Medical Aspects of Biological Warfare · 2020. 6. 30. · paramyxovirus infections, 669 Q fever...

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xxx Medical Aspects of Biological Warfare A Abbreviations, xxvii–xxxi “ABCDE” algorithm, 116 Abortions, septic Brucella and, 162–163 ACAM2000 vaccine, 115, 631–632 ACB. See Acinetobacter baumannii Acellular vaccines, 235 Acinetobacter baumannii antibiotic resistance, 328 characterization and identification of source, 327–328 epidemiological consultation, 324–327 genetic analysis, 327–328 historical perspectives, 322–324 inclusion in ESKAPE pathogens, 322, 328–332 molecular analysis, 327–328 strain collection and sampling, 327 U.S. Military Health System response, 328–332 Acronyms, xxvii–xxxi Active immunization alphavirus encephalitides, 498–501 Acute respiratory distress syndrome, 663–664 Adjuvants, vaccines, 831–832 Advanced Trauma Life Support, 110, 116, 117 Advisory Commiee on Immunization Practices, 141 Aerobiology biological aerosol exposure systems, 860–864 clinical applications in the U.S., 857–860 conceptual basis of, 857 dosimetry, 863 exposure chambers, 862 exposure systems, 860–862 generators, 861–862 Henderson apparatus, 861 monitoring and control, 862–863 offensive biological development in the U.S., 857–860 overview, 856–857 parameters impacting aerosol dosimetry, 863–864 sampling, 862 Aerosol dosimetry, 863–864 Afghanistan Acinetobacter infections, 322, 323, 324–327 Al Qaeda biological warfare program, 15 Q fever outbreak, 307 ricin as biological weapon research, 376 Aflatoxins, 443, 445 Africa Chikungunya outbreak, 674 Ebola virus epidemic, 677–678 African milk bush, 79 Agency for Healthcare Research and Quality, 329 Agent Orange, 79 Agent X, 338 Agglutination tests, 165 Agricultural terrorism, 78–80 Air Force field laboratories, 706 Al Qaeda biological warfare program, 15, 16–17 Alcide EXSPORE, 883 Alibek, Dr. Kenneth, 254, 339 Alibekov, Colonel Kanatjan, 254, 339 Alphavirus encephalitides active immunization, 498–501 antigenicity, 483–486 clinical disease, 492–496 diagnosis of, 492–496 differential diagnosis of, 495–496 eastern equine encephalitis, 484–485, 493–494 epidemiology and ecology, 486–488 genetic relationships, 483–486 historical perspectives, 481–483 immune effector mechanisms, 496–497 immunoprophylaxis, 496–501 medical countermeasures, 773–776 medical management, 496 passive immunization, 497–498 pathogenesis, 490–492 prevention of, 496 replication of, 488––490 significance of, 482–483 therapeutics, 501 Venezuelan equine encephalitis, 483–484, 485, 492–493, 773–774 virion structure, 488––490 western equine encephalitis, 484, 485–486, 494–495 American Biological Safety Association, 889–890 Aminoglycoside toxicity differentiating from botulism, 343 Aminoglycosides brucellosis treatment, 166–167 AML. See Area Medical Laboratory Amnesic shellfish poisoning description of toxin, 467–468 diagnosis of, 468–469 inhalation-acquired disease, 468 mechanism of action, 468 medical management, 469 oral ingestion, 468 signs and symptoms, 468 Amoxicillin anthrax treatment, 140 glanders treatment, 204 melioidosis prophylaxis, 236 “AMPLE” history, 117 Anaplasmosis, 654–655 Angel’s trumpet, 449 Angiotensin-converting enzyme inhibitors, 417 Animal and Plant Health Inspection Service, 80, 897–899, 902–904 Animal care, 888–889 Animal disease models, 186–189, 382–384, 406, 587, 888–889 Animal diseases African milk bush aack, 79 alphavirus encephalitides, 481–501 anthrax aacks by Germany in 1915-1916, 43–44, 78 Clostridium perfringens diseases, 362–367 coxiellosis, 310 deaths as indicator of biological agent aack, 40 filoviruses, 580 foot and mouth disease, 78–79 glanders, 186–189, 191–193 Hendra virus, 549, 552–553, 669 Nipah virus, 549–552, 553–554, 669–670 occurring simultaneously with human disease, 41 Animal Efficacy Rule, 272, 931–932 Animal poisons, 422 Anthrax accidental release of, 49–50, 130 active immunization, 140–142 aacks by Germany in 1915-1916, 43–44, 78 aacks in US, 2001, 47–48, 130 INDEX

Transcript of Medical Aspects of Biological Warfare · 2020. 6. 30. · paramyxovirus infections, 669 Q fever...

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AAbbreviations, xxvii–xxxi“ABCDE” algorithm, 116Abortions, septic

Brucella and, 162–163ACAM2000 vaccine, 115, 631–632ACB. See Acinetobacter baumanniiAcellular vaccines, 235Acinetobacter baumannii

antibiotic resistance, 328characterization and identification of source, 327–328epidemiological consultation, 324–327genetic analysis, 327–328historical perspectives, 322–324inclusion in ESKAPE pathogens, 322, 328–332molecular analysis, 327–328strain collection and sampling, 327U.S. Military Health System response, 328–332

Acronyms, xxvii–xxxiActive immunization

alphavirus encephalitides, 498–501Acute respiratory distress syndrome, 663–664Adjuvants, vaccines, 831–832Advanced Trauma Life Support, 110, 116, 117Advisory Committee on Immunization Practices, 141Aerobiology

biological aerosol exposure systems, 860–864clinical applications in the U.S., 857–860conceptual basis of, 857dosimetry, 863exposure chambers, 862exposure systems, 860–862generators, 861–862Henderson apparatus, 861monitoring and control, 862–863offensive biological development in the U.S., 857–860overview, 856–857parameters impacting aerosol dosimetry, 863–864sampling, 862

Aerosol dosimetry, 863–864Afghanistan

Acinetobacter infections, 322, 323, 324–327Al Qaeda biological warfare program, 15Q fever outbreak, 307ricin as biological weapon research, 376

Aflatoxins, 443, 445Africa

Chikungunya outbreak, 674Ebola virus epidemic, 677–678

African milk bush, 79Agency for Healthcare Research and Quality, 329Agent Orange, 79Agent X, 338Agglutination tests, 165Agricultural terrorism, 78–80Air Force field laboratories, 706Al Qaeda

biological warfare program, 15, 16–17Alcide EXSPORE, 883Alibek, Dr. Kenneth, 254, 339Alibekov, Colonel Kanatjan, 254, 339Alphavirus encephalitides

active immunization, 498–501antigenicity, 483–486

clinical disease, 492–496diagnosis of, 492–496differential diagnosis of, 495–496eastern equine encephalitis, 484–485, 493–494epidemiology and ecology, 486–488genetic relationships, 483–486historical perspectives, 481–483immune effector mechanisms, 496–497immunoprophylaxis, 496–501medical countermeasures, 773–776medical management, 496passive immunization, 497–498pathogenesis, 490–492prevention of, 496replication of, 488––490significance of, 482–483therapeutics, 501Venezuelan equine encephalitis, 483–484, 485, 492–493, 773–774virion structure, 488––490western equine encephalitis, 484, 485–486, 494–495

American Biological Safety Association, 889–890Aminoglycoside toxicity

differentiating from botulism, 343Aminoglycosides

brucellosis treatment, 166–167AML. See Area Medical LaboratoryAmnesic shellfish poisoning

description of toxin, 467–468diagnosis of, 468–469inhalation-acquired disease, 468mechanism of action, 468medical management, 469oral ingestion, 468signs and symptoms, 468

Amoxicillinanthrax treatment, 140glanders treatment, 204melioidosis prophylaxis, 236

“AMPLE” history, 117Anaplasmosis, 654–655Angel’s trumpet, 449Angiotensin-converting enzyme inhibitors, 417Animal and Plant Health Inspection Service, 80, 897–899, 902–904Animal care, 888–889Animal disease models, 186–189, 382–384, 406, 587, 888–889Animal diseases

African milk bush attack, 79alphavirus encephalitides, 481–501anthrax attacks by Germany in 1915-1916, 43–44, 78Clostridium perfringens diseases, 362–367coxiellosis, 310deaths as indicator of biological agent attack, 40filoviruses, 580foot and mouth disease, 78–79glanders, 186–189, 191–193Hendra virus, 549, 552–553, 669Nipah virus, 549–552, 553–554, 669–670occurring simultaneously with human disease, 41

Animal Efficacy Rule, 272, 931–932Animal poisons, 422Anthrax

accidental release of, 49–50, 130active immunization, 140–142attacks by Germany in 1915-1916, 43–44, 78attacks in US, 2001, 47–48, 130

INDEX

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Aum Shinrikyo cult attacks, 13, 46–47bioterrorism attacks, 13–15characteristics of organism, 131–132clinical disease, 135–138cutaneous, 135–136diagnosis of, 138–139epidemiology of, 132foodborne, 72gastrointestinal, 138, 650historical perspectives, 130–131incidence in the US, 132inhalational, 136–137medical countermeasures, 752, 754, 757–761meningitis, 137oropharyngeal, 138pathogenesis, 132–135prophylactic treatment after exposure, 140, 760–761Russian epidemic, 9treatment of, 139–140vaccine side effects, 142vaccines, 10, 113, 114, 753–758WHO surveillance and control guidelines, 140

Anthrax vaccine adsorbed, 754, 757–758Anthrolysin O, 135Antibacterial monoclonal antibodies, 837–839Antibiotic resistance diseases, 655–656Antibiotic susceptibility testing, 727Antibiotics

Animal Efficacy Rule, 272anthrax treatment, 139–140bacterial disease treatment, 759–760brucellosis treatment, 166–167, 768–769Clostridium perfringens treatment, 363glanders treatment, 202–204, 766–767melioidosis treatment, 233–234, 766multidrug-resistant bacterial infections, 328plague treatment, 272, 765Q fever, 771–772tularemia treatment, 292–294, 763–764

Antibodiesantibacterial monoclonal antibodies, 837–839antibody generations, 832–835antitoxin monoclonal antibodiesantiviral monoclonal antibodies, 839–842biodefense development, 832–842development of new therapeutic formats, 832–835ricin treatment, 388

Anticholinergic plants, 450Anticrop agents

produced by the US military, 5Anticrop terrorism, 79Antigen-presenting cells, 404–406Antigenic shift, 658Antihypertensives, 417Antimicrobial Resistance Monitoring and Research Program,

331–332Antimicrobial susceptibility testing, 727Antitoxin monoclonal antibodies, 835–837Antitoxins

C. botulinum pre- and postexposure prophylaxis, 347for C. botulinum, 345–346for Clostridium perfringens, 363

Antivenoms, 432Antiviral agents

hemorrhagic fever-causing mammarenaviruses, 531–532smallpox, 787–788viral hemorrhagic fevers, 790–791

Antiviral monoclonal antibodies, 839–842Aquariums

palytoxin exposure, 471–472Arachnids, 419–420ARDS. See Acute respiratory distress syndromeArea Medical Laboratory, 117, 705Argentinian hemorrhagic fever, 520, 526, 528, 530Armed Forces Health Surveillance Center, 329Armed Forces Medical Policy Council, 921ARMoR. See Antimicrobial Resistance Monitoring and Research

ProgramArmy field laboratories, 705Army Public Health Command, 324Army Techniques Publication, 716Army Techniques Publication No. 5-19, 95Arthritis

brucellosis and, 164Asahara, Shoko, 46, 339Asia

Chikungunya outbreak, 674melioidosis incidence, 227plague pandemic, 251

Aspergillus, 76Association for Assessment and Accreditation of Laboratory

Animal Care, 889Association of Professionals in Infection Control and Epidemiol-

ogy, 329ATLS. See Advanced Trauma Life SupportATP-binding cassette proteins, 190–191Aum Shinrikyo cult

bioterrorism attacks, 13, 46–47C. botulinum research program, 72, 339

Aureomycinglanders treatment, 204

Australiamelioidosis studies, 233–234paramyxovirus infections, 669Q fever outbreak, 306

Automated identification systems, 724–727Autotransporter proteins

glanders virulence mechanism, 190–191plaque virulence factor, 263

Autumn crocus, 447Avian influenza A virus, 19–22, 657–660, 661–662Avian influenza H5N1 virus, 662–663Avian influenza H7N9 virus, 663–664Azithromycin

glanders treatment, 204

BBacillus aerogenes capsulatus, 362Bacillus anthracis

accidental release of, 49–50, 130active immunization, 140–142attacks by Germany in 1915-1916, 43–44, 78attacks in US, 2001, 47–48, 130Aum Shinrikyo cult attacks, 13, 46–47bioterrorism attacks, 13–15characteristics of, 131–132confirmatory tests for, 131–132cutaneous anthrax, 135–136diagnosis of, 138–139epidemiology of, 132foodborne, 72gastrointestinal anthrax, 138, 650historical perspectives, 130–131inhalational anthrax, 136–137

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medical countermeasures, 752, 754, 757–761meningitis, 137oropharyngeal anthrax, 138pathogenesis, 132–135prophylactic treatment after exposure, 140, 760–761Russian anthrax epidemic and, 9treatment of, 139–140vaccine for US military, 10vaccines, 10, 113, 114, 753–758

Bacillus cereus, 132, 134Bacillus welchii, 362Bacterial culture techniques

glanders, 198–199tularemia, 293

Bacteriophages, 202Baghdad, Iraq

Acinetobacter infections, 325–326, 328BALB/c mice, 186, 188, 205Balkengrippe. See Q feverBangladesh

Nipah virus outbreak, 553–554, 670BAT, 345Bats

influenza viruses in, 664–666BCA agar, 199BCX4430, 791Bedbugs

as plague vector, 256–257Bee venom, 420, 421Belladonna, 449Belladonna toxicity

differentiating from botulism, 343Bergendorff, Roger, 16Beta-bungarotoxin, 367Biochemical identification, 199Biocrimes, 12Biodefense and Pandemic Vaccine and Drug Development Act

Renewal of 2011, 933Biofire Defense FilmArray, 702Biological aerosol exposure systems, 860–864Biological agents. See also specific agents by name

accidental release of, 49–50biocrimes, 12biological surety, 896–911biosafety levels, 122characteristics of, 742consequences of, 96–98critical agents for health preparedness, 113delivery systems developed by Iraq, 11disarmament, 17–18dual use research of concern, 19–22early use of, 2–3hospital infection control precautions, 121the Iranian program, 12the Iraq program, 10–11the Libyan program, 12the North Korean program, 12pan-hazard preparedness, 17–24produced by the US military, 5prophylaxis against diseases caused by Category A agents, 119regulated biological select agents and toxins, 703risk assessment systems, 95the South African program, 11–12the Soviet program, 8–10study of natural outbreaks for potential bioweapon use, 50–54the Syrian program, 12therapy of diseases caused by Category A agents, 119

the US program, 4–8use during the World Wars, 3–4

Biological and Toxin Weapons Convention, 375Biological Defense Research Program Laboratories, 888Biological Incident Annex, 94, 98Biological Integrated Detection System, 112Biological Personnel Reliability Program, 898, 901, 905–908Biological safety. See BiosafetyBiological safety cabinets, 860Biological select agents and toxins

biosafety, 904–905biosecurity, 908–910centralized management of, 901control of, 898–899identifying, 904incident response and emergency management, 910–911inventory and accountability, 900–901inventory audits, 901–902inventory discrepancies, 911list of Tier 1 agents and toxins, 898permissible toxin amounts, 903personnel reliability, 905–908registration for possession, use, and transfer of, 899reporting theft, loss, or release of, 903–904restricted experiments, 904sample criteria for retaining or destroying, 901security breaches, 911security risk assessment, 900theft, loss or release of, 910transfers, 902–903

Biological suretybiological select agent and toxin transfers, 902–903biological select agents and toxins inventory and accountabil-

ity, 900–901biological select agents and toxins inventory audits, 901–902biosafety, 904–905biosecurity, 908–910centralized management of long-term biological select agents

and toxins, 901control of biological select agents and toxins, 898–899identifying select agents and toxins, 904incident response and emergency management, 910–911information security, 909–910international rules and treaties to limit or ban biological

weapons use, 896inventory discrepancies, 911operational security, 909overview, 897–898personnel reliability, 905–908personnel security, 909physical security, 909registration for possession, use, and transfer of biological

select agents and toxins, 899reporting theft, loss, or release of biological select agents and

toxins, 903–904restricted experiments, 904security breaches, 911security risk assessment, 900theft, loss or release, 910

Biological Surety Program, 888Biological terrorism. See BioterrorismBiological warfare

impact of advanced molecular techniques on epidemiology of, 58–59

Biological Weapons Convention, 8, 11, 17–18, 179, 338, 375, 897Biologics Control Act, 926Biomarkers, 716–718

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Biopreparat, 9, 10Biosafety

assessing individual risk, 876–877assigning agents in risk groups, 872–874Biological Defense Research Program Laboratories, 888biosafety levels, 874–876case-fatality rate by disease, 873definition of, 870documenting safety procedures, 876evolution of, 870–871human infectious dose by organism, 873laboratory animal care and use program, 888–889laboratory safety audits, 887–888laboratory worker protection, 876medical surveillance, 880–881microbiological practices, 884–886personal protective equipment, 878–880physical barriers, 877–878precautions employed, 122the profession, 889–890program elements required for containment and maximum

containment laboratories, 876–886program management role, 886–889protecting the community and environment, 881–882risk groups, 872solid and liquid waste inactivation and disposal, 882–884

BioSense 2.0 program, 57, 58BioShield Act of 2004, 932–933Biosurety Program, 888. See also Biological suretyBiosurveillance, 739–741Bioterrorism. See also Medical countermeasures; specific agents by

nameagricultural, 78–80case studies, 43–49casualty management, 110–124consequence management, 94–96consequences of, 96–98historical perspectives, 13–17hospital infection control precautions, 121impact of advanced molecular techniques on epidemiology of,

58–59improving recognition and surveillance of, 56–58infectious diseases resulting from, 121local and national response, 98–102recovery, 103–105risk assessment systems, 95samples to obtain from victims, 118signs of C. botulinum attack, 346–347

Bioterrorism Act, 897BioThrax, 140–141, 754, 757BioThreat Alert Lateral Flow Assay, 386BioWatch program, 56, 101Bites, venomous, 418Bivalent botulinum toxoid, 347Bivalent recombinant botulinum vaccine, 348Black Death plague, 2–3, 250–251“Black Maria,” 858Black rats

plague transmission role, 257Black tar heroin, 342Bloomberg, Michael

ricin attacks in 2004, 48, 377Bolivian hemorrhagic fever, 520, 526, 530Borreliosis, 652–654BotDB resource, 348Botulinum immune globulin, 347

Botulinum toxinantitoxins, 345–346bioterrorist attack signs, 346–347botulinum neurotoxin production, 340–341clinical disease, 341–342description of agent, 72–73, 340–341diagnosis of, 343–344diagnostic assays, 343–344foodborne botulism, 72–73, 342, 344historical perspectives, 338–340inhalation-acquired botulism, 342, 344pathogenesis, 341prophylactic treatment, 347, 794–795symptoms of, 342therapeutic drug research, 348–349treatment of, 345–349vaccine research, 348, 793–794

BPRP. See Biological Personnel Reliability ProgramBrazilian hemorrhagic fever, 521Brevetoxins, 463, 465–467Brooke Army Medical Center

Acinetobacter infections, 324Brucella

host specificity, 161lipopolysaccharide epitopes, 161–162nomenspecies, 160–161virulence factors, 162

Brucella abortus, 163Brucella canis, 162Brucella melitensis, 164Brucella suis

development as biological weapon, 160Brucellosis

clinical manifestations, 164–165diagnosis of, 165–166epidemiology of, 162historical perspectives, 160infectious agent characteristics, 160–162medical countermeasures, 768–770minimum inhibitory concentration breakpoint ranges, 167pathogenesis, 163prophylactic treatment, 167, 769–770symptoms and signs of, 164treatment of, 166–167vaccines, 768

BSAT. See Biological select agents and toxinsBubonic plague, 265, 267Buffalopox, 623, 628Bundibugyo virus, 571–575, 589, 592BurkDiff, 200Burkholderia mallei

animal disease models, 186–189attacks by Germany in 1915-1916, 43–44, 78biochemical identification, 199characteristics of, 181–182clinical disease in animals, 191–193clinical disease in humans, 193–198clinical features of laboratory-acquired infections, 196–197control of, 208–109decontamination, 208–109diagnosis in equines, 202differentiation from B. pseudomallei, 181, 182epidemiology of, 182–183growth characteristics, 198historical perspectives, 179–181host immunity, 205–206

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identification of, 199–201immunological detection, 201immunotherapies, 208intracellular characteristics, 186isolation of organism, 198–199laboratory diagnosis, 198–202medical countermeasures, 766–768military relevance, 178–179morphology, 198nucleic acid-based identification, 199–201pathogenesis, 184–191prophylactic treatment, 205–209, 767–768septicemia, 195serologic diagnosis, 201–202transmission of, 183–184treatment of, 202–204vaccines, 206, 207–208, 766virulence mechanisms, 189–191

Burkholderia pseudomalleicandidate virulence factors, 228–230characteristics of, 224–225clinical disease, 227, 230–232diagnosis of, 232–233differentiation from B. mallei, 181, 182epidemiology of, 226medical countermeasures, 766–768military relevance, 225–226pathogenesis, 226–227prevention of, 234–236prevention of disease, 234–236treatment of, 233–234

Burnet, Dr. Frank Macfarlane, 306Bush, George H., 10Bush, George W., 22, 114BWC. See Biological Weapons ConventionByetta, 417

CCaffa

plague pandemic, 250, 252CAFOs. See Concentrated animal feeding operationsCalifornia

plague pandemic, 251Camelpox, 623Camp Detrick, Maryland

biological warfare agents research, 857–858, 923–925Burkholderia mallei infections, 178, 183, 194–195, 196–197

Campylobacter jejuni, 73, 77, 650–651Canada

alphavirus encephalitides outbreaks, 482Capsular polysaccharides, 235Captopril, 417Cardiotoxic plants, 448–449Cardiotoxins, 440–441, 448Cardiovascular system

Staphylococcal enterotoxin B effects, 407–408Caribbean Islands

Chikungunya outbreak, 674Castor beans, 375, 377, 382, 446Casualty management

alerting authorities, 118–123chemical protection, 113diagnosis of casualties, 118, 120disinfecting or decontaminating, 116–117epidemiological investigation, 123–124establishing diagnosis, 117–118immunologic protection, 113–116

infection control, 118, 121maintaining level of proficiency, 124maintaining level of suspicion, 110–12managing psychological aftermath, 123–124physical protection, 112–113primary assessment, 116prophylaxis against diseases caused by Category A agents, 119protecting self, 112–116providing therapy, 118psychological effects of biological attacks, 123–124saving patient’s life, 116secondary assessment, 116–118therapy of diseases caused by Category A agents, 119

Catalytic A-chain, 377–378, 380, 390Cationic liposome DNA complexes, 208Cats

plague transmission role, 257Cavanaugh, Lieutenant Colonel Dan C., 252C57Bl/6 mice, 186, 188CBRNE Command, 705CDC. See Centers for Disease Control and PreventionCeftazidime

glanders treatment, 204melioidosis treatment, 233

Cell-free translation assay, 386, 387Cell-mediated immune responses, 205Cellular stress response inhibitors, 391Centers for Disease Control and Prevention

BioSense 2.0 program, 57BSAT forms, 899, 902–904case definition for brucellosis, 165Division of Select Agent and Toxins, 860, 897–898Emergency Operations Center, 345epidemiological investigative assistance, 123Laboratory Registration and Select Agent Transfer Program, 897Laboratory Response Network, 14, 22, 101, 122, 386, 704,

727–728Morbidity and Mortality Weekly Report, 259plague diagnosis procedures, 270plague treatment procedures, 272procedures for isolation and presumptive identification of

Y. pestis, 269public health preparedness capabilities, 102Select Agents and Toxins Program, 375smallpox specimen collection, 628

Centipedes, 443Central America

alphavirus encephalitides outbreaks, 482, 487–488Chikungunya outbreak, 674

Central Intelligence Agency, 8, 377CFT. See Cell-free translation assay; Complement fixation testChapare virus, 521, 523–524Chemical Battalions, 117Chemical-Biological Incident Response Force, 117, 123Chemical Corps, 116Chemical nerve agent poisoning

differentiating from botulism, 343Chemical protection, 113Chemical Warfare Service, 5Chemical Weapons Convention, 375CHEMPACKs, 102Chikungunya, 673–674China

accusations of US biowarfare attacks, 6–7Avian influenza H7N9 virus infections, 663–664plague pandemic, 251severe fever with thrombocytopenia syndrome virus, 675–676

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Chloramphenicolglanders treatment, 204melioidosis treatment, 234plague treatment, 272

Chloroform:methanol residue vaccine, 312Chloroquine

Q fever treatment, 311Cholera, 647–649Cidofovir, 635Ciguatoxic fish, 422, 462Cilastatin

melioidosis treatment, 233Ciprofloxacin

anthrax exposure prophylaxis, 10, 140anthrax treatment, 139plague treatment, 272

Civil Support Teams, 123Clavulanate

glanders treatment, 204melioidosis prophylaxis, 236

CLIA. See Clinical Laboratory Improvement AmendmentsClindamycin

anthrax treatment, 140Clinical Laboratory Improvement Amendments, 702–703Clinical Laboratory Improvement Program, 702–703Clinical Laboratory Standards Institute, 166CLIP. See Clinical Laboratory Improvement ProgramClorox Ultra Germicidal Bleach, 883Clostridium argentinense, 340Clostridium baratii, 340Clostridium botulinum

antitoxins, 345–346bioterrorist attack signs, 346–347botulinum neurotoxin production, 340–341clinical disease, 341–342description of agent, 72–73diagnosis of, 343–344diagnostic assays, 343–344foodborne botulism, 72–73, 342, 344, 651historical perspectives, 338–340inhalation-acquired botulism, 342, 344pathogenesis, 341prophylactic treatment, 347symptoms of, 342therapeutic drug research, 348–349treatment of, 345–349vaccine research, 348

Clostridium butyricum, 340Clostridium perfringens alpha toxin, 362–363Clostridium perfringens epsilon toxin

chemical properties, 364description of, 363–365diseases, 363historical perspectives, 362–363mechanism of action, 364–365medical management, 366–367natural occurrence of, 363–364physical properties, 364signs and symptoms of, 365–366toxin types, 362

Clostridium perfringens type D, 365–366Clostridium welchii, 362Cnidarians, 420–422Co-trimoxazole, 203Colony collapse disorder, 678Colorado potato beetle, 79Common source outbreaks, 40

Community Emergency Response Team Program, 100Competent medical authority, 907Complement fixation test, 201, 202Comprehensive Health Surveillance, 739Comprehensive Preparedness Guide 201, 95Concentrated animal feeding operations, 79Confirmation identification methods, 709–716Congo

incidence of human plague cases, 259Congressional Office Building

ricin bioterrorism attack, 16Consequence management

Comprehensive Preparedness Guide 201, 95consequences of biological incidents, 96–98definition of, 94local and national response, 98–102National Disaster Recovery Framework, 94recovery, 103–105risk assessment systems, 95

Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological and Toxin Weapons and on their Destruction, 8, 11, 17–18, 179, 338, 375

Cooperative Biological Engagement Program, 10Corals

palytoxin exposure, 469, 471–472Coronaviruses, 666–669Countermeasures. See Medical countermeasuresCowpox, 623, 628Coxiella burnetti

characteristics of, 307–309diagnosis of, 311disease in animals, 310disease in humans, 310epidemiology of, 309–310historical perspectives, 306medical countermeasures, 770–772military relevance, 306–307pathogenesis, 309postexposure prophylaxis, 772treatment of, 311vaccines, 312, 770–771

Coxiellosis, 310Critical control points, 81Crocus, 447Crooker, Michael, 16Crop diseases, 79Cruikshank, George, 918Cryptosporidiosis, 75Cryptosporidium parvum, 75, 77, 78Culture-based methods, 722–724, 727–728Cutaneous anthrax, 135–136Cutaneous plague, 268–269Cyanogenic plants, 448Cysticercosis, 77Cytotoxic plants, 446–447Czechoslovakia

use of biological agents during World War II, 4

DDalles, Oregon

Salmonella typhimurium attacks, 1984, 44–46Darwin Prospective Melioidosis Study, 227, 230, 234Daschle, Tom

anthrax attack, 2001, 47–48Decontamination

glanders, 208–109Decontamination procedures, 104, 116–117

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Defence Science and Technology Laboratory, 388Defense Laboratory Network, 706–707Delaware

alphavirus encephalitides outbreaks, 482Dengue fever, 671–672Department of Defense Global Emerging Infections Surveillance

and Response System, 324, 329, 331Dermal exposure

palytoxin, 471Derrick, Dr. Edward Holbrook, 306Despeciated equine heptavalent antitoxin, 345DHHS. See U.S. Department of Health and Human ServicesDHS. See U.S. Department of Homeland SecurityDiagnostic tests, in vivo/in vitro, 728Digital imaging, 202Dilger, Anton, 44, 78, 178Diphtheria

differentiating from botulism, 343Disinfection procedures, 116–117Division of Select Agent and Toxins, 860, 897–898DNA assays, 199–201DNA vaccines, 500DoD-Geis. See Department of Defense Global Emerging Infections

Surveillance and Response SystemDominant-negative inhibitors, 366Dominican Republic

cholera outbreak, 648Domoic acid, 463, 467–469Dosimetry, 863Doxycycline

anthrax exposure prophylaxis, 140anthrax treatment, 139brucellosis treatment, 166–167glanders treatment, 203–204melioidosis treatment, 234plague postexposure prophylaxis, 273plague treatment, 272Q fever treatment, 311

Drug-resistant bacteria. See Multidrug-resistant organismsDryvax, 631–632Dual use research of concern, 19–20DURC. See Dual use research of concernDutschke, Everett, 16, 377Dysentery, 363

EEastern equine encephalitis, 484–485, 493–494Ebola virus, 118, 571, 573–575, 580–592, 596–598, 677–678ECL. See ElectrochemiluminescenceEczema vaccinatum, 633Edema toxin, 132–135Ehrlich, Paul, 375Ehrlichiosis, 654–655“Eight Ball,” 859, 925Electrochemiluminescence, 385, 386, 387, 730–732Electronic Surveillance System for the Early Notification of

Community-based Epidemics, 57ELISA. See Enzyme-linked immunosorbent assaysEmergency management, 910–911Emergency Operations Center, 345Emergency support functions, 98, 101, 123Emergency Use Authorization, 703, 740–741, 925–926, 929Emerging infectious diseases

antibiotic resistance, 655–656avian influenza, 657–660bacterial diseases, 647–657chikungunya, 673–674

coronaviruses, 666–669definition of, 646Dengue fever, 671–672Ebola epidemic in West Africa, 677–678factors contributing to, 646foodborne diseases, 650–652genetically engineered organisms, 679–681genomic epidemiology, 656–657high-throughput DNA sequencing, 678–679H1N1 influenza pandemic, 660–661human infection with avian influenza viruses, 661–664influenza viruses in bats, 664–666mosquitoborne viruses, 670–674paramyxoviruses, 669–670swine influenza, 660–661synthetic biology, 681tickborne diseases, 652–655tickborne phleboviruses, 675–677viral diseases, 657–679waterborne diseases, 647–650West Nile virus, 672–673

Encephalitis. See Alphavirus encephalitidesEncephalomyelitis

nonviral causes of, 496viral causes of, 495

Endocarditis, Q fever, 310Endopep-MS, 344England

plague pandemic, 250Enhanced Response Force Package Teams, 123Enrofloxacin

glanders treatment, 204Enterohemorrhagic E. Coli, 74Enterotoxemia, 363, 365Envenomation, 417, 418Environmental niche modeling, 583Environmental Protection Agency, 101Enzootic

definition of, 249Enzyme-linked immunosorbent assays

botulism diagnosis, 344brucellosis diagnosis, 165, 166filoviruses diagnosis, 593–595glanders diagnosis, 201, 202hemorrhagic fever-causing mammarenaviruses diagnosis,

529–530orthopoxviruses diagnosis, 629overview, 728–730plague diagnosis, 270Q fever diagnosis, 311ricin diagnosis, 385, 387Staphylococcal enterotoxin B diagnosis, 408

EpiCenter application, 57EPICON. See Epidemiological consultationsEpidemics

clues to an unnatural event, 39–41definition of, 38downwind plume patterns, 41Ebola virus in West Africa, 38epidemic curves, 42multiple epidemics, 40outbreak investigation, 41–43recognition of, 38–39

Epidemiological consultations, 324–327Epidemiology

accidental release of biological agents, 49–50assessment tool, 54–56

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bioterrorism events, 43–49clues to an unnatural event, 39–41, 111common source outbreaks, 40of epidemics, 38–43the epidemiological triangle, 38impact of advanced molecular techniques, 58–59improving recognition and surveillance of bioterrorism, 56–58investigations after biological attacks, 123–124point source outbreaks, 40study of natural outbreaks for potential bioweapon use, 50–54

Epizooticdefinition of, 249

Epsilon toxin vaccine, 367Equine encephalitis. See Alphavirus encephalitidesEquines

C botulinum antitoxin, 347glanders diagnosis, 202

Escherichia coli, 74, 77, 78, 377, 651–652Escherichia coli O104:H4, 652Escherichia coli O157:H7, 651–652ESKAPE pathogens, 322, 328–332Ethical issues

Animal Efficacy Rule, 931–932biodefense, ethics, and research in the 20th Century, 921–925biodefense and ethics in the 18th and 19th Centuries, 918–921Biodefense and Pandemic Vaccine and Drug Development Act

Renewal of 2011, 933BioShield Act of 2004, 932–933conflict between regulations and ethical responsibilities, 926–929current movements in the regulatory environment, 931–933dilemmas for biodefense research, 933–934DoD/FDA Memorandum of Understanding, 927impact of regulating agencies on strategic research, 925–926investigational new drug status, 927–929options for fulfilling mission and ethical responsibilities to

military personnel, 929–931overview of, 916–925Public Health Security and Bioterrorism Preparedness and

Response Act of 2002, 931summary points, 929The Turner Bill, 933

EUA. See Emergency Use AuthorizationEurope

plague pandemic, 250–251Excitatory neurotoxins, 430–432Exendin-4, 417Expeditionary Medical Dental Group, 326Exposure chambers, 862Exposure systems, 860–862Eyes

Staphylococcal enterotoxin B effects, 408

FF1 antigen, 262F1-V vaccine, 273–274Fairchild Air Force Base

ricin attacks in 2004, 377Farcy. See GlandersFavipiravir, 791FBI. See Federal Bureau of InvestigationFederal Bureau of Investigation, 14, 45, 101Federal Emergency Management Agency, 94, 100Federal Experts Security Advisory Panel, 23Federal Response Plan, 22Federal Select Agent Program, 20, 897–900, 904–906FEMA. See Federal Emergency Management Agency

Field laboratories, military, 705–706FilmArray, 738Filoviruses

behavioral modification for prevention, 586categorization of viruses, 571–572clinical presentation of disease, 590–591decontamination, 586diagnosis of, 591–595disease nomenclature, 571, 574environmental niche modeling, 583epidemiology of, 580–583epizootiology of, 580filovirion structure, 572function of, 576–579genomes, 572–573, 575geographic distribution, 574inactivation of, 586lifecyle, 573–574molecular biology, 572–583natural reservoirs of, 574–575nomenclature, 571–572pathogenesis, 587, 590prevention of, 586–587proteins, 572–573serological surveys, 583Soviet biological warfare program, 584–586taxonomy, 571transmission of, 583–584treatment of, 595, 596–598vaccines, 587, 588–589

Fimbrae, 262–263Fish, venomous, 420–422Fleas

as plague vector, 256–257plague virulence and transmission factors, 264

Floridaplague pandemic, 251

Flow cytometry, 732–733Flu Near You, 57Fluorescence in situ hybridization assay, 202Fluorescence Resonance Energy Transfer, 630Fluorescence spectroscopy, 202Fluorescent antibody staining, 166, 270–271Food, Drug, and Cosmetic Act, 926Food and Drug Administration, 82, 112, 272, 587, 702–704, 916,

926–933Food Emergency Response Network, 101Food Safety and Modernization Act, 82Food supply security, 80–82Foodborne diseases

anthrax, 72botulinum toxins, 72–73, 342, 344Campylobacter jejuni, 73, 77, 650–651Clostridium botulinum, 72–73, 342, 344, 651Clostridium perfringens diseases, 363cryptosporidiosis, 75emerging diseases, 650–652Escherichia coli, 74, 651–652gastrointestinal anthrax, 650hepatitis A, 75listeriosis, 73–74mycotoxicosis, 75–76parasites, 76–77salmonellosis, 44–46, 73, 652shigellosis, 47, 74–75threat potential, 76, 77

Foot and mouth disease, 78–79

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Force health protection, 928–929Fort Detrick, Maryland

Burkholderia mallei infections, 178, 183, 194–195, 196–197Fox squirrels

plague transmission role, 257Foxglove, 447Francisella pathogenicity island, 289Francisella tularensis

acquired, 289aerosol transmission, 288arthropod vectors, 288bacterial culture techniques, 293characteristics of, 286–287clinical manifestations, 290–292diagnosis of, 292–294direct contact, 287epidemiology of, 287–289food and water ingestion, 288laboratory-acquired disease, 289laboratory worker exposure, 296mammalian bites, 288medical countermeasures, 761–764pathogenesis, 289–290postexposure prophylaxis, 295, 764prophylactic treatment, 295–295rapid diagnostic methods, 293–294serology, 293treatment of, 294–295in unusual settings, 288–289use as biological weapon, 296vaccination with live vaccine strain, 289, 290, 295–296, 761–763

Freeman, Dr. Mavis, 306Frist, Bill

ricin attacks in 2003-2004, 48–49Fugu puffer fish, 422Fungal toxins, 443, 445

GGas gangrene, 362–363Gas masks, 112Gastroenteritis, 78Gastrointestinal diseases

anthrax, 138, 650plague, 268plant irritants, 451tularemia, 291

Genetic analysisAcinetobacter baumannii, 327–328

Genetically engineered organisms, 679–681Geneva Convention, 8, 11Geneva Protocol, 3, 6, 896–897Genomic epidemiology, 656–657Gentamicin

plague treatment, 272Germany

cholera outbreak, 647Shiga toxin deaths, 377use of biological agents during World War I and II, 3–4, 43–44,

78, 178Giardia lamblia, 78Gila monster, 417Glanders

animal disease models, 186–189attacks by Germany in 1915-1916, 43–44, 78, 178biochemical identification, 199clinical disease in animals, 191–193clinical disease in humans, 193–198

clinical features of laboratory-acquired infections, 196–197control of, 208–109decontamination, 208–109diagnosis in equines, 202epidemiology of, 182–183historical perspectives, 179–181host immunity, 205–206identification of, 199–201immunological detection, 201immunotherapies, 208infectious agent characteristics, 181–182isolation of organism, 198–199laboratory diagnosis, 198–202medical countermeasures, 766–768military relevance, 178–179morphology, 198nucleic acid-based identification, 199–201organism growth characteristics, 198pathogenesis, 184–191prophylactic treatment, 205–209, 767–768septicemic, 195serologic diagnosis, 201–202transmission of, 183–184treatment of, 202–204vaccines, 206, 207–208, 766virulence mechanisms, 189–191

Global Emerging Infections Surveillance and Response System, 324, 329

Gonyautoxins, 463Good Clinical Practices, 927, 929Government Accountability Office, 24Granulocyte colony-stimulating factor, 234Great Britain

eradication of glanders, 180use of biological agents during World War II, 4

Ground squirrelsplague transmission role, 257, 258

Guanarito virus, 521, 522, 523–524, 530–531Guillain-Barré syndrome

differentiating from botulism, 343Guinea pigs

as animal disease models, 186Gulf War

Q fever outbreak, 307

HHACCPs. See Hazard analysis critical control pointsHaffkine, Waldemar M.W., 273Hague Convention, 3HAIs. See Healthcare-assisted infectionsHaiti

cholera outbreak, 648–649Hamsters

as animal disease models, 186Handheld assay devices

overview, 733–734ricin detection, 385, 387

Harris, Larry Wayne, 13–14Hatfill, Dr. Steven J., 14HAVCR1. See Hepatitis A virus cellular receptor 1Hazard analysis critical control points, 81Hazardous Material Regulations, 902Hazardous Materials Response Unit, 117HBAT, 345Healthcare-assisted infections, 329Heartland virus, 676–677

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HematologyStaphylococcal enterotoxin B, 408

Hemolytic toxins, 437–440Hemorrhagic fever-causing mammarenaviruses

antiviral agents, 531–532clinical presentation, 522–523coagulopathies, 527–528diagnosis of, 529–530epidemiology of, 519–521historical perspectives, 519–521immune response, 528–529molecular characteristics, 524–525New World mammarenaviruses, 520–521, 523, 526–527,

528–529Old World mammarenaviruses, 519–520, 522–523, 525–526,

528passive antibody therapy, 530pathogenesis, 525–527pathology, 525–527phylogenetic relationships, 523–524reservoirs of, 521–522taxonomy, 523–524treatment of, 530–532vaccines, 530–532

Hemorrhagic toxins, 437–440Hemostasis-active toxins, 435–437Hemostasis system, 438–439Henderson apparatus, 861Hendra virus, 549, 552–553, 669Henipaviruses

anti-henipavirus immune response detection, 558–559antigen detection, 558availability of, 557–558as biological weapons, 557–558clinical presentation, 554–555diagnosis of, 558–559dissemination of, 558emergence of, 549–552epidemiology of, 552–554epizootiology of, 552–554Hendra virus, 549, 552–553historical perspectives, 549–552innate immunotherapy, 560isolation of virus, 559medical management, 559–560molecular biology of, 555–556newly identified viruses, 552next-generation sequencing, 559Nipah virus, 549–552, 553–554passive immunotherapy, 559–560pathogenesis, 557pathology, 555potential for high morbidity and lethality, 558production of, 558reverse transcription-polymerase chain reaction, 558ribavirin, 560signs and symptoms of, 554–555therapies evaluated in vitro, 560virus genome, 555virus proteins, 555–556virus structure, 555

Hepatitis A, 75, 77Hepatitis A virus cellular receptor 1, 367Heptavalent despeciated antitoxin, 346Herbal medicine

ricin poisoning, 381Hfab-BAT, 346

HHA. See Handheld assay devicesHigh-efficiency particulate air filters, 871, 877, 882High throughput DNA sequencing, 678–679High throughput screening, 390, 391Highly pathogenic avian influenza A virus, 19–22, 662–663H1N1 influenza A virus, 19, 22, 660–661H5N1 virus, 19–22Homeland Security Council, 22Homoheptamers, 365Hong Kong, China

Avian influenza H5N1 virus infections, 662–663Horses

glanders diagnosis, 202Host immunity, 205–206Host response, 741–743HTS. See High throughput screeningHuman fleas

as plague vector, 256Hussein, Saddam, 10–11Hybridization probes, 630Hydroxychloroquine

Q fever treatment, 311Hyperimmune sera, 367

IIatrogenic botulism, 342, 344IHA. See Indirect hemagglutination assayIlimaquinone, 391Illumina MiSeq instrument, 740Imipenem

glanders treatment, 204melioidosis treatment, 233

Immunization. See also Vaccinesalphavirus encephalitidesanthrax, 140–142

Immunodiagnostic methods, 728–730Immunologic protection, 113–116Immunological detection, 201Immunosorbent assays. See Enzyme-linked immunosorbent assaysImmunotherapies

glanders, 208IMP dehydrogenase inhibitors, 792In vivo/in vitro diagnostic tests, 728Inactivated vaccines, 499Incapacitating agents

produced by the US military, 5Incident Command System, 121Incident response and emergency management, 910–911IND. See Investigational new drugsIndia

Chikungunya outbreak, 674Nipah virus outbreak, 553–554plague pandemic, 251

Indian Ocean islandsChikungunya outbreak, 674

Indian Plague Commission, 256Indirect hemagglutination assay, 201Indirect immunofluorescence assay, 311Infants

botulism, 342, 346Infection control, 118, 121Infectious Diseases Society of America, 322Influenza

Avian influenza pandemic threat, 657–660H1N1 influenza pandemic, 660–661swine influenza, 660–661

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Inhalation-acquired diseaseamnesic shellfish poisoning, 468anthrax, 136–137botulism, 342, 344neurotoxic shellfish poisoning, 466palytoxin, 471paralytic shellfish poisoning, 464ricin, 382–384

Injectionsricin administration, 382

Innate immunotherapyhenipaviruses, 560

Insect stings, 420, 421Institutional Biosafety Committee, 904Integrated Consortium of Laboratory Networks, 706–707Intercellular adhesion molecule-1, 406Interferon gamma, 163, 205–206, 406Interferons, 791International Clonal Complex, 323International Committee of the Red Cross, 6International Health Regulations, 259International Society on Toxinology, 416Invasive species, 80Inventory audits, 901–902Invertebrates

as disease models, 188–189Investigational new drugs, 114–116, 345, 346, 347, 498, 927–929Iran

biological warfare agents, 12ricin as biological weapon research, 376

IraqAcinetobacter infections, 322, 323, 324–327biological warfare agents, 10–11C. botulinum research program, 339Q fever outbreak, 2005, 53–54, 307ricin as biological weapon research, 376

Iraq Survey Group, 11Iron sequestration, 263Irritants, local

plants causing, 451Ishii, General Shiro, 3–4, 5, 338Ivins, Dr. Bruce E., 15

JJapan

Aum Shinrikyo cult bioterrorism research and attacks, 13, 46–47, 72, 339

biocrimes, 12biological agent research during World War I, 3–4bioterrorism attacks, 13C. botulinum research program, 338development of Burkholderia mallei as potential biowarfare

agent, 179plague warfare research, 252–254severe fever with thrombocytopenia syndrome virus, 676

Japanese encephalitis virus, 550JBAIDS. See Joint Biological Agent Identification and Diagnostic

SystemsJellyfish stings, 420, 430, 432, 441Jewett, Frank B., 921Joint Bacterial Repository, 329Joint Biological Agent Identification and Diagnostic Systems, 112,

702–704, 738Joint Biological Integrated Detection System, 112Joint Task Force for Civil Support, 123Junín virus, 519–520, 522, 523, 526–528, 530531Justinian plague, 250

KKathmandu, Nepal

cholera outbreak, 648Kefauver-Harris Drug Amendments, 926Kennedy, John F., 7Khrushchev, Nikita, 9Killed whole cell vaccines, 206–207Kosovo

tularemia outbreak, 1999-2000, 52–53Kostov, Vladimir, 9, 376Krishnaswami, Dr. C.S., 224

LLaboratories

allies’ identification levels, 718–719antibiotic and antimicrobial susceptibility testing, 727assessing individual risk, 876–877automated identification systems, 724–727Biological Defense Research Program Laboratories, 888biosafety program element requirements, 876–886biosurveillance, 739–741civilian identification levels, 707–708Clinical Laboratory Improvement Amendments, 702–703Clinical Laboratory Improvement Program, 702–703containment and maximum containment laboratories, 876–886culture-based microbiological methods, 722–724Defense Laboratory Network, 706–707documenting safety procedures, 876early recognition of host response, 741–743electrochemiluminescence, 730–732emerging threat surveillance, 739–741enzyme-linked immunosorbent assays, 730flow cytometry, 732–733future perspectives, 734–736hand held assays, 733–734horizon-agnostic diagnostic applications, 738–739identification approaches, 719–739identification levels, 707immunodiagnostic methods, 728–730integration of in vivo and in vitro diagnostic tests, 728Joint Biological Agent Identification and Diagnostic Systems,

112, 702, 704laboratory animal care and use program, 888–889laboratory worker protection, 876MAGPIX, 733medical surveillance, 880–881microbiological culture methods, 727–728microbiological practices, 884–886military field laboratories, 705–706military identification levels, 708, 716–718molecular detection methods, 736Next Generation Diagnostic System, 702next generation molecular diagnostics, 738personal protective equipment, 878–880physical barriers, 877–878presumptive and confirmation methods, 709–716protecting the community and environment, 881–882rapid methods, 727–728real-time polymerase chain reaction, 736–738regulated biological select agents and toxins, 703research, development, test, and evaluation laboratories, 888role of military clinical and field laboratories, 705safety audits, 887–888solid and liquid waste inactivation and disposal, 882–884specimen collection and processing, 719–722

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Laboratory-acquired diseasesbotulinum intoxication, 342tularemia, 289, 296

Laboratory of HealthCare Associated Infections, 327Laboratory Registration and Select Agent Transfer Program, 897Laboratory Response Network, 14, 22, 101, 122, 386, 704, 727–728Lahore Polo Club, 204Lambert-Eaton syndrome

differentiating from botulism, 343Landstuhl Regional Medical Center

Acinetobacter infections, 323, 324–327Lassa virus, 519, 522, 523–525, 528–531Latin America

cholera outbreak, 647LcrV, 261–262Lectin B-chain, 377–378, 389–390Legionella, 308–309Legionellosis, 649–650Lethal toxin, 132–135Levofloxacin

plague postexposure prophylaxis, 273plague treatment, 272

Libyabiological warfare agents, 12

Liceas plague vector, 256–257

Linezolidanthrax treatment, 140

Lipid rafts, 364–365Lipopolysaccharide antibodies, 235, 308Liquid chromatography, 386, 387Listeria monocytogenes, 73–74Listeriosis, 73–74Liston, W.G., 256Live attenuated vaccines, 207, 273, 758, 825–826Live vaccines

alphavirus encephalitides, 498–499tularemia, 289, 290, 295–296, 761–763

Livestock. See Animal diseasesLloviu virus, 571–575, 580Local response, 98–102London, England

ricin bioterrorism attack, 16Louisiana

plague pandemic, 251LRN. See Laboratory Response NetworkLujo virus, 519–520, 523LVS tularemia vaccine, 295–296Lyme disease, 652–654Lymphocyte function-associated antigen, 406Lysosomal-associated membrane proteins, 308

MM-44 vaccine, 312Machupo virus, 520, 522, 523–524, 526–527, 531MAGPIX, 733Major histocompatibility complex, 404–405Malaysia

Nipah virus outbreak, 553paramyxovirus infections, 669–670

Malleomyces mallei, 178Mammarenaviruses. See Hemorrhagic fever-causing mammare-

navirusesManganese sequestration, 263MAP. See Mitogen-activated protein kinaseMarburg virus, 571–575, 580–592, 596–598

Marine algal toxinsamnesic shellfish poisoning, 467–469neurotoxic shellfish poisoning, 465–467palytoxin, 469–472paralytic shellfish poisoning, 463–465

Marine envenoming, 420–422Markov, Georgi, 9, 375, 376, 382Marshall, Lieutenant Colonel John D., 252Marshall Plan, 7Martha’s Vineyard, Massachusetts

tularemia outbreak, 2000, 51–52, 292Maryland

alphavirus encephalitides outbreaks, 482MASCAL. See Medical mass casualty eventMasks, 112–113Mass median aerodynamic diameter, 862Mass spectrometry, 202, 328, 344, 386, 387Massachusetts

alphavirus encephalitides outbreaks, 482tularemia outbreak, 2000, 51–52, 292

Mau-Mau attack, 79MDCK cells, 366MDR Organism Repository and Surveillance Network, 329–332MDROs. See Multidrug-resistant organismsMeadow saffron, 447MEDCOM. See U.S. Army Medical CommandMedical countermeasures

anthrax, 752, 754, 757–761bacterial diseases, 752–772botulinum neurotoxin, 793–795brucellosis, 768–770encephalitic New World alphaviruses, 773–776glanders, 766–768melioidosis, 766–768plague, 764–765Q fever, 770–772ricin, 796–797rickettsial diseases, 752–772smallpox, 776–788Staphylococcal enterotoxin B, 795–796toxins, 793–797tularemia, 761–764viral diseases, 773–793viral hemorrhagic fevers, 788–793

Medical ethics. See Ethical issuesMedical mass casualty event

casualty management, 110–124Medical Reengineering Initiative, 705Medical treatment facilities, 705Melioidosis

candidate virulence factors, 228–230clinical disease, 227, 230–232diagnosis of, 232–233epidemiology of, 226infectious agent characteristics, 224–225medical countermeasures, 766–768military relevance, 225–226pathogenesis, 226–227postexposure prophylaxis, 235–236, 767–768prevention of, 234–236treatment of, 233–234vaccines, 766

Meningitisanthrax meningitis, 137plague meningitis, 268

Merck, George W., 5Merck, George W., Jr., 921

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Meropenemglanders treatment, 204melioidosis treatment, 233

MERS. See Middle Eastern respiratory syndromeMeselson, Matthew, 9Metropolitan Medical Response System, 121Mexico

alphavirus encephalitides outbreaks, 487Meyer, Karl F., 273MHS. See Military Health SystemMice

as animal disease models, 186–188Microbiological methods

culture-based, 722–724, 727–728Microbiological practices

biosafety, 884–886MicroChem Plus, 883Middle Eastern respiratory syndrome, 666–669MIDI Sherlock Microbial Identification System, 199Military field laboratories, 705–706Military Health System

response to Acinetobacter infections, 328–332Military installations. See also U.S. military

plague risks, 252, 253Military personnel

options for fulfilling mission and ethical responsibilities, 929–931Minnesota Patriots Council, 13–14Minor Groove Binding Proteins, 630Missoula, Montana

Q fever outbreak, 306Missouri

Heartland virus, 676–677Mitogen-activated protein kinase, 134, 378MNGCs. See Multinucleated giant cellsModified Vaccinia Ankara, 632Modified vaccinia virus, 826Mold toxins, 443Molecular detection methods

Acinetobacter baumannii, 327–328next generation diagnostics, 738overview, 736

Molecular sequencing technology, 58–59Monkeypox, 623, 627–628Monoclonal antibodies

antibacterial, 837–839antitoxin, 835–837antiviral, 839–842

Monocyte chemoattractant protein-1, 205, 406Montana

Q fever outbreak, 306Morbidity and Mortality Weekly Report, 259Mosquitoborne viruses, 670–674Mousepox virus, 19MRSN. See MDR Organism Repository and Surveillance NetworkMucosal vaccines, 830–831Multidrug-resistant organisms

antibiotic resistance, 328, 655–656characterization and identification of source, 327–328epidemiological consultation, 324–327ESKAPE pathogens, 322, 328–332genetic analysis, 327–328historical perspectives, 322–324molecular analysis, 327–328strain collection and sampling, 327U.S. Military Health System response, 328–332

Multilocus sequence typing, 181, 182Multinucleated giant cells, 186, 190Multiple-locus variable number tandem repeat analysis, 182–183

Mushrooms, 422, 442, 444–445, 452Mussolini, Benito, 375Myasthenia gravis

differentiating from botulism, 343Mycotoxins, 75–76Myonecrosis, 362, 363Myotoxins, 432–435

NNational Academy of Sciences, 73, 857National Biosurveillance Integration System, 101National Committee for Clinical Laboratory Standards, 166National Disaster Medical System, 123National Disaster Recovery Framework, 94, 96, 104National Guard, 100, 123National Incident Management System, 96–97, 121National Institute of Occupational Safety and Health, 879National Institutes of Health

human genome project, 58Office of Biotechnology Activities, 898Office of Science Policy, 20

National laboratories, 122National Mitigation Framework, 96National Naval Medical Center, 328National Preparedness Goal, 94, 98National Prevention Framework, 96National response, 98–102National Response Framework, 94, 96, 98–99, 100National Response Plan, 22National Safety Council, 6National Science Advisory Board for Biodefense, 20–21National Security Council, 22National Strategy for Countering Biological Threats, 23Navy field laboratories, 706NBC News

anthrax attack, 2001, 47–48NDRF. See National Disaster Recovery FrameworkNecrotizing enteritis, 363Nectrotoxins, 442–443Nepal

cholera outbreak, 648Nephrotixic plants, 450Nephrotoxins, 442Nerve agent poisoning

differentiating from botulism, 343Neuraminidases, 365, 367Neurotoxic plants, 450Neurotoxic shellfish poisoning

description of toxin, 465–466diagnosis of, 467inhalation-acquired disease, 466mechanism of action, 466medical management, 467oral ingestion, 466signs and symptoms, 466

Neurotoxins, 340–341, 424–432New Orleans, Louisiana

plague pandemic, 251New World mammarenaviruses, 520–521, 523, 526–527, 528–529New York, New York

plague pandemic, 251West Nile virus outbreak, 1999, 50–51

Next Generation Diagnostic System, 702, 704Next generation molecular diagnostics, 738Next-generation sequencing, 559, 738–739NGDS. See Next Generation Diagnostic SystemNightshade, 449

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NIH. See National Institutes of HealthNine Mile variant, 307–308Nipah virus, 549–552, 553–554, 669–670Nixon, Richard M., 7, 338, 897Nomenspecies, 160–161North America

alphavirus encephalitides outbreaks, 482, 487North Atlantic Treaty Organization, 718–719North Carolina

alphavirus encephalitides outbreaks, 482North Carolina Disease Event Tracking and Epidemiologic Col-

lection Tool, 57North Korea

accusations of US biowarfare attacks, 6biological warfare agents, 12

Nosocomial infections, 326–327NSABB. See National Science Advisory Board for BiodefenseNucleic acid-based identification

glanders, 199–201Nucleic acid vaccines, 829–830Nunn-Lugar Biological Threat Reduction Program, 10Nuremberg Code, 921, 922Nuttall, George, 362

OObama, Barack, 48, 377, 898Occupational Safety and Health Administration

Respiratory Protection Standard, 879Oculoglandular tularemia, 291Office International des Epizooties, 180–181Office of Biotechnology Activities, 898Office of Emergency Preparedness, 22Office of Public Health Emergency Preparedness, 22Office of Science and Technology Programs, 21Office of Science Policy, 20Ofloxacin

glanders, 203Q fever treatment, 311

OFPBL agar, 199Old World mammarenaviruses, 519–520, 522–523, 525–526, 528Oleander, 440Operation Whitecoat, 6, 858, 923Operations Desert Shield/Storm

biological agents exposure, 10immunologic protection, 113pyridostigmine bromide prophylaxis, 113

Operations Enduring Freedom/Iraqi FreedomAcinetobacter infections, 322, 323, 324–327Q fever outbreak, 53–54, 307

Oral ingestionamnesic shellfish poisoning, 468neurotoxic shellfish poisoning, 466palytoxin, 470–471paralytic shellfish poisoning, 464ricin, 380–382

Oropharyngeal anthrax, 138Orthopoxviruses

as biological warfare agents, 622–623characteristics of, 617–622classification, 617clinical aspects of infections, 624–628diagnosis of, 628–630entry into cells, 618immunodiagnosis, 629medical management, 630–635monkeypox, 627–628morphogenesis and egress, 619

morphology, 617–618nucleic acid diagnosis, 629–630pathogenesis, 621–622phenotypic diagnosis, 628–629phylogenetic relationships, 620–621prophylaxis, 630–634replication, 619specimen collection and handling, 628treatment of, 624–635

Outbreak investigations, 41–43

Pp38 mitogen activated protein kinase, 391Pacific Yew tree, 449Paclitaxel, 416–417Pakistan

glanders outbreak, 204Palytoxin

dermal exposure, 471description of toxin, 469–470diagnosis of, 472exposure through home aquaria, 471–472inhalation-acquired disease, 471mechanism of action, 470medical management, 472oral ingestion, 470–471signs and symptoms, 470–472

Pan-hazard preparedness, 17–24Pandemics

Avian influenza threat, 657–660Paralytic neurotoxins, 424–430Paralytic shellfish poisoning

cause of death, 464description of toxin, 463diagnosis of, 465differentiating from botulism, 343inhalation-acquired disease, 464mechanism of action, 463–464medical management, 465oral ingestion, 464signs and symptoms, 464

Paramyxoviruses, 669–670Parasites, 76–77Passive antibody therapy

hemorrhagic fever-causing mammarenaviruses, 530Passive hemagglutination antibody detection, 270Passive immunotherapy

alphavirus encephalitides, 497–498bacterial diseases, 758–759botulinum toxins, 794henipaviruses, 559–560Staphylococcal enterotoxin B, 795–796viral hemorrhagic fevers, 792

PBT. See Pentavalent botulinum toxoidpCD, 261PCR. See Polymerase chain reaction assaysPeake, Lieutenant General James B., 324Penicillin

anthrax exposure prophylaxis, 140anthrax treatment, 139

PennsylvaniaLegionnaires’ disease outbreak, 649

Pensacola, Floridaplague pandemic, 251

Pentavalent botulinum toxoid, 347, 793Personal protective equipment, 860–861, 877–880Personnel reliability programs, 898, 901, 905–908

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PFGE. See Pulsed field gel electrophoresisPhage shock protein response, 263Pharyngeal plague, 268Phleboviruses, 675–677Phospholipases, 135Physical protection, 112–113PLA2 toxins, 432–434Plague

antibiotic treatment, 272autotransporter proteins, 263biochemistry of, 255–256as biological warfare agent, 252–254Black Death, 250–251bubonic plague, 265, 267clinical manifestations, 265–269cutaneous, 268–269diagnosis of, 269–271endemic disease, 251–252epidemiology of, 256–259F1 antigen, 262fimbrae, 262–263first pandemic, 250gastrointestinal, 268growth characteristics, 254–255historical perspectives, 249–251incidence of, 259–261infectious agent characteristics, 254–256iron sequestration, 263isolation of patients, 271–272Justinian plague, 250laboratory confirmation, 269–271mammals known to harbor plague in the US, 257manganese sequestration, 263medical countermeasures, 764–765meningitis, 268morphology, 254pathogenesis, 264–265phage shock protein response, 263pharyngeal, 268plasminogen activator, 262pneumonic, 259, 267, 268postexposure prophylaxis, 273, 765prevention of, 272–273second pandemic, 250–251septicemic, 265–267signs and symptoms, 269small RNAs, 263surface structures, 263taxonomy, 254third pandemic, 251transmission of, 2–3treatment of, 271–274twin arginine transport, 263Type III secretion system, 261–262vaccines, 115, 273–274, 764–765virulence and transmission factors in the flea, 264virulence determinants, 261–264virulence factors in mammalian hosts, 262–263warfare and, 251–254

Plague Manual, 269Plague Vaccine USP, 273Plant poisons, 422, 440, 446–452Plaque reduction neutralization test, 629Plasminogen activator, 262pMT, 261Pneumonic plague, 259, 267, 268Pneumonic tularemia, 291–292Point source outbreaks, 40

Poisonsanimals, 422as biological warfare agents, 423definitions, 417epidemiology of, 418–423mushrooms, 422, 444–445plants, 422, 446–452research directions, 452–453

Polanduse of biological agents during World War II, 4

Poliovirus type 1, 19Polymerase chain reaction assays

Acinetobacter infection diagnosis, 328botulism diagnosis, 344brucellosis diagnosis, 161, 165filoviruses diagnosis, 593–595glanders diagnosis, 200, 202hemorrhagic fever-causing mammarenaviruses diagnosis,

529–530orthopoxviruses diagnosis, 629–630overview, 728–730real-time polymerase chain reaction, 678, 736–738ricin diagnosis, 387Staphylococcal enterotoxin B diagnosis, 408tularemia diagnosis, 293viral pathogen diagnosis, 678–679

Polysaccharide-based subunit vaccines, 207–208Portal Shield, 112Powered air-purifying respirators, 879Poxviruses, 617pPCP, 261Prairie dogs

plague transmission role, 257, 258President’s Disaster Relief Fund, 100Presumptive identification methods, 709–716Primary atypical pneumonia, 307Primates, nonhuman

as animal disease models, 188Project 112, 7Project BioShield Act, 22–23, 740, 926Pronase, 367Protective clothing, 112–113Protein kinases, 391, 406Protein subunit vaccines, 207Protein tyrosine kinases, 406Proteolysis, 364Proteus OX-19, 4Protoxin, 367PTA. See Pteroic acidPteroic acid, 390Public health preparedness, 102Public Health Security and Bioterrorism Preparedness and Re-

sponse Act of 2002, 931Public Health Service Act, 925, 926Public Readiness and Emergency Preparedness Act, 925Puffer fish, 422Pulpy kidney disease, 365Pulsed field gel electrophoresis, 325, 327, 328Purple foxglove, 447Putin, Vladimir, 10Pyridostigmine bromide, 113

QQ fever

diagnosis of, 311disease in animals, 310disease in humans, 310

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epidemiology of, 309–310Gulf War, 307historical perspectives, 306infectious agent, 307–309Iraq outbreak, 2005, 53–54, 307medical countermeasures, 770–772military relevance, 306–307outbreaks during World War II, 8, 306–307pathogenesis, 309postexposure prophylaxis, 772treatment of, 311vaccines, 115, 312, 770–771

Q-Vax, 312Queensland, Australia

Q fever outbreak, 306Quorum sensing systems, 191

RRajneesh, Bhagwan Shree, 13, 44–46Rajneeshee cult

bioterrorism attacks, 13, 44–46Raman spectroscopy, 202RANTES protein, 206Rat fleas

as plague vector, 256Rats

plague transmission role, 257, 258Ravn virus, 571–575Raxibacumab

anthrax treatment, 140Reagan, Ronald, 9Real-time Outbreak and Disease Surveillance Laboratory, 57Real-time polymerase chain reaction, 678, 736–738Recombinant granulocyte colony-stimulating factor, 234Recombinant vaccine vectors, 826–827Recovery operations, 103–105Red tides, 466Reference laboratories, 122Registered Biosafety Professional, 889–890Research, development, test, and evaluation laboratories, 888Research ethics. See Ethical issuesRespiratory Protection Standard, 879Respiratory system

Staphylococcal enterotoxin B effects, 407Respiratory tularemia, 291Reston virus, 571–575, 580, 587Restriction fragment-length polymorphism, 629–630RevCons, 17Reverse transcription-polymerase chain reaction, 558, 678Review conferences, 17Rhodesia

biological warfare agents, 11–12Ribavirin

henipavirus treatment, 560viral hemorrhagic fever treatment, 790–791

Ribosome inactivating proteins, 377Richardson, Shannon Guess, 16, 48, 377Ricin

activity assay, 386antibody treatment, 388attacks in US, 2003-2004, 48–49biochemical identification, 377–378as biological warfare agent, 376bioterrorism attacks, 13, 15–16, 376–377cause of death, 384–385cellular stress response inhibitors, 391description of agent, 377–379

detection of, 385–386diagnosis of, 386–387enzyme-linked immunosorbent assays, 385, 387handheld assay detection devices, 385, 387historical perspectives, 375–376inhalation of, 382–384injection of, 382liquid chromatography/mass spectrometry, 386, 387medical countermeasures, 796–797medical management, 387–391oral intoxication, 380–382pathogenesis, 378–379pathology, 379–385ricin A chain inhibitors, 390–391sample verification platforms, 385–386signs and symptoms of, 379–385small molecule inhibitors, 389–390Soviet Union attacks, 9supportive and specific therapy, 389transport inhibitors, 391vaccines, 387–388, 796

Rifampinbrucellosis treatment, 167

Riluzole, 366Ring vaccination, 115RIPs. See Ribosome inactivating proteinsRisk assessment systems, 95Risk communication, 115, 124RiVax, 388Rock squirrels

plague transmission role, 257, 258Roosevelt, Franklin D., 5, 858RTA. See Catalytic A-chainRTB. See Lectin B-chainRussell, Findlay E., 416RVEc, 388

SSabiá virus, 521, 523–524, 531Sacroilitis

brucellosis and, 164Safety audits, 887–888Saint Joseph, Missouri

Heartland virus, 676–677Salmonella

bioterrorism attacks, 13, 44–46food- and waterborne, 44–46, 73, 652

Salmonella typhimuriumattacks in Dalles, Oregon, 1984, 44–46food and waterborne, 73

Salmonellosisattacks in Dalles, Oregon, 1984, 44–46food and waterborne, 73

Sample verification platforms, 385–386San Francisco, California

plague pandemic, 251Sarin

bioterrorism attacks, 13SARS, 666Saudi Arabia

Middle Eastern respiratory syndrome, 666–669Saxitoxins, 463–465Scolopendrid centipede, 443Scorpion stings, 419–420, 430–432, 442–443Sea snakes, 420–422Secreted proteins, 189–190Secretory systems, 189–190

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Security risk assessment, 900Select Agent List, 22Select Agent Program, 14, 23Select Agent Regulations, 900, 902Select Agents and Toxins Program, 375Senate Office Building

anthrax attack, 2001, 47–48ricin attacks in 2004, 48–49, 377

Sentinel laboratories, 122Septic abortions

Brucella and, 162–163Septicemic disease

plague, 265–267septicemic glanders, 195tularemia, 292

Sequence types, 328Sequencing technology, 58–59Serologic diagnoses

filoviruses, 583glanders, 201–202plague, 270tularemia, 293

Severe acute respiratory syndrome, 666Severe fever with thrombocytopenia syndrome virus, 675–676Shiga toxins, 74, 377, 651–652Shigella dysenteriae

attacks in Dallas, Texas, 1996, 47food and waterborne, 74–75

Shigella sonnei, 78Shigellosis

attacks in Dallas, Texas, 1996, 47food and waterborne, 74–75

Shipping standards, 723Sialidases, 365Simonson, Stewart, 340Singapore Armed Forces

melioidosis cases, 225Skin diseases

cutaneous anthrax, 135–136cutaneous plague, 268–269

Skin irritationplants causing, 451

Small molecule inhibitors, 389–390Small RNAs, 263Smallpox

as biological warfare agents, 622–623biothreat policy, 634characteristics of virus, 617–622classification, 617clinical aspects of infections, 624–626diagnosis of, 628–630entry into cells, 618immunodiagnosis, 629impact on Native Americans, 3medical countermeasures, 776–788medical management, 630–635morphogenesis and egress, 619morphology, 617–618nucleic acid diagnosis, 629–630outbreak in Yugoslavia, 39pathogenesis, 621–622phenotypic diagnosis, 628–629phylogenetic relationships, 620–621preparedness, 18–19prophylaxis, 630–634replication, 619Soviet Union production of virus, 9specimen collection and handling, 628

treatment of, 624–635vaccine, 114–115, 777–787WHO eradication program, 9

Smallpox Response Plan, 628Smuggling risks, 80Snakes, venomous, 418–419, 424–426, 428–430, 432–442Soman

pyridostigmine bromide prophylaxis, 113South Africa

biological warfare agents, 11–12South America

alphavirus encephalitides outbreaks, 482Chikungunya outbreak, 674

South Koreasevere fever with thrombocytopenia syndrome virus, 676

Soviet Unionaccidental anthrax release, 49–50, 130accusations of US biowarfare attacks, 6–7biological warfare agents, 8–10C. botulinum research program, 338–339filoviruses biological warfare program, 584–586plague warfare research, 254ricin as biological weapon research, 376

Specimen collection, 719–722Spider bites, 419–420, 421, 430, 432, 442–443Spokane, Washington

ricin attacks in 2004, 377Squirrels

plague transmission role, 257–258Stafford Act, 98, 100Stalin, Joseph, 9Standing operating procedures, 876Staphylococcal enterotoxin B

animal models, 405–406cardiovascular symptoms, 407–408characterization of, 404–405clinical disease, 406–408detection of, 408development of therapeutics, 409diagnosis of, 408fever onset and duration, 407headache onset and duration, 407hematology, 408host response, 405–406medical countermeasures, 795–796medical management, 408–409nausea and vomiting, 407ocular effects, 408respiratory symptoms, 407signs and symptoms, 406–408vaccines, 409, 795

Staphylococcus aureusanimal models, 405–406cardiovascular symptoms, 407–408characterization of toxins, 404–405clinical disease, 406–408detection of, 408development of therapeutics, 409diagnosis of, 408fever onset and duration, 409headache onset and duration, 407hematology, 408host response, 405–406medical management, 408–409nausea and vomiting, 407ocular effects, 408respiratory symptoms, 407signs and symptoms, 406–408vaccines, 409

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State response planning, 102Sternberg, Surgeon General George, 918Stevens, Robert, 14Stillmark, Peter Hermann, 375Stimson, Henry L., 921Stingrays, 421–422Stings, venomous, 418Strategic National Stockpile, 22–23, 102, 123, 631–632Streptococcus pyogenes

animal models, 405–406cardiovascular symptoms, 407–408characterization of toxins, 404–405clinical disease, 406–408detection of, 408development of therapeutics, 409diagnosis of, 408fever onset and duration, 409headache onset and duration, 407hematology, 408host response, 405–406medical management, 408–409nausea and vomiting, 407ocular effects, 408respiratory symptoms, 407signs and symptoms, 406–408vaccines, 409

Streptomycinbrucellosis treatment, 166–167glanders treatment, 204

Strokedifferentiating from botulism, 343

Structural vaccinology, 829Subunit vaccines, 827–829Sudan virus, 571–575, 587–589, 597Sulfadiazine

glanders treatment, 204Superantigens, 404Supportive therapy

ricin, 389Staphylococcal enterotoxin B, 408

Surface polysaccharides, 189Surface structures, 263Suzuki, Dr. Mitsuru, 12Sverdlovsk, Soviet Union

accidental anthrax release, 49–50, 130Swine influenza, 660–661Syndromic surveillance, 56–57Synthetic biology, 681Syria

biological warfare agents, 12ricin as biological weapon research, 376

Systems vaccinology, 829

TT-cell receptors, 404–405T-cells

response to Brucella, 163Tactical Combat Casualty Care, 140Taenia solium, 76–77Taï virus, 571–575, 580, 587, 589Tanzania

Chikungunya outbreak, 673–674Tapeworms, 76–77Technical Escort Units, 117Terrorism, biological. See BioterrorismTetrodotoxin, 422, 426, 430

Texasplague pandemic, 251

Thailandbotulinum toxin foodborne outbreak, 339–340melioidosis incidence, 227

Thompson, Diane, 12Thrombocytopenia syndrome, 675–676Tickborne disease

anaplasmosis, 654–655borreliosis, 652–654differentiating from botulism, 343Ehrlichiosis, 654–655Heartland virus, 676–677paralysis caused by Ixodidae family, 419–420phleboviruses, 675–677severe fever with thrombocytopenia syndrome virus, 675–676

TMP-SMXmelioidosis treatment and prophylaxis, 234, 236

Tokyo, JapanAum Shinrikyo cult anthrax attacks, 13, 46–47

Toll-like receptors, 404Torovirus, 78Toxic shock syndrome, 404–405, 408Toxins

arachnids, 419–420biological surety, 896–911as biological warfare agents, 423bites, 418botulinum toxins, 72–73, 340–349, 793–795cardiotoxins, 440–441classes, 424–452cnidarians, 420–422definitions, 417epidemiology of, 418–423excitatory neurotoxins, 430–432fish, 420–422hemolytic toxins, 437–440hemorrhagic toxins, 437–440hemostasis-active toxins, 435–437insects, 420, 421marine algal, 462–473medical countermeasures, 793–797myotoxins, 432–435nectrotoxins, 442–443nephrotoxins, 442origin of word, 2paralytic neurotoxins, 424–430research directions, 452–453scorpions, 419–420sea snakes, 420–422snakes, 418–419spiders, 419–420, 421staphylococcal enterotoxin B, 404–409, 795–796stings, 418

Transport inhibitors, 391Tree squirrels

plague transmission role, 257Trimethoprim

glanders treatment, 204Tularemia

aerosol transmission, 288arthropod vectors, 288bacterial culture techniques, 293clinical manifestations, 290–292diagnosis of, 292–294direct contact, 287epidemiology of, 287–289food and water ingestion, 288

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infectious agent, 286–287Kosovo outbreak, 1999-2000, 52–53laboratory-acquired, 289laboratory worker exposure, 296mammalian bites, 288Martha’s Vineyard outbreak, 2000, 51–52, 292medical countermeasures, 761–764pathogenesis, 289–290postexposure prophylaxis, 295, 764prophylactic treatment, 295–295rapid diagnostic methods, 293–294serology, 293treatment of, 294–295in unusual settings, 288–289use as biological weapon, 296vaccination with live vaccine strain, 289, 290, 295–296, 761–763

The Turner Bill, 933Twin arginine transport, 263Type III secretion system, 261–262Typhoidal tularemia, 291, 292

UU.K. Laboratory of HealthCare Associated Infections, 327Ukraine

plague pandemic, 250, 252Ulceroglandular tularemia, 291, 292UN Special Commission, 10, 11United States Naval Ship Comfort, 323, 325University of Pittsburgh, 57UNSCOM. See UN Special CommissionUruguay Round Agreement on the Application of Sanitary and

Phytosanitary Measures, 80U.S. Army Center for Health Promotion and Preventive Medicine, 324U.S. Army Medical Command, 329U.S. Army Medical Research and Materiel Command, 329U.S. Army Medical Research Institute of Infectious Diseases

anthrax sample testing, 14–15biosafety, 880–881casualty management, 110–124creation of, 8, 923ricin vaccine research, 388tularemia vaccine, 295–296

U.S. Congressanthrax attacks in US, 2001, 47–48, 130ricin bioterrorism attack, 16, 377

U.S. Department of Agriculture, 5, 23, 44, 80, 101–102, 703, 897U.S. Department of Defense, 57, 112, 324, 329, 331–332, 628, 704,

888, 927–931U.S. Department of Energy, 58U.S. Department of Health and Human Services, 20, 21–22,

100–102, 703, 897U.S. Department of Homeland Security, 23, 56, 94, 101–102U.S. Department of State, 102U.S. Department of Transportation, 902U.S. Environmental Protection Agency, 882–883U.S. Food and Drug Administration, 82, 112, 272, 587, 702–704,

916, 926–933U.S. military. See also specific wars by name

biological warfare agents, 4–8Health System response to Acinetobacter infectionslaboratories, 705–708, 716–718options for fulfilling mission and ethical responsibilities to

military personnel, 929–931plague risks at military installations, 252, 253

U.S. National Science Advisory Board for Biosecurity, 59U.S. Postal Service

anthrax attacks in 2001, 47–48, 130

ricin attacks in 2003-2004, 48–49ricin bioterrorism attack, 16

USA PATRIOT Act, 897, 900USAMRIID. See U.S. Army Medical Research Institute of Infec-

tious DiseasesUSDA. See U.S. Department of Agriculture

VV3526 vaccine, 500Vaccine Adverse Event Reporting System, 757Vaccines

ACAM2000 vaccine, 115adjuvants, 831–832adverse events, 757–758alphavirus encephalitides, 498–501, 773–776, 777–787, 789–790anthrax, 10, 113, 114, 140–141, 753–758bacterial diseases, 753–756botulinum toxin, 348, 793–794brucellosis, 768Clostridium perfringens, 363, 366–367filoviruses, 587, 588–589glanders, 206, 207–208, 766inactivated, 499live attenuated vaccines, 207, 273, 758, 825–826live vaccine strains, 289, 290, 295–296, 498–499melioidosis, 234–236, 766mucosal vaccines, 830–831nucleic acid vaccines, 829–830orthopoxviruses, 630–634plague, 115, 273–274, 764–765Q fever, 115, 312, 770–771recombinant vaccine vectors, 826–827ricin, 387–388, 796rickettsial diseases, 753–754ring vaccination, 115smallpox, 114–115, 777–787Staphylococcal enterotoxin B, 409, 795Staphylococcus aureus, 409Streptococcus pyogenes, 409subunit vaccines, 827–829trends in biodefense development, 824–825tularemia, 289, 290, 295–296, 761–763viral hemorrhagic fevers, 788–790whole cell vaccines, 312yellow fever, 115

Vaccinia immune globulin, 633, 634Vaccinia virus, 825–826Variola virus, 617, 622–623–626Vascular leak syndrome, 376Venezuelan equine encephalitis, 483–484, 485, 492–493, 773–774Venezuelan hemorrhagic fever, 521, 530Venoms

arachnids, 419–420as biological warfare agents, 423bites, 418cnidarians, 420–422definitions, 417epidemiology of, 418–423fish, 420–422insects, 420, 421research directions, 452–453scorpions, 419–420sea snakes, 420–422snakes, 418–419spiders, 419–420, 421stings, 418

Verotoxin, 377

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VHF. See Viral hemorrhagic feversVibrio cholerae, 77, 647–649Vibrioses, 649Vietnam War

melioidosis cases, 225plague incidence, 252plague prevention, 249

Viral hemorrhagic fevers, 725, 788–793Virginia

alphavirus encephalitides outbreaks, 482Virtual screening, 390, 391Virulence factors

glanders, 191melioidosis, 228–230

Virus-like particles, 828Virus replicon particle vaccines, 501, 827Virus-Toxin Law, 926

WW bombs, 376Walter Reed Army Institute of Research, 324, 327, 328–330Walter Reed Army Medical Center

Acinetobacter infections, 323, 324–327War Bureau of Consultants, 857War Research Service, 921War Reserve Service, 5Washington

plague pandemic, 251ricin attacks in 2004, 377

Washington, George, 918Waste disposal, 882–884Water Sentinel program, 78Water supply

bioterrorism concerns, 77–78security of, 80–82

Waterborne diseasescholera, 647–649cryptosporidiosis, 75emerging diseases, 647–650Escherichia coli, 74hepatitis A, 75Legionellosis, 649–650listeriosis, 73–74parasites, 76–77salmonellosis, 73shigellosis, 74–75threat potential, 76, 77vibrioses, 649

Weapons of Mass Destruction-Civil Support Teams, 123Weekly Epidemiological Record, 259Welch, William, 362West Africa

Ebola virus epidemic, 677–678West Nile virus

New York City outbreak, 1999, 50–51yearly spread of activity across the U.S., 1999-2004, 672–673

Western blot assay, 202Western equine encephalitis, 484, 485–486, 494–495, 774–776Whitmore, Captain Alfred, 224WHO. See World Health OrganizationWhole cell vaccines, 312Whole genome sequencing, 656–657Wicker, Roger

ricin attacks in 2004, 48–49, 377Wood rats

plague transmission role, 258Working Group on Civilian Biodefense, 272, 273

World Health Assembly, 18World Health Organization

anthrax surveillance and control guidelines, 140attempted investigation of biologic agent use during World

War II, 6Plague Manual, 269smallpox eradication program, 9Weekly Epidemiological Record, 259

World Trade Organization, 80World War I and II

gas gangrene, 363plague attacks, 252–254plague outbreak, 252Q fever outbreaks, 8, 306–307ricin as biological weapon research, 376use of biological agents, 3–4, 43–44, 78

Wound botulism, 342, 344WRAIR. See Walter Reed Army Institute of Research

XXoma 3AB, 346

YYellow fever, 115Yellow Fever Commission, 918Yellow fever virus, 827Yellow oleander, 440Yeltsin, Boris, 10, 338–339Yersinia pestis

antibiotic treatment, 272autotransporter proteins, 263biochemistry of, 255–256as biological warfare agent, 252–254Black Death, 250–251bubonic plague, 265, 267characteristics of, 254–256clinical manifestations, 265–269cutaneous plague, 268–269diagnosis of, 269–271differentiation from Y. pseudotuberculosis, 254endemic disease, 251–252epidemiology of, 256–259F1 antigen, 262fimbrae, 262–263first pandemic, 250gastrointestinal plague, 268growth characteristics, 254–255historical perspectives, 249–251incidence of, 259–261iron sequestration, 263isolation of patients, 271–272Justinian plague, 250laboratory confirmation, 269–271manganese sequestration, 263medical countermeasures, 764–765morphology, 254pathogenesis, 264–265phage shock protein response, 263pharyngeal plague, 268plague meningitis, 268plasminogen activator, 262pneumonic plague, 267, 268postexposure prophylaxis, 273, 765prevention of, 272–273second pandemic, 250–251septicemic plague, 265–267

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signs and symptoms, 269small RNAs, 263surface structures, 263taxonomy, 254third pandemic, 251treatment of, 271–274twin arginine transport, 263Type III secretion system, 261–262vaccines, 115, 273–274, 764–765virulence and transmission factors in the flea, 264virulence determinants, 261–264virulence factors in mammalian hosts, 262–263warfare and, 251–254

Yersinia pseudotuberculosis, 254, 255YopK, 262Yugoslavia

smallpox outbreak, 39

ZZmapp, 792Zoonotic illnesses. See Animal diseases

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