Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu.
Laboratory of Infection Research, School of Medicine, Federal University of Bahia, Salvador, Brazil.
Clin Infect Dis. 2017 Nov 13;65(11):1829-1836. doi: 10.1093/cid/cix672.
The explosive spread of Zika virus (ZIKV) and associated microcephaly present an urgent need for sensitive and specific serodiagnostic tests, particularly for pregnant women in dengue virus (DENV)-endemic regions. Recent reports of enhanced ZIKV replication by dengue-immune sera have raised concerns about the role of previous DENV infection on the risk and severity of microcephaly and other ZIKV complications.
Enzyme-linked immunosorbent assays (ELISAs) based on ZIKV and DENV nonstructural protein 1 (NS1) were established to test acute, convalescent phase, and post-convalescent phase serum/plasma samples from reverse-transcription polymerase chain reaction-confirmed cases including 20 primary ZIKV, 25 ZIKV with previous DENV, 58 secondary DENV, and 16 primary DENV1 infections.
ZIKV-NS1 immunoglobulin M (IgM) and immunoglobulin G (IgG) ELISAs combined can detect ZIKV infection with a sensitivity of 95% and specificity of 66.7%. The ZIKV-NS1 IgG cross-reactivity by samples from secondary DENV infection cases ranged from 66.7% to 28.1% (within 1 month to 1-2 years post-illness, respectively). Addition of DENV1-NS1 IgG ELISA can distinguish primary ZIKV infection; the ratio of absorbance of ZIKV-NS1 to DENV1-NS1 IgG ELISA can distinguish ZIKV with previous DENV and secondary DENV infections with a sensitivity of 87.5% and specificity of 81.3%. These findings were supported by analysis of sequential samples.
An algorithm for ZIKV serodiagnosis based on 3 simple ELISAs is proposed to distinguish primary ZIKV, ZIKV with previous DENV, and secondary DENV infections; this could be applied to serodiagnosis for ZIKV, serosurveillance, and monitoring ZIKV infection during pregnancy to understand the epidemiology, pathogenesis, and complications of ZIKV in dengue-endemic regions.
寨卡病毒（ZIKV）的爆发式传播以及由此引发的小头症，对灵敏且特异的血清学诊断检测提出了迫切需求，尤其是对登革热病毒（DENV）流行地区的孕妇而言。最近有报道称，登革热免疫血清会增强 ZIKV 的复制，这引发了人们对既往 DENV 感染在小头症及其他 ZIKV 并发症的风险和严重程度中所起作用的担忧。
建立了基于寨卡病毒和登革热病毒非结构蛋白 1（NS1）的酶联免疫吸附试验（ELISA），以检测逆转录聚合酶链反应确认的病例的急性期、恢复期和恢复期后血清/血浆样本，包括 20 例原发性 ZIKV、25 例 ZIKV 合并既往 DENV 感染、58 例继发性 DENV 感染和 16 例原发性 DENV1 感染。
ZIKV-NS1 免疫球蛋白 M（IgM）和 IgG ELISA 联合检测可使 ZIKV 感染的检出率达到 95%，特异性为 66.7%。继发于 DENV 感染病例的 ZIKV-NS1 IgG 交叉反应率范围为 66.7%至 28.1%（分别为发病后 1 个月至 1-2 年）。增加 DENV1-NS1 IgG ELISA 可区分原发性 ZIKV 感染；ZIKV-NS1 与 DENV1-NS1 IgG ELISA 的吸光度比值可区分既往 DENV 合并 ZIKV 感染和继发于 DENV 感染的 ZIKV 感染，其灵敏度为 87.5%，特异性为 81.3%。这些发现得到了连续样本分析的支持。
提出了一种基于 3 种简单 ELISA 的寨卡病毒血清学诊断算法，用于区分原发性 ZIKV、ZIKV 合并既往 DENV 感染和继发于 DENV 感染的 ZIKV 感染；这可应用于寨卡病毒的血清学诊断、血清学监测和妊娠期 ZIKV 感染监测，以了解寨卡病毒在登革热流行地区的流行病学、发病机制和并发症。
