title: Identification of Serologic Markers for School-Aged Children With Congenital Rubella Syndrome.
abstract: 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.
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Terri B
authors.initials: TB
authors.lastname: Hyde
authors.affiliation: São Paulo State Health Department.
authors.forename: Helena Keico
authors.initials: HK
authors.lastname: Sato
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: LiJuan
authors.initials: L
authors.lastname: Hao
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia Pan American Health Organization, Washington, D. C.
authors.forename: Brendan
authors.initials: B
authors.lastname: Flannery
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Wannemuehler
authors.affiliation: São Paulo State Health Department.
authors.forename: Flávia Helena
authors.initials: FH
authors.lastname: Ciccone
authors.affiliation: Children's Institute, University Hospital, University of São Paulo (USP).
authors.forename: Heloisa
authors.initials: H
authors.lastname: de Sousa Marques
authors.affiliation: Hospital São Paulo, Federal University de São Paulo.
authors.forename: Lily Yin
authors.initials: LY
authors.lastname: Weckx
authors.affiliation: School of Medical Sciences of Santa Casa.
authors.forename: Marco Aurélio
authors.initials: MA
authors.lastname: Sáfadi
authors.affiliation: School of Medical Sciences, USP, Campinas.
authors.forename: Eliane
authors.initials: E
authors.lastname: de Oliveira Moraes
authors.affiliation: University Hospital, USP, Ribeirão Preto.
authors.forename: Marisa Mussi
authors.initials: MM
authors.lastname: Pinhata
authors.affiliation: University Hospital of Botucatu.
authors.forename: Jaime
authors.initials: J
authors.lastname: Olbrich Neto
authors.affiliation: Audiology Research Center, Hospital for Rehabilitation of Cranofacial Abnormalities, USP, Bauru, Brazil.
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Bevilacqua
authors.affiliation: Division of Education and Rehabilitation for Communication Disturbances, Catholic University of São Paulo.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Tabith Junior
authors.affiliation: Division of Otorhinolaryngology, USP Medical School.
authors.forename: Tatiana Alves
authors.initials: TA
authors.lastname: Monteiro
authors.affiliation: Adolfo Lutz Institute, São Paulo.
authors.forename: Cristina Adelaide
authors.initials: CA
authors.lastname: Figueiredo
authors.affiliation: Pan American Health Organization, Washington, D. C.
authors.forename: Jon K
authors.initials: JK
authors.lastname: Andrus
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Reef
authors.affiliation: Pan American Health Organization, Washington, D. C.
authors.forename: Cristiana M
authors.initials: CM
authors.lastname: Toscano
authors.affiliation: Pan American Health Organization, Washington, D. C.
authors.forename: Carlos
authors.initials: C
authors.lastname: Castillo-Solorzano
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Icenogle
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D000915:Antibody Affinity; D015415:Biomarkers / Q000097:blood*; D002648:Child; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D012410:Rubella Syndrome, Congenital / Q000175:diagnosis*; D012412:Rubella virus; D012574:Schools; D013334:Students
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D007074:Immunoglobulin G
keywords: CRS; biomarkers; congenital rubella syndrome; immune response; rubella; serology