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Communicable Diseases of the Developing World pp 1–36Cite as

Clinical Management of Ebola Virus Disease: Current and Future Approaches

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Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 29))

Abstract

Ebola virus disease (EVD) is a notoriously dreadful disease. The acute viral syndrome, which has an incubation period ranging from 2 to 21 days, is characterized by fever and diarrhea, along with bleeding diathesis. Mortality rates are high. The natural reservoir is thought to be the fruit bat of the Pteropodidae family. Nonhuman primates, including monkeys, chimpanzees, and gorillas, are primary hosts to the virus. Transmission occurs through direct contact with bodily fluids containing the virus. Currently available laboratory tests include the rapid diagnostic tests ELISA and PCR. A patient’s chance of survival depends on multiple factors, such as the initial viral load at the time of exposure, their immune response to the virus, and access to proper care. Currently, there is no specific treatment or cure; however, clinical management mainly consists of supportive measures. Novel drugs and vaccines are undergoing clinical trials to determine their safety and efficacy for use in humans.

The online version of this chapter has been revised.

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References

  1. WHO (1978) Ebola haemorrhagic fever in Sudan, 1976. Report of a WHO/International Study Team. Bull World Health Organ 56:247–270

    Google Scholar 

  2. Martini GA, Siegert R (1971) Marburg virus disease. Springer, Berlin

    Book  Google Scholar 

  3. Demarcus TA, Tripple MA, Ostrowski SR (1999) US policies for disease control among imported nonhuman primates. J Infect Dis 179(Suppl 1):282–283

    Google Scholar 

  4. Jahrling PB, Geisbert TW, Dalgard DW (1990) Preliminary report: isolation of Ebola virus from monkeys imported to USA. Lancet 335:502–505

    Article  CAS  PubMed  Google Scholar 

  5. Peters CJ, Jahrling PB, et al (1991) Filoviruses. Emerging viruses. Oxford University Press, New York

    Google Scholar 

  6. Le Guenno B, Formenty P, Wyers M, et al (1995) Isolation and partial characterization of a new strain of Ebola virus. Lancet 345:1271–1274

    Article  PubMed  Google Scholar 

  7. Junfa Y, Zhang Y, Jialu L, et al (2012) Serological evidence of ebolavirus infection in bats, China. J Virol 9:236

    Article  Google Scholar 

  8. Barrette RW, Metwally SA, Rowland JM, et al (2009) Discovery of swine as a host for the Reston ebolavirus. Science 325:204–206

    Article  CAS  PubMed  Google Scholar 

  9. Leroy EM, Kumulungi B, Pourrut X, et al (2005) Fruit bats as reservoirs of Ebola virus. Nature 438:575–576

    Article  CAS  PubMed  Google Scholar 

  10. Gonzalez JP, Pourrut X, Leroy E (2007) Ebolavirus and other filovirus. Curr Top Microbiol Immunol 315:363–387

    CAS  PubMed  Google Scholar 

  11. Walsh PD, Abernethy KA, Magdalena B, et al (2003) Catastrophic ape decline in western equatorial Africa. Nature 422:611–614

    Article  CAS  PubMed  Google Scholar 

  12. Vogel G (2003) Conservation biology can great apes be saved from Ebola? Science 300(5626):1645

    Article  CAS  PubMed  Google Scholar 

  13. Baron RC, Zubeir OA (1983) Ebola virus disease in southern Sudan: hospital dissemination and intrafamilial spread. Bull World Health Organ 61:997–1003

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Richards GA, Murphy S, Jobson R, et al (2000) Unexpected Ebola virus in a tertiary setting: clinical and epidemiologic aspects. Crit Care Med 28:240–244

    Article  CAS  PubMed  Google Scholar 

  15. Miranda ME, White ME, Dayrit MM, et al (1991) Seroepidemiological study of filovirus related to Ebola in the Philippines. Lancet 337:425–426

    Article  CAS  PubMed  Google Scholar 

  16. CDC (1990) Update: filovirus infection in animal handlers. MMWR Morb Mortal Wkly Rep 39:221

    Google Scholar 

  17. Miranda ME, Ksiazek TG, Retuya TJ, et al (1999) Epidemiology of Ebola (subtype Reston) virus in the Philippines, 1996. J Infect Dis 179(Suppl 1):115–119

    Article  Google Scholar 

  18. Emond RT, Evans B, Bowen ET, et al (1977) A case of Ebola virus infection. Br Med J 2:541–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Akinfeyeva LA, Vasilyevich IV, Ginko ZI, et al (2005) A case of Ebola hemorrhagic fever. Infektsionnye Bolezni 3:85–88

    Google Scholar 

  20. Borisevich IV, Markin VA, Firsova IV, et al (2006) Hemorrhagic (Marburg, Ebola, Lassa, and Bolivian) fevers: epidemiology, clinical pictures, and treatment. Vopr Virusol 51:8–16

    CAS  PubMed  Google Scholar 

  21. Schoepp RJ, Rossi CA, Khan SH, et al (2014) Undiagnosed acute viral febrile illnesses, Sierra Leone. Emerg Infect Dis 20:1176–1182

    Article  PubMed  PubMed Central  Google Scholar 

  22. Shuaib F, Gunnala R, Musa EO, et al (2014) Ebola virus disease outbreak – Nigeria, July-September 2014. MMWR Morb Mortal Wkly Rep 63:867–872

    PubMed  PubMed Central  Google Scholar 

  23. WHO (2014) Disease outbreak news: Ebola virus disease – Mali. http://www.who.int/csr/don/31-october-2014-ebola/en/. Retrieved 28 June 2015

  24. WHO (2014) Disease outbreak news: Ebola virus disease update – Senegal. http://www.who.int/csr/don/2014_08_30_ebola/en/. Retrieved 28 June 2015

  25. Georges AJ, Leroy EM, Renaut AA, et al (1999) Ebola hemorrhagic fever outbreaks in Gabon, 1994–1997: epidemiologic and health control issues. J Infect Dis 179(Suppl 1):65–75

    Article  Google Scholar 

  26. Pourrut X, Kumulungui B, Wittmann T, et al. (2005) The natural history of Ebola virus in Africa. Microbes Infect 7:1005–1014

    Article  PubMed  Google Scholar 

  27. Leroy EM, Epelboin A, Mondonge V, et al (2009) Human Ebola outbreak resulting from direct exposure to fruit bats in Luebo, Democratic Republic of Congo, 2007. Vector Borne Zoonotic Dis 9:723–728

    Article  PubMed  Google Scholar 

  28. Rodriguez LL, De Roo A, Guimard Y, et al (1999) Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis 179(Suppl 1):170–176

    Article  Google Scholar 

  29. Christie A, Davies-wayne GJ, Cordier LT, et al (2015) Possible sexual transmission of Ebola virus – Liberia, 2015. MMWR Morb Mortal Wkly Rep 64:479–481

    PubMed  PubMed Central  Google Scholar 

  30. Rowe AK, Bertolli J, Khan AS, et al (1999) 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 179(Suppl 1):28–35

    Article  Google Scholar 

  31. Mupapa K, Massamba M, Kibadi K, et al (1999) Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. International Scientific and Technical Committee. J Infect Dis 179(Suppl 1):18–23

    Article  Google Scholar 

  32. WHO (1978) Ebola haemorrhagic fever in Zaire, 1976. Bull World Health Organ 56:271–293

    Google Scholar 

  33. Bausch DG, Towner JS, Dowell SF, et al (2007) Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. J Infect Dis 196(Suppl 2):142–147

    Article  Google Scholar 

  34. Sagripanti JL, Rom AM, Holland LE (2010) Persistence in darkness of virulent alphaviruses, Ebola virus, and Lassa virus deposited on solid surfaces. Arch Virol 155:2035–2039

    Article  CAS  PubMed  Google Scholar 

  35. Franz DR, Jahrling PB, Friedlander AM, et al (1997) Clinical recognition and management of patients exposed to biological warfare agents. JAMA 278:399–411

    Article  CAS  PubMed  Google Scholar 

  36. Johnson E, Jaax N, White J, et al (1995) Lethal experimental infections of rhesus monkeys by aerosolized Ebola virus. Int J Exp Pathol 76:227–236

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Lamunu M, Lutwama JJ, Kamugisha J, et al (2004) Containing a haemorrhagic fever epidemic: the Ebola experience in Uganda (October 2000-January 2001). Int J Infect Dis 8:27–37

    Article  CAS  PubMed  Google Scholar 

  38. WHO (2015) Emergency guideline: implementation and management of contact tracing for Ebola virus disease. http://www.who.int/csr/resources/publications/ebola/contact-tracing/en/. Retrieved 31 Jan 2016

  39. WHO (2001) Outbreak of Ebola haemorrhagic fever, Uganda, August 2000–January 2001. Wkly Epidemiol Rec 76:41–46

    Google Scholar 

  40. Muyembe-tamfum JJ, Kipasa M, Kiyungu C, et al (1999) Ebola outbreak in Kikwit, Democratic Republic of the Congo: discovery and control measures. J Infect Dis 179:259–262

    Article  Google Scholar 

  41. Kuhn JH, Becker S, Ebihara H, et al (2010) Proposal for a revised taxonomy of the family Filoviridae: classification, names of taxa and viruses, and virus abbreviations. Arch Virol 55:2083–2103

    Article  CAS  Google Scholar 

  42. Muhlberger E (2007) Filovirus replication and transcription. Futur Virol 2:205–215

    Article  Google Scholar 

  43. Crary SM, Towner JS, Honig JE, et al (2003) Analysis of the role of predicted RNA secondary structures in Ebola virus replication. Virology 306:210–218

    Article  CAS  PubMed  Google Scholar 

  44. Sanchez AA, Khan S, Zaki SR, et al (2001) Filoviridae: Marburg and Ebola viruses. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  45. Nanbo A, Watanabe S, Halfmann P, et al (2013) The spatio-temporal distribution dynamics of Ebola virus proteins and RNA in infected cells. Sci Rep 3:1206

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Feldmann H, Klenk HD, Sanchez A (1993) Molecular biology and evolution of filoviruses. Arch Virol Suppl 7:81–100

    Article  CAS  PubMed  Google Scholar 

  47. Carette JE, Raaben M, Wong AC (2011) Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 477:340–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Yonezawa A, Cavrois M, Greene WC (2005) Studies of Ebola virus glycoprotein-mediated entry and fusion by using pseudotyped human immunodeficiency virus type 1 virions: involvement of cytoskeletal proteins and enhancement by tumor necrosis factor alpha. J Virol 79:918–926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wit E, Feldmann H, Munster VJ (2011) Tackling Ebola: new insights into prophylactic and therapeutic intervention strategies. Genome Med 3(1):5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Wahl-Jensen V, Kurz SK, Hazelton PR, et al (2005) Role of Ebola virus secreted glyco-proteins and virus-like particles in activation of human macrophages. J Virol 79:2413–2419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Feldmann HV, Volchkiva AV, Stroeher U, et al (2001) Biosynthesis and role of filoviral glycoprotein. J Gen Virol 82:2839–2848

    Article  CAS  PubMed  Google Scholar 

  52. Sanchez A, Yang ZY, Nabel GJ, et al (1998) Biochemical analysis of the secreted and virion glycoproteins of Ebola virus. J Virol 72:6442–6447

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Volchkov VE, Volchkova VA, Slenczka W, et al (1998) Release of viral glycoproteins during Ebola virus infection. Virology 245:110–119

    Article  CAS  PubMed  Google Scholar 

  54. Yang Z, Delgado R, Todd RF, et al. (1998) Distinct cellular interactions of secreted and transmembrane Ebola virus glycoproteins. Science 279:1034–1037

    Article  CAS  PubMed  Google Scholar 

  55. Dolnik O, Volchkova V, Garten W, et al (2004) Ectodomain shedding of the glycoprotein GP of Ebola virus. EMBO J 23:2175–2184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Volchova VA, Klenk HD, Volchkov VE (1999) Delta-peptide is the carboxy-terminal cleavage fragment of the nonstructural small glycoprotein sGP of Ebola virus. Virology 265:164–171

    Article  CAS  Google Scholar 

  57. Sanchez A, Trappier SG, Mahy BW, et al (1996) The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc Natl Acad Sci U S A 93:3602–3607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Volchkov VE, Becker S, Volchkova VA, et al (1995) GP mRNA of Ebola virus is edited by the Ebola virus polymerase and by T7 and vaccinia virus polymerases. Virology 214:421–430

    Article  CAS  PubMed  Google Scholar 

  59. Reid SP, Leung LW, Hartman AL, et al (2006) Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation. J Virol 80:5156–5167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Jasenosky LD, Neumann G, Lukashevich I, et al (2001) Ebola virus VP40-induced particle formation and association with the lipid bilayer. J Virol 75:5205–5214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Zhang AP, Abelson DM, Bornholdt ZA, et al (2012) The ebolavirus VP24 interferon antagonist: know your enemy. Virulence 3:440–445

    Article  PubMed  PubMed Central  Google Scholar 

  62. Najjar I, Fagard R (2010) STAT1 and pathogens, not a friendly relationship. Biochimie 92:425–444

    Article  CAS  PubMed  Google Scholar 

  63. Hoenen T, Groseth A, Kolesnikova L, et al (2006) Infection of naive target cells with virus-like particles: implications for the function of Ebola virus VP24. J Virol 80:7260–7264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Leung DW, Prins KC, Basler CF, et al (2010) Ebolavirus VP35 is a multifunctional virulence factor. Virulence 1:526–531

    Article  PubMed  PubMed Central  Google Scholar 

  65. Basler CF, Wang X, Muhlberger E, et al (2000) The Ebola virus VP35 protein functions as a type I IFN antagonist. Proc Natl Acad Sci U S A 97:12289–12294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Reid SP, Cardenas WB, Basler CF (2005) Homo-oligomerization facilitates the interferon-antagonist activity of the ebolavirus VP35 protein. Virology 341:179–189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Johnson RF, Mccarthy SE, Godleweski PJ, et al (2006) Ebola virus VP35–VP40 interaction is sufficient for packaging 3E-5E minigenome RNA into virus-like particles. J Virol 80:5135–5144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Muhlberger E, Lotfering B, Klenk HD, et al (1998) Three of the four nucleocapsid proteins of Marburg virus, NP, VP35, and L, are sufficient to mediate replication and transcription of Marburg virus-specific monocistronic minigenomes. J Virol 72:8756–8764

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Haasnoot J, De Vries W, Geutjes EJ, et al (2007) The Ebola virus VP35 protein is a suppressor of RNA silencing. PLoS Pathog 3:e86

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Feng Z, Cerveny M, Yan Z, et al (2007) The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR. J Virol 81:182–192

    Article  CAS  PubMed  Google Scholar 

  71. Ramanathan CS, Taylor EW (1997) Computational genomic analysis of hemorrhagic fever viruses. Viral selenoproteins as a potential factor in pathogenesis. Biol Trace Elem Res 56:93–106

    Article  CAS  PubMed  Google Scholar 

  72. Ricetti MM, Guidi GC, Perona G, et al (1994) Selenium enhances glutathione peroxidase activity and prostacyclin release in cultured human endothelial cells. Concurrent effects on mRNA levels. Biol Trace Elem Res 46:113–123

    Article  CAS  PubMed  Google Scholar 

  73. Schiavon R, Freeman GE, Guidi GC, et al (1984) Selenium enhances prostacyclin production by cultured endothelial cells: possible explanation for increased bleeding times in volunteers taking selenium as a dietary supplement. Thromb Res 34:389–396

    Article  CAS  PubMed  Google Scholar 

  74. Saeed MF, Kolokoltsov AA, Albrecht T, et al (2010) Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes. PLoS Pathog 6:e1001110

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Weik M, Modrof J, Klenk HD, et al (2002) Ebola virus VP30-mediated transcription is regulated by RNA secondary structure formation. J Virol 76:8532–8539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Martinez MJ, Biedenkopf N, Volchkova V, et al (2008) Role of Ebola virus VP30 in transcription reinitiation. J Virol 82:12569–12573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Watanabe S, Noda T, Halfmann P, et al (2007) Ebola virus (EBOV) VP24 inhibits transcription and replication of the EBOV genome. J Infect Dis 196(Suppl 2):S284–S290

    Article  CAS  PubMed  Google Scholar 

  78. Francica JR, Varela-Rohena A, Medvec A, et al (2010) Steric shielding of surface epitopes and impaired immune recognition induced by the ebola virus glycoprotein. PLoS Pathog 6:e1001098

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Noda T, Sagara H, Suzuki E, et al (2002) Ebola virus VP40 drives the formation of virus-like filamentous particles along with GP. J Virol 76:4855–4865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Timminis J, Schoehn G, Ricard-blum S, et al. (2003) Ebola virus matrix protein VP40 interaction with human cellular factors Tsg101 and Nedd4. J Mol Biol 326:493–502

    Article  Google Scholar 

  81. Bavari S, Bocio CM, Wiegand E, et al (2002) Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses. J Exp Med 195:593–602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Basler CF, Mikulasova A, Martinez-sobrido L, et al (2003) The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J Virol 77:7945–7956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Wahl-Jensen VM, Afanasieva TA, Seebach J, et al (2005) Effects of Ebola virus glycoproteins on endothelial cell activation and barrier function. J Virol 79:10442–10450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Geisbert TW, Hensley LE, Larsen T, et al (2003) Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. Am J Pathol 163:2347–2370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Bah EI, Lamah MC, Fletcher T, et al (2015) Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med 372:40–47

    Article  CAS  PubMed  Google Scholar 

  86. Chertow DS, Kleine C, Edwards JK, et al (2014) Ebola virus disease in West Africa – clinical manifestations and management. N Engl J Med 371:2054–2057

    Article  PubMed  Google Scholar 

  87. Qin E, Zhao M, Wang Y, et al (2015) Clinical features of patients with Ebola virus disease in Sierra Leone. Clin Infect Dis 7:29

    Google Scholar 

  88. Feldmann H, Geisbert TW (2011) Ebola haemorrhagic fever. Lancet 377:849–862

    Article  PubMed  PubMed Central  Google Scholar 

  89. Kortepeter MG, Bausch DG, Bray M (2011) Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis 204(Suppl 3):810–816

    Article  Google Scholar 

  90. Maganga GD, Kapethshi J, Berthet N (2014) Ebola virus disease in the Democratic Republic of Congo. N Engl J Med 371:2083–2091

    Article  CAS  PubMed  Google Scholar 

  91. Schieffelin JS, Shaffer JG, Goba A (2014) Clinical illness and outcomes in patients with Ebola in Sierra Leone. N Engl J Med 371:2092–2100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. CDC (2015) Ebola virus disease: case definition for Ebola virus disease. http://www.cdc.gov/vhf/ebola/healthcare-us/evaluating-patients/case-definition.html

  93. WHO (2014) Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker. Interim emergency guidance – generic draft for West African adaptation. WHO, Geneva

    Google Scholar 

  94. WHO (2014) Case definition recommendations for Ebola or Marburg virus disease. Accessed 11 May 2015

    Google Scholar 

  95. Fowler RA, Fletcher T, Fischer WA, et al (2014) Caring for critically ill patients with ebola virus disease. Perspectives from West Africa. Am J Respir Crit Care Med 190:733–737

    Article  PubMed  Google Scholar 

  96. Wolf T, Kann G, Becker S, et al (2015) Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care. Lancet 385:1428–1435

    Article  PubMed  Google Scholar 

  97. Lyon GM, Mehta AK, Varkey JB, et al (2014) Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med 371:2402–2409

    Article  CAS  PubMed  Google Scholar 

  98. Uyeki TM et al (2016) Clinical management of Ebola virus disease in the United States and Europe. N Engl J Med 374:636–646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Leroy EM, Baize S, Volchkov VE, et al (2000) Human asymptomatic Ebola infection and strong inflammatory response. Lancet 355:2210–2215

    Article  CAS  PubMed  Google Scholar 

  100. Clark DV, Kibuuka H, Millard M, et al (2015) Long-term sequelae after Ebola virus disease in Bundibugyo, Uganda: a retrospective cohort study. Lancet Infect Dis 15:905–912

    Article  PubMed  Google Scholar 

  101. Kraft CS, Hewlett AL, Koepsell S, et al (2015) The use of TKM-100802 and convalescent plasma in 2 patients with Ebola virus disease in the United States. Clin Infect Dis. doi:10.1093/cid/civ334

    Article  PubMed  PubMed Central  Google Scholar 

  102. Varkey JB, Shantha JG, Crozier I (2015) Persistence of Ebola virus in ocular fluid during convalescence. N Engl J Med 372:2423–2427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Dunning J, Sahr F, Rojek A, Gannon F, Carson G, Idriss B, et al (2016) Experimental treatment of Ebola virus disease with TKM-130803: a single-arm phase 2 clinical trial. PLoS Med 13(4):e1001997. doi:10.1371/journal.pmed.1001997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Chua AC, Cunningham J, Moussy F, et al (2015) The case for improved diagnostic tools to control Ebola virus disease in West Africa and how to get there. PLoS Negl Trop Dis 9:e0003734

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. O’Dempsky T, Khan SH, Bausch DG (2015) Rethinking the discharge policy for Ebola convalescents in an accelerating epidemic. Am J Trop Med Hyg 92:238–239

    Article  Google Scholar 

  106. WHO Ebola Response Team (2014) Ebola virus disease in West Africa – the first 9 months of the epidemic and forward projections. N Engl J Med 371:1481–1495

    Article  PubMed Central  CAS  Google Scholar 

  107. Rao M, Bray M, Alving CR (2002) Induction of immune responses in mice and monkeys to Ebola virus after immunization with liposome-encapsulated irradiated Ebola virus: protection in mice requires CD4(+) T cells. J Virol 76:9176–9185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Geisbert TW, Pushko P, Anderson K (2002) Evaluation in nonhuman primates of vaccines against Ebola virus. Emerg Infect Dis 8:503–507

    Article  PubMed  PubMed Central  Google Scholar 

  109. Jahrling PB, Geisbert J, Swearengen JR (1996) Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses. Arch Virol Suppl 11:135–140

    CAS  PubMed  Google Scholar 

  110. Martin JE, Sullivan NJ, Enama ME (2006) A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clin Vaccine Immunol 13:1267–1277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Jeffs LB, Palmer LR, Ambegia EG (2005) A scalable, extrusion-free method for efficient liposomal encapsulation of plasmid DNA. Pharm Res 22:362–372

    Article  CAS  PubMed  Google Scholar 

  112. Sullivan NJ, Sanchez A, Rollin PE (2000) Development of a preventive vaccine for Ebola virus infection in primates. Nature 408:605–609

    Article  CAS  PubMed  Google Scholar 

  113. Ledgerwood JE, Costner P, Desai N (2010) A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine 29:304–313

    Article  CAS  PubMed  Google Scholar 

  114. Swenson DL, Wang D, Luo M (2008) Vaccine to confer to nonhuman primates complete protection against multi-strain Ebola and Marburg virus infections. Clin Vaccine Immunol 15:460–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Mellquist-Riemenschneider JL, Garrison AR, Geisbert AR (2003) Comparison of the protective efficacy of DNA and baculovirus-derived protein vaccines for EBOLA virus in guinea pigs. Virus Res 92:187–193

    Article  CAS  PubMed  Google Scholar 

  116. Konduru K, Bradfute SB, Jacques J (2011) Ebola virus glycoprotein Fc fusion protein confers protection against lethal challenge in vaccinated mice. Vaccine 29:2968–2977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Swenson DL, Warfield KL, Wenson DL (2005) Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections. Vaccine 23:3033–3042

    Article  CAS  PubMed  Google Scholar 

  118. Warfield KL, Bosio CM, Welcher BC (2003) Ebola virus-like particles protect from lethal Ebola virus infection. Proc Natl Acad Sci U S A 100:15889–15894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Warfield KL, Posten NA, Swenson DL, et al (2007) Filovirus-like particles produced in insect cells: immunogenicity and protection in rodents. J Infect Dis 196(Suppl 2):S421–S429

    Article  CAS  PubMed  Google Scholar 

  120. Hoenen T, Groseth A, De Kok-Mercado F, et al (2011) Mini-genomes, transcription and replication competent virus-like particles and beyond: reverse genetics systems for filoviruses and other negative stranded hemorrhagic fever viruses. Antivir Res 91:195–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Halfmann P, Ebihara H, Marzi A (2009) Replication-deficient ebolavirus as a vaccine candidate. J Virol 83:3810–3815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Jones SM, Feldmann H, Stroher U (2005) Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nat Med 11:786–790

    Article  CAS  PubMed  Google Scholar 

  123. Jones SM, Stroher U, Fernando L (2007) Assessment of a vesicular stomatitis virus-based vaccine by use of the mouse model of Ebola virus hemorrhagic fever. J Infect Dis 196(Suppl 2):S404–S412

    Article  CAS  PubMed  Google Scholar 

  124. Geisbert TW, Daddario-Dicaprio KM, Lewis MG (2008) Vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates. PLoS Pathog 4:e1000225

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. Qiu X, Fernando L, Alimonti J (2009) Mucosal immunization of cynomolgus macaques with the VSVDeltaG/ZEBOVGP vaccine stimulates strong ebola GP-specific immune responses. PLoS One 4:e5547

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Tsuda Y, Safronetz D, Brown K, et al (2011) Protective efficacy of a bivalent recombinant vesicular stomatitis virus vaccine in the Syrian hamster model of lethal Ebola virus infection. J Infect Dis 204(Suppl 3):S1090–S1097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Feldmann H, Jones SM, Daddario-Dicaprio KM (2007) Effective post-exposure treatment of Ebola infection. PLoS Pathog 3:e2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Henao-Restrepo AM et al (2015) Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomized trail. Lancet 386:857–866

    Article  CAS  PubMed  Google Scholar 

  129. Bukreyev A, Yang L, Zaki SR (2006) A single intranasal inoculation with a paramyxovirus-vectored vaccine protects guinea pigs against a lethal-dose Ebola virus challenge. J Virol 80:2267–2279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Bukreyev A, Rollin PE, Tate MK (2007) Successful topical respiratory tract immunization of primates against Ebola virus. J Virol 81:6379–6388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Blaney JE, Wirblich C, Papaneri AB (2011) Inactivated or live-attenuated bivalent vaccines that confer protection against rabies and Ebola viruses. J Virol 85:10605–10616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Kudoyarova-Zubavichene NM, Sergeyev NN, Chepurnov AA (1999) Preparation and use of hyperimmune serum for prophylaxis and therapy of Ebola virus infections. J Infect Dis 179(Suppl 1):S218–S223

    Article  PubMed  Google Scholar 

  133. Warren TK, Warfield KL, Wells J (2010) Antiviral activity of a small-molecule inhibitor of filovirus infection. Antimicrob Agents Chemother 54:2152–2159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Kinch MS, Yunus AS, Lear C (2009) FGI-104: a broad-spectrum small molecule inhibitor of viral infection. Am J Transl Res 1:87–98

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Aman MJ, Kinch MS, Warsfield K, et al (2009) Development of a broad-spectrum antiviral with activity against Ebola virus. Antivir Res 83:245–251

    Article  CAS  PubMed  Google Scholar 

  136. Panchal RG, Reid SP, Tran JP, et al (2012) Identification of an antioxidant small-molecule with broad-spectrum antiviral activity. Antivir Res 93:23–29

    Article  CAS  PubMed  Google Scholar 

  137. Bray M, Davis K, Geisbert T (1998) A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever. J Infect Dis 178:651–661

    Article  CAS  PubMed  Google Scholar 

  138. Agrawal N, Dasaradhi PV, Mohmmed A, et al (2003) RNA interference: biology, mechanism, and applications. Microbiol Mol Biol Rev 67:657–685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Geisbert TW, Lee AC, Robbins M, et al (2010) Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study. Lancet 375:1896–1905

    Article  CAS  PubMed  Google Scholar 

  140. Thi EP, Mire CE, Lee AC, et al (2015) Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates. Nature 521:362–365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Swenson DL, Warfield KL, Warren TK, et al (2009) Chemical modifications of antisense morpholino oligomers enhance their efficacy against Ebola virus infection. Antimicrob Agents Chemother 53:2089–2099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Enterlein S, Warfield KL, Swenson DL (2006) VP35 knockdown inhibits Ebola virus amplification and protects against lethal infection in mice. Antimicrob Agents Chemother 50:984–993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Warfield KL, Swenson DL, Olinger GG (2006) Gene-specific countermeasures against Ebola virus based on antisense phosphorodiamidate morpholino oligomers. PLoS Pathog 2:e1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Parren PW, Geisbert TW, Maruyama T, et al (2002) Pre- and postexposure prophylaxis of Ebola virus infection in an animal model by passive transfer of a neutralizing human antibody. J Virol 76:6408–6412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Murin CD, Fusco ML, Bornholdt ZA, et al (2014) Structures of protective antibodies reveal sites of vulnerability on Ebola virus. Proc Natl Acad Sci U S A 111:17182–17187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Qiu X, Wong G, Audet J, et al (2014) Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 514:47–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Mccarthy M (2014) US signs contract with ZMapp maker to accelerate development of the Ebola drug. BMJ 349:g5488

    Article  PubMed  Google Scholar 

  148. Bray M, Driscoll J, Huggins JW (2000) Treatment of lethal Ebola virus infection in mice with a single dose of an S-adenosyl-L-homocysteine hydrolase inhibitor. Antivir Res 45:135–147

    Article  CAS  PubMed  Google Scholar 

  149. Hensley LE, Stevens EL, Yan SB, et al (2007) Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever. J Infect Dis 196(Suppl 2):S390–S399

    Article  CAS  PubMed  Google Scholar 

  150. Marlar RA, Kleiss AJ, Griffin JH (1981) Human protein C: inactivation of factors V and VIII in plasma by the activated molecule. Ann N Y Acad Sci 370:303–310

    Article  CAS  PubMed  Google Scholar 

  151. Sakata Y, Curriden S, Lawrence D, et al (1985) Activated protein C stimulates the fibrinolytic activity of cultured endothelial cells and decreases antiactivator activity. Proc Natl Acad Sci U S A 82:1121–1125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Geisbert TW, Young HA, Jahrling PB, et al (2003) Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis 188:1618–1629

    Article  CAS  PubMed  Google Scholar 

  153. Geisbert TW, Hensley LE, Jahrling PB, et al (2003) Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet 362:1953–1958

    Article  CAS  PubMed  Google Scholar 

  154. Furuta Y, Takahashi K, Fukuda Y, et al (2002) In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob Agents Chemother 46:977–981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Furuta Y, Gowen BB, Takahashi K (2013) Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antivir Res 100:446–454

    Article  CAS  PubMed  Google Scholar 

  156. Baranovich T, Wong SS, Armstrong J, et al (2013) T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J Virol 87:3741–3751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Gowen BB, Wong MH, Jung KH, et al (2007) In vitro and in vivo activities of T-705 against arenavirus and bunyavirus infections. Antimicrob Agents Chemother 51:3168–3176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Ostereich L, Ludtke A, Wurr S, et al (2014) Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antivir Res 105:17–21

    Article  CAS  Google Scholar 

  159. Sissoko D et al (2016) Experimental treatment with Favipiravir for Ebola virus disease (the JIKI trail): a historically controlled, single-arm proof-of-concept trail in Guinea. PLoS Med 13(3):e1001967. doi:10.1371/journal.pmed.1001967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Kamat SS, Burgos ES, Raushel FM (2013) Potent inhibition of the C-P lyase nucleosidase PhnI by Immucillin-A triphosphate. Biochemistry 52:7366–7368

    Article  CAS  PubMed  Google Scholar 

  161. Warren TK, Wells J, Panchal RG, et al (2014) Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature 508:402–405

    Article  CAS  PubMed  Google Scholar 

  162. Johansen LM, Brannan JM, Delos SE, et al (2013) FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection. Sci Transl Med 5:190ra79

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  163. Bishop BM (2015) Potential and emerging treatment options for Ebola virus disease. Ann Pharmacother 49:196–206

    Article  CAS  PubMed  Google Scholar 

  164. Madrid PB, Chopra S, Manger ID, et al (2013) A systematic screen of FDA-approved drugs for inhibitors of biological threat agents. PLoS One 8:e60579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. De Lamballerie X, Boisson V, Reynier JC, et al (2008) On chikungunya acute infection and chloroquine treatment. Vector Borne Zoonotic Dis 8:837–839

    Article  PubMed  Google Scholar 

  166. Huggins JW (1989) Prospects for treatment of viral hemorrhagic fevers with ribavirin, a broad-spectrum antiviral drug. Rev Infect Dis 11(Suppl 4):S750–S761

    Article  CAS  PubMed  Google Scholar 

  167. Mendoza EJ et al (2016) Progression of Ebola therapeutics during the 2014-2015 outbreak. Trends Mol Med 22:164–173

    Article  PubMed  Google Scholar 

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Acknowledgment

We would like to thank Dr. Mikiko Senga, Epidemiology, World Health Organization (WHO), for her invaluable inputs in the epidemiology section of the chapter and her guidance during chapter preparation.

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Authors and Affiliations

  1. Clinical Praxis, Schulstrasse 36, Hilden, 40721, Germany

    Aaruni Saxena

  2. Health Service Research, Rede Metropolitana de Saúde, Sarandí, Brazil

    Mauricio Ferri

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  1. Aaruni Saxena
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  2. Mauricio Ferri
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Correspondence to Mauricio Ferri .

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  1. Division of Medicinal & Process Chemistry, Central Drug Research Institute, Lucknow, Uttar Pradesh, India

    Anil Kumar Saxena

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Saxena, A., Ferri, M. (2015). Clinical Management of Ebola Virus Disease: Current and Future Approaches. In: Saxena, A. (eds) Communicable Diseases of the Developing World. Topics in Medicinal Chemistry, vol 29. Springer, Cham. https://doi.org/10.1007/7355_2015_5003

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