In utero human cytomegalovirus infection is associated with increased levels of putatively protective maternal antibodies in nonprimary infection: evidence for boosting but not protection

2021 ◽  
Author(s):  
Jeffrey R Dorfman ◽  
Sashkia R Balla ◽  
Jayani Pathirana ◽  
Michelle J Groome ◽  
Shabir A Madhi ◽  
...  
Keyword(s):  
In Utero ◽  
Maternal Antibodies ◽  
Glycoprotein B ◽  
Hiv Status ◽  
Maternal Infection ◽  
Congenital Cmv Infection ◽  
Maternal Hiv ◽  
Cytomegalovirus Infections ◽  
Reduced Risk ◽  
Congenital Cmv

Abstract Background Although primary maternal cytomegalovirus infections are associated with higher risk of in utero transmission, most fetal infections worldwide result from nonprimary maternal infections. Antibodies directed at glycoprotein B and the gH/gL/pUL128-130-131 pentamer can neutralize virus, and higher levels of antibody directed at several particular pentamer epitopes defined by monoclonal antibodies (mAbs) are associated with reduced risk of fetal cytomegalovirus transmission during primary maternal infection. This had not been explored in maternal nonprimary infection. Methods In a setting where most maternal cytomegalovirus infections are nonprimary, 42 mothers of infants with congenital CMV infections (transmitters) were compared to 75 cytomegalovirus-seropositive mothers whose infants were cytomegalovirus-uninfected (nontransmitters). Control infants were matched by sex, maternal HIV status and gestational age. We measured the ability of maternal antibodies to block three key pentameric epitopes: one in the gH subunit, another straddling UL130/UL131 and the third straddling gH/gL/UL128/UL130. We tested if levels of antibodies directed at these epitopes were higher in nontransmitters compared to transmitters. Results Levels of all three putatively protective pentamer-directed antibodies were significantly higher in transmitters compared to nontransmitters. In contrast, antibodies targeting an epitope on glycoprotein B were not different. Total antibody specific for pentamer and for gB were also higher in transmitters. Conclusions We found no evidence that higher levels of any CMV-specific antibodies were associated with reduced risk of congenital CMV infection in nonprimary maternal infection. Instead, we found higher maternal antibody targeting epitopes on CMV pentamer in transmitters than nontransmitters, providing evidence for antibody boosting but not protection.

scholarly journals Recurrent maternal CMV infection associated with symptomatic congenital infection: results from a questionnaire study in Portugal

2019 ◽  
Vol 3 (1) ◽  
pp. e000455
Author(s):  
Paulo Paixão ◽  
Maria João Brito ◽  
Daniel Virella ◽  
Maria Teresa Neto
Keyword(s):  
Primary Infection ◽  
Recurrent Infection ◽  
Congenital Infection ◽  
High Avidity ◽  
Maternal Infection ◽  
Cmv Infection ◽  
Congenital Cmv Infection ◽  
Missed Diagnosis ◽  
Congenital Cmv

ObjectiveHuman cytomegalovirus (CMV) is the most widespread agent of congenital infection in humans and is still a challenging issue. Despite lower rates of vertical transmission being associated with recurrent infection when compared with primary infection, the first still represents the majority of congenital infections worldwide. Based on data from active reporting, we explored the influence of maternal primary/non-primary infection both on the presentation and outcome of congenital CMV infection in early childhood.DesignInfants with positive viruria during the first 3 weeks of life were reported through the Portuguese Paediatric Surveillance Unit.PatientsInfants born between 2006 and 2011 with confirmed congenital CMV infection.MethodsMaternal infection was considered primary if CMV IgG seroconversion occurred during pregnancy or low avidity IgG was documented; it was considered non-primary if positive IgG was documented before pregnancy or high avidity CMV IgG was present early in pregnancy. Follow-up questionnaires were sent up to 6 years of age.ResultsForty confirmed cases of congenital CMV infection were reported (6.6:105 live births, 95% CI 4.81 to 8.92); 22 out of 40 were asymptomatic. The odds for non-primary maternal infection if the offspring was symptomatic at birth were 6.2 (95% CI 1.2 to 32.27).ConclusionThe reported number of confirmed cases of congenital CMV infection was much lower than expected. Under-reporting and missed diagnosis were considered possible reasons. Non-primary maternal infections were associated with symptomatic congenital CMV infection in the offspring. Maternal recurrent infections can have a significant impact on the total number of symptomatic infections in Portugal.

scholarly journals Meconium pseudocyst associated with congenital CMV infection

2015 ◽  
Vol 19 (2) ◽  
Author(s):  
Sucari Vlok ◽  
Vicci Du Plessis
Keyword(s):  
Peritoneal Cavity ◽  
Rare Complication ◽  
Bowel Perforation ◽  
In Utero ◽  
Cmv Infection ◽  
Congenital Cmv Infection ◽  
Meconium Pseudocyst ◽  
Congenital Cmv

Meconium pseudocyst is a rare complication of fetal bowel perforation in utero, following extravasation and localised containment of meconium within the intra-peritoneal cavity.

scholarly journals Cytomegalovirus Genotype and Virulence in Infants with Congenital Infection

2021 ◽  
Author(s):  
Hong-bo Hu ◽  
Jian-gang Wu ◽  
Jian-jun Sun ◽  
Qiao-ying Peng ◽  
Xiao-peng Shang
Keyword(s):  
Congenital Infection ◽  
Nested Polymerase Chain Reaction ◽  
Symptomatic Disease ◽  
Congenital Cmv Infection ◽  
Glycoprotein H ◽  
Polymerase Chain ◽  
Cmv Disease ◽  
Conformation Polymorphism ◽  
Reduced Risk ◽  
Congenital Cmv

Abstract Objective Cytomegalovirus (CMV) virulence may depend on genetic variability in several regions of the genome. This study aimed to assess specific CMV genotypes' association with the severity of symptomatic congenital CMV disease at birth. Methods CMV glycoprotein B (gB), glycoprotein N (gN), glycoprotein H (gH), and UL144 strains were identified by nested polymerase chain reaction, restriction fragment length polymorphism, and heteroduplex mobility assay single-stranded conformation polymorphism in 50 infants infected congenitally and 25 asymptomatic infants. Results gN1 (p = 0.010) and UL144-B (p = 0.034) genotypes were associated, by logistic regression, with reduced risk of developing symptomatic congenital CMV infection. gN1 (p = 0.020) and gN3 (p = 0.022) genotypes were associated with reduced risk of severe symptomatic disease. Conversely, gB1 (p = 0.018) was the most virulent genotype and was associated with severe symptoms. Conclusion An association among gB1, gN1, gN3, and UL144-B genotypes of CMV and severity of congenital CMV disease might exist. gB, gN, and UL144 genotypes could be important virological markers of infant infection.

Congenital cytomegalovirus infection presenting as a fetal intra-abdominal cyst

2019 ◽  
Vol 8 (2) ◽  
Author(s):  
Emily Mills ◽  
Mary Beth Janicki ◽  
Reinaldo Figueroa
Keyword(s):  
Maternal Serum ◽  
Free Fluid ◽  
High Avidity ◽  
Maternal Infection ◽  
Cmv Infection ◽  
Female Fetus ◽  
Congenital Cmv Infection ◽  
Abdominal Cyst ◽  
Infectious Etiology ◽  
Congenital Cmv

Abstract Background Fetal intra-abdominal cysts have an incidence of 1/500–1/1000 live births. Cysts can be physiologic or pathologic and can either spontaneously regress or require intervention and treatment. Cytomegalovirus (CMV) is the most common cause of congenital infection in the USA with an incidence of 0.2–2%. The risk of transmission is greatest with a primary maternal infection and the severity of fetal injury increases when transmission occurs in the first half of the pregnancy. An infectious etiology for a fetal intra-abdominal cyst has not been reported to the best of our knowledge. Case presentation A 31-year-old multigravida presented at 19 weeks’ gestation for an anatomical survey. The female fetus was noted to have a 2.4 × 2.0 × 3.1 cm echolucent cyst in the right side of the abdomen. Three weeks later, the cyst was not seen; however, there was free fluid and a few echogenic areas within the fetal abdomen. Maternal serum tested positive for CMV IgM and IgG titers, and the CMV IgG avidity test was 0.75, consistent with high avidity. At 27 weeks’ gestation, ascites remained and a pericardial effusion was noted. Amniocentesis resulted in >2,000,000 copies of CMV DNA by polymerase chain reaction (PCR) in the amniotic fluid. The patient underwent termination of the pregnancy at 29 weeks of gestation. Conclusion It would be important to consider an infectious etiology in the differential diagnosis of fetal intra-abdominal cysts as the outcome in the fetus with congenital CMV infection could be much different. Amniocentesis is considered the best option for the diagnosis of fetal congenital CMV infection if performed after 21 weeks’ gestation and more than 6 weeks from maternal infection.

scholarly journals Genotypes of glycoprotein B gene among the Indian symptomatic neonates with congenital CMV infection

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Agniswar Sarkar ◽  
Dipanwita Das ◽  
Sabbir Ansari ◽  
Rajendra Prasad Chatterjee ◽  
Lopamudra Mishra ◽  
...  
Keyword(s):  
Glycoprotein B ◽  
Cmv Infection ◽  
Congenital Cmv Infection ◽  
Congenital Cmv
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