J. Pharm. Technol. Res. Manag.

Ebola Hemorrhagic Fever: Recent Update On Disease Status, Current Therapies And Advances In Treatment

Jaskaran Singh, Thapa Komal, Sandeep Arora, Amarjot Kaur and Thakur Gurjeet Singh

KEYWORDS

Filovirus; Ebola; Single-stranded ribonucleic acid; GRADE; vaccines; rVSV-EBOV; Favipiravir; ZMapp.

PUBLISHED DATE November 2017
PUBLISHER The Author(s) 2017. This article is published with open access at www.chitkara.edu.in/publications
ABSTRACT

Swiftly growing viruses are a major intimidation to human health. Such viruses are extremely pathogenic like Ebola virus, influenza virus, HIV virus, Zika virus etc . Ebola virus, a type of Filovirus, is an extremely infectious, single-stranded ribonucleic acid virus that infects both humans and apes, prompting acute fever with hemorrhagic syndrome. The high infectivity, severity and mortality of Ebola has plagued the world for the past fifty years with its first outbreak in 1976 in Marburg, Germany, and Frankfurt along with Belgrade and Serbia. The world has perceived about 28,000 cases and over 11,000 losses. The high lethality of Ebola makes it a candidate for use in bioterrorism thereby arising more concern. New guidelines have been framed for providing best possible care to the patients suffering from Ebola virus i.e Grading of Recommendation Assessment, Development And Evaluation (GRADE) methodology to develop evidence-based strategy for the treatment in future outbreak of Ebola virus. No drugs have been approved, while many potent drugs like rVSV-EBOV, Favipiravir, ZMapp are on clinical test for human safety. In this review we will discover and discuss perspective aspects that lead to the evolution of different Ebola variants as well as advances in various drugs and vaccines for treatment of the disease.

Page(s) 217–234
URL http://dspace.chitkara.edu.in/jspui/bitstream/123456789/670/1/JPTRM%205-2-6.pdf
ISSN Print : 2321-2217, Online : 2321-2225
DOI 10.15415/jptrm.2017.52013
REFERENCES
  • Ansari, A.A. (2014). Clinical features and pathobiology of Ebola virus infection. Journal of autoimmunity, 55, 1–9. https://doi.org/10.1016/j.jaut.2014.09.001
  • Barrette, R.W., Xu, L., Rowland, J.M. and McIntosh, M.T. (2011). Current perspectives on the phylogeny of Filoviridae. Infection, genetics and evolution, 11(7), 1514–1519. https://doi.org/10.1016/j.meegid.2011.06.017
  • Beeching, N.J., Fenech, M. and Houlihan, C.F. (2014). Ebola virus disease. BMJ, 349, g7348. https://doi.org/10.1136/bmj.g7348
  • Bishop, B.M. (2015). Potential and emerging treatment options for Ebola virus disease. Annals of Pharmacotherapy, 49(2), 196–206. https://doi.org/10.1177/1060028014561227
  • Bradfute, S.B. (2017). The early clinical development of Ebola virus treatments. Expert opinion on investigational drugs, 26(1), 1–4. https://doi.org/10.1080/13543784.2017.1260545
  • Brainard, J., Hooper, L., Pond, K., Edmunds, K. and Hunter, P.R. (2015). Risk factors for transmission of Ebola or Marburg virus disease: a systematic review and meta-analysis. International journal of epidemiology, 45(1), 102–116. https://doi.org/10.1093/ije/dyv307
  • Chertow, D.S., Uyeki, T.M. and DuPont, H.L. (2015). Loperamide therapy for voluminous diarrhea in Ebola virus disease. The Journal of infectious diseases, 211(7), 1036–1037. https://doi.org/10.1093/infdis/jiv001
  • Clark, D.V., Jahrling, P.B. and Lawler, J.V. (2012). Clinical management of filovirusinfected patients. Viruses, 4(9), 1668–1686. https://doi.org/10.3390/v4091668
  • Cook, B.W., Cutts, T.A., Nikiforuk, A.M., Poliquin, P.G., Strong, J.E. and Theriault, S.S. (2015). Evaluating environmental persistence and disinfection of the Ebola virus Makona variant. Viruses, 7(4), 1975–1986. https://doi.org/10.3390/v7041975
  • Dallatomasina, S., Crestani, R., Sylvester Squire, J., Declerk, H., Caleo, G.M., Wolz, A., Stinson, K., Patten, G., Brechard, R., Gbabai, O.B.M. and Spreicher, A. (2015). Ebola outbreak in rural West Africa: epidemiology, clinical features and outcomes. Tropical Medicine & International Health, 20(4), 448-454. https://doi.org/10.1111/tmi.12454
  • Davidson, E., Bryan, C., Fong, R.H., Barnes, T., Pfaff, J.M., Mabila, M., Rucker, J.B. and Doranz, B.J. (2015). Mechanism of binding to Ebola virus glycoprotein by the ZMapp, ZMAb, and MB-003 cocktail antibodies. Journal of virology, 89(21), 10982–10992. https://doi.org/10.1128/JVI.01490-15
  • de La Vega, M.A., Stein, D. and Kobinger, G.P. (2015). Ebolavirus evolution: past and present. PLoS pathogens, 11(11), e1005221. https://doi.org/10.1371/journal.ppat.1005221
  • de Wit, E., Feldmann, H. and Munster, V.J. (2011). Tackling Ebola: new insights into prophylactic and therapeutic intervention strategies. Genome medicine, 3(1), 5. https://doi.org/10.1186/gm219
  • Dolzhikova, I.V., Zubkova, O.V., Tukhvatulin, A.I., Dzharullaeva, A.S., Tukhvatulina, N.M., Shcheblyakov, D.V., Shmarov, M.M., Tokarskaya, E.A., Simakova, Y.V., Egorova, D.A. and Scherbinin, D.N. (2017). 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. Human Vaccines & Immunotherapeutics, 13(3), 613–620. https://doi.org/10.1080/21645515.2016.1238535
  • Dörnemann, J., Burzio, C., Ronsse, A., Sprecher, A., De Clerck, H., Van Herp, M., Kolié, M.C., Yosifiva, V., Caluwaerts, S., McElroy, A.K. and Antierens, A. (2017). First newborn baby to receive experimental therapies survives ebola virus disease. The Journal of infectious diseases, 215(2), 171–174. https://doi.org/10.1093/infdis/jiw493
  • Drosten, C., Kümmerer, B.M., Schmitz, H. and Günther, S. (2003). Molecular diagnostics of viral hemorrhagic fevers. Antiviral research, 57(1), 61–87. https://doi.org/10.1016/S0166-3542(02)00201-2
  • Dunning, J., Sahr, F., Rojek, A., Gannon, F., Carson, G., Idriss, B., Massaquoi, T., Gandi, R., Joseph, S., Osman, H.K. and Brooks, T.J. (2016). Experimental treatment of Ebola virus disease with TKM-130803: a single-arm phase 2 clinical trial. PLoS medicine, 13(4), e1001997. https://doi.org/10.1371/journal.pmed.1001997
  • Dyall, J., Hart, B.J., Postnikova, E., Cong, Y., Zhou, H., Gerhardt, D.M., Freeburger, D., Michelotti, J., Honko, A.N., DeWald, L.E. and Bennett, R.S. (2017). Interferon-β and Interferon-γ Are Weak Inhibitors of Ebola Virus in Cell- Based Assays. The Journal of Infectious Diseases, 215(9), 1416–1420. https://doi.org/10.1093/infdis/jix134
  • Fedson, D.S. and Rordam, O.M. (2015). Treating Ebola patients: a ‘bottom up’approach using generic statins and angiotensin receptor blockers. International Journal of Infectious Diseases, 36, 80–84. https://doi.org/10.1016/j.ijid.2015.04.019
  • Fischer, W.A., Uyeki, T.M. and Tauxe, R.V. (2015). Ebola virus disease: What clinicians in the United States need to know. American journal of infection control, 43(8), 788–793. https://doi.org/10.1016/j.ajic.2015.05.005
  • Florescu, D.F. and Keck, M.A. (2014). Development of CMX001 (Brincidofovir) for the treatment of serious diseases or conditions caused by dsDNA viruses. Expert review of anti-infective therapy, 12(10), 1171–1178. https://doi.org/10.1586/14787210.2014.948847
  • Fowler, R.A., Fletcher, T., Fischer, W.A., Lamontagne, F., Jacob, S., Brett-Major, D., Lawler, J.V., Jacquerioz, F.A., Houlihan, C., O’Dempsey, T. and Ferri, M. (2014). Caring for critically ill patients with Ebola virus disease. Perspectives from West Africa. American journal of respiratory and critical care medicine, 190(7), 733–737. https://doi.org/10.1164/rccm.201408-1514CP
  • Francesconi, P., Yoti, Z., Declich, S., Onek, P.A., Fabiani, M., Olango, J., Andraghetti, R., Rollin, P.E., Opira, C., Greco, D. and Salmaso, S. (2003). Ebola hemorrhagic fever transmission and risk factors of contacts, Uganda. Emerging infectious diseases, 9(11), 1430. https://doi.org/10.3201/eid0911.030339
  • Gatherer, D. (2014). The 2014 Ebola virus disease outbreak in West Africa.Journal of General Virology, 95(8), 1619–1624. https://doi.org/10.1099/vir.0.067199-0
  • Gebretadik, F.A., Seifu, M.F. and Gelaw, B.K. (2015). Review on Ebola Virus Disease: Its Outbreak and Current Status. Epidemiology (sunnyvale), 5(204), 2161–1165.
  • Geisbert, T.W., Hensley, L.E., Jahrling, P.B., Larsen, T., Geisbert, J.B., Paragas, J., Young, H.A., Fredeking, T.M., Rote, W.E. and Vlasuk, G.P. (2003). Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. The Lancet, 362(9400), 1953–1958. https://doi.org/10.1016/S0140-6736(03)15012-X
  • Georges, A.J., Leroy, E.M., Renaut, A.A., Benissan, C.T., Nabias, R.J., Ngoc, M.T., Obiang, P.I., Lepage, J.P.M., Bertherat, E.J., Bénoni, D.D. and Wickings, E.J. (1999). Ebola hemorrhagic fever outbreaks in Gabon, 1994–1997: epidemiologic and health control issues. The Journal of infectious diseases, 179(Supplement_1), S65–S75. https://doi.org/10.1086/514290
  • Gignoux, E., Azman, A.S., De Smet, M., Azuma, P., Massaquoi, M., Job, D., Tiffany, A., Petrucci, R., Sterk, E., Potet, J. and Suzuki, M. (2016). Effect of artesunate–amodiaquine on mortality related to Ebola virus disease. New England Journal of Medicine, 374(1), 23–32. https://doi.org/10.1056/NEJMoa1504605
  • Haque, A., Hober, D. and Blondiaux, J. (2015). Addressing therapeutic options for Ebola virus infection in current and future outbreaks. Antimicrobial agents and chemotherapy, 59(10), 5892–5902. https://doi.org/10.1128/AAC.01105-15
  • Heald, A.E., Iversen, P.L., Saoud, J.B., Sazani, P., Charleston, J.S., Axtelle, T., Wong, M., Smith, W.B., Vutikullird, A. and Kaye, E. (2014). Safety and pharmacokinetic profiles of phosphorodiamidate morpholino oligomers with activity against ebola virus and marburg virus: results of two single ascending dose studies. Antimicrobial agents and chemotherapy, AAC–03442. https://doi.org/10.1128/AAC.03442-14
  • Henao-Restrepo, A.M., Camacho, A., Longini, I.M., Watson, C.H., Edmunds, W.J., Egger, M., Carroll, M.W., Dean, N.E., Diatta, I., Doumbia, M. and Draguez, B. (2017). 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!). The Lancet, 389(10068), 505–518. https://doi.org/10.1016/S0140-6736(16)32621-6
  • Hensley, L.E., Jones, S.M., Feldmann, H., Jahrling, P.B. and Geisbert, T.W. (2005). Ebola and Marburg viruses: pathogenesis and development of countermeasures. Current molecular medicine, 5(8), 761–772. https://doi.org/10.2174/156652405774962344
  • Howlett, P., Brown, C., Helderman, T., Brooks, T., Lisk, D., Deen, G., Solbrig, M. and Lado, M. (2016). Ebola virus disease complicated by late-onset encephalitis and polyarthritis, Sierra Leone. Emerging infectious diseases, 22(1), 150. https://doi.org/10.3201/eid2201.151212
  • Hunt, L., Gupta-Wright, A., Simms, V., Tamba, F., Knott, V., Tamba, K., Heisenberg-Mansaray, S., Tamba, E., Sheriff, A., Conteh, S. and Smith, T. (2015). Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study. The Lancet infectious diseases, 15(11), 1292–1299. https://doi.org/10.1016/S1473-3099(15)00144-9
  • Johansen, L.M., Brannan, J.M., Delos, S.E., Shoemaker, C.J., Stossel, A., Lear, C., Hoffstrom, B.G., DeWald, L.E., Schornberg, K.L., Scully, C. and Lehár, J. (2013). FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection. Science translational medicine, 5(190), 190ra79. https://doi.org/10.1126/scitranslmed.3005471
  • Keshwara, R., Johnson, R.F. and Schnell, M.J. (2017). Toward an effective Ebola virus vaccine. Annual review of medicine, 68, 371–386. https://doi.org/10.1146/annurev-med-051215-030919
  • Khan, A.S., Tshioko, F.K., Heymann, D.L., Le Guenno, B., Nabeth, P., Kerstiëns, B., Fleerackers, Y., Kilmarx, P.H., Rodier, G.R., Nkuku, O. and Rollin, P.E. (1999). The reemergence of Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995. The Journal of infectious diseases, 179(Supplement_1), S76–S86. https://doi.org/10.1086/514306
  • Kilgore, P.E., Grabenstein, J.D., Salim, A.M. and Rybak, M. (2015). Treatment of Ebola virus disease. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 35(1), 43–53. https://doi.org/10.1002/phar.1545
  • Kortepeter, M.G., Martin, J.W., Rusnak, J.M., Cieslak, T.J., Warfield, K.L., Anderson, E.L. and Ranadive, M.V. (2008). Managing potential laboratory exposure to Ebola virus by using a patient biocontainment care unit. Emerging infectious diseases, 14(6), 881. https://doi.org/10.3201/eid1406.071489
  • Ledgerwood, J.E., DeZure, A.D., Stanley, D.A., Coates, E.E., Novik, L., Enama, M.E., Berkowitz, N.M., Hu, Z., Joshi, G., Ploquin, A. and Sitar, S. (2017). Chimpanzee adenovirus vector Ebola vaccine. New England Journal of Medicine, 376(10), 928–938. https://doi.org/10.1056/NEJMoa1410863
  • Leroy, E.M., Gonzalez, J.P. and Baize, S. (2011). Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa. Clinical Microbiology and Infection, 17(7), 964–976. https://doi.org/10.1111/j.1469-0691.2011.03535.x
  • Leung, L.W., Hartman, A.L., Martinez, O., Shaw, M.L., Carbonnelle, C., Volchkov, V.E., Nichol, S.T. and Basler, C.F. (2006). Ebola virus VP24 binds karyopherin α1 and blocks STAT1 nuclear accumulation. Journal of virology, 80(11), 5156–5167. https://doi.org/10.1128/JVI.02349-05
  • MacDermott, N. and Herberg, J.A. (2017). Ebola: lessons learned. Paediatrics and Child Health, 27(3), 128–134. https://doi.org/10.1016/j.paed.2016.11.007
  • Madrid, P.B., Panchal, R.G., Warren, T.K., Shurtleff, A.C., Endsley, A.N., Green, C.E., Kolokoltsov, A., Davey, R., Manger, I.D., Gilfillan, L. and Bavari, S. (2015). Evaluation of Ebola virus inhibitors for drug repurposing. ACS infectious diseases, 1(7), 317–326. https://doi.org/10.1021/acsinfecdis.5b00030
  • Matua, G.A., Van der Wal, D.M. and Locsin, R.C. (2015). Ebolavirus and haemorrhagic syndrome. Sultan Qaboos University Medical Journal, 15(2), e171.
  • Milligan, I.D., Gibani, M.M., Sewell, R., Clutterbuck, E.A., Campbell, D., Plested, E., Nuthall, E., Voysey, M., Silva-Reyes, L., McElrath, M.J. and De Rosa, S.C. (2016). Safety and immunogenicity of novel adenovirus type 26–and modified vaccinia Ankara–vectored Ebola vaccines: a randomized clinical trial. Jama, 315(15), 1610–1623. https://doi.org/10.1001/jama.2016.4218
  • Osterholm, M.T., Moore, K.A., Kelley, N.S., Brosseau, L.M., Wong, G., Murphy, F.A., Peters, C.J., LeDuc, J.W., Russell, P.K., Van Herp, M. and Kapetshi, J. (2015). Transmission of Ebola viruses: what we know and what we do not know. MBio, 6(2), e00137–15. https://doi.org/10.1128/mBio.00137-15
  • Passi, D., Sharma, S., Dutta, S.R., Dudeja, P. and Sharma, V. (2015). Ebola virus disease (the killer virus): another threat to humans and bioterrorism: brief review and recent updates. Journal of clinical and diagnostic research: JCDR, 9(6), LE01. https://doi.org/10.7860/JCDR/2015/13062.6100
  • Prevail, I.I. and Multi-National PREVAIL II Study Team. (2016). A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection. The New England journal of medicine, 375(15), 1448. https://doi.org/10.1056/NEJMoa1604330
  • Qiu, X., Audet, J., Lv, M., He, S., Wong, G., Wei, H., Luo, L., Fernando, L., Kroeker, A., Bovendo, H.F. and Bello, A. (2016). Two-mAb cocktail protects macaques against the Makona variant of Ebola virus. Science translational medicine, 8(329), 329ra33. https://doi.org/10.1126/scitranslmed.aad9875
  • Qiu, X., Wong, G., Audet, J., Bello, A., Fernando, L., Alimonti, J.B., Fausther- Bovendo, H., Wei, H., Aviles, J., Hiatt, E. and Johnson, A. (2014). Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp™. Nature, 514(7520), 47. https://doi.org/10.1038/nature13777
  • Regules, J.A., Beigel, J.H., Paolino, K.M., Voell, J., Castellano, A.R., Hu, Z., Mu-oz, P., Moon, J.E., Ruck, R.C., Bennett, J.W. and Twomey, P.S. (2017). A recombinant vesicular stomatitis virus Ebola vaccine. New England Journal of Medicine, 376(4), 330–341. https://doi.org/10.1056/NEJMoa1414216
  • Sagui, E., Janvier, F., Baize, S., Foissaud, V., Koulibaly, F., Savini, H., Maugey, N., Aletti, M.,Granier,H. and Carmoi, T. (2015). Severe Ebola Virus Infection With Encephalopathy: Evidence for Direct Virus Involvement. Clinical Infectious Diseases, 61(10), 1627–1628. https://doi.org/10.1093/cid/civ606
  • Sameem, R. and Dias, S. (2017). Ebola virus: Promising vaccine candidates. Vac-cin Res Open J, 1(1), 33–38.
  • Saurabh, S., & Prateek, S. (2017). Role of contact tracing in containing the 2014 Ebola outbreak: a review. African Health Sciences, 17(1), 225–236. https://doi.org/10.4314/ahs.v17i1.28
  • Sharma, R. and Ketki Jangid, A. (2017). Ebola Vaccine: How Far are we? Journal of clinical and diagnostic research: JCDR, 11(5), DE01. https://doi.org/10.1080/21645515.2017.1356960
  • Shiwani, H.A., Pharithi, R.B., Khan, B., Egom, C.B.A., Kruzliak, P., Maher, V. and Egom, E.E.A. (2017). An update on the 2014 Ebola outbreak in Western Africa. Asian Pacific journal of tropical medicine, 10(1), 6–10. https://doi.org/10.1016/j.apjtm.2016.12.008
  • Sissoko, D., Laouenan, C., Folkesson, E., M’lebing, A.B., Beavogui, A.H., Baize, S., Camara, A.M., Maes, P., Shepherd, S., Danel, C. and Carazo, S. (2016). Experimental treatment with favipiravir for Ebola virus disease (the JIKI Trial): a historically controlled, single-arm proof-of-concept trial in Guinea. PLoS medicine, 13(3), e1001967. https://doi.org/10.1371/journal.pmed.1001967
  • Sridhar, S. (2015). Clinical development of Ebola vaccines. Therapeutic advances in vaccines, 3(5-6), 125–138. https://doi.org/10.1177/2051013615611017
  • Sweiti, H., Ekwunife, O., Jaschinski, T. and Lhachimi, S.K. (2017). Repurposed Therapeutic Agents Targeting the Ebola Virus: A Systematic Review. Current Therapeutic Research, 84, 10–21. https://doi.org/10.1016/j.curtheres.2017.01.007
  • Tapia, M.D., Sow, S.O., Lyke, K.E., Haidara, F.C., Diallo, F., Doumbia, M., Traore, A., Coulibaly, F., Kodio, M., Onwuchekwa, U. and Sztein, M.B. (2016). Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial. The Lancet infectious diseases, 16(1), 31–42. https://doi.org/10.1016/S1473-3099(15)00362-X
  • Thi, E.P., Mire, C.E., Lee, A.C., Geisbert, J.B., Zhou, J.Z., Agans, K.N., Snead, N.M., Deer, D.J., Barnard, T.R., Fenton, K.A. and MacLachlan, I. (2015). Lipid nanoparticle siRNA treatment of Ebola virus Makona infected nonhuman primates. Nature, 521(7552), 362. https://doi.org/10.1038/nature14442
  • Turone, F. (2014). Doctors trial amiodarone for Ebola in Sierra Leone. BMJ: British Medical Journal, 349.
  • Van Griensven, J., Edwards, T., De Lamballerie, X., Semple, M.G., Gallian, P., Baize, S., Horby, P.W., Raoul, H., Magassouba, N.F., Antierens, A. and Lomas, C. (2016). Evaluation of convalescent plasma for Ebola virus disease in Guinea. New England Journal of Medicine, 374(1), 33–42. https://doi.org/10.1056/NEJMoa1511812
  • Volchkov, V.E., Nichol, S.T., Martinez, C.F.O., Shaw, M.L., Carbonnelle, C., St Patrick Reid, L.W.L. and Hartman, A.L. (2006). Ebola Virus VP24 Binds Karyopherin. J. Virol, 80(11), 5156. https://doi.org/10.1128/JVI.02349-05
  • Wambani, R.J., Ogola, P.E., Arika, W.M., Rachuonyo, H.O. and Burugu, M.W. (2016). Ebola Virus Disease: A Biological and Epidemiological Perspective of a Virulent Virus. J Infect Dis Diagn, 1(103), 2.
  • Warren, T.K., Jordan, R., Lo, M.K., Ray, A.S., Mackman, R.L., Soloveva, V., Siegel, D., Perron, M., Bannister, R., Hui, H.C. and Larson, N. (2016). Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature, 531(7594), 381–385. https://doi.org/10.1038/nature17180
  • Warren, T.K., Wells, J., Panchal, R.G., Stuthman, K.S., Garza, N.L., Van Tongeren, S.A., Dong, L., Retterer, C.J., Eaton, B.P., Pegoraro, G. and Honnold, S. (2014). Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature, 508(7496), 402. https://doi.org/10.1038/nature13027
  • Weingartl, H.M., Embury-hyatt, C., Nfon, C., Leung, A., Smith, G. and Kobinger, G. (2012). Transmission of Ebola virus from pigs to non-human primates. Scientific Reports (Nature Publisher Group), 2, 811. https://doi.org/10.1038/srep00811
  • West, T.E. and von Saint André-von Arnim, A. (2014). Clinical presentation and management of severe Ebola virus disease. Annals of the American Thoracic Society, 11(9), 1341–1350. https://doi.org/10.1513/AnnalsATS.201410-481PS
  • Wolf, T., Kann, G., Becker, S., Stephan, C., Brodt, H.R., de Leuw, P., Grünewald, T., Vogl, T., Kempf, V.A., Keppler, O.T. and Zacharowski, K. (2015). Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. The Lancet, 385(9976), 1428–1435. https://doi.org/10.1016/S0140-6736(14)62384-9