Global and Regional Congenital Cytomegalovirus (CMV) Epidemiology and Burden: Systematic Review and Meta-Analysis

Ssentongo, Paddy; Hehnly, Christine; Birungi, Patricia; Roach, Mikayla A.; Spady, Jada; Fronterrè, Claudio; Wang, Ming; Murray‐Kolb, Laura E.; Al‐Shaar, Laila; Chinchilli, Vernon M.; Broach, James R.; Ericson, Jessica E.

doi:10.2139/ssrn.3777198

Cited by 2 publications

(3 citation statements)

References 99 publications

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“…The burden of STORCH infections in Latin American countries is estimated to be considerable. [18][19][20][21] As the prevalence of these maternal infections can be reduced by Public Health measures, this group of congenital anomalies is a preventable group for which it is valuable to have good estimates of baseline prevalence in order to encourage any actions that will reduce the prevalence, including screening (which is variable across countries) and the development of vaccines.…”

Section: Open Accessmentioning

confidence: 99%

Prevalence of microcephaly: the Latin American Network of Congenital Malformations 2010–2017

Morris

Orioli

Benavides‐Lara

et al. 2021

bmjpo

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ObjectiveThe Latin American Network of Congenital Malformations: ReLAMC was established in 2017 to provide accurate congenital anomaly surveillance. This study used data from ReLAMC registries to quantify the prevalence of microcephaly from 2010 to 2017 (before, during and after the Zika virus epidemic).DesignNine ReLAMC congenital anomaly registries provided case-level data or aggregate data for any live births, still births or terminations of pregnancy with microcephaly. Births to pregnant women infected with Zika virus first occurred in Brazil in 2015, and in the remaining registry areas in 2016 with the exception of Chile that did not experience Zika virus. Therefore the prevalence of microcephaly for 2010–2014 and individual years 2015, 2016 and 2017 was estimated using multilevel random effect Poisson models. Clinical classification and characteristics of the cases were compared pre and post Zika for all centres providing individual case-level data.ResultsThe prevalence of microcephaly for all registries excluding Brazil was 2.3 per 10 000 (95% CI 2.0 to 2.6) for 2010–2014 rising to 5.4 (95% CI 4.8 to 6.0) in 2016 and 5.9 (95% CI 5.3 to 6.6) in 2017. Brazil had a prevalence of 0.6 per 10 000 (95% CI 0.5 to 0.6) in 2010–2014, rising to 5.8 (95% CI 5.6 to 6.1) in 2015, 8.0 (95% CI 7.6 to 8.3) in 2016 and then falling in 2017. Only 29 out of 687 cases of microcephaly were reported as congenital Zika syndrome in countries excluding Brazil.ConclusionsThe prevalence of microcephaly was influenced both by Zika causing congenital Zika syndrome and by increased reporting awareness.

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Section: Open Accessmentioning

confidence: 99%

Prevalence of microcephaly: the Latin American Network of Congenital Malformations 2010–2017

Morris

Orioli

Benavides‐Lara

et al. 2021

bmjpo

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“…For expectant mothers and their health care providers, congenital cytomegalovirus (cCMV) infections are a major global concern as they represent the most common infectious cause of birth defects and brain damage including sensorineural hearing loss and neurodevelopmental delays (1)(2)(3). Worldwide, about 0.7% of newborns are diagnosed with a congenital infection at birth but the incidence rate is correlated to the socioeconomic status of the population with lower to middle income countries indicating a three-fold higher overall case prevalence rate compared to high income countries (4). Despite the severe clinical impact and financial burden placed on affected families and the health care system, more than four decades of clinical research have not resulted in an effective, licensed vaccine to prevent cCMV infection.…”

Section: Introductionmentioning

confidence: 99%

“…While most cCMV transmissions occur in seropositive pregnancies, likely as the result of a reinfection or reactivation event (1), overall, a lower congenital transmission rate is observed in seropositive pregnant women compared to age and income-matched seronegative pregnant women (7), indicating that pre-existing, CMV specific, adaptive immune responses can provide some level of protection from transplacental transmission. Hence, while initial CMV vaccine trials attempted to induce broad immune responses using serially passaged, live-attenuated HCMV strains (8), more recent approaches have largely relied on inducing a strong, neutralizing antibody response against dominant membrane glycoproteins (3,4). The most widely examined HCMV vaccine target is glycoprotein B (gB), a large, highly glycosylated class III viral fusogen found on the viral surface where it mediates fusion of the viral and cellular membrane enabling virus entry (9).…”

Section: Introductionmentioning

confidence: 99%

The pentameric complex is not required for vertical transmission of cytomegalovirus in seronegative pregnant rhesus macaques

Wang,

Taher,

Kreklywich

et al. 2023

Preprint

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Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neonatal neurological impairment but essential virological determinants of transplacental CMV transmission remain unclear. The pentameric complex (PC), composed of five subunits, glycoproteins H (gH), gL, UL128, UL130, and UL131A, is essential for efficient entry into non-fibroblast cells in vitro. Based on this role in cell tropism, the PC is considered a possible target for CMV vaccines and immunotherapies to prevent cCMV. To determine the role of the PC in transplacental CMV transmission in a non-human primate model of cCMV, we constructed a PC-deficient rhesus CMV (RhCMV) by deleting the homologues of the HCMV PC subunits UL128 and UL130 and compared congenital transmission to PC-intact RhCMV in CD4+ T cell-depleted or immunocompetent RhCMV-seronegative, pregnant rhesus macaques (RM). Surprisingly, we found that the transplacental transmission rate was similar for PC-intact and PC-deleted RhCMV based on viral genomic DNA detection in amniotic fluid. Moreover, PC-deleted and PC-intact RhCMV acute infection led to similar peak maternal plasma viremia. However, there was less viral shedding in maternal urine and saliva and less viral dissemination in fetal tissues in the PC-deleted group. As expected, dams inoculated with PC-deleted RhCMV demonstrated lower plasma IgG binding to PC-intact RhCMV virions and soluble PC, as well as reduced neutralization of PC-dependent entry of the PC-intact RhCMV isolate UCD52 into epithelial cells. In contrast, binding to gH expressed on the cell surface and neutralization of entry into fibroblasts by the PC-intact RhCMV was higher for dams infected with PC-deleted RhCMV compared to those infected with PC-intact RhCMV. Our data demonstrates that the PC is dispensable for transplacental CMV infection in our non-human primate model.

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Global and Regional Congenital Cytomegalovirus (CMV) Epidemiology and Burden: Systematic Review and Meta-Analysis

Cited by 2 publications

References 99 publications

Prevalence of microcephaly: the Latin American Network of Congenital Malformations 2010–2017

Prevalence of microcephaly: the Latin American Network of Congenital Malformations 2010–2017

The pentameric complex is not required for vertical transmission of cytomegalovirus in seronegative pregnant rhesus macaques

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