Section Clinical Tropical Medicine, Department for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany.
German Centre for Infection Research (DZIF), associated partner Heidelberg University Hospital, Heidelberg, Germany.
PLoS Negl Trop Dis. 2021 Apr 19;15(4):e0009336. doi: 10.1371/journal.pntd.0009336. eCollection 2021 Apr.
Serological diagnosis of Zika virus (ZIKV) infection is challenging because of the antibody cross-reactivity among flaviviruses. At the same time, the role of Nucleic Acid Testing (NAT) is limited by the low proportion of symptomatic infections and the low average viral load. Here, we compared the diagnostic performance of commercially available IgM, IgAM, and IgG ELISAs in sequential samples during the ZIKV and chikungunya (CHIKV) epidemics and co-circulation of dengue virus (DENV) in Brazil and Venezuela.
METHODOLOGY/PRINCIPAL FINDINGS: Acute (day of illness 1-5) and follow-up (day of illness ≥ 6) blood samples were collected from nine hundred and seven symptomatic patients enrolled in a prospective multicenter study between June 2012 and August 2016. Acute samples were tested by RT-PCR for ZIKV, DENV, and CHIKV. Acute and follow-up samples were tested for IgM, IgAM, and IgG antibodies to ZIKV using commercially available ELISAs. Among follow-up samples with a RT-PCR confirmed ZIKV infection, anti-ZIKV IgAM sensitivity was 93.5% (43/46), while IgM and IgG exhibited sensitivities of 30.3% (10/33) and 72% (18/25), respectively. An additional 24% (26/109) of ZIKV infections were detected via IgAM seroconversion in ZIKV/DENV/CHIKV RT-PCR negative patients. The specificity of anti-ZIKV IgM was estimated at 93% and that of IgAM at 85%.
CONCLUSIONS/SIGNIFICANCE: Our findings exemplify the challenges of the assessment of test performance for ZIKV serological tests in the real-world setting, during co-circulation of DENV, ZIKV, and CHIKV. However, we can also demonstrate that the IgAM immunoassay exhibits superior sensitivity to detect ZIKV RT-PCR confirmed infections compared to IgG and IgM immunoassays. The IgAM assay also proves to be promising for detection of anti-ZIKV seroconversions in sequential samples, both in ZIKV PCR-positive as well as PCR-negative patients, making this a candidate assay for serological monitoring of pregnant women in future ZIKV outbreaks.
由于黄病毒之间存在抗体交叉反应，因此寨卡病毒（ZIKV）感染的血清学诊断具有挑战性。同时，由于症状感染比例低和平均病毒载量低，核酸检测（NAT）的作用有限。在这里，我们比较了在巴西和委内瑞拉 ZIKV 和基孔肯雅热（CHIKV）流行以及登革热病毒（DENV）同时流行期间，商业上可用的 IgM、IgAM 和 IgG ELISA 在连续样本中的诊断性能。
方法/主要发现：从 2012 年 6 月至 2016 年 8 月间参加一项前瞻性多中心研究的 907 例有症状患者中采集了急性（发病第 1-5 天）和随访（发病后第 6 天及以上）血样。用 RT-PCR 对急性样本进行 ZIKV、DENV 和 CHIKV 检测。用商业上可用的 ELISA 对急性和随访样本进行 ZIKV 抗体 IgM、IgAM 和 IgG 检测。在 RT-PCR 证实的 ZIKV 感染的随访样本中，抗 ZIKV IgAM 的敏感性为 93.5%（43/46），而 IgM 和 IgG 的敏感性分别为 30.3%（10/33）和 72%（18/25）。在 ZIKV/DENV/CHIKV RT-PCR 阴性患者中，通过 IgAM 血清转化检测到另外 24%（26/109）的 ZIKV 感染。抗 ZIKV IgM 的特异性估计为 93%，抗 ZIKV IgAM 的特异性估计为 85%。
结论/意义：我们的发现说明了在 DENV、ZIKV 和 CHIKV 同时流行期间，在真实环境中评估 ZIKV 血清学检测试验性能的挑战。然而，我们也可以证明，与 IgG 和 IgM 免疫测定相比，IgAM 免疫测定在检测 ZIKV RT-PCR 确认感染方面具有更高的敏感性。该 IgAM 测定法在检测连续样本中的抗 ZIKV 血清转化方面也很有前景，无论是在 ZIKV PCR 阳性还是 PCR 阴性患者中，这使其成为未来 ZIKV 暴发时孕妇血清学监测的候选检测方法。
