Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 110 Potential Weapons of Biologic, Radiologic, and Chemical Terrorism

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.2 Potential Weapons of Terrorism  Bacteria  Viruses  Biotoxins  Chemical weapons  Nerve agents and mustard gas  Radiologic weapons

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.3 Bacteria and Viruses  Anthrax  Bacillus anthracis Aerobic gram-positive bacterium Aerobic gram-positive bacterium  Dormant form viable for decades  Inhalational, cutaneous, gastrointestinal  Enters the body via the skin or mucous membranes of the respiratory tract  Not transmitted person to person

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.4 Inhalational Anthrax  Anthrax spores deposit in alveolar space  Even with treatment, mortality can be high  Clinical latency 2 days to 4 weeks  Mature bacilli release toxins Hemorrhage, edema, and necrosis Hemorrhage, edema, and necrosis If toxins reach critical level, antibiotics cannot prevent death If toxins reach critical level, antibiotics cannot prevent death  Initial symptoms  Fever, cough, malaise, weakness  Second stage (2–3 days later)  Sudden increase in fever, severe respiratory distress, septicemia, hemorrhagic meningitis, and shock

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.5 Cutaneous Anthrax  Symptoms 1–7 days after exposure to spores  Broken skin most vulnerable  Injury can develop anywhere spores land  Initial lesion: small papule or vesicle associated with local itching 2 days: lesion enlarges into painless ulcer with necrotic core 2 days: lesion enlarges into painless ulcer with necrotic core 7–10 days after symptoms: black eschar forms, then dries, loosens, and sloughs off by days 12–14 7–10 days after symptoms: black eschar forms, then dries, loosens, and sloughs off by days 12–14  In most cases, lesions resolve without complications or scarring  Treatment is usually successful, but 20% die without antibiotic treatment

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.6 Treatment of Anthrax Infection  Respiratory  IV ciprofloxacin  IV doxycycline  Raxibacumab (not yet tested in humans)  Cutaneous  Oral ciprofloxacin  Oral doxycycline

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.7 Pre-Exposure Vaccination  BioThrax (formerly known as Anthrax Vaccine Adsorbed, or AVA)  Licensed for use in United States  Inactivated cell-free preparation  3 subQ injections 2 weeks apart, then at 6, 12, and 18 months  Annual boosters recommended  Persons at high risk should be vaccinated Military personnel and those who handle animal products from anthrax-endemic areas, including veterinarians, laboratory workers, and others Military personnel and those who handle animal products from anthrax-endemic areas, including veterinarians, laboratory workers, and others

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.8 Postexposure Prophylaxis  Oral antibiotics + Anthrax vaccine  Vaccine at 0, 2, and 4 weeks  BioThrax not currently licensed for postexposure use  Emergency use: investigational new drug application

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.9 Francisella tularensis (Tularemia) “Rabbit Fever” and “Deer Fly Fever”  Potentially fatal  Skin, mucous membranes, GI tract, or lungs  Acute influenza-like symptoms initially  Pneumonia and pleuritis can develop  Treatment  IM streptomycin or IM gentamicin  Mass outbreak and prophylaxis: oral doxycycline or ciprofloxacin

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.10 Yersinia pestis  Gram-negative bacillus  Plague  Two principal forms  Bubonic: tender, enlarged, and inflamed lymph nodes Rarely develops into pneumonic Rarely develops into pneumonic Not transmitted person to person Not transmitted person to person  Pneumonic: inflammation of the lungs Transmitted by cough Transmitted by cough

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.11 Pneumonic Plague  Transmitted person to person  Acquired by inhaling aerosolized Yersinia pestis  With no treatment, rapidly progresses to respiratory failure and death  Treatment is streptomycin (IM) and gentamicin (IM or IV)  Mass casualty—oral doxycycline or ciprofloxacin

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.12 Smallpox  No proven treatment  Highly contagious; fatality rate 30%  ACAM2000 approved vaccine  Imvamune (in clinical trials)  Vaccine produces high level of immunity for 5–10 years (before exposure or within a few days of exposure)  Pathogenesis and clinical manifestations  Transmission

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.13 Smallpox Vaccine  Efficacy  Duration of protection  Administration  Interpreting the response

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.14 Smallpox Vaccine  Adverse effects  Mild effects Local inflammation, along with swelling and tenderness in regional lymph nodes Local inflammation, along with swelling and tenderness in regional lymph nodes Transient symptoms (fever, headache, muscle aches, fatigue) Transient symptoms (fever, headache, muscle aches, fatigue)  Moderate to severe Eczema vaccinatum, generalized vaccinia, progressive vaccinia, postvaccinial encephalitis, fetal vaccinia, possible cardiac effects Eczema vaccinatum, generalized vaccinia, progressive vaccinia, postvaccinial encephalitis, fetal vaccinia, possible cardiac effects Vaccinia immune globulin (VIG) and cidofovir (Vistide) Vaccinia immune globulin (VIG) and cidofovir (Vistide)  Who should not be vaccinated?  Persons with eczema, atopic dermatitis, immunodeficiency, pregnancy  Persons living with someone who has contraindications

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.15 Biotoxins  Botulinum toxin  Clostridium botulinum  Blocks release of acetylcholine from cholinergic neurons  With no treatment, rapidly leads to paralysis and respiratory failure and death  Classic symptoms: double vision, blurred vision, drooping eyelids, slurred speech, dry mouth, dysphagia, muscle weakness, descending flaccid paralysis

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.16 Botulinum Toxin  Treatment  Prolonged supportive care Fluid/nutritional support Fluid/nutritional support Mechanical ventilation Mechanical ventilation  Immediate infusion of botulinum antitoxin

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.17 Ricin  Toxin present in castor beans  Extraction from the “mash” when beans are processed to make castor oil  Powder, pellet, mist, or dissolved in water or a weak acid  Inhibits protein synthesis  Treatment is purely supportive  No antidote for ricin  Vaccine in development

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.18 Ricin: Clinical Manifestations  Inhalation  In a few hours: coughing, chest tightness, difficulty breathing, nausea, muscle aches  Later: severely inflamed/edematous airway; cyanosis and death can follow  Ingestion  Intestinal and gastric hemorrhage, vomiting, diarrhea; then liver, spleen, kidneys may fail; death within 10–12 days of ingestion  Injection  Severe symptoms and death; impractical route for terrorism

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.19 Chemical Weapons  Nerve agents  Produce a state of cholinergic crisis, characterized by excessive muscarinic stimulation and depolarizing neuromuscular blockade  Treatment: mechanical ventilation, atropine, pralisoxime, and diazepam

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.20 Chemical Weapons  Sulfur mustard (mustard gas)  Alkylating agent and vesicant  Can be vaporized into air or released into water supply  Injuries severe, but fatality rate is low  During World War I: killed less than 5% of victims  Symptoms of toxicity depend on the dose, the tissue involved, and the duration of exposure  Treatment: rapid decontamination, supportive care, and drug therapy

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.21 Radiologic Weapons  Nuclear bombs  Immediate and delayed impact  Nuclear power plant attack  Radiation exposure in area  Dirty bombs (radiologic dispersion devices)  Radioactive material formulated into powder or pellets

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.22 Drugs for Radiation Emergencies  Potassium iodide  Prompt treatment necessary  Penetrate zinc trisodium and penetrate calcium trisodium  Treatment within 24 hours most effective  Prussian blue (Radiogardase)