Abstract
The use of microorganisms as agents of biological warfare is considered inevitable for several reasons, including ease of production and dispersion, delayed onset, ability to cause high rates of morbidity and mortality, and difficulty in diagnosis. Biological agents that have been identified as posing the greatest threat are variola major (smallpox), Bacillus anthracis (anthrax), Yersinia pestis (plague), Clostridium botulinum toxin (botulism), Francisella tularensis (tularaemia), filoviruses (Ebola hemorrrhagic fever and Marburg hemorrhagic fever), and arenaviruses Lassa (Lassa fever) and Junin (Argentine hemorrhagic fever). The pathogenesis, clinical manifestations, diagnosis, and treatment of these agents are discussed. Rapid identification and diagnosis using molecular diagnostic techniques such as PCR is an essential element in the establishment of coordinated laboratory response systems and is the focus of current research and development. Molecular techniques for detection and identification of these organisms are reviewed.
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Davis CJ: Nuclear blindness: An overview of the biological weapons programs of the former Soviet Union and Iraq. Emerg Infect Dis 1999;5:509–512
George GW, Cieslak TJ, Pavlin JA, Eitzen EM: Biological warfare: A historical perspective. JAMA 1997;278:412–417
Torok TJ: A large community outbreak of salmonellosis caused by intentional contamination of restaurant salad bars. JAMA 1997;278:389–395
Okumura T, Takasu N, Ishimatsu S, et al.: Report on 640 victims of the Tokyo subway sarin attack. Ann Emerg Med 1996;28:129–135
Committee on Environmental Health and Committee on Infectious Diseases: Chemical—biological terrorism and its impact on children: A subject review. Pediatrics 2000;105:662–670
Centers for Disease Control and Prevention: Biological and chemical terrorism: Strategic plan for preparedness and response. Recommendations of the CDC Strategic Planning Workgroup. MMWR Morb Mortal Wkly Rep 2000;49:1–14
Franz DR, Jahrling PB, Friedlander AM, et al.: Clinical recognition and management of patients exposed to biological warfare agents. JAMA 1997;278:399–410
Jortani SA, Snyder JW, Valdes R: The role of the clinical laboratory in managing chemical or biological terrorism. Clin Chem 2000;46:1883–1893
Kortepeter MG, Parker GW: Potential biological weapons threats. Emerg Infect Dis 1999;5:523–527
Cieslak TJ, Eitzen EM: Clinical and epidemiologic principles of anthrax. Emerg Infect Dis 1999;5:552–555
Office of Technology Assessment, US Congress. Proliferation of weapons of mass destruction. Publication OTA-ISC-559. U.S. Government Printing Office, Washington, DC, 1993, pp. 53–55
Meselson M, Guilllimin J, Hugh-Jones M, et al.: The Sverdlovsk anthrax outbreak of 1979. Science 1994;266:1202–1208
Inglesby TV, Henderson DA, Bartlett JF, et al.: Anthrax as a biological weapon: medical and public health management. JAMA 1999;281:1735–1745
Dixon TC, Meselson M, Guillemin J, Hanna PC: Medical progress: Anthrax. N Engl J Med 1999;341:815–826
Pile JC, Malone JD, Eitzen EM, Friedlander AM: Anthrax as a potential biological warfare agent. Arch Intern Med 1998;158:420 34
Zoon K: Vaccines, pharmaceutical products, and bioterrorism: Challenges for the U.S. Food and Drug Administration. Emerg Infect Dis 1999;5:534–536
Russell PK: Vaccines in civilian defense against bioterrorism. Emerg Infect Dis 1999;5:531–533
Kortepeter M, Christopher G, Cieslak T, et al.: USAMRIID’s medical management of biological casualties handbook, 4th ed. U.S. Government Printing Office, Washington, DC, 2001 (http://www.usamriid.army.mil/education/bluebook.html)
Stepanov AV, Marinin LI, Pomerantsev AP, Staritsin NA: Development of novel vaccines against anthrax in man. J Biotechnol 1996;44:155–160
Knisely RF: Selective medium for Bacillus anthracis. J Bacteriol 1996;92:784–786
Higgins JA, Ibrahim MS, Knauert FK, et al.: Sensitive and rapid identification of biological threat agents. Ann N Y Acad Sci 1999;894:130–148
Ibrahim MS, Lofts RS, Jahrling PB, et al.: Real-time microchip PCR for detecting single-base differences in viral and human DNA. Anal Chem 1998;70:2013–2017
Belgrader P, Benett W, Hadley D, et al.: Rapid pathogen detection using a microchip PCR array instrument. Clin Chem 1998;44:2191–2194
What’s new in NAI (nonproliferation, arms control, and international security). http://www.llnl.gov/nai/new.html (accessed 4/12/01)
Lawrence Livermore National Laboratory: New Technologies Engineering Division. http://www.llnl.gov/nai/new.html (accessed 4/12/01)
Arita I: Virological evidence for the success of the smallpox eradication programme. Nature 1979;279:293–298
Alibek K: Biohazard. Random House, Inc, New York, NY, 1999
Henderson DA, Inglesby TV, Bartlett JG, et al.: Smallpox as a biological weapon: Medical and public health management. JAMA 1999;281:2127–2137
Henderson DA: Smallpox: Clinical and epidemiologic features. Emerg Infect Dis 1999;5:537–539
Ropp SL, Knight JC, Massung RF, Esposito JJ: PCR strategy for identification and differentiation of smallpox and other orthopoxviruses. J Clin Microbiol 1995;33:2069–2076
Meyer H, Ropp SL, Esposito JJ: Gene for A-type inclusion body protein is useful for a polymerase chain reaction assay to differentiate orthopoxviruses. J Virol Methods 1997;64:217–221
Neubauer H, Reischl U, Ropp S, Esposito JJ, Wolf H, Meyer H: Specific detection of monkeypox virus by polymerase chain reaction. J Virol Methods 1998;74:201–207
Ibrahim MS, Esposito JJ, Jahrling PB, Lofts RS: The potential of 5′ nuclease PCR for detecting a single-base polymorphism in orhtopoxvirus. Mol Cell Probes 1997;11:143–147
The Johns Hopkins University Center for Civilian Biodefense Studies. http://www.llnl.gov/nai/new.html (accessed 4/12/01)
The Johns Hopkins University Center for Civilian Biodefense Studies: Meeting of the WHO Variola Research Committee unofficial memo. http://www.llnl.gov/nai/new.html (accessed 4/12/01)
Slack P: The black death past and present. Trans R Soc Trop Med Hyg 1989;83:461–463
Inglesby TV, Dennis DT, Henderson DA, et al.: Plague as a biological weapon: medical and public health management. JAMA 2000;283:2281–2290
Cornelis GR: Molecular and cell biology aspects of plague. Proc Natl Acad Sci U S A 2000;97:8778–8783
Centers for Disease Control and Prevention: Fatal human plague. MMWR Morb Mortal Wkly Rep 1997;278:380–382
Higgins JA, Ezzell J, Hinnebusch BJ, Shipley M, Henchal EA, Ibrahim MS: 5′ nuclease PCR assay to detect Yersinia pestis. J Clin Microbiol 1998;36:2284–2288
Cherington M: Clinical spectrum of botulism. Muscle Nerve 1998;21:701–710
McGrath S, Dooley JS, Haylock RW: Quantification of Clostridium botulinum toxin gene expression by competitive reverse transcription-PCR. Appl Environ Microbiol 2000;66:1423–1428
Williamson JL, Rocke TE, Aiken JM: In situ detection of the Clostridium botulinum type c1 toxin gene in wetland sediments with a nested PCR assay. Appl Environ Microbiol 1999;65:3240–3243
Kakinuma H, Muruyama H, Yamakawa K, Nakamura S, Takahashi H: Application of nested polymerase chain reaction for the rapid diagnosis of infant botulism type B. Acta Paediatr Jpn 1997;39:346–348
Aranda E, Rodriguez MM, Asensio MA, Cordoba JJ: Detection of Clostridium botulinum types A, B, E and F in foods by PCR and DNA probe. Lett Appl Microbiol 1997;25:186–190
Lindstrom MK, Jankol HM, Hielm S, Hyytia EK, Korkeala HJ: Identification of Clostridium botulinum with API 20 A, Rapid ID 32 A and RapID ANA II. FEMS Immunol Med Microbiol 1999;24:267–274
Cieslak TJ, Christopher GW, Kortepeter MG, et al.: Immunization against potential biological warfare agents. Clin Infect Dis 2000;30:843–850
Dolan SA, Dommaraju CB, DeGuxman GB: Detection of Francisella tularensis in clinical specimens by use of polymerase chain reaction. Clin Infect Dis 1998;26:764–765
Johansson A, Berglund L, Eriksson U, et al.: Comparative analysis of PCR versus culture for diagnosis of ulceroglandular tularemia. J Clin Microbiol 2000;38:22–26
Higgins JA, Hubalek A, Halouzka J, et al.: Detection of Francisella tularensis in infected mammals and vectors using a probe-based polymerase chain reaction. Am J Trop Med Hyg 2000;62:310–318
Zaki SR, Goldsmith CS: Pathologic features of filovirus infections in humans. Curr Top Microbiol Immunol 1999;235:97–116
Feldmann H, Kiley MP: Classification, structure, and replication of filoviruses. Curr Top Microbiol Immunol 1999;235:1–21
Khan AS, Sanchez A, Pflieger AK: Filoviral haemorrhagic fevers. Br Med Bull 1998;54:675–692
Yang ZY, Duckers HJ, Sullivan NJ, Sanchez A, Nabel EG, Nabel GJ: Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury. Nat Med 2000;6:886–889
Peters CJ, Khan AS: Filovirus diseases. Curr Top Microbiol Immunol 1999;235:85–95
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Broussard, L.A. Biological Agents: Weapons of Warfare and Bioterrorism. Molecular Diagnosis 6, 324–333 (2001). https://doi.org/10.1007/BF03262068
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DOI: https://doi.org/10.1007/BF03262068