Association of Occupational and Environmental Clinics Edward W. Cetaruk, M.D. Toxicology Associates University of Colorado Health Sciences Center Denver, Colorado, USA Worker Preparedness and Response to Bioterrorism

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 History of Biological Warfare

Anthrax Letters United States

Anthrax Anthrax Botulinum Toxin A Botulinum Toxin A Brucellosis Brucellosis Glanders Glanders Marburg Virus Marburg Virus Plague Plague Q Fever Q Fever Salmonella Salmonella Smallpox Smallpox Staph Enterotoxin B Staph Enterotoxin B Monkey Pox Monkey Pox Ricin Ricin Tularemia Tularemia VEE VEE VHFs VHFs Weaponized Biowarfare Agents

Biological Agents of Highest Concern Category A Variola major (Smallpox) Variola major (Smallpox) Bacillus anthracis (Anthrax) Bacillus anthracis (Anthrax) Yersinia pestis (Plague) Yersinia pestis (Plague) Francisella tularensis (Tularemia) Francisella tularensis (Tularemia) Botulinum toxin (Botulism) Botulinum toxin (Botulism) Filoviruses and Arenaviruses (Viral hemorrhagic fevers) Filoviruses and Arenaviruses (Viral hemorrhagic fevers) ALL suspected or confirmed cases should be reported to health authorities immediately ALL suspected or confirmed cases should be reported to health authorities immediately

Anthrax 1-5 Days++ Plague 2-3 Days Q Fever Days Tularemia 2-10 Days Smallpox 7-17 Days Viral encephalitides V(2-6d); E&W (7-14 d) VHFs4-21 Days Botulinum toxin 1-5 Days Staph. enterotoxin B 1-6 Hours Incubation Periods of Selected Biological Agents

Anthrax8,000 (or fewer) spores Plague organisms Q Fever 1-10 organisms Tularemia organisms Smallpox organisms Viral encephalitides organisms VHFs1-10 organisms Botulinum toxin ug/kg Infective Aerosol Doses of Selected Biological Agents

(bronchioles) 1-5 (alveoli) 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 Maximum human respiratory infection is a particle that falls within the 1 to 5 micron size Less Severe More Severe Aerosol Size and Infectivity

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

Primary Care Personnel Primary Care Personnel Hospital ER Staff Hospital ER Staff Public Health Professionals Public Health Professionals Emergency Response Personnel Emergency Response Personnel Laboratory Personnel Laboratory Personnel Law Enforcement Law Enforcement Public Public Military Military Bioterrorism : Who are First Responders?

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 Plan Exposure 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 Equipment Respirators Powered Air-Purifying Respirator (PAPR) HEPA filter face masks (N95, N100) Respirators must be in compliance with OSHA respiratory standard (29 CFR ) Respirators must be fit tested

Powered Air Purifying Respirator ( PAPR)

PPE Respirators Respirators should be used in accordance with a respiratory-protection program that complies with the OSHA respiratory-protection standard (29 CFR ). N95N100

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 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 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 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 Nothing (beards, head coverings, etc.) passes between the skin of the face and the respirator’s sealing edge Personal Protective Equipment Respirators

PPE Dermal 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 3 Anthrax as a Biological Weapon Objectives: 1)To understand the microbiology and epidemiology of anthrax 2)To understand the pathophysiology of the different anthrax clinical syndromes 3)To be able to recognize cutaneous anthrax 4)To be able to recognize an intentional anthrax release 5)To be able to treat patients with anthrax

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 Anthrax Microbiology & Epidemiology

Source: WHO World Anthrax Data Site Anthrax Worldwide Occurrence

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 Pathophysiology

Cutaneous Gastrointestinal Inhalational Multiple forms can be seen as the result of a BW attack Anthrax Clinical Syndromes

Anthrax Gastrointestinal Abdominal pain, usually accompanied by bloody vomiting or diarrhea, followed by fever and signs of sever infection 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 GI anthrax is sometimes seen as mouth and throat ulcerations with tender neck glands and fever Develops after ingestion of contaminated, poorly cooked meat. Develops after ingestion of contaminated, poorly cooked meat. Incubation period: 1–7 days Incubation period: 1–7 days Case-fatality: 25–90% (role of early antibiotic treatment is undefined) 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)Begins as a papule, progresses through a vesicular stage to a depressed black necrotic ulcer (eschar) Edema, redness, and/or necrosis without ulceration may occurEdema, redness, and/or necrosis without ulceration may occur Form most commonly encountered in naturally occurring casesForm most commonly encountered in naturally occurring cases Incubation period: 1–12 daysIncubation period: 1–12 days Case-fatality:Case-fatality: Without antibiotic treatment:20%Without antibiotic treatment:20% With antibiotic treatment:1%With antibiotic treatment:1%

JAMA. 2002;287: Hospital Day 5 2 months after discharge Hospital Day 12 Cutaneous Anthrax

Incubation Period: 1-6 days 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 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 Early Symptoms: malaise, fever, fatigue, non- productive cough, chest discomfort Confusion, neck stiffness, and headache suggest meningitis (seen in 50% of patients) 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

Presenting Symptoms Symptomsn=10 Fever, chills10 Sweats, often drenching 7 Fatigue, malaise, lethargy 10 Cough9 Nausea or vomiting 9 Dyspnea8 Chest discomfort or pleurisy7 Myalgias6 Headache5 Confusion4 Abdominal pain 3 Sore throat 2 Rhinorrhea1 Emerg Infect Dis vol.7, no. 6, 2001

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 Diagnosis

Acute Treatment Usually futile in severe mediastinitis patients who inhaled or ingested spores Ciprofloxacin mg IV q 8 to 12 hr Doxycycline mg IV q 12 hr Vaccination 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 Anthrax Treatment

FDA approved 1970 FDA approved 1970 Cell Free filtrate (NO organisms, dead or alive) Cell Free filtrate (NO organisms, dead or alive) Adverse effects 1-3% Adverse effects 1-3% Bioport Corporation Bioport Corporation Anthrax Vaccine

Laboratory Workers Increased number of highly pathogenic bacterial and viral samples Increased number of highly pathogenic bacterial and viral samples Increased need for universal precautions Increased need for universal precautions Increased need for security, including maintaining chain of custody for forensic samples Increased need for security, including maintaining chain of custody for forensic samples Increased need for decontamination procedures Increased need for decontamination procedures Laboratory Response Network (LRN) Laboratory Response Network (LRN)

Laboratory Workers Decontamination and Disinfection Effective sporicidal solutions: Commercially-available bleach diluted to 0.5% Sodium hypochlorite (1 part household bleach to 9 parts water) 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 Rinse off concentrated bleach to avoid caustic effects Approved sporicidal agents Approved sporicidal agents