Advertisement

Virologica Sinica

, Volume 33, Issue 4, pp 323–334 | Cite as

Serological Investigation of Laboratory-Confirmed and Suspected Ebola Virus Disease Patients During the Late Phase of the Ebola Outbreak in Sierra Leone

  • Yang Liu
  • YuLan Sun
  • Wei Wu
  • AQian Li
  • XianDa Yang
  • Shuo Zhang
  • Chuan Li
  • QiuDong Su
  • ShaoJian Cai
  • DaPeng Sun
  • HaiYang Hu
  • Zhe Zhang
  • XiuXu Yang
  • Idrissa Kamara
  • Sheku Koroma
  • Gerald Bangura
  • Alie Tia
  • Abdul Kamara
  • Matt Lebby
  • Brima Kargbo
  • Jiandong Li
  • Shiwen Wang
  • XiaoPing Dong
  • YueLong Shu
  • WenBo Xu
  • George F. Gao
  • GuiZhen Wu
  • DeXin Li
  • William J. Liu
  • MiFang Liang
Research Article

Abstract

This study aimed to investigate the serological characteristics of Ebola virus (EBOV) infection during the late phase of the Ebola outbreak in Sierra Leone. In total, 877 blood samples from 694 suspected Ebola virus disease (EVD) cases assessed from March to December 2015, were analyzed via real-time reverse transcription polymerase chain reaction (RT-PCR) for viral RNA and enzyme-linked immunosorbent assay (ELISA) and Luminex to detect antibodies against EBOV. Viral load and EBOV-specific IgM/IgG titers displayed a declining trend during March to December 2015. Viral RNA load decreased rapidly at earlier stages after disease onset, while EBOV-specific IgM and IgG still persisted in 58.1% (18/31) and 93.5% (29/31) of the confirmed EVD patients and in 3.8% (25/663) and 17.8% (118/663) of the RNA-negative suspected patients in the later phase, respectively. Dynamic analysis of longitudinally collected samples from eight EVD patients revealed typically reversed trends of declining viral load and increasing IgM and/or IgG titers in response to the EBOV infection. The present results indicate that certain populations of Sierra Leone developed immunity to an EBOV infection in the late phase of the outbreak, providing novel insights into the risk assessment of EBOV infections among human populations.

Keywords

Ebola virus (EBOV) Late phase Serologic investigation IgM IgG 

Notes

Acknowledgements

Hundreds of Chinese and Sierra Leonean staff on-site participated in specimen collection, transportation, detection, and data analysis. We especially acknowledge the excellent work of six previous detection teams of China CDC (mobile and fixed lab) and indispensable support (materials and reagents) of the National Institute for Viral Disease Control and Prevention, China CDC. We also express our deep condolences to Dr. Abdul Kamara of the Ministry of Health and Sanitation, Sierra Leone who contributed a lot to this project but passed on after the successful control of Ebola epidemic in Sierra Leone. We also appreciate Dr. Zheng Xing and Dr. Feng Liu for the useful comments of this manuscript. This study was supported by National Mega project for Infectious Disease, Ministry of Science and technology (Grant Nos. 2016ZX10004222-002, 2016ZX10004222-003), National Natural Science Foundation of China (Grant Nos. 81373141 and 81401312) and National key project of Ebola research, National Natural Science Foundation of China (NSFC, Grant No. 81590763).

Author Contributions

M Liang, JL, DL, GW, FG, AK, M Lebby, and BK designed the study, YL, WW, YS, Xianda Yang, AL, CL, QS, SC, DS, HH, ZZ, Xiuxu Yang, IK, SK, GB, AT, and JL prepared the reagents, assessed the specimens, and acquired the data. YL, M Liang, JL, and DL analyzed the data. YL, SZ, AL, JL, and M Liang wrote and edited the manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

This study did not involve human experimentation, and all the blood samples were collected from Ebola patients with prior consent of the Ministry of Health and Sanitation of Sierra Leone. Biosafety evaluations were approved by the National Institute for Viral Disease Control and Prevention, China CDC. All experimental operations were handled following the Standard Operational Protocol approved by China CDC.

References

  1. Ayouba A, Toure A, Butel C, Keita AK, Binetruy F, Sow MS, Foulongne V, Delaporte E, Peeters M (2017) Development of a sensitive and specific serological assay based on Luminex technology for detection of antibodies to Zaire Ebola virus. J Clin Microbiol 55:165–176CrossRefPubMedGoogle Scholar
  2. Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N, Soropogui B, Sow MS, Keita S, De Clerck H, Tiffany A, Dominguez G, Loua M, Traore A, Kolie M, Malano ER, Heleze E, Bocquin A, Mely S, Raoul H, Caro V, Cadar D, Gabriel M, Pahlmann M, Tappe D, Schmidt-Chanasit J, Impouma B, Diallo AK, Formenty P, Van Herp M, Gunther S (2014) Emergence of Zaire Ebola virus disease in Guinea. N Engl J Med 371:1418–1425CrossRefPubMedGoogle Scholar
  3. Blackley DJ, Wiley MR, Ladner JT, Fallah M, Lo T, Gilbert ML, Gregory C, D’Ambrozio J, Coulter S, Mate S, Balogun Z, Kugelman J, Nwachukwu W, Prieto K, Yeiah A, Amegashie F, Kearney B, Wisniewski M, Saindon J, Schroth G, Fakoli L, Diclaro JW 2nd, Kuhn JH, Hensley LE, Jahrling PB, Stroher U, Nichol ST, Massaquoi M, Kateh F, Clement P, Gasasira A, Bolay F, Monroe SS, Rambaut A, Sanchez-Lockhart M, Scott Laney A, Nyenswah T, Christie A, Palacios G (2016) Reduced evolutionary rate in reemerged Ebola virus transmission chains. Sci Adv 2:e1600378CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bower H, Glynn JR (2017) A systematic review and meta-analysis of seroprevalence surveys of ebolavirus infection. Sci Data 4:160133CrossRefPubMedPubMedCentralGoogle Scholar
  5. Broadhurst MJ, Brooks TJ, Pollock NR (2016) Diagnosis of Ebola virus disease: past, Present, and Future. Clin Microbiol Rev 29:773–793CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bustin SA, Benes V, Nolan T, Pfaffl MW (2005) Quantitative real-time RT-PCR-a perspective. J Mol Endocrinol 34:597–601CrossRefPubMedGoogle Scholar
  7. de La Vega MA, Caleo G, Audet J, Qiu X, Kozak RA, Brooks JI, Kern S, Wolz A, Sprecher A, Greig J, Lokuge K, Kargbo DK, Kargbo B, Di Caro A, Grolla A, Kobasa D, Strong JE, Ippolito G, Van Herp M, Kobinger GP (2015) Ebola viral load at diagnosis associates with patient outcome and outbreak evolution. J Clin Invest 125:4421–4428CrossRefGoogle Scholar
  8. Dean NE, Halloran ME, Yang Y, Longini IM (2016) Transmissibility and pathogenicity of ebola virus: a systematic review and meta-analysis of household secondary attack rate and asymptomatic infection. Clin Infect Dis 62:1277–1286CrossRefPubMedPubMedCentralGoogle Scholar
  9. Deen GF, Broutet N, Xu W, Knust B, Sesay FR, McDonald SLR, Ervin E, Marrinan JE, Gaillard P, Habib N, Liu H, Liu W, Thorson AE, Yamba F, Massaquoi TA, James F, Ariyarajah A, Ross C, Bernstein K, Coursier A, Klena J, Carino M, Wurie AH, Zhang Y, Dumbuya MS, Abad N, Idriss B, Wi T, Bennett SD, Davies T, Ebrahim FK, Meites E, Naidoo D, Smith SJ, Ongpin P, Malik T, Banerjee A, Erickson BR, Liu Y, Liu Y, Xu K, Brault A, Durski KN, Winter J, Sealy T, Nichol ST, Lamunu M, Bangura J, Landoulsi S, Jambai A, Morgan O, Wu G, Liang M, Su Q, Lan Y, Hao Y, Formenty P, Stroher U, Sahr F (2017) Ebola RNA persistence in semen of Ebola virus disease survivors—final report. N Engl J Med 377:1428–1437CrossRefPubMedGoogle Scholar
  10. Gao GF, Feng Y (2014) On the ground in Sierra Leone. Science 346:666CrossRefPubMedGoogle Scholar
  11. Garske T, Cori A, Ariyarajah A, Blake IM, Dorigatti I, Eckmanns T, Fraser C, Hinsley W, Jombart T, Mills HL, Nedjati-Gilani G, Newton E, Nouvellet P, Perkins D, Riley S, Schumacher D, Shah A, Van Kerkhove MD, Dye C, Ferguson NM, Donnelly CA (2017) Heterogeneities in the case fatality ratio in the West African Ebola outbreak 2013-2016. Philos Trans R Soc Lond B Biol Sci 372:20160308CrossRefPubMedPubMedCentralGoogle Scholar
  12. Glynn JR, Bower H, Johnson S, Houlihan CF, Montesano C, Scott JT, Semple MG, Bangura MS, Kamara AJ, Kamara O, Mansaray SH, Sesay D, Turay C, Dicks S, Wadoum REG, Colizzi V, Checchi F, Samuel D, Tedder RS (2017) Asymptomatic infection and unrecognised Ebola virus disease in Ebola-affected households in Sierra Leone: a cross-sectional study using a new non-invasive assay for antibodies to Ebola virus. Lancet Infect Dis 17:645–653CrossRefPubMedGoogle Scholar
  13. Heinz F, Anthony S, Thoms G (2013) Filoviridae: Marburg and Ebola viruses. In: Knipe D, Howley P (eds) Fields virology, Chapter 32, 6th edn. Williams and Wilkins, Baltimore, pp 945–947Google Scholar
  14. Ksiazek TG, West CP, Rollin PE, Jahrling PB, Peters CJ (1999) ELISA for the detection of antibodies to Ebola viruses. J Infect Dis 179(Suppl 1):S192–198CrossRefPubMedGoogle Scholar
  15. Lequin RM (2005) Enzyme immunoassay (EIA)/enzyme-linked immunosorbent assay (ELISA). Clin Chem 51:2415–2418CrossRefPubMedPubMedCentralGoogle Scholar
  16. Leroy EM, Baize S, Volchkov VE, Fisher-Hoch SP, Georges-Courbot MC, Lansoud-Soukate J, Capron M, Debre P, McCormick JB, Georges AJ (2000) Human asymptomatic Ebola infection and strong inflammatory response. Lancet 355:2210–2215CrossRefPubMedGoogle Scholar
  17. Li A, Li W, Li J, Zhang S, Qu J, Li C, Zhang Q, Liang M, Li D (2014) Development of real-time RT-PCR assay for detection of Zaire Ebolavirus. Chin J Exp Clin Virol 28:321–323 (in Chinese) Google Scholar
  18. Lu HJ, Qian J, Kargbo D, Zhang XG, Yang F, Hu Y, Sun Y, Cao YX, Deng YQ, Su HX, Dafae F, Sun Y, Wang CY, Nie WM, Bai CQ, Xia ZP, Liu K, Kargbo B, Gao GF, Jiang JF (2015) Ebola Virus Outbreak Investigation, Sierra Leone, September 28-November 11, 2014. Emerg Infect Dis 21:1921–1927CrossRefPubMedPubMedCentralGoogle Scholar
  19. Lucht A, Grunow R, Moller P, Feldmann H, Becker S (2003) Development, characterization and use of monoclonal VP40-antibodies for the detection of Ebola virus. J Virol Methods 111:21–28CrossRefPubMedGoogle Scholar
  20. Lucht A, Grunow R, Otterbein C, Moller P, Feldmann H, Becker S (2004) Production of monoclonal antibodies and development of an antigen capture ELISA directed against the envelope glycoprotein GP of Ebola virus. Med Microbiol Immunol 193:181–187CrossRefPubMedGoogle Scholar
  21. Niikura M, Ikegami T, Saijo M, Kurane I, Miranda ME, Morikawa S (2001) Detection of Ebola viral antigen by enzyme-linked immunosorbent assay using a novel monoclonal antibody to nucleoprotein. J Clin Microbiol 39:3267–3271CrossRefPubMedPubMedCentralGoogle Scholar
  22. Pang Z, Li A, Li J, Qu J, He C, Zhang S, Li C, Zhang Q, Liang M, Li D (2014) Comprehensive multiplex one-step real-time TaqMan qRT-PCR assays for detection and quantification of hemorrhagic fever viruses. PLoS ONE 9:e95635CrossRefPubMedPubMedCentralGoogle Scholar
  23. Rougeron V, Feldmann H, Grard G, Becker S, Leroy EM (2015) Ebola and Marburg haemorrhagic fever. J Clin Virol 64:111–119CrossRefPubMedGoogle Scholar
  24. Schoepp RJ, Rossi CA, Khan SH, Goba A, Fair JN (2014) Undiagnosed acute viral febrile illnesses, Sierra Leone. Emerg Infect Dis 20:1176–1182CrossRefPubMedPubMedCentralGoogle Scholar
  25. Southern TR, Racsa LD, Albarino CG, Fey PD, Hinrichs SH, Murphy CN, Herrera VL, Sambol AR, Hill CE, Ryan EL, Kraft CS, Campbell S, Sealy TK, Schuh A, Ritchie JC, Lyon GM 3rd, Mehta AK, Varkey JB, Ribner BS, Brantly KP, Stroher U, Iwen PC, Burd EM (2015) Comparison of filmarray and quantitative real-time reverse transcriptase pcr for detection of Zaire Ebolavirus from contrived and clinical specimens. J Clin Microbiol 53:2956–2960CrossRefPubMedPubMedCentralGoogle Scholar
  26. Sow MS, Etard JF, Baize S, Magassouba N, Faye O, Msellati P, Toure A 2nd, Savane I, Barry M, Delaporte E (2016) New evidence of long-lasting persistence of Ebola virus genetic material in semen of survivors. J Infect Dis 214:1475–1476CrossRefPubMedGoogle Scholar
  27. Uyeki TM, Mehta AK, Davey RT Jr, Liddell AM, Wolf T, Vetter P, Schmiedel S, Grunewald T, Jacobs M, Arribas JR, Evans L, Hewlett AL, Brantsaeter AB, Ippolito G, Rapp C, Hoepelman AI, Gutman J (2016) Clinical management of Ebola virus disease in the United States and Europe. N Engl J Med 374:636–646CrossRefPubMedPubMedCentralGoogle Scholar
  28. Varkey JB, Shantha JG, Crozier I, Kraft CS, Lyon GM, Mehta AK, Kumar G, Smith JR, Kainulainen MH, Whitmer S, Stroher U, Uyeki TM, Ribner BS, Yeh S (2015) Persistence of Ebola virus in ocular fluid during convalescence. N Engl J Med 372:2423–2427CrossRefPubMedPubMedCentralGoogle Scholar
  29. Wang Q, Zhang Y, Nie K, Wang H, Du H, Song J, Xiao K, Lei W, Guo J, Wei H, Cai K, Wang Y, Wu J, Gerald B, Kamara IL, Liang M, Wu G, Dong X (2016) Establishment of quality control system of nucleic acid detection for ebola virus in sierra leone-china friendship biological safety laboratory. Bing du xue bao 32:210–214 (in Chinese) PubMedGoogle Scholar
  30. WHO (2016) Situation report: Ebola virus disease. Accessed 30 March 2016Google Scholar
  31. WHO (2016) Statement on the 9th meeting of the IHR Emergency Committee regarding the Ebola outbreak in West Africa. 29 March 2016Google Scholar
  32. Wu W, Zhang S, Qu J, Zhang Q, Li C, Li J, Jin C, Liang M, Li D (2014) Simultaneous detection of IgG antibodies associated with viral hemorrhagic fever by a multiplexed Luminex-based immunoassay. Virus Res 187:84–90CrossRefPubMedGoogle Scholar
  33. Zhou R, Sun L, Liu Y, Wu W, Li C, Liang M, Qiu P (2016) Research of human-mouse chimeric antibodies against ebola virus nucleoprotein. Bing du xue bao 32:14–18 (in Chinese) PubMedGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Yang Liu
    • 1
    • 8
  • YuLan Sun
    • 2
    • 8
  • Wei Wu
    • 1
  • AQian Li
    • 1
  • XianDa Yang
    • 3
    • 8
  • Shuo Zhang
    • 1
  • Chuan Li
    • 1
  • QiuDong Su
    • 1
    • 8
  • ShaoJian Cai
    • 4
    • 8
  • DaPeng Sun
    • 5
    • 8
  • HaiYang Hu
    • 6
    • 8
  • Zhe Zhang
    • 7
    • 8
  • XiuXu Yang
    • 7
    • 8
  • Idrissa Kamara
    • 8
    • 9
  • Sheku Koroma
    • 8
    • 9
  • Gerald Bangura
    • 8
    • 9
  • Alie Tia
    • 8
    • 9
  • Abdul Kamara
    • 9
  • Matt Lebby
    • 9
  • Brima Kargbo
    • 9
  • Jiandong Li
    • 1
  • Shiwen Wang
    • 1
  • XiaoPing Dong
    • 1
  • YueLong Shu
    • 1
  • WenBo Xu
    • 1
  • George F. Gao
    • 1
    • 10
  • GuiZhen Wu
    • 1
  • DeXin Li
    • 1
  • William J. Liu
    • 1
    • 8
  • MiFang Liang
    • 1
  1. 1.Key Laboratory of Medical Virology and Viral Diseases, Ministry of Health, National Institute for Viral Disease Control and Prevention (IVDC)Chinese Center for Disease Control and Prevention (China CDC)BeijingChina
  2. 2.Beijing Center for Disease Control and Prevention (Beijing CDC, China)BeijingChina
  3. 3.Jilin Provincial Center for Disease Control and Prevention (Jilin CDC, China)JilinChina
  4. 4.Fujian Provincial Center for Disease Control and Prevention (Fujian CDC, China)FuzhouChina
  5. 5.Shandong Provincial Center for Disease Control and Prevention (Shandong CDC, China)JinanChina
  6. 6.Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu CDC, China)NanjingChina
  7. 7.Beijing Institute of BiotechnologyBeijingChina
  8. 8.Sierra Leone-China Friendship Biological Safety Laboratory (SLE-CHN Bio-safety Lab)FreetownSierra Leone
  9. 9.The Ministry of Health and Sanitation (MoHS, SL)FreetownSierra Leone
  10. 10.CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of MicrobiologyChinese Academy of SciencesBeijingChina

Personalised recommendations