Diagnostic performance of anti-Zika virus IgM, IgAM and IgG ELISAs during co-circulation of Zika, dengue, and chikungunya viruses in Brazil and Venezuela.
Diagnostic performance of anti-Zika virus IgM, IgAM and IgG ELISAs during co-circulation of Zika, dengue, and chikungunya viruses in Brazil and Venezuela.
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DOI：
10.1371/journal.pntd.0009336
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发表时间：
2021-04
影响因子：
3.8
通讯作者：
IDAMS Clinical Study Group
中科院分区：
文献类型：
--
作者：
Morales I;Rosenberger KD;Magalhaes T;Morais CNL;Braga C;Marques ETA;Calvet GA;Damasceno L;Brasil P;Bispo de Filippis AM;Tami A;Bethencourt S;Alvarez M;Martínez PA;Guzman MG;Souza Benevides B;Caprara A;Quyen NTH;Simmons CP;Wills B;de Lamballerie X;Drexler JF;Jaenisch T;IDAMS Clinical Study Group
由于黄病毒之间的抗体交叉反应，寨卡病毒 (ZIKV) 感染的血清学诊断具有挑战性。与此同时，核酸检测（NAT）的作用受到有症状感染比例低和平均病毒载量低的限制。在这里，我们比较了巴西和委内瑞拉寨卡病毒和基孔肯雅热 (CHIKV) 流行以及登革热病毒 (DENV) 共同传播期间市售 IgM、IgAM 和 IgG ELISA 在连续样本中的诊断性能。从 2012 年 6 月至 2016 年 8 月期间参加一项前瞻性多中心研究的 907 名有症状患者中采集了急性（发病第 1-5 天）和随访（发病 ≥ 6 天）血液样本。通过 RT-PCR 检测了急性样本中的 ZIKV、DENV 和 CHIKV。使用市售 ELISA 检测急性和后续样本中的 ZIKV IgM、IgAM 和 IgG 抗体。在经 RT-PCR 证实 ZIKV 感染的后续样本中，抗 ZIKV IgAM 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%，IgAM 的特异性为 85%。我们的研究结果例证了在 DENV、ZIKV 和 CHIKV 共同传播期间，在现实环境中评估 ZIKV 血清学测试的测试性能所面临的挑战。然而，我们还可以证明，与 IgG 和 IgM 免疫测定相比，IgAM 免疫测定在检测 ZIKV RT-PCR 确诊感染方面表现出更高的灵敏度。 IgAM 检测还被证明有望用于检测连续样本中的抗 ZIKV 血清转化，无论是 ZIKV PCR 阳性还是 PCR 阴性患者，这使其成为未来 ZIKV 爆发时孕妇血清学监测的候选检测方法。寨卡病毒 (ZIKV) 通过受感染的伊蚊叮咬传播，但也可以通过性传播或母婴垂直传播。相同的蚊子传播登革热病毒（DENV）和基孔肯雅病毒（CHIKV），引起相似的临床症状。 2015 年至 2017 年间发生在太平洋和美洲的寨卡病毒流行与新生儿先天性畸形有关，其中最突出的是小头畸形。由于大多数感染是无症状的，因此通过间接血清学检测进行诊断是一个重要的策略。另一方面，许多血清学检测受到先前感染密切相关病毒（例如登革热病毒）引起的交叉反应的影响。本研究评估了三种市售且广泛使用的免疫测定法，用于检测 ZIKV 的 IgG、IgM 或 IgA 和 M (IgAM) 抗体。我们的结果表明，IgAM 检测效果最佳，可检测出约 90% 的 RT-PCR 确诊感染。我们还检测到了 RT-PCR 未检测到的其他感染。这项研究的优势在于，它是在美洲地区的两个不同国家进行的，这两个国家有多种虫媒病毒流行，并且可以使用来自个体患者的连续血液样本来评估测试随着时间的推移的表现。
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. 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%. 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. Zika virus (ZIKV) is transmitted through the bite of infected Aedes mosquitos but can also be transmitted sexually or vertically from mother-to-child. The same mosquitoes transmit dengue virus (DENV) and chikungunya virus (CHIKV), which cause similar clinical syndromes. The ZIKV epidemics in the Pacific and the Americas that occurred between 2015 and 2017 were linked to congenital abnormalities, most prominently microcephaly, in newborns. Because most infections are asymptomatic, diagnosis via indirect serological assays is an important strategy. On the other hand, many serological assays are affected by cross-reactivity resulting from prior infections by closely related viruses, such as DENV. This study evaluated three commercially available and widely used immunoassays that detect IgG, IgM or IgA and M (IgAM) antibodies to ZIKV. Our results suggest that the IgAM test performs best by detecting around 90% of RT-PCR confirmed infections. We also detected additional infections that were not detected by RT-PCR. The strength of this study is that it was carried out in two different countries of the American region where several arboviruses are endemic and that sequential blood samples from individual patients were available to evaluate the performance of the tests over time.
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影响因子：
11.8
作者：
Foy BD;Kobylinski KC;Chilson Foy JL;Blitvich BJ;Travassos da Rosa A;Haddow AD;Lanciotti RS;Tesh RB
通讯作者：
Tesh RB
DOI：
10.1056/nejmoa1602412
发表时间：
2016-12-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brasil P;Pereira JP Jr;Moreira ME;Ribeiro Nogueira RM;Damasceno L;Wakimoto M;Rabello RS;Valderramos SG;Halai UA;Salles TS;Zin AA;Horovitz D;Daltro P;Boechat M;Raja Gabaglia C;Carvalho de Sequeira P;Pilotto JH;Medialdea-Carrera R;Cotrim da Cunha D;Abreu de Carvalho LM;Pone M;Machado Siqueira A;Calvet GA;Rodrigues Baião AE;Neves ES;Nassar de Carvalho PR;Hasue RH;Marschik PB;Einspieler C;Janzen C;Cherry JD;Bispo de Filippis AM;Nielsen-Saines K
通讯作者：
Nielsen-Saines K
DOI：
10.1016/j.diagmicrobio.2017.04.002
发表时间：
2017-07-01
影响因子：
2.9
作者：
Kadkhoda, Kamran;Gretchen, Ainsley;Racano, Adrianna
通讯作者：
Racano, Adrianna
影响因子：
7.7
作者：
Henderson, Alasdair D.;Aubry, Maite;Kucharski, Adam J.
通讯作者：
Kucharski, Adam J.
影响因子：
3.8
作者：
Brasil P;Calvet GA;Siqueira AM;Wakimoto M;de Sequeira PC;Nobre A;Quintana Mde S;Mendonça MC;Lupi O;de Souza RV;Romero C;Zogbi H;Bressan Cda S;Alves SS;Lourenço-de-Oliveira R;Nogueira RM;Carvalho MS;de Filippis AM;Jaenisch T
通讯作者：
Jaenisch T