NS1 特异性抗体反应有助于在高度流行地区识别登革热和 Zika 儿童。

NS1-Specific Antibody Response Facilitates the Identification of Children With Dengue and Zika in Hyperendemic Areas.

机构信息

From the División de Inmunología, Programa de Medicina, Facultad de Salud, Universidad Surcolombiana, Neiva, Huila, Colombia.

Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá, Colombia.

出版信息

Pediatr Infect Dis J. 2024 Feb 1;43(2):178-185. doi: 10.1097/INF.0000000000004163. Epub 2023 Nov 13.

DOI:10.1097/INF.0000000000004163

PMID:37963312

Abstract

BACKGROUND

Infections by dengue virus (DENV) and Zika virus (ZIKV) have some similar symptoms and a cross-reactive immune response, although with different risk populations and outcomes. Here, we evaluated the virologic characteristics and the nonstructural protein 1 (NS1)-specific antibody responses to DENV and ZIKV in children suspected of dengue in different epidemiologic moments in Colombia.

METHODS

Viral RNA, circulating NS1 and IgM/IgG specific for DENV and ZIKV were performed by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) in 301 children suspected of dengue enrolled in a hospital setting during the ZIKV epidemic and a primary healthcare setting during a DENV epidemic. For the detection of DENV and ZIKV-specific IgM, an NS1-based ELISA was validated using characterized pediatric samples. Clinical and laboratory parameters were also evaluated.

RESULTS

DENV RNA or NS1 antigen was detected in the plasma of 62% of children, and in none, the ZIKV RNA was found. NS1-based ELISA for DENV and ZIKV IgM showed a sensitivity/specificity of 90/84% and 73/98%, respectively. Of 114 children without detectable viremia or antigenemia, 30.7%, 17.5%, 22% and 30% were IgM-DENV + , IgM-ZIKV + , IgM-DENV + ZIKV + and IgM-DENV - ZIKV - , respectively. The ZIKV/DENV IgM-NS1 ratio allows the identification of the infecting orthoflavivirus in 88% of the children with IgM-DENV + ZIKV + , confirming a high predominance of DENV infections in the 2 pediatric settings.

CONCLUSION

Overall, 88% of the children with clinical suspicion of dengue had an identifiable orthoflaviviral infection, with 80% caused by DENV, 7% by ZIKV and 0.7% classified as recent infections or coinfection, demonstrating active viral cocirculation in the pediatric population of southern Colombia. The IgM-NS1 detection improved the identification of orthoflaviviral infections in children without viremia or antigenemia, suggesting it is a helpful complementary tool for medical personnel in tropical regions with high viral cocirculation and different clinical scenes.

摘要

背景

登革热病毒（DENV）和寨卡病毒（ZIKV）的感染有一些相似的症状和交叉反应性免疫反应，尽管其风险人群和结果不同。在这里，我们评估了在哥伦比亚不同流行病学时期怀疑患有登革热的儿童中，DENV 和 ZIKV 的病毒学特征和非结构蛋白 1（NS1）特异性抗体反应。

方法

在寨卡病毒流行期间在医院环境中以及登革热流行期间在初级保健环境中，对 301 名疑似登革热的儿童进行了逆转录定量聚合酶链反应和酶联免疫吸附试验（ELISA）检测病毒 RNA、循环 NS1 和针对 DENV 和 ZIKV 的 IgM/IgG。为了检测 DENV 和 ZIKV 特异性 IgM，使用经过表征的儿科样本验证了基于 NS1 的 ELISA。还评估了临床和实验室参数。

结果

在 62%的儿童的血浆中检测到 DENV RNA 或 NS1 抗原，而在任何儿童的血浆中均未发现 ZIKV RNA。基于 NS1 的 ELISA 对 DENV 和 ZIKV IgM 的灵敏度/特异性分别为 90/84%和 73/98%。在 114 名未检测到病毒血症或抗原血症的儿童中，30.7%、17.5%、22%和 30%分别为 IgM-DENV + 、IgM-ZIKV + 、IgM-DENV + ZIKV + 和 IgM-DENV - ZIKV - 。ZIKV/DENV IgM-NS1 比值可在 88%的 IgM-DENV + ZIKV + 儿童中鉴定出感染的正黄病毒，证实在这 2 个儿科环境中 DENV 感染占主导地位。

结论

总体而言，88%的临床疑似登革热儿童有可识别的黄病毒感染，其中 80%由 DENV 引起，7%由 ZIKV 引起，0.7%归类为近期感染或合并感染，表明在哥伦比亚南部儿科人群中存在活跃的病毒共流行。IgM-NS1 检测提高了对无病毒血症或抗原血症儿童的黄病毒感染的识别，表明在病毒共流行且临床场景不同的热带地区，它是医务人员的有用辅助工具。