Risk Factors for and Clinical Outcome of Congenital Cytomegalovirus Infection in a Peri-Urban West-African Birth Cohort

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most prevalent congenital infection worldwide. Epidemiology and clinical outcomes are known to vary with socio-economic background, but few data are available from developing countries, where the overall burden of infectious diseases is frequently high. METHODOLOGY/PRINCIPAL FINDINGS: As part of an ongoing birth cohort study in The Gambia among term infants, urine samples were collected at birth and tested by PCR for the presence of CMV DNA. Risk factors for transmission and clinical outcome were assessed, including placental malaria infection. Babies were followed up at home monthly for morbidity and anthropometry, and at one year of age a clinical evaluation was performed. The prevalence of congenital CMV infection was 5.4% (40/741). A higher prevalence of hepatomegaly was the only significant clinical difference at birth. Congenitally infected children were more often first born babies (adjusted odds ratio (OR) 5.3, 95% confidence interval (CI) 2.0-13.7), more frequently born in crowded compounds (adjusted OR 2.9, 95%CI 1.0-8.3) and active placental malaria was more prevalent (adjusted OR 2.9, 95%CI 1.0-8.4). These associations were corrected for maternal age, bed net use and season of birth. During the first year of follow up, mothers of congenitally infected children reported more health complaints for their child. CONCLUSIONS/SIGNIFICANCE: In this study, the prevalence of congenital CMV among healthy neonates was much higher than previously reported in industrialised countries, and was associated with active placental malaria infection. There were no obvious clinical implications during the first year of life. The effect of early life CMV on the developing infant in the Gambia could be mitigated by environmental factors, such as the high burden of other infections.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Epstein-Barr virus but not cytomegalovirus is associated with reduced vaccine antibody responses in Gambian infants.

BACKGROUND: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are persistent herpesviruses that have various immunomodulatory effects on their hosts. Both viruses are usually acquired in infancy in Sub-Saharan Africa, a region where childhood vaccines are less effective than in high income settings. To establish whether there is an association between these two observations, we tested the hypothesis that infection with one or both viruses modulate antibody responses to the T-cell independent meningococcal polysaccharide vaccine and the T-cell dependent measles vaccines. METHODOLOGY/PRINCIPAL FINDINGS: Infection with EBV and CMV was diagnosed by the presence of virus-specific IgM in the peripheral blood or by the presence of IgG at higher levels than that found in umbilical cord blood. Anti-meningococcus IgG and IgM were quantified by ELISA. Anti-measles antibody responses were quantified by haemagglutinin antibody inhibition assay. Infants infected with EBV had reduced IgG and IgM antibody responses to meningococcal polysaccharides and to measles vaccine. Infection with CMV alone predicted no changes in the response to meningococcal polysaccharide. While CMV alone had no discernable effect on the antibody response to measles, the response of infants infected with both CMV and EBV was similar to that of infants infected with neither, suggesting that the effects of CMV infection countered the effects of EBV on measles antibody responses. CONCLUSIONS: The results of this exploratory study indicate that infection with EBV is associated with reduced antibody responses to polysaccharides and to measles vaccine, but suggest that the response to T-cell dependent antigens such as measles haemagglutinin may be restored by infection with CMV

Antibody responses to meningococcus A and C, grouped by EBV/CMV serostatus at eleven months.

<p>*Calculated by linear regression model. Significant values in bold.</p><p>Infection with EBV at eleven months predicts reduced antibody responses to both meningococcus A and C, but infection with CMV has no effect. Groups refer to EBV and CMV serostatus at the time of sampling at 11 months.</p

Study Design.

<p><b>A</b> Study design showing times at which samples were collected, EBV and CMV serology was carried out, vaccines were administered and vaccine-specific responses were measured. <b>B</b> numbers of infants in the cohort and involved in analysis, and numbers infected with EBV and CMV at nine and eleven months.</p

Background characteristics of babies born with and without congenital CMV infection recruited January 2002 to January 2005.

<p>IQR = inter quartile range; sd = standard deviation</p

Infection with EBV but not CMV downregulates antibody responses to measles.

<p>Infection with EBV is associated with reduced antibody responses to measles unless infants are coinfected with CMV. Plots of serum haemagglutinin-inhibiting activity at eleven months of age, plotted against the serostatus at <b>A</b> the time of vaccination at nine months of age and <b>B</b> the time of sampling at eleven months of age. Titres are expressed as log₂. Grey bars indicate medians. Significances refer to the statistical interaction between the effects of EBV and CMV infection.</p

Primers used for quantification of EBV by real-time PCR.

<p>Primers used for quantification of EBV by real-time PCR.</p

Clinical characteristics of children with and without congenital CMV infection who already reached one year of age.

<p>Clinical characteristics of children with and without congenital CMV infection who already reached one year of age.</p

Clinical characteristics at birth of children with and without congenital CMV infection.

<p>IQR = inter quartile range; sd = standard deviation</p><p>Neurological score following Dubrovnivc: maximum score = 35</p