Congenital cytomegalovirus infection is a major public health problem, with an estimated 4,000 to 6,000 affected newborns showing symptoms annually in the United States alone [13]. While generally considered an unrecognized cause of morbidity in neonates, congenital CMV can cause serious illnesses, such as extended petechiae, hepatitis, pneumonitis, enteritis, nephritis, hemolysis, and bone marrow suppression in infants born small for gestation [14]. Additionally, the CMV infection is linked to severe neurodevelopmental impairments in cognitive and auditory functions. This is particularly significant in countries with low-resource settings including Nepal, where access to healthcare is not readily accessible and available to all infants due to geographical variations, inefficient public transport systems in rural areas, and inequitable services thus early detection and management of such cases will be delayed [15].
The prevalence of congenital CMV infection is not well recognized in Nepal due to limited data, documentation, and research in this area. Health strategies at the national level have not been effectively integrated into programs related to congenital disorders, including CMV infection in infants. Most national health policies have not prioritized such conditions (i.e., CMV infection) as it contributes to significant infant morbidity and thus requires a much-needed public health response of wide scope for congenital CMV infections among the national health priorities of health issues [16]. There is no universal screening program for CMV infections at birth among infants in Nepal. A recent meta-analysis indicates that the prevalence of congenital CMV infections in lower-middle-income countries (LMICs) was three times higher than in high-income countries due to increased rates of maternal CMV seroprevalence, increased HIV prevalence at the population level, and young age at childbirth [17]. A recent study in Kathmandu Nepal, showed that over 2% of neonates tested positive for CMV, an indication of the magnitude of the problem [18]. However limited evidence is available about the prevalence and burden of congenital CMV infection among infants in Nepal. Universal screening for identification of congenital CMV infections at birth may contribute to timely identification and management and reduction of its complications.
The diagnosis of congenital CMV infection is confirmed by demonstrating the presence of infectious virus, viral antigens, or viral DNA in saliva or urine from infected infants [2, 14]. In this case, the quantitative CMV DNA PCR test from a Urine sample was performed. PCR-based assays for the detection of CMV DNA in saliva or urine from neonates are now considered the standard diagnostic method to confirm congenital CMV infection [19]. Regular monitoring of CMV viral load via PCR in immunocompromised children allowed for early detection of asymptomatic reactivation.
Anti-viral therapy and symptomatic care have been recommended as the standard of care for the treatment of postnatal CMV infection in infants. Ganciclovir and valganciclovir are recommended antiviral therapy for postnatal CMV infections [20]. Oral valganciclovir (15 to 16 mg/kg/dose every 12 hours) is recommended for infants who can take oral therapy. However, if infant is too sick and or unable to take oral medication, then intravenous ganciclovir (6 mg/kg/dose every 12 hours) will be a first-line medication that can be transitioned to oral valganciclovir when they are stable and able to take oral therapy [20]. The duration of therapy will depend on three weeks to a few months or longer therapy based on the infant’s clinical condition to resolve CMV-associated viremia and end-organ disease.
The intravenous ganciclovir (GCV), a synthetic nucleoside guanine analog, is the most commonly used medication for CMV illness among infants and children [21]. In the prior retrospective study involving 100 infants infected with CMV, intravenous ganciclovir was recommended as the most effective drug for the treatment of CMV infection in infants. It reduced inflammatory reactions and enhanced immunity without increasing the adverse reactions of the drug [22]. Valganciclovir, an L-valyl ester of ganciclovir, is well absorbed after oral administration and rapidly break down to ganciclovir in the intestines and liver [20]. Similar to current treatment recommendations, the 4 months old infant with CMV infection was prescribed oral Valganciclovir 16mg/kg/dose every 12 hours for 6 months [20, 23] The primary side effects of ganciclovir are thrombocytopenia, fever, diarrhea, anemia, and neutropenia. Ganciclovir has a high cellular toxicity. Valganciclovir is a prodrug of ganciclovir that, in contrast to ganciclovir, is quickly converted to ganciclovir in the intestinal wall and liver after being adequately absorbed from the gastrointestinal tract in children. About 60% of ganciclovir from valganciclovir is bioavailable in its whole [24]. Valganciclovir exhibits the same toxicity and resistance mutations as ganciclovir. The primary benefit of this medication is its oral dosing capability for valganciclovir, which is enhanced by meal absorption [25].
Infants with virologically confirmed congenital CMV infection should have a complete physical examination and selective laboratory and imaging studies to determine the severity of the illness. Children at risk for disabilities should have early intervention and proper counseling of parents to achieve the best performance. A Complete physical examination and cranial Imaging studies of the head are required to assess the neurological problem in infants [13]. Infants who are on antiviral medication should be periodically follow-up with providers to monitor for clinical response and virologic response and tested for CBC with differential and platelets count, CMV PCR, and liver function tests.