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Identification of Serologic Markers for School-Aged Children With Congenital Rubella Syndrome
Terri B Hyde1, Helena Keico Sato2, LiJuan Hao1
1Centers for Disease Control and Prevention, Atlanta, Georgia.
Insights
Identifying congenital rubella syndrome (CRS) in older children is now possible using novel laboratory biomarkers. This breakthrough aids in better disease burden estimates and monitoring rubella virus control programs.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Congenital rubella syndrome (CRS) diagnosis is difficult in children over 12 months old.
- Traditional laboratory markers for congenital rubella virus (RUBV) infection are not detectable in older children.
Purpose of the Study:
- To establish reliable laboratory biomarkers for identifying CRS in school-aged children.
- To develop classification rules for improved CRS diagnosis in older pediatric populations.
Main Methods:
- Compared immune responses to RUBV in children with CRS, their mothers, and children without CRS.
- Analyzed serum samples for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG responses to viral proteins (E1, E2, C) using immunoblots.
- Developed classification rules based on immunoblot fluorescent signals and RUBV-specific IgG concentrations.
Main Results:
- Children with CRS showed distinct patterns in IgG response to viral proteins compared to mothers and controls.
- Specific ratios of viral protein signals to RUBV-specific IgG concentration differentiated children with CRS.
- Developed classification rules demonstrated high specificity (>65% sensitivity) for identifying CRS.
Conclusions:
- This study presents the first classification rules for identifying CRS in school-aged children using laboratory biomarkers.
- These biomarkers can enhance the accuracy of CRS burden of disease estimates.
- Improved diagnostic tools will support better monitoring of rubella virus control programs.
Background:
Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months.
Methods:
We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals.
Results:
We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity.
Conclusions:
This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs.
