Hemorrhagic Fever Viruses as Biological Weapons

  • Allison Groseth
  • Steven Jones
  • Harvey Artsob
  • Heinz Feldmann
Part of the Emerging Infectious Diseases of the 21st Century book series (EIDC)

7. Conclusions

In addition to causing illness and death, a biological attack would aim to cause fear in the general populace and, thus, result in social and economic disruption. Based on their fearsome reputation and dramatization by the popular media, VHF agents would be excellent candidates to serve this purpose. Given the potential for a biological attack to occur, it is of the utmost importance that resources and knowledge are made available to deal effectively with such a situation in a safe and timely manner.


Nonhuman Primate Hemorrhagic Fever Rift Valley Fever Rift Valley Fever Virus Biological Weapon 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Alibek, K., and Handelman, S. (1999). Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World, Told from the Inside by the Man Who Ran It. Random House, New York.Google Scholar
  2. Bazhutin, N., Belanov, E., Spiridonov, V., Voitenko, A., Krivenchuk, N., Krotov, S., Omel’chenko, N., Tereshchenko, A., and Khomichev, V. (1992). The effect of the methods for producing an experimental Marburg virus infection on the characteristics of the course of the disease in green monkeys. Vopr. Virusol. 37:153–156.PubMedGoogle Scholar
  3. Belanov, E., Muntianov, V., Kriuk, V., Sokolov, A., Bormotov, N., P’iankov, O., and Sergeev, A. (1996). Survival of Marburg virus infectivity on contaminated surfaces and in aerosols. Vopr. Virusol. 41:32–34.PubMedGoogle Scholar
  4. Borio, L., Inglesby, T., Peters, C., Schmaljohn, A., Hughes, J., Jahrling, P., Ksiazek, T., Johnson, K., Meyerhoff, A., Toole, T., Ascher, M., Bartlett, J., Breman, J., Eitzen, E. Jr., Hamburg, M., Hauer, J., Henderson, D., Johnson, R., Kwik, G., Layton, M., Lillibridge, S., Nabel, G., Osterholm, M., Perl, T., Russell, P., and Tonat, K. [Working Group on Civilian Biodefense]. (2002). Hemorrhagic fever viruses as biological weapons: medical and public health management. J.A.M.A. 287:2391–2405.PubMedGoogle Scholar
  5. Bray, M., Davis, K., Geisbert, T., Schmaljohn, C., and Huggins, J. (1998). A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever. J. Infect. Dis. 178:651–661.PubMedGoogle Scholar
  6. Brown, J., Dominik, J., and Morrissey, R. (1981). Respiratory infectivity of a recently isolated Egyptian strain of Rift Valley fever virus. Infect. Immun. 33:848–853.PubMedGoogle Scholar
  7. Buckley, S., and Casals, J. (1970). Lassa fever, a new virus disease of man from West Africa. 3. Isolation and characterization of the virus. Am. J. Trop. Med. Hyg. 19:680–691.PubMedGoogle Scholar
  8. Center for Nonproliferation Studies. (2000). Chemical and biological weapons: Possession and programs past and present. Google Scholar
  9. Centers for Disease Control and Prevention. (2001). Outbreak of Ebola hemorrhagic fever, Uganda, August 2000–January 2001. MMWR Morb. Mort. Wkly. Rep. 50:73–77.Google Scholar
  10. Centers for Disease Control and Prevention. (1994). Arenavirus infection—Connecticut, 1994. MMWR Morb. Mort. Wkly. Rep. 43:635–636.Google Scholar
  11. Centers for Disease Control and Prevention (2000). Biological and chemical terrorism: Strategic plan for preparedness and response. Recommendations of the CDC Strategic Planning Workgroup. MMWR Recomm. Rep. 49:1–14.Google Scholar
  12. Colebunders, R., and Borchert, M. (2000). Ebola haemorrhagic fever-a review. J. Infect. 40:16–20.PubMedCrossRefGoogle Scholar
  13. Cosgriff, T., Morrill, J., Jennings, G., Hodgson, L., Slayter, M., Gibbs, P., and Peters, C. (1989). Hemostatic derangement produced by Rift Valley fever virus in rhesus monkeys. Rev. Infect. Dis. 11(Suppl 4):S807–S814.PubMedGoogle Scholar
  14. Cummins, D., Bennett, D., Fisher-Hoch, S., Farrar, B., Machin, S., and McCormick, J. (1992). Lassa fever encephalopathy: clinical and laboratory findings. J. Trop. Med. Hyg. 9:197–201.Google Scholar
  15. Cummins, D., McCormick, J., Bennett, D., Samba, J., Farrar, B., Machin, S., and Fisher-Hoch, S. (1990a). Acute sensorineural deafness in Lassa fever. J.A.M.A. 264:2119.Google Scholar
  16. Cummins, D., Molinas, F., Lerer, G., Maiztegui, J., Faint, R., and Machin, S. (1990b). A plasma inhibitor of platelet aggregation in patients with Argentine hemorrhagic fever. Am. J. Trop. Med. Hyg. 42:470–475.PubMedGoogle Scholar
  17. de Bracco, M., Rimoldi, M., Cossio, P., Rabinovich, A., Maiztegui, J., Carballal, G., and Arana, R. (1978). Argentine hemorrhagic fever. Alterations of the complement system and anti-Junin-virus humoral response. N. Engl. J. Med. 299:216–221.PubMedCrossRefGoogle Scholar
  18. Dowell, S., Mukunu, R., Ksiazek, T., Kahn, A., Rollin, P., and Peters, C. (1995). Transmission of Ebola hemorrhagic fever: a study of risk factors in family members, Kikwit, Democratic Republic of the Congo. J. Infect. Dis. 179(Suppl 1): S87–S91.Google Scholar
  19. Enria, D., Briggiler, A., Fernandez, N., Levis, S., and Maiztegui, J. (1984). Importance of dose of neutralising antibodies in treatment of Argentine haemorrhagic fever with immune plasma. Lancet 2:255–256.PubMedCrossRefGoogle Scholar
  20. Enria, D., and Maiztegui, J. (1994). Antiviral treatment of Argentine hemorrhagic fever. Antiviral Res. 23:23–31.PubMedCrossRefGoogle Scholar
  21. Feldmann, H., Jones, S., Klenk, H.-D., and Schnittler, H. (2003). Ebola virus: from discovery to vaccine. Nat. Rev. Immunol. 3:677–685.PubMedCrossRefGoogle Scholar
  22. Fisher-Hoch, S., Platt, G., Neild, G., Southee, T., Baskerville, A., Raymond, R., Lloyd, G., and Simpson, D. (1985). Pathophysiology of shock and hemorrhage in a fulminating viral infection (Ebola). J. Infect. Dis. 152:887–894.PubMedGoogle Scholar
  23. Frame, J., Verbrugge, G., Gill, R., and Pinneo, L. (1984). The use of Lassa fever convalescent plasma in Nigeria. Trans. R. Soc. Trop. Med. Hyg. 78:319–324.PubMedCrossRefGoogle Scholar
  24. Garbutt, M., Liebscher, R., Wahl-Jensen, V., Jones, S., Moeller, P., Wagner, R., Volchkov, V., Klenk, H.D., Feldmann, H., and Stroeher, U. (2004). Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses. J. Virol. 78:5458–5465.PubMedCrossRefGoogle Scholar
  25. Gargan, T. 2nd, Clark, G., Dohm, D., Turell, M., and Bailey, C. (1988). Vector potential of selected North American mosquito species for Rift Valley fever virus. Am. J. Trop. Med. Hyg. 38:440–446.PubMedGoogle Scholar
  26. Geisbert, T., Hensley, L., Jahrling, P., Larsen T., Geisbert, J., Paragas, J., Young, H., Fredeking, T., Rote, W., and Vlasuk, G. (2003). Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet 362:1953–1958.PubMedCrossRefGoogle Scholar
  27. Geisbert, T., Pushko, P., Anderson, K., Smith, J., Davis, K., and Jahrling, P. (2002). Evaluation in nonhuman primates of vaccines against Ebola virus. Emerg. Infect. Dis. 8:503–507.PubMedGoogle Scholar
  28. Global Proliferation of Weapons of Mass Destruction (1996). Hearings Before the Permanent Subcommittee on Investigations of the Committee on Governmental Affairs, United States Senate, 104th Cong, 1st and 2nd Sess.Google Scholar
  29. Harrison, L., Halsey, N., McKee, K., Peters, C., Barrera Oro, J., Briggiler, A., Feuillade, M., Maiztegui, J. (1999). Clinical case definitions for Argentine hemorrhagic fever. Clin. Infect. Dis. 28:1091–1094.PubMedGoogle Scholar
  30. Hart, M. (2003). Vaccine research efforts for filoviruses. Int. J. Parasitol. 33:583–595.PubMedCrossRefGoogle Scholar
  31. Hensley, L., Young, H., Jahrling, P., and Geisbert, T. (2002). Proinflammatory response during Ebola virus infection of primate models: possible involvement of the tumor necrosis factor receptor superfamily. Immunol. Lett. 80:169–179.PubMedCrossRefGoogle Scholar
  32. Huggins, J. (1989). Prospects for treatment of viral hemorrhagic fevers with ribavirin, a broad-spectrum antiviral drug. Rev. Infect. Dis. 11(Suppl 4):S750–S761.PubMedGoogle Scholar
  33. Huggins, J., Zhang, Z., and Bray, M. (1999). Antiviral drug therapy of filovirus infections: S-adenosylhomocysteine hydrolase inhibitors inhibit Ebola virus in vitro and in a lethal mouse model. J. Infect. Dis. 179(Suppl 1):S240–S247.PubMedGoogle Scholar
  34. Jaax, N., Davis, K., Geisbert, T., Vogel, P., Jaax, G., Topper, M., and Jahrling, P. (1996). Lethal experimental infection of rhesus monkeys with Ebola-Zaire (Mayinga) virus by the oral and conjunctival route of exposure. Arch. Pathol. Lab. Med. 120:140–155.PubMedGoogle Scholar
  35. Jahrling, P., Peters, C., and Stephen, E. (1984). Enhanced treatment of Lassa fever by immune plasma combined with ribavirin in cynomolgus monkeys. J. Infect. Dis. 149:420–427.PubMedGoogle Scholar
  36. Johnson, K., Kuns, M., Mackenzie, R., Webb, P., and Yunker, C. (1966). Isolation of Machupo virus from wild rodent Calomys callosus. Am. J. Trop. Med. Hyg. 15:103–106.PubMedGoogle Scholar
  37. Johnson, K., Mackenzie, R., Webb, P., and Kuns, M. (1965). Chronic infection of rodents by Machupo virus. Science. 150:1618–1619.PubMedGoogle Scholar
  38. Jones, S., Geisbert, T., Ströher, U., Geisbert, J., Bray, M., Jahrling, P., Geisbert, T., and Feldmann, H. (2003). Replicating vectors for vaccine development. Symposium on Viral hemorrhagic Fevers, Vaccine Research Center, NIAID, NIH, DHHS, Bethesda, Md.Google Scholar
  39. Jouan, A., Coulibaly, I., Adam, F., Philippe, B., Riou, O., Leguenno, B., Christie, R., Ould Merzoug, N., Ksiazek, T., and Digoutte, J. (1989). Analytical study of a Rift Valley fever epidemic. Res. Virol. 140:175–186.PubMedGoogle Scholar
  40. Kaplan, D. (2000). Aum Shinrikyo. In: Tucker, J. (ed.), Toxic Terror: Assessing Terrorist Use of Chemical and Biological Weapons. MIT Press, Cambridge, mass., pp. 207–226.Google Scholar
  41. Kenyon, R., McKee, K. Jr., Zack, P., Rippy, M., Vogel, A., York, C., Meegan, J., Crabbs, C., and Peters, C. (1992). Aerosol infection of rhesus macaques with Junin virus. Intervirology 33:23–31.PubMedGoogle Scholar
  42. Knobloch, J., McCormick, J., Webb, P., Dietrich, M., Schumacher, H., and Dennis, E. (1980). Clinical observations in 42 patients with Lassa fever. Tropenmed. Parasitol. 31:389–398.PubMedGoogle Scholar
  43. LeDuc, J. (1989). Epidemiology of hemorrhagic fever viruses. Rev. Infect. Dis. 11(Suppl 4):S730–S735.PubMedGoogle Scholar
  44. Maiztegui, J., McKee, K. Jr., Barrera Oro J., Harrison, L., Gibbs, P., Feuillade, M., Enria, D., Briggiler, A., Levis, S., Ambrosio, A., Halsey, N., and Peters, C. (1998). Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever. AHF Study Group. J. Infect. Dis. 177:277–283.PubMedCrossRefGoogle Scholar
  45. Martini, G. (1969). Marburg agent disease in man. Trans. R. Soc. Trop. Med. Hyg. 63:295–302.PubMedCrossRefGoogle Scholar
  46. McCormick, J., King, I., Webb, P., Johnson, K., O’Sullivan, R., Smith, E., Trippel, S., and Tong, T. (1987). A case-control study of the clinical diagnosis and course of Lassa fever. J. Infect. Dis. 155:445–455.PubMedGoogle Scholar
  47. McKee, K. Jr., Huggins, J., Trahan, C., and Mahlandt, B. (1988). Ribavirin prophylaxis and therapy for experimental argentine hemorrhagic fever. Antimicrob. Agents Chemother. 32:1304–1309.PubMedGoogle Scholar
  48. Meegan J., and Shope, R. (1981). Emerging concepts on Rift Valley fever. Perspect. Virol. 11:267–387.Google Scholar
  49. Miller, J., Engelberg, S., and Broad, W. (2002). Germs: Biological Weapons and America’s Secret War. GK Hall, Waterville, Me.Google Scholar
  50. Murphy, F., Simpson, D., Whitfield, S., Zlotnik, I., and Carter, G. (1971). Marburg virus infection in monkeys. Ultrastructural studies. Lab. Invest. 24:279–291.PubMedGoogle Scholar
  51. Neumann, G., Feldmann, H., Watanabe, S., Lukashevich, I., and Kawaoka, Y. (2002). Reverse genetics demonstrates that proteolytic processing of the Ebola virus glycoprotein is not essential for replication in cell culture. J. Virol. 76:406–410.PubMedCrossRefGoogle Scholar
  52. Peters, C., Jones, D., Trotter, R., Donaldson, J., White, J., Stephen, E., and Slone, T. Jr. (1988). Experimental Rift Valley fever in rhesus macaques. Arch. Virol. 99:31–44.PubMedCrossRefGoogle Scholar
  53. Peters, C., Liu, C., Anderson, G. Jr, Morrill, J., and Jahrling, P. (1989). Pathogenesis of viral hemorrhagic fevers: Rift Valley fever and Lassa fever contrasted. Rev. Infect. Dis. 11(Suppl 4):S743–S749.PubMedGoogle Scholar
  54. Peters, C., and Zaki, S. (2002). Role of the endothelium in viral hemorrhagic fevers. Crit. Care Med. 30(Suppl 5):S268–S273.PubMedCrossRefGoogle Scholar
  55. Pittman, P., Liu, C., Cannon, T., Makuch, R., Mangiafico, J., Gibbs, P., and Peters, C. (1999). Immunogenicity of an inactivated Rift Valley fever vaccine in humans: a 12-year experience. Vaccine 18:181–189.PubMedCrossRefGoogle Scholar
  56. Rodriguez, L., De Roo, A., Guimard, Y., Trappier, S., Sanchez, A., Bressler, D., Williams, A., Rowe, A., Bertolli, J., Khan, A., Ksiazek, T., Peters, C., and Nichol, S. (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):S170–S176.PubMedGoogle Scholar
  57. Roels, T., Bloom, A., Buffington, J., Muhungu, G., MacKenzie, W., Khan, A., Ndambi, R., Noah, D., Rolka, H., Peters, C., and Ksiazek, T. (1999). Ebola hemorrhagic fever, Kikwit, Democratic Republic of the Congo, 1995: risk factors for patients without a reported exposure. J. Infect. Dis. 179(Suppl 1):S92–S97.PubMedGoogle Scholar
  58. Samoilovich, S., Carballal, G., and Weissenbacher, M. (1983). Protection against a pathogenic strain of Junin virus by mucosal infection with an attenuated strain. Am. J. Trop. Med. Hyg. 32:825–828.PubMedGoogle Scholar
  59. Schnittler, H., and Feldmann, H. (2003). Viral hemorrhagic fever — a vascular disease. Thromb. Haemost. 89:967–972.PubMedGoogle Scholar
  60. Schnittler, H., and Feldmann, H. (1998). Marburg and Ebola hemorrhagic fevers: does the primary course of infection depend on the accessibility of organ-specific macrophages? Clin. Infect. Dis. 27:404–406.PubMedCrossRefGoogle Scholar
  61. Simpson, D. (1969). Marburg agent disease. Trans. R. Soc. Trop. Med. Hyg. 63:303–309.PubMedCrossRefGoogle Scholar
  62. Slenczka, W. (1999). The Marburg virus outbreak of 1967 and subsequent episodes. Curr. Top. Microbiol. Immunol. 235:49–75.PubMedGoogle Scholar
  63. Smithburn, K., Mahaffy, A., Haddow, A., Kitchen, S., and Smith, J. (1949). Rift Valley fever: accidental infection among laboratory workers. J. Immunol. 62:213–227.PubMedGoogle Scholar
  64. Stephenson, E., Larson, E., Dominik, J. (1984). Effect of environmental factors on aerosol-induced Lassa virus infection. J. Med. Virol. 14:295–303.PubMedGoogle Scholar
  65. Ströher, U., West, E., Bugany, H., Klenk, H.-D., Schnittler, H., and Feldmann, H. (2001). Infection and activation of monocytes by Marburg and Ebola viruses. J. Virol. 75:11025–11033.PubMedCrossRefGoogle Scholar
  66. Sullivan, N., Geisbert, T., Geisbert, J., Xu, L., Yang, Z., Roederer, M., Koup, R., Jahrling, P., and Nabel, G. (2003). Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates. Nature 424:681–684.PubMedCrossRefGoogle Scholar
  67. Sullivan, N., Sanchez, A., Rollin, P., Yang, Z., and Nabel, G. (2000). Development of a preventive vaccine for Ebola virus infection in primates. Nature. 408:605–609.PubMedCrossRefGoogle Scholar
  68. Swanapoel, R., and Coetzer, J. (1994). Rift Valley Fever. In: Infectious Diseases of Livestock With Special Reference to Southern Africa. New York, Oxford University Press.Google Scholar
  69. Swanepoel, R., Shepherd, A., Leman, P., Shepherd, S., McGillivray, G., Erasmus, M., Searle, L., and Gill, D. (1987). Epidemiologic and clinical features of Crimean-Congo hemorrhagic fever in southern Africa. Am. J. Trop. Med. Hyg. 36:120–32.PubMedGoogle Scholar
  70. ter Meulen, J., Lukashevich, I., Sidibe, K., Inapogui, A., Marx, M., Dorlemann, A., Yansane, M., Koulemou, K., Chang-Claude, J., and Schmitz, H. (1996). Hunting of peridomestic rodents and consumption of their meat as possible risk factors for rodent-to-human transmission of Lassa virus in the Republic of Guinea. Am. J. Trop. Med. Hyg. 55:661–666.PubMedGoogle Scholar
  71. Vainrub B, and Salas R. (1994). Latin American hemorrhagic fever. Infect. Dis. Clin. North. Am. 8:47–59.PubMedGoogle Scholar
  72. van Eeden, P., van Eeden, S., Joubert, J., King, J., van de Wal, B., and Michell, W. (1985). A nosocomial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part II. Management of patients. S. Afr. Med. J. 68:718–721.PubMedGoogle Scholar
  73. Villinger, F., Rollin, P., Brar, S., Chikkala, N., Winter, J., Sundstrom, J., Zaki, S., Swanepoel, R., Ansari, A., and Peters, C. (1999). Markedly elevated levels of interferon (IFN)-gamma, IFN-alpha, interleukin (IL)-2, IL-10, and tumor necrosis factor-alpha associated with fatal Ebola virus infection. J. Infect. Dis. 179(Suppl 1):S188–S191.PubMedGoogle Scholar
  74. Volchkov, V., Volchkova, V., Muhlberger, E., Kolesnikova, L., Weik, M., Dolnik, O., and Klenk, H.-D. (2001). Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP gene and viral cytotoxicity. Science 291:1965–1969.PubMedCrossRefGoogle Scholar
  75. World Health Organization. (1978). Ebola hemorrhagic fever in Zaire, 1976. Bull. World Health Org. 56:271–293.Google Scholar
  76. Zaki, S., and Goldsmith, C. (1999). Pathologic features of filovirus infection in humans. Curr. Top. Microbiol. Immunol. 235:97–115.PubMedGoogle Scholar
  77. Zaki, S., Shieh, W., Greer, P., Goldsmith, C., Ferebee, T., Katshitshi, J., Tshioko, F., Bwaka, M., Swanepoel, R., Calain, P., Khan, A., Lloyd, E., Rollin, P., Ksiazek, T., and Peters, C. (1999). A novel immunohistochemical assay for the detection of Ebola virus in skin: implications for diagnosis, spread, and surveillance of Ebola hemorrhagic fever. J. Infect. Dis. 179(Suppl 1):S36–S47.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Allison Groseth
    • 1
  • Steven Jones
    • 1
  • Harvey Artsob
    • 1
  • Heinz Feldmann
    • 1
  1. 1.National Laboratory for Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Health Canada, Canadian Science Centre for Human and Animal Health, Department of Medical MicrobiologyUniversity of ManitobaWinnipegCanada

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