the questionnaire, 91 % were unaware of the precise transmission route of CMV, 33 % wrongly thought thatin utero therapy for congenital CMV infection was a current standard of care in France, and less than half were familiar with the HAS (Haute Autorité de Santé) and CNGOF (Collège National des Gynécologues et Obstétriciens Français) recommendations. When respondents' knowledge of CMV was greater, patients were given more hygiene counseling. Between 2011 and 2018, knowledge improved among doctors and midwives concerning the route of transmission, the symptoms in adults, and the long-term effects of CMV infection.Knowledge is improving among healthcare providers, but gaps remain. To bridge these gaps, health care providers should improve their knowledge about congenital CMV by various means: medical reviews, continuing medical education, meetings, conferences, the Internet. Moreover, greater knowledge will allow for more effective counseling of pregnant women, as recommended by HCSP and CNGOF in France.

Supplementary Figure: Ganciclovir Therapy for Congenital Cytomegalovirus Infection in Six Infants

Supplementary Figure: Ganciclovir Therapy for Congenital Cytomegalovirus Infection in Six Infants

Ganciclovir Therapy for Congenital Cytomegalovirus Infection in Six Infants

Congenital cytomegalovirus (CMV) infection is common, and its morbidity rate is high. Ganciclovir (GCV) treatment has been used for congenital CMV infection, but there are few reports on viral loads associated with GCV therapy. A real-time PCR assay was used to monitor viral load in 6 cases of symptomatic CMV infection that received GCV therapy. Initially GCV was given at a dose of 5-12 mg/kg/d for 2-7 weeks. In 2 cases, additional doses were given as symptoms returned. After GCV administration, active signs of chorioretinitis, thrombocytopenia and anemia disappeared or improved in all cases. During GCV therapy, viral loads decreased while patients improved clinically and increased again when GCV therapy was stopped. Although CMV DNA continued to be detectable for a long period, clinical findings did not always worsen. In 2 cases, an improvement of hearing loss was observed. GCV therapy transiently suppresses the CMV concentrations. Subsequent increases of viral titers do not appear to be correlated with the clinical course or neurologic outcome.

Antiviral therapy of congenital cytomegalovirus infection

Congenital infection caused by human cytomegalovirus (CMV) is a common occurrence, but its significance is underappreciated. In the developed world, congenital CMV infection confers a tremendous medical and economic burden on society. In recent years, appreciation of the scope of disability produced by such infections in newborns, which includes neurodevelopmental sequelae and sensorineural hearing loss (SNHL), has increased. Although much of the injury produced by infection in utero likely is irreversible, antiviral therapy of newborns with CMV infection is an option available to clinicians. Currently three antivirals are licensed for treatment of CMV: ganciclovir (and its prodrug, valganciclovir), foscarnet, and cidofovir. Novel antiviral therapies, which employ mechanisms of action that differ from these agents, also are in development. Experience with these agents in the setting of congenital and perinatal CMV infection is limited, but encouraging data come from a controlled clinical trial indicating that ganciclovir therapy may be of value in limiting the neurodevelopmental injury, particularly SNHL, caused by congenital infection. Newborn screening programs for CMV infection need to be developed and implemented. Infants with congenital CMV infection, once identified, could then be considered as candidates for antiviral therapy, and careful neurodevelopmental and hearing screening follow-up care plans could be established. CMV vaccines, once available, may ultimately be the best control strategy for this important public health problem.

先天性サイトメガロウイルス感染症と感音難聴

Cytomegalovirus (CMV) in the most frequent cause of congenital infections in humans. The neurodevelopmental outcome of infected neonates is well documented and includes a significant risk of sensorineural hearing loss (SNHL).We studied five SNHL subjects with congenital CMV infection. All 5 infected subjects were found to have bilateral progressive SNHL and the deterionation to profound occurred during the first two years of life.Transient evoked otoacoustic emissions (TEOAEs) were recorded in 2 subjects and the TEOAEs of all 4 ears were abnormal. These effects confirmed that hearing loss associated with congenital CMV infection was due to cochlear dysfunction at least, as literature on the histopathology had indicated.One of the five subjects was asymptomatic. The etiology of hearing loss in children often is not identified and we concluded that SNHL in some children was caused by congenital CMV infection.Because the majority of infants with congenital CMV infection are asymptomatic at birth, routine screening of all newborns for congenital CMV infection should be carried out and the management of infected children should include periodic assessments. As the therapy for congenital CMV infection is not effective, CMV vaccination for women of child bearing age should be considered. In the future, vaccination will significantly reduce the prevalence of hearing loss in children.