Congenital Cytomegalovirus Infection: New Prospects for Prevention and Therapy.

Division of Pediatric Infectious Diseases and Immunology, Department of Pediatrics, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota Medical School, 2001 6th Street Southeast, Minneapolis, MN 55455, USA.
Pediatric Clinics of North America (Impact Factor: 2.12). 04/2013; 60(2):335-349. DOI: 10.1016/j.pcl.2012.12.008
Source: PubMed


Cytomegalovirus is the commonest congenital viral infection in the developed world, with an overall prevalence of approximately 0.6%. Approximately 10% of congenitally infected infants have signs and symptoms of disease at birth, and these symptomatic infants have a substantial risk of subsequent neurologic sequelae. These include sensorineural hearing loss, mental retardation, microcephaly, development delay, seizure disorders, and cerebral palsy. Antiviral therapy for children with symptomatic congenital cytomegalovirus infection is effective at reducing the risk of long-term disabilities and should be offered to families with affected newborns. An effective preconceptual vaccine against CMV could protect against long-term neurologic sequelae and other disabilities.

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    • "CMV is a leading cause of congenital infections all around the world [2–4]. Congenital infections with CMV may be asymptomatic [5] or may lead to hearing impairment, mental retardation, cerebral palsy [6], and neurodevelopmental disabilities [2, 4]. The incidence of congenital CMV infection is about 1%-7% of births [4]. "
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    ABSTRACT: Background Cytomegalovirus causes congenital infections all around the world. The seroepidemiology of cytomegalovirus infection in pregnant women in Mexico is largely unknown. We sought to determine the seroprevalence of cytomegalovirus infection in pregnant women in Durango City, Mexico; and to determine seroprevalence association with socio-demographic, clinical and behavioral characteristics of pregnant women. Methods Through a cross-sectional study design, 343 pregnant women were examined for anti-cytomegalovirus IgG and IgM antibodies in Durango City, Mexico. We used a standardized questionnaire to obtain the general characteristics of the pregnant women. Multivariate analysis was performed to determine the association of cytomegalovirus infection with the characteristics of the pregnant women. Results Anti-CMV IgG and IgM antibodies were detected in 225 (65.6%) and in none of the 343 pregnant women studied, respectively. Multivariate analysis showed that CMV exposure was associated with increasing age (OR = 1.67; 95% CI: 1.01-2.76; P = 0.04). Other women characteristics including socioeconomic status, education, blood transfusion, transplantation, sexual promiscuity and number of previous pregnancies or deliveries did not show an association with CMV exposure. Conclusions This is the first seroepidemiology study of CMV infection in pregnant women in Mexico. A number of known factors associated with CMV infection were not associated with CMV exposure in the women studied. Further studies to determine routes of CMV infection in pregnant women in Mexico are needed.
    Full-text · Article · Sep 2014 · BMC Infectious Diseases
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    • "Its prevalence varies from 60–80% to 80–100% in developed and developing countries, respectively, depending on geography, ethnicity, and socio-economic conditions [1,3]. Prevalence tends to be high in South America, Africa, and Asia, but low in Western Europe and the United States [4]. "
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    ABSTRACT: Background This study investigated infection status and distribution of human cytomegalovirus (HCMV) serum markers in hospitalized children from the Wenzhou region. Methods This survey was performed on 10,147 hospitalized children from birth to 14 years of age in Southeastern China (Wenzhou region) from March 2010 to March 2013. IgM and IgG antibodies to HCMV were quantitatively detected by chemiluminescence immunoassay (CLIA). HCMV IgM or IgG detection rates, concentration, and distribution in various age groups were retrospectively analyzed. Results In this study of hospitalized children, the overall rates of HCMV IgM+ and IgG+ were 10.8% (1,099/10,147) and 83.0% (8,425/10,147), respectively. The lowest HCMV IgM+ rate (1.0%, P < 0.001) was observed in the group of patients <28 days of age whereas the highest HCMV IgM+ rate (19.9%, P < 0.001) occurred in the 28 days ~ 5 months old group. However, the concentrations of HCMV specific IgM in all age groups were not significantly different (P > 0.05). The HCMV IgG+ rate was highest in the <28 days group (98.1%, P < 0.001). The 28 days ~ 5 months old group had the lowest HCMV specific IgG concentrations (median, 133.9 AU/mL, P < 0.001). Among 1,099 HCMV IgM+ children, 405 (36.9%) were diagnosed with respiratory infections which pneumonia accounted for 18.2% (200/1,099) of the total population. However, children with respiratory infections had the lowest HCMV IgG concentrations (median, 161.1 AU/mL, P < 0.05). Conclusions HCMV specific antibody responses are very common in hospitalized children with respiratory infection in Wenzhou region. Protection against HCMV airway infection needs greater emphasis and further studies will be helpful to reveal the role of HCMV in children respiratory disease.
    Full-text · Article · Jul 2014 · Virology Journal
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    • "Congenital infections can cause severe sequelae among neonates including sensorineural hearing loss, cognitive impairments, and mental retardation [1] [2] [3]. In the setting of maternal primary infection or reinfection during pregnancy, HCMV can translocate the placental barrier and can cause infection of the developing fetus, with attendant morbidity and occasional mortality [4]. Unfortunately, animal models are of limited usefulness in the study of antiviral and vaccine strategies against HCMV, due to the extreme species specificity of CMVs. "
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    ABSTRACT: Development of a vaccine against congenital cytomegalovirus (CMV) infection is a public health priority, but CMVs encode immune evasion genes that complicate live virus vaccine design. To resolve this problem, this study employed guanosyl phosphoribosyl transferase (gpt) mutagenesis to generate a recombinant guinea pig CMV (GPCMV) with a knockout of a viral chemokine gene, GPCMV MIP (gp1). MIP deletion virus replicated with wild-type kinetics in cell culture but was attenuated in nonpregnant guinea pigs, demonstrating reduced viremia and reduced inflammation and histopathology (compared to a control virus with an intact GPCMV MIP gene) following footpad inoculation. In spite of attenuation, the vaccine was immunogenic, eliciting antibody responses comparable to those observed in natural infection. To assess its protective potential as a vaccine, either recombinant virus or placebo was used to immunize seronegative female guinea pigs. Dams were challenged in the early 3rd trimester with salivary gland-adapted GPCMV. Immunization protected against DNAemia (1/15 in vaccine group versus 12/13 in the control group, P < 0.01). Mean birth weights were significantly higher in pups born to vaccinated dams compared to controls (98.7 g versus 71.2 g, P < 0.01). Vaccination reduced pup mortality, from 35/50 (70%) in controls to 8/52 (15%) in the immunization group. Congenital GPCMV infection was also reduced, from 35/50 (70%) in controls to 9/52 (17%) in the vaccine group (P < 0.0001). We conclude that deletion of an immune modulation gene can attenuate the pathogenicity of GPCMV while resulting in a viral vaccine that retains immunogenicity and demonstrates efficacy against congenital infection and disease.
    Full-text · Article · Aug 2013 · Clinical and Developmental Immunology
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