Ebola virus disease: an update on post-exposure prophylaxis

William A Fischer 2nd, Pauline Vetter, Daniel G Bausch, Timothy Burgess, Richard T Davey Jr, Robert Fowler, Frederick G Hayden, Peter B Jahrling, Andre C Kalil, Douglas L Mayers, Aneesh K Mehta, Timothy M Uyeki, Michael Jacobs, William A Fischer 2nd, Pauline Vetter, Daniel G Bausch, Timothy Burgess, Richard T Davey Jr, Robert Fowler, Frederick G Hayden, Peter B Jahrling, Andre C Kalil, Douglas L Mayers, Aneesh K Mehta, Timothy M Uyeki, Michael Jacobs

Abstract

The massive outbreak of Ebola virus disease in west Africa between 2013 and 2016 resulted in intense efforts to evaluate the efficacy of several specific countermeasures developed through years of preclinical work, including the first clinical trials for therapeutics and vaccines. In this Review, we discuss how the experience and data generated from that outbreak have helped to advance the understanding of the use of these countermeasures for post-exposure prophylaxis against Ebola virus infection. In future outbreaks, post-exposure prophylaxis could play an important part in reducing community transmission of Ebola virus by providing more immediate protection than does immunisation as well as providing additional protection for health-care workers who are inadvertently exposed over the course of their work. We propose provisional guidance for use of post-exposure prophylaxis in Ebola virus disease and identify the priorities for future preparedness and further research.

Conflict of interest statement

Declaration of interests

We declare no competing interests.

Copyright © 2018 Elsevier Ltd. All rights reserved.

References

    1. WHO. Ebola situation report June 10, 2016. (accessed June 2, 2017).
    1. Dean NE, Halloran ME, Yang Y, Longini IM. Transmissibility and pathogenicity of Ebola virus: a systematic review and meta-analysis of household secondary attack rate and asymptomatic infection. Clin Infect Dis 2016; 62: 1277–86.
    1. Vetter P, Fischer WA 2nd, Schibler M, Jacobs M, Bausch DG, Kaiser L. Ebola virus shedding and transmission: review of current evidence. J Infect Dis 2016; 214: S177–84.
    1. Henao-Restrepo AM, Camacho A, Longini IM, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet 2017; 389: 505–18.
    1. WHO. Ebola situation report October 28, 2015. (accessed June 2, 2017).
    1. WHO. Ebola haemorrhagic fever in Sudan, 1976. Report of a WHO/International Study Team. Bull World Health Organ 1978; 56: 247–70.
    1. WHO. Ebola haemorrhagic fever in Zaire, 1976. Bull World Health Organ 1978; 56: 271–93.
    1. Bah EI, Lamah MC, Fletcher T, et al. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med 2015; 372: 40–47.
    1. Fischer WA 2nd, Hynes NA, Perl TM. Protecting health care workers from Ebola: personal protective equipment is critical but is not enough. Ann Intern Med 2014; 161: 753–54.
    1. Fischer WA 2nd, Weber DJ, Wohl DA. Personal protective equipment: protecting health care providers in an Ebola outbreak. Clin Ther 2015; 37: 2402–10.
    1. Fowler RA, Fletcher T, Fischer WA 2nd, et al. Caring for critically ill patients with Ebola virus disease. Perspectives from west Africa. Am J Respir Crit Care Med 2014; 190: 733–37.
    1. Wamala JF, Lukwago L, Malimbo M, et al. Ebola hemorrhagic fever associated with novel virus strain, Uganda, 2007–2008. Emerg Infect Dis 2010; 16: 1087–92.
    1. Chevalier MS, Chung W, Smith J, et al. Ebola virus disease cluster in the United States—Dallas County, Texas, 2014. Morb Mortal Wkly Rep 2014; 63: 1087–88.
    1. Parra JM, Salmeron OJ, Velasco M. The first case of Ebola virus disease acquired outside Africa. N Engl J Med 2014; 371: 2439–40.
    1. International Society for Infectious Diseases. Ebola, lab accident death: Russia (Siberia) May 24, 2004 (accessed June 2, 2017).
    1. Gunther S, Feldmann H, Geisbert TW, et al. Management of accidental exposure to Ebola virus in the biosafety level 4 laboratory, Hamburg, Germany. J Infect Dis 2011; 204: S785–90.
    1. Emond RT, Evans B, Bowen ET, Lloyd G. A case of Ebola virus infection. BMJ 1977; 2: 541–44.
    1. Agnandji ST, Huttner A, Zinser ME, et al. Phase 1 trials of rVSV Ebola vaccine in Africa and Europe. N Engl J Med 2016; 374: 1647–60.
    1. Sissoko D, Laouenan C, Folkesson E, et al. Experimental treatment with favipiravir for Ebola virus disease (the JIKI Trial): a historically controlled, single-arm proof-of-concept trial in Guinea. PLoS Med 2016; 13: e1001967.
    1. van Griensven J, Edwards T, de Lamballerie X, et al. Evaluation of convalescent plasma for Ebola virus disease in Guinea. N Engl J Med 2016; 374: 33–42.
    1. Davey RT Jr, Dodd L, Proschan MA, et al. A randomized, controlled trial of ZMapp for Ebola virus infection. N Engl J Med 2016; 375: 1448–56.
    1. Dunning J, Kennedy SB, Antierens A, et al. Experimental treatment of Ebola virus disease with brincidofovir. PLoS One 2016; 11: e0162199.
    1. Cnops L, Gerard M, Vandenberg O, et al. Risk of misinterpretation of Ebola virus PCR results after rVSV ZEBOV-GP vaccination. Clin Infect Dis 2015; 60: 1725–26.
    1. Jacobs M, Aarons E, Bhagani S, et al. Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers. Lancet Infect Dis 2015; 15: 1300–04.
    1. Kudoyarova-Zubavichene NM, Sergeyev NN, Chepurnov AA, Netesov SV. Preparation and use of hyperimmune serum for prophylaxis and therapy of Ebola virus infections. J Infect Dis 1999; 179: S218–23.
    1. Lai L, Davey R, Beck A, et al. Emergency postexposure vaccination with vesicular stomatitis virus-vectored Ebola vaccine after needlestick. JAMA 2015; 313: 1249–55.
    1. Wong KK, Davey RT Jr, Hewlett AL, et al. Use of postexposure prophylaxis after occupational exposure to Zaire ebolavirus. Clin Infect Dis 2016; 63: 376–79.
    1. Ksiazek TG, Rollin PE, Williams AJ, et al. Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis 1999; 179: S177–87.
    1. Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet 2011; 377: 849–62.
    1. Ruibal P, Oestereich L, Ludtke A, et al. Unique human immune signature of Ebola virus disease in Guinea. Nature 2016; 533: 100–04.
    1. Dahlke C, Lunemann S, Kasonta R, et al. Comprehensive characterization of cellular immune responses following Ebola virus infection. J Infect Dis 2017; 215: 287–92.
    1. Jones SM, Feldmann H, Stroher U, et al. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nat Med 2005; 11: 786–90.
    1. Marzi A, Robertson SJ, Haddock E, et al. Ebola vaccine. VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain. Science 2015; 349: 739–42.
    1. Marzi A, Engelmann F, Feldmann F, et al. Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates. Proc Natl Acad Sci USA 2013; 110: 1893–98.
    1. Feldmann H, Jones SM, Daddario-DiCaprio KM, et al. Effective post-exposure treatment of Ebola infection. PLoS Pathog 2007; 3: e2.
    1. Regules JA, Beigel JH, Paolino KM, et al. A recombinant vesicular stomatitis virus Ebola vaccine. N Engl J Med 2017; 376: 330–41.
    1. Huttner A, Dayer JA, Yerly S, et al. The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial. Lancet Infect Dis 2015; 15: 1156–66.
    1. Marzi A, Hanley PW, Haddock E, Martellaro C, Kobinger G, Feldmann H. Efficacy of vesicular stomatitis virus-Ebola virus postexposure treatment in Rhesus macaques infected with Ebola virus Makona. J Infect Dis 2016; 214: S360–66.
    1. Kobinger GP, Feldmann H, Zhi Y, et al. Chimpanzee adenovirus vaccine protects against Zaire Ebola virus. Virology 2006; 346: 394–401.
    1. Sullivan NJ, Geisbert TW, Geisbert JB, et al. Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates. Nature 2003; 424: 681–84.
    1. Sullivan NJ, Sanchez A, Rollin PE, Yang ZY, Nabel GJ. Development of a preventive vaccine for Ebola virus infection in primates. Nature 2000; 408: 605–09.
    1. Richardson JS, Yao MK, Tran KN, et al. Enhanced protection against Ebola virus mediated by an improved adenovirus-based vaccine. PLoS One 2009; 4: e5308.
    1. Geisbert TW, Bailey M, Hensley L, et al. Recombinant adenovirus serotype 26 (Ad26) and Ad35 vaccine vectors bypass immunity to Ad5 and protect nonhuman primates against ebolavirus challenge. J Virol 2011; 85: 4222–33.
    1. Ewer K, Rampling T, Venkatraman N, et al. A monovalent chimpanzee adenovirus Ebola vaccine boosted with MVA. N Engl J Med 2016; 374: 1635–46.
    1. Stanley DA, Honko AN, Asiedu C, et al. Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge. Nat Med 2014; 20: 1126–29.
    1. Wong G, Richardson JS, Pillet S, et al. Adenovirus-vectored vaccine provides postexposure protection to Ebola virus-infected nonhuman primates. J Infect Dis 2015; 212: S379–83.
    1. Zhu FC, Wurie AH, Hou LH, et al. Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a single-centre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 2017; 389: 621–28.
    1. Shukarev G, Callendret B, Luhn K, Douoguih M. A two-dose heterologous prime-boost vaccine regimen eliciting sustained immune responses to Ebola Zaire could support a preventive strategy for future outbreaks. Hum Vaccin Immunother 2017; 13: 266–70.
    1. Limberis MP, Tretiakova A, Nambiar K, et al. Adeno-associated virus serotype 9-expressed ZMapp in mice confers protection against systemic and airway-acquired Ebola virus infection. J Infect Dis 2016; 214: 1975–79.
    1. Johnson RF, Kurup D, Hagen KR, et al. An inactivated rabies virus-based Ebola vaccine, FILORAB1, adjuvanted with glucopyranosyl lipid A in stable emulsion confers complete protection in nonhuman primate challenge models. J Infect Dis 2016; 214: S342–54.
    1. Milligan ID, Gibani MM, Sewell R, et al. Safety and immunogenicity of novel adenovirus type 26- and modified vaccinia Ankara-vectored Ebola vaccines: a randomized clinical trial. JAMA 2016; 315: 1610–23.
    1. Lingemann M, Liu X, Surman S, et al. Attenuated human parainfluenza virus type 1 expressing Ebola virus glycoprotein GP administered intranasally is immunogenic in African green monkeys. J Virol 2017; 91: e02469–16.
    1. Dolzhikova IV, Zubkova OV, Tukhvatulin AI, et al. Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: an open phase I/II trial in healthy adults in Russia. Hum Vaccin Immunother 2017; 13: 613–20.
    1. Baize S, Leroy EM, Georges-Courbot MC, et al. Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients. Nat Med 1999; 5: 423–26.
    1. Prescott JB, Marzi A, Safronetz D, Robertson SJ, Feldmann H, Best SM. Immunobiology of Ebola and Lassa virus infections. Nat Rev Immunol 2017; 17: 195–207.
    1. Jahrling PB, Geisbert J, Swearengen JR, et al. Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses. Arch Virol Suppl 1996; 11: 135–40.
    1. Jahrling PB, Geisbert TW, Geisbert JB, et al. Evaluation of immune globulin and recombinant interferon-α2b for treatment of experimental Ebola virus infections. J Infect Dis 1999; 179: S224–34.
    1. Florescu DF, Kalil AC, Hewlett AL, et al. Administration of brincidofovir and convalescent plasma in a patient with Ebola virus disease. Clin Infect Dis 2015; 61: 969–73.
    1. Kraft CS, Hewlett AL, Koepsell S, et al. The use of TKM-100802 and convalescent plasma in 2 patients with Ebola virus disease in the United States. Clin Infect Dis 2015; 61: 496–502.
    1. Liddell AM, Davey RT Jr, Mehta AK, et al. Characteristics and clinical management of a cluster of 3 patients with Ebola virus disease, including the first domestically acquired cases in the United States. Ann Intern Med 2015; 163: 81–90.
    1. Lyon GM, Mehta AK, Varkey JB, et al. Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med 2014; 371: 2402–09.
    1. Mora-Rillo M, Arsuaga M, Ramirez-Olivencia G, et al. Acute respiratory distress syndrome after convalescent plasma use: treatment of a patient with Ebola virus disease contracted in Madrid, Spain. Lancet Respir Med 2015; 3: 554–62.
    1. Mupapa K, Massamba M, Kibadi K, et al. Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. International Scientific and Technical Committee. J Infect Dis 1999; 179: S18–23.
    1. Petrosillo N, Nicastri E, Lanini S, et al. Ebola virus disease complicated with viral interstitial pneumonia: a case report. BMC Infect Dis 2015; 15: 432.
    1. Sueblinvong V, Johnson DW, Weinstein GL, et al. Critical care for multiple organ failure secondary to Ebola virus disease in the United States. Crit Care Med 2015; 43: 2066–75.
    1. Zeitlin L, Whaley KJ, Olinger GG, et al. Antibody therapeutics for Ebola virus disease. Curr Opin Virol 2016; 17: 45–49.
    1. van Griensven J, Edwards T, Baize S. Efficacy of convalescent plasma in relation to dose of Ebola virus antibodies. N Engl J Med 2016; 375: 2307–09.
    1. Sahr F, Ansumana R, Massaquoi TA, et al. Evaluation of convalescent whole blood for treating Ebola virus disease in Freetown, Sierra Leone. J Infect 2017; 74: 302–09.
    1. Mire CE, Geisbert JB, Agans KN, et al. Passive immunotherapy: assessment of convalescent serum against Ebola virus Makona infection in nonhuman primates. J Infect Dis 2016; 214: S367–74.
    1. Dye JM, Herbert AS, Kuehne AI, et al. Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease. Proc Natl Acad Sci USA 2012; 109: 5034–39.
    1. Qiu X, Wong G, Audet J, et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 2014; 514: 47–53.
    1. Jacobs M, Rodger A, Bell DJ, et al. Late Ebola virus relapse causing meningoencephalitis: a case report. Lancet 2016; 388: 498–503.
    1. Schibler M, Vetter P, Cherpillod P, et al. Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report. Lancet Infect Dis 2015; 15: 1034–40.
    1. Uyeki TM, Mehta AK, Davey RT Jr, et al. Clinical management of Ebola virus disease in the United States and Europe. N Engl J Med 2016; 374: 636–46.
    1. Corti D, Misasi J, Mulangu S, et al. Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Science 2016; 351: 1339–42.
    1. Qiu X, Audet J, Lv M, et al. Two-mAb cocktail protects macaques against the Makona variant of Ebola virus. Sci Transl Med 2016; 8: 329ra33.
    1. Dowall SD, Callan J, Zeltina A, et al. Development of a cost-effective ovine polyclonal antibody-based product, EBOTAb, to treat Ebola virus infection. J Infect Dis 2016; 213: 1124–33.
    1. Zhang Q, Gui M, Niu X, et al. Potent neutralizing monoclonal antibodies against Ebola virus infection. Sci Rep 2016; 6: 25856.
    1. Wec AZ, Nyakatura EK, Herbert AS, et al. A “Trojan horse” bispecific-antibody strategy for broad protection against ebolaviruses. Science 2016; 354: 350–54.
    1. Dowell SF, Mukunu R, Ksiazek TG, Khan AS, Rollin PE, Peters CJ. Transmission of Ebola hemorrhagic fever: a study of risk factors in family members, Kikwit, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidemies a Kikwit. J Infect Dis 1999; 179: S87–91.
    1. Fallah M. A cohort study of survivors of Ebola Virus infection in Liberia (PREVAIL III). Conference on Retroviruses and Oppotunistic Infections; Boston, Massachusetts; Feb 22–25, 2016 74LB.
    1. Leroy EM, Baize S, Volchkov VE, et al. Human asymptomatic Ebola infection and strong inflammatory response. Lancet 2000; 355: 2210–15.
    1. Rowe AK, Bertolli J, Khan AS, 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 a Kikwit. J Infect Dis 1999; 179: S28–35.
    1. Richardson ET, Kelly JD, Barrie MB, et al. Minimally symptomatic infection in an Ebola ‘hotspot’: a cross-sectional serosurvey. PLoS Negl Trop Dis 2016; 10: e0005087.
    1. Glynn JR, Bower H, Johnson S, et al. 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 2017; 17: 645–53.
    1. Bower H, Glynn JR. A systematic review and meta-analysis of seroprevalence surveys of ebolavirus infection. Sci Data 2017; 4: 160133.
    1. Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res 2013; 100: 446–54.
    1. Oestereich L, Ludtke A, Wurr S, Rieger T, Munoz-Fontela C, Gunther S. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res 2014; 105: 17–21.
    1. Smither SJ, Eastaugh LS, Steward JA, Nelson M, Lenk RP, Lever MS. Post-exposure efficacy of oral T-705 (favipiravir) against inhalational Ebola virus infection in a mouse model. Antiviral Res 2014; 104: 153–55.
    1. Mentre F, Taburet AM, Guedj J, et al. Dose regimen of favipiravir for Ebola virus disease. Lancet Infect Dis 2015; 15: 150–51.
    1. Nguyen TH, Guedj J, Anglaret X, et al. Favipiravir pharmacokinetics in Ebola-infected patients of the JIKI trial reveals concentrations lower than targeted. PLoS Negl Trop Dis 2017; 11: e0005389.
    1. Warren TK, Jordan R, Lo MK, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature 2016; 531: 381–85.
    1. Dornemann J, Burzio C, Ronsse A, et al. First newborn baby to receive experimental therapies survives Ebola virus disease. J Infect Dis 2017; 215: 171–74.
    1. Lo MK, Jordan R, Arvey A, et al. GS-5734 and its parent nucleoside analog inhibit filo-, pneumo-, and paramyxoviruses. Sci Rep 2017; 7: 43395.
    1. Warren TK, Wells J, Panchal RG, et al. Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature 2014; 508: 402–05.
    1. Taylor R, Kotian P, Warren T, et al. BCX4430—a broad-spectrum antiviral adenosine analog under development for the treatment of Ebola virus disease. J Infect Public Health 2016; 9: 220–26.
    1. Giesbert TW, Lee ACH, Robbins M, et al. Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study. Lancet 2010; 375: 1896–905.
    1. Dunning J, Sahr F, Rojek A, et al. Experimental treatment of Ebola virus disease with TKM-130803: a single-arm phase 2 clinical trial. PLoS Med 2016; 13: e1001997.
    1. Thi EP, Mire CE, Lee AC, et al. Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates. Nature 2015; 521: 362–65.
    1. Gignoux E, Azman AS, de Smet M, et al. Effect of artesunate–amodiaquine on mortality related to Ebola virus disease. N Engl J Med 2016; 374: 23–32.
    1. Mate SE, Kugelman JR, Nyenswah TG, et al. Molecular evidence of sexual transmission of Ebola virus. N Engl J Med 2015; 373: 2448–54.
    1. Soka MJ, Choi MJ, Baller A, et al. Prevention of sexual transmission of Ebola in Liberia through a national semen testing and counselling programme for survivors: an analysis of Ebola virus RNA results and behavioural data. Lancet Glob Health 2016; 4: e736–43.
    1. Diallo B, Sissoko D, Loman NJ, et al. Resurgence of Ebola virus disease in Guinea linked to a survivor with virus persistence in seminal fluid for more than 500 days. Clin Infect Dis 2016; 63: 1353–56.
    1. Yamada K, Noguchi K, Komeno T, et al. Efficacy of favipiravir (T-705) in rabies postexposure prophylaxis. J Infect Dis 2016; 213: 1253–61.

Source: PubMed

3
Subscribe