Cytomegalovirus-specific CD4 and CD8 T cell responses in infants and children.

Congenital cytomegalovirus (CMV) infection is the most common congenital infection causing childhood morbidity. The pathogenetic mechanisms behind long-term sequelae are unclear, but long-standing viremia as a consequence of the inability to convert the virus to a latent state has been suggested to be involved. Whereas primary CMV infection in adults is typically rapidly controlled by the immune system, children have been shown to excrete virus for years. Here, we compare T cell responses in children with congenital CMV infection, children with postnatal CMV infection and adults with symptomatic primary CMV infection. The study groups included 24 children with congenital CMV infection, 19 children with postnatal CMV infection and eight adults with primary CMV infection. Among the infants with congenital CMV infection, 13 were symptomatic. T cell responses were determined by analysis of interferon gamma production after stimulation with CMV antigen. Our results show that whereas adults display high CMV-specific CD4 T cell responses in the initial phase of the infection, children younger than 2 years have low or undetectable responses that appear to increase with time. There were no differences between groups with regard to CD8 T cell function. In conclusion, inadequate CD 4 T cell function seems to be involved in the failure to get immune control of the CMV infection in children younger than 2 years of age with congenital as well as postnatal CMV infection.

Congenital cytomegalovirus infection: the impact of cerebral cortical malformations.

AIM: Cytomegalovirus has been suggested to have a teratogenous influence during the migration of neural cells from the ventricular zones to the cortex during the gestational period. The aim of this study was to investigate the prevalence of congenital cytomegalovirus infections in a cohort of children with neurological disability and cerebral cortical malformations recognized by neuroimaging. METHODS: Twenty-six children with neurological disability and cerebral cortical malformations were investigated retrospectively for congenital cytomegalovirus infection by analysing the dried blood spot samples for cytomegalovirus deoxynucleic acid using qualitative polymerase chain reaction. RESULTS: CMV DNA in the dried blood spot samples was found in four out of 26 children. Two of these four had severe disabilities with mental retardation, autism, spastic cerebral palsy, epilepsy and deafness. A third child had epilepsy and unilateral cerebral palsy, while the fourth had a mild motor coordination dysfunction and hearing deficit. CONCLUSION: In our study, the number of congenital cytomegalovirus infections in children with cerebral cortical malformations was higher (4/26) than expected with reference to the birth prevalence (0.2-0.5%) of congenital cytomegalovirus infection in Sweden. We thus conclude that congenital cytomegalovirus infection should be considered in children with cortical malformations of unknown origin.

Low incidence of toxoplasma infection during pregnancy and in newborns in Sweden.

To estimate the burden of disease due to congenital toxoplasmosis in Sweden the incidence of primary infections during pregnancy and birth prevalence of congenital toxoplasmosis in 40,978 children born in two regions in Sweden was determined. Women possibly infected during pregnancy were identified based on: 1, detection of specific IgG based on neonatal screening of the phenylketonuria (PKU) card blood spot followed by retrospective testing of stored prenatal samples to detect women who acquired infection during pregnancy and follow up of their children to 12 months: 2, detection of specific IgM on the PKU blood spot. The birth prevalence of congenital toxoplasmosis was 0.73/10,000 (95 % CI 0.15-2.14) (3/40,978). The incidence of primary infection during pregnancy was 5.1/10,000 (95% CI 2.6-8.9) susceptible pregnant women. The seroprevalence in the southern part was 25.7% and in the Stockholm area 14.0%. The incidence of infection during pregnancy was low, as the birth prevalence of congenital toxoplasmosis. Neonatal screening warrants consideration in view of the low cost and feasibility.

A child with muscle-eye-brain disease. Ophthalmological and neurological characteristics.

PURPOSE: To describe a child with Muscle-Eye-Brain disease (MEB), one of three types of congenital muscular dystrophy associated with ocular abnormalities. METHODS: Case report. RESULTS: The child showed severe visual impairment due to progressive myopia and retinal degeneration, a pachygyria-type of migration disorder of the brain with a nodular cortical surface, i.e. cobblestone cortex, as well as muscular weakness and severe mental retardation. CONCLUSION: Ophthalmological assessments are important to help to diagnose and follow children with congenital muscular dystrophy.

Ophthalmological findings in children with congenital toxoplasmosis. Report from a Swedish prospective screening study of congenital toxoplasmosis with two years of follow-up.

UNLABELLED: Congenital toxoplasmosis may lead to severe visual impairment or neurological sequelae in the child. PURPOSE: To study the severity of the primary and late ophthalmological dysfunction during a prospective incidence study of congenital toxoplasmosis in the Stockholm and Skåne counties. METHODS: Blood collected on phenylketonuria (PKU) cards from 40,978 consecutively born children were investigated for antitoxoplasma antibodies. Children with verified congenital toxoplasmosis were treated for 12 months with antiparasitic therapy and followed ophthalmologically, neurologically and serologically every third month. RESULTS: Three children had congenital toxoplasmosis. Two of these were asymptomatic at birth and would have escaped early detection without screening. One child had unilateral severe visual impairment and CNS involvement. The incidence of congenital toxoplasmosis was less than 1:10,000. CONCLUSION: Neonatal screening is of importance to diagnose asymptomatic infected children with congenital toxoplasmosis as treatment has been shown to reduce long-term sequelae. Ophthalmological investigations should start early and continue in co-operation with paediatricians.

Three children with congenital toxoplasmosis: early report from a Swedish prospective screening study.

The aim of this prospective study was to define the incidence of congenital toxoplasmosis in Sweden. Blood eluates collected on filter papers, Guthrie cards, from 40978 newborn babies were analysed for specific immunoglobulin M (IgM) and IgG antitoxoplasma antibodies. This is a preliminary report of three children with congenital toxoplasmosis, defined by the occurrence of antitoxoplasma-specific IgM antibodies. Two children were asymptomatic at birth. They were both normally developed at the age of 12 and 15 months, respectively. The third child had unidentified but uncomplicated symptoms of infection in the neonatal period. As a result of the screening congenital toxoplasmosis was confirmed and treatment instituted. Microphthalmus and peripheral chorioretinitis were detected in one eye. In spite of the chemotherapeutic treatment he developed hydrocephalus needing neurosurgical intervention at the age of 3 months. His development at 14 months was normal. The incidence in Sweden of congenital toxoplasmosis detected by specific IgM antitoxoplasma antibodies in blood from filter papers is less than 1:10000.

An update on EBCT (Ultrafast CT) scans for coronary artery disease.

OBJECTIVES: To determine the predictive value of electron beam computerized tomographic scans for calcium in the detection of coronary artery disease. DESIGN: Literature review and meta-analysis of published studies of electron beam computerized tomographic scans for coronary calcification. METHODS: Six studies comparing EBCT scan and coronary angiography findings comprising 2,717 patients were reviewed. Bayesian analyses were performed for the entire cohort and subgroups. Bayesian analyses plots are presented. RESULTS: EBCT scans for the detection of coronary artery disease have a sensitivity that ranges from 68% to 100% and a specificity that ranges from 31% to 74% for the presence of significant coronary disease. (Overall, sensitivity = 94%; specifity = 42%) Sensitivities and specificities of EBCT scans for any coronary disease range from 80% to 97% and 52% to 65%, respectively. (Overall, sensitivity = 91%; specificity = 55%). CONCLUSIONS: EBCT scans are being performed with increasing frequency as an adjunctive means to diagnose coronary disease. Although EBCT scans are unlikely to ever become a substitute for direct angiographic visualization of the coronary arteries, in certain instances they can be helpful in excluding or increasing the likelihood of significant coronary disease. The results of EBCT scans should be interpreted in the light of other available evidence, including such information as age, sex, the presence of risk factors for coronary disease, and the results of other tests such as ECG stress tests and imaging procedures. In general, although the presence of coronary artery calcification tends to be of more value in indicating that significant coronary disease is not present. The use of Bayesian analyses plots may prove of value in helping determine the significance of EBCT scan findings.