Summary Congenital cytomegalovirus is the most frequent, yet under-recognised, infectious cause of newborn malformation in developed countries. Despite its clinical and public health importance, ...questions remain regarding the best diagnostic methods for identifying maternal and neonatal infection, and regarding optimal prevention and therapeutic strategies for infected mothers and neonates. The absence of guidelines impairs global efforts to decrease the effect of congenital cytomegalovirus. Data in the literature suggest that congenital cytomegalovirus infection remains a research priority, but data are yet to be translated into clinical practice. An informal International Congenital Cytomegalovirus Recommendations Group was convened in 2015 to address these questions and to provide recommendations for prevention, diagnosis, and treatment. On the basis of consensus discussions and a review of the literature, we do not support universal screening of mothers and the routine use of cytomegalovirus immunoglobulin for prophylaxis or treatment of infected mothers. However, treatment guidelines for infected neonates were recommended. Consideration must be given to universal neonatal screening for cytomegalovirus to facilitate early detection and intervention for sensorineural hearing loss and developmental delay, where appropriate. The group agreed that education and prevention strategies for mothers were beneficial, and that recommendations will need continual updating as further data become available.
To assess awareness of cytomegalovirus (CMV); attitudes towards screening; and frequency of behaviors that could increase the risk of prenatal infection.
We conducted a survey among 726 women at the ...2017 Minnesota State Fair. Minnesota residents aged 18-44 were eligible if they had never been pregnant or had been pregnant within the past 10 years. We compared responses between never-pregnant and recently-pregnant women.
Only 20% of study participants had previously heard of CMV. Remarkably, recently-pregnant women were no more likely to be aware of CMV than never-pregnant women after adjusting for potential confounders. After receiving information about CMV, nearly all participants indicated they believed prenatal (96%) or newborn (96%) screening should be offered.
Although baseline awareness of CMV was low (even among recently-pregnant women), after learning more about the risks, women supported screening. Several states have passed or proposed legislation promoting CMV education and/or screening programs. We identified important gaps in knowledge about CMV among women who may benefit from education about how to reduce their risk of exposure and who may need to decide whether they would be willing to screen for CMV in the future.
Populations of human cytomegalovirus (HCMV), a large DNA virus, are highly polymorphic in patient samples, which may allow for rapid evolution within human hosts. To understand HCMV evolution, ...longitudinally sampled genomic populations from the urine and plasma of 5 infants with symptomatic congenital HCMV infection were analyzed. Temporal and compartmental variability of viral populations were quantified using high throughput sequencing and population genetics approaches. HCMV populations were generally stable over time, with ~88% of SNPs displaying similar frequencies. However, samples collected from plasma and urine of the same patient at the same time were highly differentiated with approximately 1700 consensus sequence SNPs (1.2% of the genome) identified between compartments. This inter-compartment differentiation was comparable to the differentiation observed in unrelated hosts. Models of demography (i.e., changes in population size and structure) and positive selection were evaluated to explain the observed patterns of variation. Evidence for strong bottlenecks (>90% reduction in viral population size) was consistent among all patients. From the timing of the bottlenecks, we conclude that fetal infection occurred between 13-18 weeks gestational age in patients analyzed, while colonization of the urine compartment followed roughly 2 months later. The timing of these bottlenecks is consistent with the clinical histories of congenital HCMV infections. We next inferred that positive selection plays a small but measurable role in viral evolution within a single compartment. However, positive selection appears to be a strong and pervasive driver of evolution associated with compartmentalization, affecting ≥ 34 of the 167 open reading frames (~20%) of the genome. This work offers the most detailed map of HCMV in vivo evolution to date and provides evidence that viral populations can be stable or rapidly differentiate, depending on host environment. The application of population genetic methods to these data provides clinically useful information, such as the timing of infection and compartment colonization.
Schleiss talks about the immunological basis of protection through vaccination against human Cytomegalovirus infection. The major driving force for a CMV vaccine is prevention of congenital infection ...since CMV is the most common viral cause of permanent neurodevelopmental disability in infants globally other patient populations, in particular recipients of hematopoietic stem cells and solid organ transplant (SOT) patients, could benefit from a vaccine. Several CMV vaccines which studied to date as a subunit vaccine based on the viral envelope glycoprotein.
A vaccine against congenital human cytomegalovirus (CMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity, particularly sensorineural hearing loss ...(SNHL), in newborns, and the public health impact of this infection on maternal and child health is underrecognized. Although progress toward development of a vaccine has been limited by an incomplete understanding of the correlates of protective immunity for the fetus, knowledge about some of the key components of the maternal immune response necessary for preventing transplacental transmission is accumulating. Moreover, although there have been concerns raised about observations indicating that maternal seropositivity does not fully prevent recurrent maternal CMV infections during pregnancy, it is becoming increasing clear that preconception immunity does confer some measure of protection against both CMV transmission and CMV disease (if transmission occurs) in the newborn infant. Although the immunity to CMV conferred by both infection and vaccination is imperfect, there are encouraging data emerging from clinical trials demonstrating the immunogenicity and potential efficacy of candidate CMV vaccines. In the face of the knowledge that between 20,000 and 30,000 infants are born with congenital CMV in the United States every year, there is an urgent and compelling need to accelerate the pace of vaccine trials. In this minireview, we summarize the status of CMV vaccines in clinical trials and provide a perspective on what would be required for a CMV immunization program to become incorporated into clinical practice.
Over a century of research has focused on improving our understanding of congenital cytomegalovirus (cCMV), yet it remains the most common congenital infection in the United States, affecting 3 to 6 ...per 1000 live born infants each year. Pregnancies affected by cCMV are at a heightened risk of spontaneous abortion and intrauterine fetal demise. Neonates born with cCMV are also at substantial risk for long-term neurodevelopmental sequelae and disability, including sensorineural hearing loss, even those born without clinically apparent disease. Considerable progress has been made in recent years in study of the epidemiology and transmission of cCMV, developing better diagnostic strategies, implementing newborn screening programs, improving therapeutics, and launching vaccine trials. In this article, we review recent developments in the understanding of the virology and immunobiology of cytomegalovirus. We further discuss how this knowledge informs our understanding of the pathophysiology of cCMV and directs strategies aimed at improving outcomes and quality of life for congenitally infected children. We also provide an update on the epidemiology of cCMV in the United States, evolving scientific understanding of maternal-fetal transmission, enhanced screening approaches, and recognition of neonatal and long-term sequelae. Finally, we review the current landscape of pediatric cCMV research and provide recommendations for novel and high-priority areas for future investigation.
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