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Association of Occupational and Environmental Clinics. Worker Preparedness and Response to Bioterrorism. Edward W. Cetaruk, M.D. Toxicology Associates University of Colorado Health Sciences Center Denver, Colorado, USA. Section 1 An Overview of Biological Weapons. Objectives:
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Association of Occupational and Environmental Clinics Worker Preparedness and Response to Bioterrorism Edward W. Cetaruk, M.D. Toxicology Associates University of Colorado Health Sciences Center Denver, Colorado, USA
Section 1An Overview of Biological Weapons Objectives: To be able to list biological agents that may be weaponized To describe the process of weaponization To develop an understanding of the bioterrorist threat To be able to recognize a biological attack
Probability vs. Potential Impact BIOLOGICAL AGENT NUCLEAR WEAPON IMPROVISED NUCLEAR DEVICE CHEMICAL AGENT OR TOXIC INDUSTRIAL CHEMICAL POTENTIAL IMPACT RADIOACTIVE MATERIAL PROBABILITY/LIKELIHOOD
History of Biological Warfare • Oldest of the NBC triad of agents • Used for > 2,000 years • Sieges of middle ages • Smallpox blankets given to Native Americans • Germany in World War I • Japan in World War II • Modern Bioterrorism
Aum Shinrikyo Cult • Sarin Nerve Agent attacks 1994 and 1995 • Attempted Botulinum Toxin release multiple times • Anthrax released multiple times • Attempted to obtain Ebola virus in Zaire
Weaponized Biowarfare Agents • Anthrax • Botulinum Toxin A • Brucellosis • Glanders • Marburg Virus • Plague • Q Fever • Salmonella • Smallpox • Staph Enterotoxin B • Monkey Pox • Ricin • Tularemia • VEE • VHFs
Biological Agents of Highest ConcernCategory A • Variola major (Smallpox) • Bacillus anthracis (Anthrax) • Yersinia pestis (Plague) • Francisella tularensis (Tularemia) • Botulinum toxin (Botulism) • Filoviruses and Arenaviruses (Viral hemorrhagic fevers) • ALL suspected or confirmed cases should be reported to health authorities immediately
Incubation Periods of Selected Biological Agents Anthrax 1-5 Days++ Plague 2-3 Days Q Fever 10-40 Days Tularemia 2-10 Days Smallpox 7-17 Days Viral encephalitides V(2-6d); E&W (7-14 d) VHFs 4-21 Days Botulinum toxin 1-5 Days Staph. enterotoxin B 1-6 Hours
Infective Aerosol Doses of Selected Biological Agents Anthrax 8,000 (or fewer) spores Plague 100-500 organisms Q Fever 1-10 organisms Tularemia 10-50 organisms Smallpox 10-100 organisms Viral encephalitides 10-100 organisms VHFs 1-10 organisms Botulinum toxin 0.001 ug/kg
Aerosol Size and Infectivity Infection Severity Particle Size (Micron, Mass Median Diameter) The ideal aerosol contains a homogeneous population of 2 or 3 micron particulates that contain one or more viable organisms Less Severe More Severe 18-20 15-18 7-12 4-6 (bronchioles) 1-5 (alveoli) Maximum human respiratory infection is a particle that falls within the 1 to 5 micron size
Epidemiologic Clues • Large epidemic with high illness and death rate • Immunocompromised individuals may have first susceptibility • Respiratory symptoms predominate • Infection non-endemic for region • Multiple, simultaneous outbreaks • Multi-drug-resistant pathogens • Sick or dead animals • Delivery vehicle or intelligence information
Epidemiologic Information • Travel history • Local • Distant • Infectious contacts • Employment history • Activities over the preceding 1 to 2 weeks
Section 2Bioterrorism and the Workplace Objectives: To be able to develop practices and procedures to defend workers and the workplace from a bioterrorist attack To respond the unique risks faced by first responders To be able to choose and use the correct PPE needed for biological weapons
Bioterrorism Educational Needs of the Worker • Awareness • Fundamental understanding of biowarfare agents • Recognition and handling of suspicious mail or dissemination devices • PPE and workplace safety • Recognition of bioterrorist attack • Post exposure management
Bioterrorism:Who are First Responders? • Primary Care Personnel • Hospital ER Staff • Public Health Professionals • Emergency Response Personnel • Laboratory Personnel • Law Enforcement • Public • Military
First Responders • Often dealing with unknown agent(s) • May be exposed to infectious agent • May be exposed to infectious patients • May be targeted with secondary devices • May be first to notice the epidemiological pattern of a bioweapons attack
Emergency Plan • All Hazards Approach • Identify areas with risk of exposure • Develop controls to minimize risk • Engineering Controls • Administrative Controls • Housekeeping Controls • PPE for workers • Develop response and recovery plan • Training and Exercises
Emergency PlanExposure to Biological Agent • Policies and Procedures for handling suspicious mail or packages • Plan for facility response • Plan for involving appropriate authorities • Medical Surveillance • Training and Exercises
Handling of Suspicious Mail • Do not shake, empty contents • Do not carry, show others, or allow others to examine it • Do not sniff, touch, look closely at it, or any contents that may have spilled • Leave on stable surface, alert others, leave area, close doors, shut off ventilation • Wash hands with soap and water • Notify law enforcement • Create list of persons with potential contact
Personal Protective Equipment • Level A • SCBA, Encapsulation • Level of protection for entering contaminated, unsecured scene • Level B • Level C • Level D
Personal Protective EquipmentRespirators Powered Air-Purifying Respirator (PAPR) • HEPA filter face masks (N95, N100) • Respirators must be in compliance with OSHA respiratory standard (29 CFR 1910.134) • Respirators must be fit tested
PPERespirators • Respirators should be used in accordance with a respiratory-protection program that complies with the OSHA respiratory-protection standard (29 CFR 1910.134). N95 N100
Personal Protective EquipmentRespirators • The respirator is properly positioned over your nose and mouth at all times • The top strap or head harness assembly is positioned high on the back of the head • The lower strap is worn at the back of the neck below the ears • The straps are snug enough to keep the respirator from moving but not overly tight • Nothing (beards, head coverings, etc.) passes between the skin of the face and the respirator’s sealing edge
PPEDermal Protection • Disposable • Reusable • Overgarments, Booties, Hoods, Gloves • All PPE should be decontaminated prior to leaving potentially contaminated area • PPE should be removed and discarded prior to removing face mask
Section 3Anthrax as a Biological Weapon Objectives: To understand the microbiology and epidemiology of anthrax To understand the pathophysiology of the different anthrax clinical syndromes To be able to recognize cutaneous anthrax To be able to recognize an intentional anthrax release To be able to treat patients with anthrax
AnthraxMicrobiology & Epidemiology • Bacterium • Spores may survive > 100 yrs • Worldwide soil distribution • Common disease of herbivores • Herbivores in USA vaccinated • Man infected via animal products • Woolsorter’s Disease
AnthraxWorldwide Occurrence Source: WHO World Anthrax Data Site
AnthraxPathophysiology • Spore enters skin, GI tract, or lung • Germinates in macrophage • Transported to regional lymph nodes • Local production of toxins • Swelling and Tissue Death • Toxemia
Anthrax Clinical Syndromes • Cutaneous • Gastrointestinal • Inhalational Multiple forms can be seen as the result of a BW attack
AnthraxGastrointestinal • Abdominal pain, usually accompanied by bloody vomiting or diarrhea, followed by fever and signs of sever infection • GI anthrax is sometimes seen as mouth and throat ulcerations with tender neck glands and fever • Develops after ingestion of contaminated, poorly cooked meat. • Incubation period: 1–7 days • Case-fatality: 25–90% (role of early antibiotic treatment is undefined)
Anthrax:Cutaneous • Begins as a papule, progresses through a vesicular stage to a depressed black necrotic ulcer (eschar) • Edema, redness, and/or necrosis without ulceration may occur • Form most commonly encountered in naturally occurring cases • Incubation period: 1–12 days • Case-fatality: • Without antibiotic treatment: 20% • With antibiotic treatment: 1%
Cutaneous Anthrax Hospital Day 5 Hospital Day 12 2 months after discharge JAMA. 2002;287:869-874
Inhalational Anthrax Clinical Presentation • Incubation Period: 1-6 days • A brief prodrome resembling a “viral-like” illness, characterized by muscle aches, fatigue, fever, with or without respiratory symptoms, nausea, vomiting, abdominal pain • Early Symptoms: malaise, fever, fatigue, non-productive cough, chest discomfort • Confusion, neck stiffness, and headache suggest meningitis (seen in 50% of patients)
Inhalational Anthrax Clinical Presentation • After initial onset of illness, symptoms may remain mild or even improve slightly before worsening • Terminal Phase: dyspnea, stridor, cyanosis, shock, chest wall edema, meningitis, widened mediastinum with effusion with overall toxic/septic clinical picture
Symptoms n=10 Fever, chills 10 Sweats, often drenching 7 Fatigue, malaise, lethargy 10 Cough 9 Nausea or vomiting 9 Dyspnea 8 Chest discomfort or pleurisy 7 Myalgias 6 Headache 5 Confusion 4 Abdominal pain 3 Sore throat 2 Rhinorrhea 1 Presenting Symptoms Emerg Infect Dis vol.7, no. 6, 2001
Anthrax Diagnosis • Clinical picture of sudden onset of respiratory distress with mediastinal widening on x-ray • A small number of patients may present with GI or cutaneous anthrax • Gram stain of blood and blood cultures - but these may be late findings in the course of the illness • ELISA, FA, PCR and immunohistology testing may confirm diagnosis but samples must go to reference laboratory
Anthrax Treatment • Post-exposure • Oral prophylaxis • Ciprofloxacin (500 mg PO q12 h) X 60 days and until 3 doses of vaccine • Doxycycline (100 mg PO q12 h) X 60 days and until 3 doses of vaccine • Vaccination • Acute Treatment • Usually futile in severe mediastinitis patients who inhaled or ingested spores • Ciprofloxacin - 400 mg IV q 8 to 12 hr • Doxycycline - 100 mg IV q 12 hr • Vaccination
Anthrax Vaccine • FDA approved 1970 • Cell Free filtrate (NO organisms, dead or alive) • Adverse effects 1-3% • Bioport Corporation
Laboratory Workers • Increased number of highly pathogenic bacterial and viral samples • Increased need for universal precautions • Increased need for security, including maintaining chain of custody for forensic samples • Increased need for decontamination procedures • Laboratory Response Network (LRN)
Laboratory WorkersDecontamination and Disinfection • Effective sporicidal solutions: • Commercially-available bleach diluted to 0.5% Sodium hypochlorite (1 part household bleach to 9 parts water) • Rinse off concentrated bleach to avoid caustic effects • Approved sporicidal agents
Section 4Plague as a Biological Weapon Objectives: To be able to describe the pathophysiology and epidemiology of plague. To be able to recognize and treat the different clinical forms of plague. To be able to control the secondary transmission of plague
PlagueHistory • 200,000,000 deaths • Biblical (I Sam.) - 1320 BC, Philistines • Major Pandemics • 541 - Plague of Justinian • 1346 - ‘Black Death’ • 1894 - Modern Pandemic
1894 - Began in China • 1898 - Southwest to India • 1898 - South to Vietnam • 1900 - Trans-Pacific to United States Plague Distribution
PlagueEpidemiology • Vector: fleas, >80 species • Xenopsylla cheopis (Oriental rat flea) • Fleas feed on plague-infected mammal • Bacteria multiply in gut • Coagulum blocks gut • Plague organisms are regurgitated into bite wound with next feeding Photo: Ken Gage, Ph.D., CDC, Fort Collins, CO
PlagueEpidemiology • Reservoir: mammals, >200 species. • Rattus rattus (Black rat) • Ground squirrels, prairie dogs, cats
PlaguePathogenesis • Yersinia pestis - a Gram negative, nonmotile, nonsporulating bacteria • Size: 0.5–0.8 × 1.5–2.0 µm • Normally a disease of rodents • Virulence Factors: antiphagocytic fraction 1 capsule, pH 6 antigen, antiphagocytic Yops H and E, V antigens, Yop M, and plasminogen activator
Lung Meninges Liver Spleen PlaguePathophysiology Inoculation or inhalation (1-10 organisms) (100-20,000 organisms) Macrophage Lymphatics Regional lymph nodes Blood
Bubonic PlagueClinical Presentation • Incubation 1-8 days (mode 3-5 days) • Sudden onset of flu-like syndrome • (Fever, rigors, malaise, myalgias, nausea) • Bubo formation - within 24 hours • Swollen, infected lymph node (very painful!) • Cutaneous findings in 25% of cases • Mortality: Untreated 60% Treated <5%