Congenital cytomegalovirus infection: Clinical presentation, epidemiology, diagnosis and prevention

Zuylen, Wendy J. van; Hamilton, Stuart T.; Naing, Zin; Hall, Beverly A.; Shand, Antonia; Rawlinson, William D.

doi:10.1177/1753495x14552719

Cited by 48 publications

(37 citation statements)

References 84 publications

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“…An estimated 2000 Australian children are born with congenital CMV each year, with 25% developing life-long sequelae, including hearing loss and mental disability. 1 Higher rates of CMV infection occur with increasing age (seroprevalence: 34.9% for <20 years of age, 72.4% for >50 years of age), household crowding and attendance at childcare. 2 Children shed high levels of CMV in saliva and urine and frequently acquire CMV from other children.…”

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confidence: 99%

Prevalence of cytomegalovirus carriage among childcare staff

Zuylen

Zheng

Hamilton

et al. 2017

J Paediatrics Child Health

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Primary cytomegalovirus (CMV) infection during pregnancy carries a high risk (~30%) of transplacental transmission to the developing fetus, which may result in congenital CMV and consequent disease in the newborn. An estimated 2000 Australian children are born with congenital CMV each year, with 25% developing life-long sequelae, including hearing loss and mental disability.1 Higher rates of CMV infection occur with increasing age (seroprevalence: 34.9% for <20 years of age, 72.4% for >50 years of age), household crowding and attendance at childcare. 2Children shed high levels of CMV in saliva and urine and frequently acquire CMV from other children.1,2 Exposure of childcare staff through changing nappies (diapers), feeding and contact with contaminated environmental surfaces potentially increases their risk of acquiring CMV. Data from France and other developed countries show higher rates of paediatric shedding in childcare (50% in childcare vs. 20% in controls in emergency department at age of 3 months to 6 years), measured using sensitive and specific assays such as salivary real-time polymerase chain reaction. 2 However, no published study has determined prevalence of CMV in childcare staff in Australia, and shedding of this virus from saliva or other sites has not been examined systematically.We examined CMV excretion among childcare staff from two childcare centres in Sydney using our published methods for viral sampling of nasal and clothing surfaces 3 under South Eastern Sydney Local Health District ethics approval no. 10332. We tested 114 clothing samples and 125 nasal samples collected from 20 childcare staff from two university childcare centres in Sydney over 5 weeks in 2011. 3 DNA was extracted and real-time polymerase chain reaction (assay limit of detection 10 copies) was performed using CMV major immediate early gene primers. Of 125 nasal swabs tested, 6 (5%) were positive for CMV DNA, giving rise to an overall CMV excretion rate of 30% (6/20) among childcare staff. However, of 114 clothing swabs tested, none were positive for CMV DNA, which suggests clothing was unlikely to be a vector of fomite transmission at these childcare centres, contrasting our previous findings for respiratory virus detection on clothes of childcare staff. 4The CMV detection rate among nasal secretions of childcare staff suggests there is a need for education regarding effective hygiene measures to prevent CMV transmission and acquisition, particularly for pregnant staff. Measures shown to reduce CMV infection include not sharing food, utensils, cups or washcloths with a child; regular handwashing; and not kissing a child on or near the mouth. 4 Until an effective therapy is available, educating childcare staff regarding these hygiene measures remains the best preventive strategy for congenital CMV infection and subsequently congenital CMV disease.

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confidence: 99%

Prevalence of cytomegalovirus carriage among childcare staff

Zuylen

Zheng

Hamilton

et al. 2017

J Paediatrics Child Health

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“…This translates to an estimated 120,000 infants born each year in developed countries with congenital CMV infection, of whom ϳ25% develop symptoms, including sensorineural hearing loss (SNHL), vision loss, seizures, and mental disability (1)(2)(3)(5)(6)(7). Congenital CMV infection has also been associated with fetal death in utero, neonatal death, intrauterine growth restriction (IUGR), preterm birth, and preeclampsia (5,(8)(9)(10)(11)(12).…”

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confidence: 99%

Human Cytomegalovirus Modulates Expression of Noncanonical Wnt Receptor ROR2 To Alter Trophoblast Migration

Zuylen

Ford

Wong

et al. 2016

J Virol

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Maternal primary cytomegalovirus (CMV) infection, reactivation, or reinfection with a different viral strain may cause fetal injury and adverse pregnancy outcomes. Increasing evidence indicates that fetal injury results not only from direct viral cytopathic damage to the CMV-infected fetus but also from indirect effects through placental infection and dysfunction. CMV alters Wingless (Wnt) signaling, an essential cellular pathway involved in placentation, as evidenced by reduced transcription of canonical Wnt target genes and decreased Wnt3a-induced trophoblast migration. Whether CMV affects the noncanonical Wnt signaling pathway has been unclear. This study demonstrates for the first time that CMV infection inhibits Wnt5a-stimulated migration of human SGHPL-4 trophoblasts and that inhibition of the pathway restores normal migration of CMV-infected cells. Western blot and real-time PCR analyses show increased expression of noncanonical Wnt receptor ROR2 in CMV-infected trophoblasts. Mimicking the CMV-induced ROR2 protein expression via ectopic expression inhibited Wnt5a-induced trophoblast migration and reduced T cell-specific factor (TCF)/lymphoid enhancer-binding factor (LEF)-mediated transcription as measured using luciferase reporter assays. Gene silencing using small interfering RNA (siRNA) duplexes decreased ROR2 transcript and protein levels. In contrast, proliferation of SGHPL-4 trophoblasts, measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was not affected. The siRNA-mediated downregulation of ROR2 in trophoblasts rescued CMV-induced reduction in trophoblast migration. These data suggest a mechanism where CMV alters the expression of the Wnt receptor ROR2 to alter Wnt5a-mediated signaling and inhibit trophoblast motility. Inhibition of this mechanism may be a target for therapeutic intervention for CMV-induced placental damage and consequent fetal damage in congenital CMV infections. IMPORTANCEMaternal primary cytomegalovirus (CMV) infection, reactivation, or reinfection with a different viral strain may cause fetal injury and adverse pregnancy outcomes. Increasing evidence indicates that fetal injury results not only from direct viral cytopathic damage to the CMV-infected fetus but also from indirect effects through placental infection and placental dysfunction. No effective therapy is currently proven to prevent or treat congenital CMV infection. Understanding the molecular underpinnings of CMV infection of the placenta is essential for therapeutic innovations and vaccine design. CMV alters canonical Wingless (Wnt) signaling, an essential cellular pathway involved in placental development. This study suggests a mechanism in which CMV alters the expression of noncanonical Wnt receptor ROR2 to alter motility of placental cells, which has important implications in the pathogenesis of CMV-induced placental dysfunction. Inhibition of this mechanism may be a target for therapeutic intervention for CMV-induced placental damage and consequent fetal damage in con...

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“…При этом основным резервуаром распро-странения цитомегаловируса являются организован-ные дети раннего возраста, которые могут инфициро-вать как своих родителей, так и женщин, работающих в детских дошкольных учреждениях [1,3,59,60]. Поскольку цитомегаловирус чувствителен к высыха-нию и детергентам, то эффективной профилактикой инфицирования признано мытье рук и предметов с мылом [5,61,62].…”

Section: профилактикаunclassified

“…Профилактика цитомегаловирусной инфекции у беременных женщин путем распространения ин-формации о заболевании и обучения несложным гигиеническим мероприятиям является важной стра-тегией снижения частоты врожденной цитомегалови-русной инфекции [62]. С этой целью необходимо ши-рокое распространение памятки о правилах общения беременных женщин с маленькими детьми: 1.…”

Section: профилактикаunclassified