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An abstract of the article "Congenital cytomegalovirus infection: an interesting case of clinical, molecular and pathologic correlations," S. Visentin and colleagues is presented.

The present study aims to provide the sequential immunological, clinical and virological events occurring in a CMV-infected pregnant woman experiencing intrauterine CMV transmission. In brief, a case of primary CMV infection occurred in a 36-year-old pregnant woman. The patient exhibited early-sustained viremia and viruria, detectable presence of CMV in saliva concomitant with a strong CMV-specific cell-mediated response (427 EliSpots). CMV was detected in the amniotic fluid at 15 weeks of pregnancy (>1 × 106 CMV copies/mL). The pregnancy was deliberately interrupted at 16 weeks of gestation. Fetal histological and pathological examinations revealed placentitis and fetal brain alterations as microcephaly and cortical dysplasia. Interestingly, this clinical report shows: (1) there was a rapid and sustained CMV-specific cell mediated immune response (Th1) in association with low IgG avidity (Th2) correlated with fetal CMV transmission. (2) The levels of CMV-specific cell-mediated immune response persisted at high levels up to 200 weeks after infection despite clinical and viral clearance. (3) The histological and pathological evidence suggests that a potent pro-inflammatory condition at the placental level may lead to cCMV.

Congenital cytomegalovirus (CMV) infection represents a relevant cause of deafness and neurological damage in newborns. Intrauterine CMV transmission might result after primary or nonprimary infections, though at different rates (30% versus 0.2%, respectively). At present, a prenatal diagnosis of CMV infection is based mainly on maternal serology, the detection of CMV-DNA in amniotic fluid and fetal blood, and ultrasound (US) and magnetic resonance imaging (MRI). Recent evidences suggest that congenital CMV infection may be an immune-mediated disease and that evaluation of humoral and especially T-cell immunities may improve the overall prenatal diagnosis. This review summarizes the most recent advancements in the diagnosis of maternal and prenatal CMV infections., (Copyright © 2017 American Society for Microbiology.)

Cytomegalovirus (CMV) enzyme-linked immunosorbent spot (ELISPOT) and CMV QuantiFERON assays were examined as potential biomarkers predictive of congenital CMV (cCMV) transmission. Fifty-seven pregnant women with primary CMV infection and 23 with nonprimary CMV infection were recruited in the study. Maternal age, CMV IgG avidity, viremia, and viruria were also included among the potential predictors. Spearman's statistical correlation analysis revealed a positive correlation between the CMV ELISPOT and CMV QuantiFERON assay results (P < 0.001), but only the CMV ELISPOT assay correlated with cCMV (P < 0.001). cCMV was positively correlated with maternal viremia and viruria (P < 0.05) and negatively correlated with CMV IgG avidity (P < 0.01). Maternal age and CMV QuantiFERON assay results were not statistically associated with cCMV. CMV-specific cell-mediated immunity detected by the CMV ELISPOT assay plays a critical role in cCMV., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Human cytomegalovirus (CMV) infection is a major cause of congenital infection leading to birth defects and sensorineural anomalies, including deafness. Recently, cell-mediated immunity (CMI) in pregnant women has been shown to correlate with congenital CMV transmission. In this study, two interferon gamma release assays (IGRA), the CMV enzyme-linked immunosorbent spot (ELISPOT) and CMV QuantiFERON assays, detecting CMV-specific CMI were compared. These assays were performed for 80 CMV-infected (57 primarily and 23 nonprimarily) pregnant women and 115 controls, including 89 healthy CMV-seropositive pregnant women without active CMV infection, 15 CMV-seronegative pregnant women, and 11 seropositive or seronegative nonpregnant women. Statistical tests, including frequency distribution analysis, nonparametric Kruskal-Wallis equality-of-populations rank test, Wilcoxon rank sum test for equality on unmatched data, and lowess smoothing local regression, were employed to determine statistical differences between groups and correlation between the assays. The CMV ELISPOT and CMV QuantiFERON assay data were not normally distributed and did not display equal variance. The CMV ELISPOT but not CMV QuantiFERON assay displayed significant higher values for primarily CMV-infected women than for the healthy seropositive pregnant and nonpregnant groups (P = 0.0057 and 0.0379, respectively) and those with nonprimary infections (P = 0.0104). The lowess local regression model comparing the assays on an individual basis showed a value bandwidth of 0.8. Both assays were highly accurate in discriminating CMV-seronegative pregnant women. The CMV ELISPOT assay was more effective than CMV-QuantiFERON in differentiating primary from the nonprimary infections. A substantial degree of variability exists between CMV ELISPOT and CMV QuantiFERON assay results for CMV-seropositive pregnant women., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Background: Human cytomegalovirus (CMV) represents one of the leading causes of congenital infections worldwide. Early diagnosis of fetal infection and consequent rapid therapeutic intervention with immunoglobulin treatment may prevent fetal transmission and virus-related sequelae. In this study, the cell-mediated immunity and immunoglobulin avidity were evaluated as potential predictors of congenital transmission of the infection., Methods: CMV immunoglobulin G (IgG) avidity and CMV enzyme-linked immunospot (ELISpot) assays were employed in 80 pregnant women including 57 primary and 23 nonprimary CMV infections. Congenital infection was assessed using CMV DNA quantitative polymerase chain reaction on amniotic fluid or offspring urine. Logistic regression and receiver operating characteristic statistical methods were employed to determine the association with congenital infection., Results: Low CMV IgG avidity (25%) alone correlated with a probability of congenital transmission of 18.2% (95% confidence interval, 7.7%-28.8%). In contrast to the expectations, an increase in CMV ELISpot levels was statistically associated with congenital transmission (P = .006). The combined use of CMV ELISpot and low CMV IgG avidity resulted in a higher level of association than either method alone with the incidence of fetal transmission (area under the curve, 0.8685)., Conclusions: CMV-specific cell-mediated immunity represents a relevant marker in assessing the likelihood of congenital CMV transmission, particularly in combination with CMV IgG avidity., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: We investigated the kinetics of cytomegalovirus (CMV) clearance in blood and urine and the relationship between the viral load in blood at birth and the development of late-onset sequelae in asymptomatic congenital CMV infection., Methods: Thirty-three newborns with congenital asymptomatic CMV infection born to women with primary CMV infection during pregnancy were enrolled. CMV infection was monitored by polymerase chain reaction analysis of blood and urine. The follow-up examination was concluded at 6 years of age., Results: Ten infants developed postnatal sequelae, whereas twenty-three infants remained asymptomatic. Fifty percent of babies cleared CMV in blood and urine within 3 and 36 months, respectively. Logistic multivariate regression revealed that the risk of neonatal clinical disease crossed the level of 50% with a DNAemia at birth of ≥ 12,000 copies/mL (P = .0002). The risk of hearing deficit crossed the level of 50% with a DNAemia at birth of ≥ 17,000 copies/mL (P = .0001). No significant difference was found between the kinetics of CMV clearance in asymptomatic children as compared to babies with late-onset disease., Conclusions: Asymptomatic newborns with a CMV DNAemia at birth of ≥ 12,000 copies/mL were more likely to experience CMV-related sequelae. The risk of hearing deficit increased with a viral load in blood of ≥ 17,000 copies/mL., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The more effective way of transmission of GB virus C (GBV-C) is parenteral, but sexual and vertical transmission seem to be the main way of spreading. We evaluated the prevalence and the effect of GBV-C infection on pregnant women, vertical transmission and viral effects on the newborn., Study Design: This study has consecutively enrolled 879 pregnant women. All patients had blood sampling to determine GBV-C RNA, serologic tests for chronic viral infections and seric tests of hepatic damage. The newborns from infected mothers had blood sampling to detect the presence of GBV-C at birth, and after 3 and 6 months. Positive babies were checked until 18 months., Results: 36 (4.1%) women resulted GBV-C positive. Among the positive patients none presented complications during pregnancy. Neither embryonic-fetal abnormalities nor relevant differences in fetal birth weight and week of gestation at delivery were found. 20 out of 36 babies had a follow-up. At birth, 13 (65%) babies were positive. 4 out of 9 vaginal deliveries (44%) and 9 out of 11 cesarean sections (82%) resulted positive to GBV-C RNA. The risk of GBV-C vertical transmission was not significantly increased by type of delivery (p=0.274). At 3 months, 13 babies were GBV-C positive (65%) and 7 were negative (35%). At the end of the follow-up, 9 babies were positive (45%), while 11 were negative (55%)., Conclusion: The percentage of patients positive to GBV-C RNA was comparatively high (4.1%). This prevalence, in a population without particular risk factors, confirms that common ways of transmission, such as the sexual and vertical ones, might have an important role in viral diffusion. Our data suggest that the infection does not influence the course of pregnancy. The rate of transmission found in our study is high. Type of delivery does not seem to be actually involved in vertical transmission and the protective role of cesarean section has not been confirmed.

Vertical transmission of HBV from HBsAg carrier mothers to their infants occurs frequently and very early in life. The HBsAg titer, the presence of HBeAg and acute HBV infection in the mother are usually considered facilitating factors; on the contrary anti-HBs and anti-HBe titer would be effectively protecting. However anti-HBc does not prevent HBsAg infection at all. In order to obtain information on the rate of HBV transmission in conditions considered at lower risk, we identified a group of pregnant women who were asymptomatic chronic HBsAg carriers and followed their children for several months after birth with clinical and laboratory examinations. All the 13 mothers were positive for HBsAg, anti-HBe, anti-HBc and negative for anti-HBs and HBeAg. All infants were controlled monthly in the first year of life and then at 16, 20, 24 months. The relatives controlled in the same period proved negative for HBV markers. All infants were negative for antigens at the birth and positive for anti-HBe and anti-HBc. These antibodies disappeared after 3-7 months after birth, indicating maternal transmission. All infants remained negative for HBsAg, HBeAg, anti-HBe and liver enzyme tests during the period of observation (24 months). These observations indicate that in our population the transmission of HBsAg from chronic carrier mothers to their children is not a frequent occurrence; probably the presence of anti-HBe has been protective.(ABSTRACT TRUNCATED AT 250 WORDS)

We report the case of a newborn of an HBsAg carrier mother who was infected by vertical transmission and developed a subclinical hepatitis B at four months of age, notwithstanding the passive-active prophylaxis performed right after birth. The mother's HBV marker status was: HBsAg positive, HBeAg positive, anti-HBc IgM positive at low titer, anti-HBc IgG negative, anti-HBs negative, anti-HBe negative. It is assumed that the absence of anti-HBC antibodies might have favoured, perhaps in utero, the HBV infection whose antigenic expression was subsequently delayed by HBIg administered at birth. These findings suggest that the positivity for anti-HBc IgM must be considered an additional marker of maternal infectivity especially in the absence of anti-HBc IgG antibodies.

Previous studies have confirmed the superiority of HBIG versus ISG and multiple dose versus single dose of HBIG (Beasley) and the time of first HBIG administration in preventing HBV infection. In all studies many treated infants became HBsAg or anti-HBs positive after the HBIG stopped. The present study was undertaken to evaluate the efficacy of multiple dose HBIG therapy in preventing HBV infection, and to establish the optimal dose, the frequency of the dose, the time of administration during the first year of life and to control the occurrence of HBsAg or active anti-HBs during the first two years of life. Seven infants of mothers positive for HBsAg and HBeAg, or positive for HBsAg but negative for HBeAg and anti-HBe, or with hepatitis B in the last trimester of pregnancy, received HBIG at high titer at dose of 0.5 ml/kg from first day until near 5 months of life and then 0.5-0.3 ml/kg until 12 months of life. The interval between the administration was established on the basis of the anti-HBs titer lower than 32. It was not a fixed interval but variable in different cases. Passive anti-HBs antibodies were almost always above 32 during the treatment period with HBIG. All patients remained negative for HBV markers and for liver enzyme tests during the period of the study. HBIG, administered in the first year of life at high dose and at intervals depending upon serum anti-HBs titer (32) systematically controlled, is efficient in preventing the hepatitis B infection in infants at high risk.(ABSTRACT TRUNCATED AT 250 WORDS)