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Cytomegalovirus Kinetics Following Primary Infection in Healthy Women.

ABSTRACT: The kinetics of cytomegalovirus (CMV) DNA in infected asymptomatic hosts are largely unknown. We measured viral load (VL) in 124 fluid samples (oral, urine, vaginal, blood) collected from 21 women who acquired CMV. A quantitative real-time polymerase chain reaction assay of US17, which correlated with clinical assays, was used. VL decreased following primary infection in all fluids. The geometric mean VL of vaginal fluid was significantly higher than that of other sources: oral (3.89; 95% confidence interval [CI], 1.43-10.57), urine (6.36; 95% CI, 2.48-16.32), and whole blood (11.88; 95% CI, 4.12-34.20). Vaginal CMV shedding may provide a route for sexual and possibly perinatal transmission.

SUBMITTER: Forman MS

PROVIDER: S-EPMC5461424 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Cytomegalovirus Kinetics Following Primary Infection in Healthy Women.

Forman Michael S MS Vaidya Dhananjay D Bolorunduro Oluwaseyi O Diener-West Marie M Pass Robert F RF Arav-Boger Ravit R

The Journal of infectious diseases 20170501 10

The kinetics of cytomegalovirus (CMV) DNA in infected asymptomatic hosts are largely unknown. We measured viral load (VL) in 124 fluid samples (oral, urine, vaginal, blood) collected from 21 women who acquired CMV. A quantitative real-time polymerase chain reaction assay of US17, which correlated with clinical assays, was used. VL decreased following primary infection in all fluids. The geometric mean VL of vaginal fluid was significantly higher than that of other sources: oral (3.89; 95% confid ...[more]

PMID: 28431127

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Project description:Cytomegalovirus (CMV) is the leading infectious agent causing congenital sensorineural hearing loss and psychomotor retardation. CMV vaccine is currently unavailable and treatment options in pregnancy are limited. Susceptible pregnant women caring for children are at high risk for primary infection. CMV educational and hygienic measures have the potential to prevent primary maternal infection.A mixed interventional and observational controlled study was conducted to investigate the effectiveness of hygiene information among pregnant women at risk for primary CMV infection for personal/occupational reasons. In the intervention arm, CMV-seronegative women, identified at the time of maternal serum screening for fetal aneuploidy at 11-12 weeks of gestation, were given hygiene information and prospectively tested for CMV until delivery. The comparison arm consisted of women enrolled at delivery who were neither tested for nor informed about CMV during pregnancy, and who had a serum sample stored at the screening for fetal aneuploidy. By design, groups were homogeneous for age, parity, education, and exposure to at least one risk factor. The primary outcome was CMV seroconversion. Acceptance of hygiene recommendations was a secondary objective and was measured by a self-report.Four out of 331 (1.2%) women seroconverted in the intervention group compared to 24/315 (7.6%) in the comparison group (delta = 6.4%; 95% CI 3.2-9.6; P < 0.001). There were 3 newborns with congenital infection in the intervention group and 8 in the comparison group (1 with cerebral ultrasound abnormalities at birth). Ninety-three percent of women felt hygiene recommendations were worth suggesting to all pregnant women at risk for infection.This controlled study provides evidence that an intervention based on the identification and hygiene counseling of CMV-seronegative pregnant women significantly prevents maternal infection. While waiting for CMV vaccine to become available, the intervention described may represent a responsible and acceptable primary prevention strategy to reduce congenital CMV.

Project description:BackgroundCytomegalovirus (CMV) is a leading infectious cause of neurologic deficits, both in the settings of congenital and perinatal infection, but few animal models exist to study neurodevelopmental outcomes. This study examined the impact of neonatal guinea pig CMV (GPCMV) infection on spatial learning and memory in a Morris water maze (MWM) model.MethodsNewborn pups were challenged intraperitoneally (i.p.) with a pathogenic red fluorescent protein-tagged GPCMV, or sham inoculated. On days 15-19 post infection (p.i.), pups were tested in the MWM. Viral loads were measured in blood and tissue by quantitative PCR (qPCR), and brain samples collected at necropsy were examined by histology and immunohistochemistry.ResultsViremia (DNAemia) was detected at day 3 p.i. in 7/8 challenged animals. End-organ dissemination was observed, by qPCR, in the lung, liver, and spleen. CD4-positive (CD4+) and CD8-positive (CD8+) T cell infiltrates were present in brains of challenged animals, particularly in periventricular and hippocampal regions. Reactive gliosis and microglial nodules were observed. Statistically significant spatial learning and memory deficits were observed by MWM, particularly for total maze distance traveled (p < 0.0001).ConclusionNeonatal GPCMV infection in guinea pigs results in cognitive defects demonstrable by the MWM. This neonatal guinea pig challenge model can be exploited for studying antiviral interventions.ImpactCMV impairs neonatal neurocognition and memory in the setting of postnatal infection. The MWM can be used to examine memory and learning in a guinea pig model of neonatal CMV infection. CD4+ and CD8+ T cells infiltrate the brain following neonatal CMV challenge. This article demonstrates that the MWM can be used to evaluate memory and learning after neonatal GPCMV challenge. The guinea pig can be used to examine central nervous system pathology caused by neonatal CMV infection and this attribute may facilitate the study of vaccines and antivirals.

Dataset Information

Cytomegalovirus Kinetics Following Primary Infection in Healthy Women.

Publications

Cytomegalovirus Kinetics Following Primary Infection in Healthy Women.

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