Chẩn đoán huyết thanh virus Zika (ZIKV) bằng phương pháp ELISA mới dựa trên NS1 không có sự phản ứng chéo với kháng thể virus dengue: một nghiên cứu đa nhóm về hiệu suất xét nghiệm, 2015 đến 2016

Eurosurveillance - Tập 21 Số 50 - 2016
Katja Steinhagen1, Christian Probst1, Christiane Radzimski1, Jonas Schmidt‐Chanasit2,3, Petra Emmerich3, Marjan Van Esbroeck4, Janke Schinkel5, Martin P. Grobusch6,7, Abraham Goorhuis6, Jens M. Warnecke1, Erik Lattwein1, Lars Komorowski1, Andrea Deerberg1, Sandra Saschenbrecker1, W. Stöcker1, W Schlumberger1
1Institute for Experimental Immunology, EUROIMMUN AG, Lübeck, Germany
2German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel, Hamburg, Germany
3WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany
4National Reference Center for Arboviruses, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
5Department of Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Public Health Service, Amsterdam, the Netherlands
6Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
7Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany

Tóm tắt

Chẩn đoán huyết thanh virus Zika (ZIKV) gặp khó khăn do sự phản ứng chéo cao giữa các flavivirus. Chúng tôi đã đánh giá hiệu suất chẩn đoán của một phương pháp ELISA chống ZIKV mới dựa trên protein phi cấu trúc 1 (NS1) tái tổ hợp của virus Zika. Độ nhạy của xét nghiệm được kiểm tra bằng cách sử dụng huyết thanh từ 27 bệnh nhân có kết quả RT-PCR xác nhận và 85 bệnh nhân nghi ngờ nhiễm ZIKV. Tính đặc hiệu được phân tích bằng cách sử dụng huyết thanh từ 1.015 cá nhân khỏe mạnh. Mẫu từ 252 bệnh nhân nhiễm virus dengue (n = 93), virus Tây Nile (n = 34), virus viêm não Nhật Bản (n = 25), virus chikungunya (n = 19) hoặc Plasmodium spp. (n = 69) và từ 12 cá nhân đã tiêm vaccine sốt vàng cũng được kiểm tra. Trong các mẫu ZIKV xác nhận được thu thập trong vòng ≥ 6 ngày sau khi khởi phát triệu chứng, độ nhạy của ELISA là 58.8% (khoảng tin cậy (CI): 36.0–78.4) cho IgM, 88.2% (95% CI: 64.4–98.0) cho IgG, và 100% (95% CI: 78.4–100) cho IgM/IgG, với độ đặc hiệu 99.8% (95% CI: 99.2–100). Không phát hiện sự phản ứng chéo với kháng thể virus dengue ở mức cao. Trong số các bệnh nhân có khả năng có kháng thể phản ứng chéo, tỷ lệ dương tính với chống ZIKV lần lượt là 0.8% (95% CI: 0–3.0) và 0.4% (95% CI: 0–2.4) cho IgM và IgG. Cung cấp độ đặc hiệu cao và phản ứng chéo thấp, ELISA dựa trên NS1 có tiềm năng hỗ trợ trong việc tư vấn cho bệnh nhân, phụ nữ mang thai và khách du lịch sau khi trở về từ các vùng dịch ZIKV.

Từ khóa


Tài liệu tham khảo

European Centre for Disease Prevention and Control (ECDC). Rapid risk assessment: Zika virus epidemic in the Americas: potential association with microcephaly and Guillain-Barré syndrome. Stockholm: ECDC; 10 Dec 2015. Available from: http://ecdc.europa.eu/en/publications/Publications/zika-virus-americas-association-with-microcephaly-rapid-risk-assessment.pdf

Fauci, 2016, Zika Virus in the Americas--Yet Another Arbovirus Threat., N Engl J Med, 374, 601, 10.1056/NEJMp1600297

European Centre for Disease Prevention and Control (ECDC). Zika virus outbreak in the America's and the pacific; epidemiological situation 20 may 2016. Stockholm: ECDC; 2016. Available from: http://ecdc.europa.eu/en/healthtopics/zika_virus_infection/zika-outbreak/Pages/epidemiological-situation.aspx

Duffy, 2009, Zika virus outbreak on Yap Island, Federated States of Micronesia., N Engl J Med, 360, 2536, 10.1056/NEJMoa0805715

Gould, 2008, Pathogenic flaviviruses., Lancet, 371, 500, 10.1016/S0140-6736(08)60238-X

Lanciotti, 2008, Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007., Emerg Infect Dis, 14, 1232, 10.3201/eid1408.080287

Cao-Lormeau, 2016, Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study., Lancet, 387, 1531, 10.1016/S0140-6736(16)00562-6

Martines, 2016, Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses--Brazil, 2015., MMWR Morb Mortal Wkly Rep, 65, 159, 10.15585/mmwr.mm6506e1

Mlakar, 2016, Zika Virus Associated with Microcephaly., N Engl J Med, 374, 951, 10.1056/NEJMoa1600651

Johansson, 2016, Zika and the Risk of Microcephaly., N Engl J Med, 375, 1, 10.1056/NEJMp1605367

Bingham, 2016, Comparison of Test Results for Zika Virus RNA in Urine, Serum, and Saliva Specimens from Persons with Travel-Associated Zika Virus Disease - Florida, 2016., MMWR Morb Mortal Wkly Rep, 65, 475, 10.15585/mmwr.mm6518e2

Gourinat, 2015, Detection of Zika virus in urine., Emerg Infect Dis, 21, 84, 10.3201/eid2101.140894

Corbett, 2015, Preexisting neutralizing antibody responses distinguish clinically inapparent and apparent dengue virus infections in a Sri Lankan pediatric cohort., J Infect Dis, 211, 590, 10.1093/infdis/jiu481

Puschnik, 2013, Correlation between dengue-specific neutralizing antibodies and serum avidity in primary and secondary dengue virus 3 natural infections in humans., PLoS Negl Trop Dis, 7, e2274, 10.1371/journal.pntd.0002274

Lindenbach, 2003, Molecular biology of flaviviruses., Adv Virus Res, 59, 23, 10.1016/S0065-3527(03)59002-9

Muller, 2013, The flavivirus NS1 protein: molecular and structural biology, immunology, role in pathogenesis and application as a diagnostic biomarker., Antiviral Res, 98, 192, 10.1016/j.antiviral.2013.03.008

MacKenzie, 1996, Immunolocalization of the dengue virus nonstructural glycoprotein NS1 suggests a role in viral RNA replication., Virology, 220, 232, 10.1006/viro.1996.0307

Winkler, 1988, Evidence that the mature form of the flavivirus nonstructural protein NS1 is a dimer., Virology, 162, 187, 10.1016/0042-6822(88)90408-4

Flamand, 1999, Dengue virus type 1 nonstructural glycoprotein NS1 is secreted from mammalian cells as a soluble hexamer in a glycosylation-dependent fashion., J Virol, 73, 6104, 10.1128/JVI.73.7.6104-6110.1999

Brown, 2016, Extended surface for membrane association in Zika virus NS1 structure., Nat Struct Mol Biol, 23, 865, 10.1038/nsmb.3268

Lee, 1989, The synthesis and maturation of a non-structural extracellular antigen from tick-borne encephalitis virus and its relationship to the intracellular NS1 protein., J Gen Virol, 70, 335, 10.1099/0022-1317-70-2-335

Alcon, 2002, Enzyme-linked immunosorbent assay specific to Dengue virus type 1 nonstructural protein NS1 reveals circulation of the antigen in the blood during the acute phase of disease in patients experiencing primary or secondary infections., J Clin Microbiol, 40, 376, 10.1128/JCM.40.02.376-381.2002

Macdonald, 2005, NS1 protein secretion during the acute phase of West Nile virus infection., J Virol, 79, 13924, 10.1128/JVI.79.22.13924-13933.2005

Matheus, 2016, Specificity of Dengue NS1 Antigen in Differential Diagnosis of Dengue and Zika Virus Infection., Emerg Infect Dis, 22, 1691, 10.3201/eid2209.160725

Cleton, 2015, Spot the difference-development of a syndrome based protein microarray for specific serological detection of multiple flavivirus infections in travelers., PLoS Negl Trop Dis, 9, e0003580, 10.1371/journal.pntd.0003580

Huzly, 2016, High specificity of a novel Zika virus ELISA in European patients after exposure to different flaviviruses., Euro Surveill, 21, 30203, 10.2807/1560-7917.ES.2016.21.16.30203

Pan American Health Organization, World Health Organization (WHO). Zika virus (ZIKV) Surveillance in the Americas: Interim guidance for laboratory detection and diagnosis. 2015. Available from: http://iris.paho.org/xmlui/bitstream/handle/123456789/18602/zikavirusinterim_jan2015.pdf?sequence=1&isAllowed=y

Zentrale Ethikkommission bei der Bundesärztekammer. Die (Weiter-) Verwendung von menschlichen Körpermaterialien für Zwecke der medizinischen Forschung (2003) [The (further) use of human body samples for the purpose of medical research (2003)]: Berlin: Zentrale Ethikkommussion bei der Bundesärztekammer. Available from: http://www.zentrale-ethikkommission.de/downloads/Koerpermat.pdf

Bossuyt, 2015, STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies., BMJ, 351, h5527, 10.1136/bmj.h5527

Gyurech, 2016, False positive dengue NS1 antigen test in a traveller with an acute Zika virus infection imported into Switzerland., Swiss Med Wkly, 146, w14296

Rubin, 2016, Zika Virus and Microcephaly., N Engl J Med, 374, 984, 10.1056/NEJMe1601862

Scholzen, 2013, How malaria modulates memory: activation and dysregulation of B cells in Plasmodium infection., Trends Parasitol, 29, 252, 10.1016/j.pt.2013.03.002

Vaughn, 1997, Dengue in the early febrile phase: viremia and antibody responses., J Infect Dis, 176, 322, 10.1086/514048

World Health Organization (WHO). Zika virus–Fact sheet. Updated 6 September 2016. Geneva: WHO. [Accessed 9 Dec 2016]. Available from: http://www.who.int/mediacentre/factsheets/zika/en/

Thông tin
Thông tin xuất bản

Eurosurveillance

Tập 21 Số 50

Thông tin tác giả