The “Silent” Global Burden of Congenital Cytomegalovirus

Abstract

SUMMARYHuman cytomegalovirus (CMV) is a leading cause of congenital infections worldwide. In the developed world, following the virtual elimination of circulating rubella, it is the commonest nongenetic cause of childhood hearing loss and an important cause of neurodevelopmental delay. The seroprevalence of CMV in adults and the incidence of congenital CMV infection are highest in developing countries (1 to 5% of births) and are most likely driven by nonprimary maternal infections. However, reliable estimates of prevalence and outcome from developing countries are not available. This is largely due to the dogma that maternal preexisting seroimmunity virtually eliminates the risk for sequelae. However, recent data demonstrating similar rates of sequelae, especially hearing loss, following primary and nonprimary maternal infection have underscored the importance of congenital CMV infection in resource-poor settings. Although a significant proportion of congenital CMV infections are attributable to maternal primary infection in well-resourced settings, the absence of specific interventions for seronegative mothers and uncertainty about fetal prognosis have discouraged routine maternal antibody screening. Despite these challenges, encouraging results from prototype vaccines have been reported, and the first randomized phase III trials of prenatal interventions and prolonged postnatal antiviral therapy are under way. Successful implementation of strategies to prevent or reduce the burden of congenital CMV infection will require heightened global awareness among clinicians and the general population. In this review, we highlight the global epidemiology of congenital CMV and the implications of growing knowledge in areas of prevention, diagnosis, prognosis, and management for both low (50 to 70%)- and high (>70%)-seroprevalence settings.

How does cytomegalovirus factor into diseases of aging and vaccine responses, and by what mechanisms?

“…CMV infection has been considered a disease of poverty and continues to be strongly patterned by socioeconomic status in the US and globally (Hotez 2008;Manicklal et al 2013). Indeed, there is a substantial body of evidence suggesting that CMV is socioeconomically (e.g., educational attainment and income) patterned across the life course.…”

Expression of human cytomegalovirus components in the brain tissues of patients with Rasmussen’s encephalitis

“…HCMV was found to have a 70%-90% prevalence in the general population and persists for the lifetime of the host after primary infection (Britt, 2015). Approximately 30% of pregnant women experiencing primary HCMV infection will transmit the virus to their developing fetuses during some stage of pregnancy, resulting in a congenital HCMV infection rate of 1%-7% at birth (Manicklal et al, 2013;Britt, 2015). Congenital HCMV infection may either be asymptomatic or cause hearing impairment, mental retardation, cerebral palsy, and neuron developmental disabilities (Manicklal et al, 2013).…”

“…Approximately 30% of pregnant women experiencing primary HCMV infection will transmit the virus to their developing fetuses during some stage of pregnancy, resulting in a congenital HCMV infection rate of 1%-7% at birth (Manicklal et al, 2013;Britt, 2015). Congenital HCMV infection may either be asymptomatic or cause hearing impairment, mental retardation, cerebral palsy, and neuron developmental disabilities (Manicklal et al, 2013). Whether the childhood neurological disorder of RE patients has any link to HCMV infection is thus of considerable sci-entific and clinical interest.…”

Congenital cytomegalovirus infection: Diagnosis, treatment, and prevention

“…Ча-стота врожденной цитомегаловирусной инфекции составляет в мире в среднем около 1%; в развитых странах эта инфекция встречается реже, чем в разви-вающихся: 0,2-2 и 0,6-5,4% соответственно [2,[6][7][8][9]. Специфические антитела к цитомегаловирусу также реже обнаруживаются у беременных женщин в раз-РОССИЙСКИЙ ВЕСТНИК ПЕРИНАТОЛОГИИ И ПЕДИАТРИИ, 2017; 62: (1) ROSSIYSKIY VESTNIK PERINATOLOGII I PEDIATRII, 2017; 62: (1) витых странах -у 40-70%, против 80-100% в раз-вивающихся странах [3,9] Таким образом, частота врожденной цитомегаловирусной инфекции выше в странах с более высоким распространением серо-позивности среди населения, где врожденная инфек-ция обусловлена непервичной (non-primary) цито-мегаловирусной инфекцией у беременных женщин [9][10][11][12].…”

“…Однако последние исследования по-казали, что тяжесть течения и последствия врожден-ной цитомегаловирусной инфекции могут значимо не различаться при первичной и непервичной цито-мегаловирусной инфекции [10][11][12]14].…”