澳大利亚巴尔马森林病毒和罗斯河病毒疾病作为基孔肯雅热病毒感染的潜在血清学误诊：酶联免疫吸附试验与中和试验结果比较。

Potential Serological Misdiagnosis of Barmah Forest Virus and Ross River Virus Diseases as Chikungunya Virus Infections in Australia: Comparison of ELISA with Neutralization Assay Results.

机构信息

Australian Defence Force Malaria and Infectious Disease Institute, Weary Dunlop Drive, Gallipoli Barracks, Enoggera, QLD 4051, Australia.

Queensland Institute of Medical Research-Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia.

出版信息

Viruses. 2024 Feb 29;16(3):384. doi: 10.3390/v16030384.

DOI:10.3390/v16030384

PMID:38543750

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10974935/

Abstract

To evaluate the frequency of errors in the diagnosis of medical laboratory-diagnosed Chikungunya virus (CHIKV) infections in Australia, we studied 42 laboratory-diagnosed CHIKV serum samples from one Queensland medical laboratory by ELISA IgG/IgM and measured the specific neutralization antibodies (Nab) against Barmah Forest virus (BFV), CHIKV and Ross River virus (RRV). The sero-positivity rates for the sera were as follows: anti-BFV IgG 19% (8/42), IgM 2.4% (1/42) and Nab 16.7% (7/42); anti-CHIKV IgG 90.5% (38/42), IgM 21.4% (9/42) and Nab 90.5% (38/42); anti-RRV IgG 88.1% (37/42), IgM 28.6% (12/42) and Nab 83.2% (35/42), respectively. Among the samples with multiple antibody positivity, 2.4% (1/42) showed triple ELISA IgM, and 14.3% (6/42) exhibited double IgM RRVCHIKV; 9.5% (4/42) showed triple IgG, 76.2% (32/42) displayed double IgG RRVCHIKV, 4.8% (2/42) showed IgG BFVRRV and 4.8% (2/42) showed IgG BFV+CHIKV; and 9.5% (4/42) showed triple Nab and 69% (29/42) exhibited double Nab RRVCHIKV, respectively. Our analysis of the single-virus infection control Nab results suggested no cross-neutralization between RRV and BFV, and only mild cross-neutralization between CHIKV and RRV, BFV and CHIKV, all with a ≥4-fold Nab titre ratio difference between the true virus infection and cross-reactivity counterpart virus. Subsequently, we re-diagnosed these 42 patients as 1 BFV, 8 CHIKV and 23 RRV single-virus infections, along with five RRV/BFV and four RRV/CHIKV double infections, and one possible RRV/BFV or RRVCHIKV, respectively. These findings suggests that a substantial proportion of medically attended RRV and BFV infections were misdiagnosed as CHIKV infections, highlighting the imperative need for diagnostic laboratory tests capable of distinguishing between CHIKV infections and actively co-circulating RRV and BFV. For a correct diagnosis, it is crucial to consider reliable diagnostic methods such as the neutralization assay to exclude RRV and BFV.

摘要

为了评估澳大利亚医学实验室诊断的基孔肯雅热病毒（CHIKV）感染诊断错误的频率，我们通过 ELISA IgG/IgM 对昆士兰一家医学实验室的 42 份实验室诊断的 CHIKV 血清样本进行了研究，并测量了针对巴姆森林病毒（BFV）、CHIKV 和罗斯河病毒（RRV）的特异性中和抗体（Nab）。血清的血清阳性率如下：抗 BFV IgG 19%（8/42）、IgM 2.4%（1/42）和 Nab 16.7%（7/42）；抗 CHIKV IgG 90.5%（38/42）、IgM 21.4%（9/42）和 Nab 90.5%（38/42）；抗 RRV IgG 88.1%（37/42）、IgM 28.6%（12/42）和 Nab 83.2%（35/42）。在具有多种抗体阳性的样本中，2.4%（1/42）显示三重 ELISA IgM，14.3%（6/42）显示双重 IgM RRVCHIKV；9.5%（4/42）显示三重 IgG，76.2%（32/42）显示双重 IgG RRVCHIKV，4.8%（2/42）显示 IgG BFVRRV 和 4.8%（2/42）显示 IgG BFV+CHIKV；9.5%（4/42）显示三重 Nab，69%（29/42）显示双重 Nab RRVCHIKV。我们对单一病毒感染对照 Nab 结果的分析表明，RRV 和 BFV 之间没有交叉中和，CHIKV 和 RRV、BFV 和 CHIKV 之间只有轻微的交叉中和，所有真实病毒感染与交叉反应对应病毒之间的 Nab 效价比差异均≥4 倍。随后，我们将这 42 名患者重新诊断为 1 名 BFV、8 名 CHIKV 和 23 名 RRV 单病毒感染，以及 5 名 RRV/BFV 和 4 名 RRV/CHIKV 双重感染，以及 1 名可能的 RRV/BFV 或 RRVCHIKV。这些发现表明，相当一部分医学上的 RRV 和 BFV 感染被误诊为 CHIKV 感染，这凸显了对能够区分 CHIKV 感染和活跃共循环的 RRV 和 BFV 的诊断实验室检测的迫切需求。为了正确诊断，必须考虑使用中和测定等可靠的诊断方法来排除 RRV 和 BFV。