Hyde Terri B, Sato Helena Keico, Hao LiJuan, Flannery Brendan, Zheng Qi, Wannemuehler Kathleen, Ciccone Flávia Helena, de Sousa Marques Heloisa, Weckx Lily Yin, Sáfadi Marco Aurélio, de Oliveira Moraes Eliane, Pinhata Marisa Mussi, Olbrich Neto Jaime, Bevilacqua Maria Cecilia, Tabith Junior Alfredo, Monteiro Tatiana Alves, Figueiredo Cristina Adelaide, Andrus Jon K, Reef Susan E, Toscano Cristiana M, Castillo-Solorzano Carlos, Icenogle Joseph P
Centers for Disease Control and Prevention, Atlanta, Georgia.
São Paulo State Health Department.
J Infect Dis. 2015 Jul 1;212(1):57-66. doi: 10.1093/infdis/jiu604. Epub 2014 Oct 31.
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.
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.
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.
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.
先天性风疹综合征(CRS)病例在大龄儿童中难以识别,因为先天性风疹病毒(RUBV)感染的实验室标志物在12个月龄后不会持续存在。
我们纳入了1998年至2003年出生的CRS患儿,将他们对RUBV的免疫反应与其母亲以及一组年龄相仿的非CRS患儿的免疫反应进行比较。收集了人口统计学数据和血清。检测血清中的抗RUBV免疫球蛋白G(IgG)、IgG亲和力以及对3种病毒结构蛋白(E1、E2和C)的IgG反应,通过免疫印迹荧光信号反映。
我们纳入了32例CRS患儿、31位母亲和62例非CRS患儿。与母亲相比,CRS患儿对C的免疫印迹信号强度以及C信号与RUBV特异性IgG浓度的比值更高(两者P均<0.029),而E1信号与RUBV特异性IgG浓度的比值更低(P = 0.001)。与非CRS患儿相比,CRS患儿具有更多的RUBV特异性IgG(P < 0.001)、更强的C信号(P < 0.001)和更强的E2信号(P≤0.001)。两种区分CRS患儿与非CRS患儿的分类规则特异性均为100%,敏感性>65%。
本研究首次利用实验室生物标志物建立了学龄儿童CRS的分类规则。这些生物标志物应有助于改进疾病负担估计以及监测CRS控制项目。