Journal of microbiology, epidemiology and immunobiologyJournal of microbiology, epidemiology and immunobiology0372-93112686-7613Central Research Institute for Epidemiology42110.36233/0372-9311-2018-3-105-116IN VITRO DIAGNOSIS FOR EBOLA VIRUS DISEASE. A COMPARISON OF CURRENT TECHNIQUES AND DIAGNOSTIC ASSAYSSementsovaA. O.Koltsovo, Novosibirsk Regionfake@neicon.ruDedkovV. G.fake@neicon.ruTernovoyV. A.Koltsovo, Novosibirsk Regionfake@neicon.ruChubE. V.Koltsovo, Novosibirsk Regionfake@neicon.ruPyankovS. A.Koltsovo, Novosibirsk Regionfake@neicon.ruAgafonovA. P.Koltsovo, Novosibirsk Regionfake@neicon.ruMaksyutovR. A.Koltsovo, Novosibirsk Regionfake@neicon.ruMaleevV. V.fake@neicon.ruPopovaA. Yu.Moscowfake@neicon.ruState Research Center of Virology and Biotechnology «Vector»Central Research Institute of EpidemiologyState Institute of Occupational HealthFederal Service for Surveillance on Consumer Rights Protection and Human WellbeingRussian Medical Academy of Postgraduate Education250720189531051162508201925082019Copyright © 2018, Sementsova A.O., Dedkov V.G., Ternovoy V.A., Chub E.V., Pyankov S.A., Agafonov A.P., Maksyutov R.A., Maleev V.V., Popova A.Y.2018<p>Ebola virus disease is dangerous viral infection, occurring in the form of hemorrhagic fever, characterized by acute clinical symptoms and high mortality rate due to multiple organ failure. Ebola virus natural foci are located in forested areas of the central and western parts of Africa. It was believed for many years, the incidence of Ebola virus disease has been sporadic and the burden of it is true only in endemic areas. However, the unprecedented Ebola epidemic caused by Zaire virus in 2013 — 2016, has significantly changed our understanding of this disease and the patterns of its distribution. We have also identified weaknesses in the organization of anti-epidemic measures, the effectiveness of which was not very effective at the onset of the epidemic, in particular due to weak development of in vitro diagnostics (IVD). However, during the elimination of the epidemic in West Africa, anti-epidemic system has been modified substantially, largely due to quickly developed IVD kits. This review is devoted to analysis of trends in IVD for Ebola virus disease based on the experience obtained in the course of the West-African epidemic in 2013 — 2016.</p>Ebola fevermolecular diagnosticsimmunochromotographyELISAлихорадка Эболамолекулярная диагностикаиммунохроматографияИФА[1. Пьянков С.А., Пьянков О.В., Найденова Е.В., Агафонов А.П., Boiro M.Y., Солодкий В.В., Зайковская А.В., Максимов Н.Л., Маренникова С.С., Бочаров Е.Ф., Офицеров В.И., Лопатин А.А., Щербакова С.А., Кутырев В.В., Михеев В.Н., Демина Ю.В. Опыт использования метода ИФА для выявления антител к вирусу Эбола при работе бригады СПЭБ в республике Гвинея. Проблемы особо опасных вирусных инфекций. 2016, 3: 71-75.][2. РУ № РЗН 2013/1322 на медицинское изделие «Набор реагентов для амплификации кДНК вируса Эбола (Заир, Судан) с гибридизационно-флуоресцентной детекцией в режиме реального времени (для приборов Rotor Gene 6000) «Вектор ПЦР РВ-Эбола-RG» по ТУ 9398-017-05664012-2011.][3. Терновой В.А., Семенцова А.О., Чуб Е.В., Пьянков О.В., Локтев В.Б., Агафонов А.П. Высокоэффективное хMAP-мультеплексирование для обнаружения и идентификации геморрагических лихорадок, включая Эбола. Проблемы особоопасных инфекций. 2015, 3: 94-97.][4. Щелканов М.Ю., Магассуба Н.Ф., Дедков В.Г., Шипулин Г.А., Галкина И.В., Попова А.Ю., Малеев В.В. Природный резервуар филовирусов и типы связанных с ними эпидемических вспышек на территории Африки. Вестник РАМН. 2017, 72 (2): 112-119. doi: 10.15690/vramn803.][5. Boisen M.L., Cross R.W., Hartnett J.N. et al. Field validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection. J. Infect. Dis. 2016, 214 (Suppl. 3): S203-S209.][6. Broadhurst M.J., Brooks T.J., Pollock N.R. Diagnosis of Ebola Virus Disease: Past, Present, and Future. Clin. Microbiol. Rev. 2016, 29 (4): 773-793. doi: 10.1128/CMR.00003-16.][7. Cherpillod P., Schibler M., Vieille G. et al. Ebola virus disease diagnosis by real-time RT-PCR: A comparativestudy of 11 different procedures. J. Clin. Virol. 2016, 77: 9-14.][8. Dedkov V.G., Magassouba N.F., Safonova M.V. et al. Development and evaluation of a real-time RT-PCR assay for the detection of Ebola virus (Zaire) during an Ebola outbreak in Guinea in 2014-2015. J. Virol. Methods. 2016, 228: 26-30. doi: 10.1016/j.jviromet.2015.11.007.][9. de La Vega M-A., Bello A., Chaillet P. et al. Diagnosis and management of Ebola samples in the laboratory. Expert Review of Anti-infective Therapy. 2016, doi: 10.1080/14787210.2016.1176912.][10. El Sayed S.M., Abdelrahman A.A., Ozbak H.A. et al. Updates in diagnosis and management of Ebola hemorrhagic fever. J. Res. Med. Sci. 2016, 21: 84. doi: 10.4103/1735-1995.192500. eCollection 2016.][11. Erickson B.R., Sealy T.K., Flietstra T. et al. Ebola virus disease diagnostics, Sierra Leone: Analysis of Real-time Reverse Transcription-Polymerase Chain Reaction Values for Clinical Blood and Oral Swab Specimens. J. Infect. Dis. 2016, 214, Suppl. 3: S258-S262.][12. Ebola haemorrhagic fever in Zaire, 1976. Report of an International Commission. Bull World Health Organ. 1978, 56 (2): 271-293.][13. Ebola haemorrhagic fever in Sudan, 1976. Report of a WHO / International study team. Bull World Health Organ. 1978, 56 (2): 247-270.][14. Gibb T.R., Norwood D.A., Jr., Woollen N. et al. Development and evaluation of a fluorogenic 5' nuclease assay to detect and differentiate between Ebola virus subtypes Zaire and Sudan. J. Clin. Microbiol. 2001, 39: 4125-4130.][15. Geisbert T.W., Jahrling P.B. Use of immunoelectron microscopy to show Ebola virus during the 1989 United States epizootic. J. Clin. Pathol. 1990, 43 (10): 813-816. doi: 10.1136/jcp.43.10.813.][16. Gilbert S.C., Warimwe G.M. Rapid development of vaccines against emerging pathogens: The replication-deficient simian adenovirus platform technology. Vaccine. 2017, 35: 4461-4464. doi: 10.1016/j.vaccine.2017.04.085.][17. Gire S.K., Goba A., Andersen K.G. et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science. 2014, 345 (6202): 1369-1372. doi:10.1126/science.1259657.][18. Goto M., Honda E., Ogura A. et al. Colorimetric detection of loop-mediated isothermal amplification reaction by using hydroxynaphthol blue. Biotechniques. 2009, 46: 167-172.][19. Huan L., Wang H., Wei L. et al. Survey and visual detection of Zaire ebolavirus in clinical samples targeting the nucleoprotein genein Sierra Leone. Frontiersin Microbiology. 2015, 6: 1332-1339.][20. Huang Y., Wei H., Wang Y. et al. Rapid detection of filoviruses by real-time TaqMan polymerase chain reaction assays. Virol. Sin. 2012, 27: 273-277.][21. Huang Y., Zhu Y., Yang M. et al. Nucleoprotein-based indirect enzyme-linked immunosorbent assay (indirect ELISA) for detecting antibodies specific to Ebola virus and Marbug virus. Virol. Sin. 2014, 29: 372-380 14.][22. https://www.cdc.gov/vhf/ebola/outbreaks/history/chronology.][23. Ikegami T., Saijo M., Niikura M. et al. Immunoglobulin G enzyme-linked immunosorbent assay using truncated nucleoproteins of Reston Ebola virus. Epidemiol. Infect. 2003, 130: 533-539.][24. Jiang S., Wang K., Li C. et al. Mathematical models for devising the optimal Ebola virus disease eradication. J. Transl. Med. 2017, 15 (1): 124-134. doi: 10.1186/s12967-017-1224-6.][25. King A.M.Q., Adams M.J., Carstens E.B. et al. Virus taxonomy, classification and nomenclature of viruses. Ninth Report of the International Committee on Taxonomy of Viruses, 2012.][26. Krahling V., Becker D., Rohde C. et al. Development of an antibody capture ELISA using inactivated Ebola Zaire Makona virus. Med. Microbiol. Immunol. 2015, 205 (2): 173-183. doi 10.1007/s00430-015-0438-6.][27. Ksiazek T.G., West C.P., Rollin P.E. et al. ELISA for the detection of antibodies to Ebola viruses. J. Infect. Dis. 1999, 179 (Suppl. 1): S192-S198.][28. Kuhn H.J., Dodd E.L., Wahl-Jensen V. et al. Evaluation of perceived threat differences posed by filovirus variants. Biosec. Bioterr. 2011, 9 (4): 361-371.][29. Kurosaki Y., Magassouba N., Oloniniyi O.K. et al. Development and evaluation of reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay coupled with a portable device for rapid diagnosis of Ebola virus diseases in Guinea. PLoS Negl. Trop. Dis. 2016, 10:e004472. DOI:10.1371/journal.pntd.0004472.][30. Le Guenno B., Formenty P., Wyers M. et al. Isolation and partial characterisation of a new strain of Ebola virus. Lancet. 1995, 345 (8960): 1271-1274. doi: 10.1016/s0140-6736 (95)90925-7.][31. Lefebvre A., Fiet C., Belpois-Duchamp C. et al. Case fatality rates of Ebola virus diseases: A metaanalysis of World Health Organization data. Med. Mal. Infect. 2014, 44 (9): 412-416.][32. Ma Y., Zhang B., Wang M. et al. Enhancement of polymerase activity of the large fragment in DNA polymerase I from geobacillus stearothermophilus by Site-Directed Mutagenesis at the active site. Biomed Res. Int. 2016, 2016: 2906484.][33. Macneil A., Reed Z., Rollin P.E. Serologic cross-reactivity of human IgM and IgG antibodies to five species of Ebola virus. PLoS Negl. Trop. Dis. 2011, 5: e1175 17.][34. Marie-Astrid Vernet M., Reynard S., Fizet A. et al. Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea. JCI Insight. 2017, 2 (6): e88864. doi: 10.1172/jci.insight.88864.][35. Nakayama E., Yokoyama A., Miyamoto H. et al. Enzyme linked immunosorbent assay for detection of filovirus species specific antibodies. Clin. Vaccine Immunol. 2010, 17: 1723-1728.][36. Notomi T., Okayama H., Masubuchi H. et al. Loop-mediated isothermal amplification of DNA. Nucleic Acids Res. 2000, 28: E63.][37. Panning M., Laue T., Olschlager S. et al. Diagnostic reverse-transcription polymerase chain reaction kit for filoviruses based on the strain collections of all European biosafety level 4 laboratories. J. Infect. Dis. 2007; 196 (Suppl. 2): S199-S204.][38. Parida M., Posadas G., Inoue S. et al. Real-time reverse transcription loop-mediated isothermal amplification for rapid detection of West Nile virus. J. Clin. Microbiol. 2004, 42: 257-263.][39. Pinsky B.A., Sahoo M.K., Sandlund J. et al. Analytical performance characteristics of the Cepheid GeneXpert Ebola Assay for the detection of Ebola virus. PLoS One. 2015, 10 (11): e0142216.][40. Rowe A.K., Bertolli J., Khan A.S. et al. Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidemies à Kikwit. J. Infect. Dis. 1999, 179 (Suppl. 1): S28-35.][41. Saijo M., Niikura M., Morikawa S. et al. Enzyme-linked immunosorbent assays for detection of antibodies to Ebola and Marburg viruses using recombinant nucleoproteins. J. Clin. Microbiol. 2001, 39 (1): 1-7.][42. Sanchez A., Ksiazek T.G., Rollin P.E. et al. Detection and molecular characterization of Ebola viruses causing disease in human and nonhuman primates. J. Infect. Dis. 1999, 179 (Suppl 1): S164-169.][43. Sobarzo A., Perelman E., Groseth A. et al. Profiling the native specific human humoral immune response to Sudan Ebola virus strain Gulu by chemiluminescence enzyme-linked immunosorbent assay. Clin. Vaccine Immunol. 2012, 19: 1844-1852.][44. Southern T.R., Racsa L.D., Albari o C.G. et al. Comparison of FilmArray and quantitative real-time reverse transcriptase PCR for detection of Zaire Ebola virus from contrived and clinical specimens. J. Clin. Microbiol. 2015, 53 (9): 2956-2960.][45. Tomita N., Mori Y., Kanda H., Notomi T. Loop-Mediated Isothermal Amplification (LAMP) of gene sequences and simple visual detection of products. Nat Protoc. 2008, 3: 877-882.][46. Towner J.S., Rollin P.E., Bausch D.G. et al. Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome. J. Virol. 2004, 78: 4330-4341.][47. World Health Organization, 2015a. Selection and use of Ebola in vitro diagnostic assays. Emergency guidance. http://www.who.int/csr/resources/publications/ebola/ivd-assays/en/ (29.06.2016).][48. World Health Organization (2015b). Annex. 2. Considerations for the selection of PCRs for the diagnosis of Ebola disease. http://www.who.int/csr/resources/publications/ebola/ivd-assays/en/(29.06.2016).]