Northwest Center for Public Health Practice University of Washington School of Public Health and Community Medicine 1 Preparing for and Responding to Bioterrorism: Information for the Public Health Workforce

UW Northwest Center for Public Health Practice 2 AcknowledgementsAcknowledgements This presentation, and the accompanying instructor’s manual, were prepared by Jennifer Brennan Braden, MD, MPH, at the Northwest Center for Public Health Practice in Seattle, WA, for the purpose of educating public health employees in the general aspects of bioterrorism preparedness and response. Instructors are encouraged to freely use all or portions of the material for its intended purpose. The following people and organizations provided information and/or support in the development of this curriculum. A complete list of resources can be found in the accompanying instructor’s guide. Patrick O’Carroll, MD, MPH Project Coordinator Centers for Disease Control and Prevention Judith Yarrow Design and Editing Health Policy and Analysis; University of WA Washington State Department of Health Jeff Duchin, MD Jane Koehler, DVM, MPH Communicable Disease Control, Epidemiology and Immunization Section Public Health - Seattle and King County Ed Walker, MD; University of WA Department of Psychiatry

UW Northwest Center for Public Health Practice 3 Diseases of Bioterrorist Potential: Plague and Botulism CDC, AFIP

UW Northwest Center for Public Health Practice 4 Diseases of Bioterrorist Potential Learning Objectives Describe the epidemiology, mode of transmission, and presenting symptoms of disease caused by the CDC-defined Category A agents Identify the infection control and prophylactic measures to implement in the event of a suspected or confirmed Category A case or outbreak Describe the epidemiology, mode of transmission, and presenting symptoms of disease caused by the CDC-defined Category A agents Identify the infection control and prophylactic measures to implement in the event of a suspected or confirmed Category A case or outbreak

UW Northwest Center for Public Health Practice 5 Plague History & Significance 14 th Century: “Black Death” responsible for >20million deaths in Europe Used as a BW agent by Japan in WW II Studied by Soviet and, to a smaller extent, U.S. BW programs 1995: Larry Wayne Harris arrested for illicit procurement of culture via mail 14 th Century: “Black Death” responsible for >20million deaths in Europe Used as a BW agent by Japan in WW II Studied by Soviet and, to a smaller extent, U.S. BW programs 1995: Larry Wayne Harris arrested for illicit procurement of culture via mail

UW Northwest Center for Public Health Practice 6 Plague Epidemiology Caused by Yersinia pestis About cases/year U.S. Mainly SW states Human plague occurs from bite of an infected flea (bubonic) Only pneumonic form of plague is spread person-to-person Last case of person-to-person transmission in U.S. occurred in 1924 Caused by Yersinia pestis About cases/year U.S. Mainly SW states Human plague occurs from bite of an infected flea (bubonic) Only pneumonic form of plague is spread person-to-person Last case of person-to-person transmission in U.S. occurred in 1924

UW Northwest Center for Public Health Practice 7 Yersinia Pestis Gram negative, non- motile, non-spore- forming bacillus Resistant to freezing temperature and drying, killed by heat and sunlight Gram negative, non- motile, non-spore- forming bacillus Resistant to freezing temperature and drying, killed by heat and sunlight Source: Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases, Fort Collins, CO

UW Northwest Center for Public Health Practice 8 Plague Case Definition Characterized by fever, chills, headache, malaise, prostration, & leukocytosis that manifests in one or more of the following clinical forms: Characterized by fever, chills, headache, malaise, prostration, & leukocytosis that manifests in one or more of the following clinical forms: Regional lymphadenitis (bubonic) Regional lymphadenitis (bubonic) Septicemia w/o evident bubo (septicemic) Septicemia w/o evident bubo (septicemic) Plague pneumonia Plague pneumonia Pharyngitis & cervical lymphadenitis (pharyngeal) Pharyngitis & cervical lymphadenitis (pharyngeal) Characterized by fever, chills, headache, malaise, prostration, & leukocytosis that manifests in one or more of the following clinical forms: Characterized by fever, chills, headache, malaise, prostration, & leukocytosis that manifests in one or more of the following clinical forms: Regional lymphadenitis (bubonic) Regional lymphadenitis (bubonic) Septicemia w/o evident bubo (septicemic) Septicemia w/o evident bubo (septicemic) Plague pneumonia Plague pneumonia Pharyngitis & cervical lymphadenitis (pharyngeal) Pharyngitis & cervical lymphadenitis (pharyngeal) MMWR 1997;46(RR-10)

UW Northwest Center for Public Health Practice 9 Plague Case Definition, cont. Laboratory criteria for diagnosis: Presumptive Elevated serum antibody titers to Y. pestis F1 antigen (w/o documented 4-fold change) in a patient with no history of plague vaccination OR Detection of F1 antigen in a clinical specimen by fluorescent assay Confirmatory Isolation of Y. pestis from a clinical specimen OR 4-fold or greater change in serum antibody titer to Y. pestis F1 antigen Laboratory criteria for diagnosis: Presumptive Elevated serum antibody titers to Y. pestis F1 antigen (w/o documented 4-fold change) in a patient with no history of plague vaccination OR Detection of F1 antigen in a clinical specimen by fluorescent assay Confirmatory Isolation of Y. pestis from a clinical specimen OR 4-fold or greater change in serum antibody titer to Y. pestis F1 antigen MMWR 1997;46(RR-10)

UW Northwest Center for Public Health Practice 10 Plague: Case Classification Suspected: Clinically compatible case w/o presumptive or confirmatory lab results Probable: Clinically compatible case with presumptive lab results Confirmed: Clinically compatible case with confirmatory lab results Suspected: Clinically compatible case w/o presumptive or confirmatory lab results Probable: Clinically compatible case with presumptive lab results Confirmed: Clinically compatible case with confirmatory lab results MMWR 1997;46(RR-10)

UW Northwest Center for Public Health Practice 11 Plague Clinical Forms Bubonic plague Most common naturally-occurring form Mortality 60% untreated, <5% treated Primary or secondary septicemic plague Pneumonic plague Most likely BT presentation From aerosol or septicemic spread to lungs Survival unlikely if treatment not initiated w/in 24 hours of the onset of symptoms Bubonic plague Most common naturally-occurring form Mortality 60% untreated, <5% treated Primary or secondary septicemic plague Pneumonic plague Most likely BT presentation From aerosol or septicemic spread to lungs Survival unlikely if treatment not initiated w/in 24 hours of the onset of symptoms

UW Northwest Center for Public Health Practice 12 Pneumonic Plague Clinical Presentation Incubation: 1-6 days (usually 2-4 days) Acute onset of fever with cough, dyspnea, and chest pain Hemoptysis characteristic; watery or purulent sputum also possible Prominent GI symptoms may be present, including nausea, vomiting, diarrhea, and abdominal pain Incubation: 1-6 days (usually 2-4 days) Acute onset of fever with cough, dyspnea, and chest pain Hemoptysis characteristic; watery or purulent sputum also possible Prominent GI symptoms may be present, including nausea, vomiting, diarrhea, and abdominal pain

UW Northwest Center for Public Health Practice 13 Pneumonic Plague Clinical Presentation Other symptoms include headache, chills, malaise, myalgias Rarely, cervical bubo present Rapid progression to respiratory failure & shock Other symptoms include headache, chills, malaise, myalgias Rarely, cervical bubo present Rapid progression to respiratory failure & shock

UW Northwest Center for Public Health Practice 14 Bubonic Plague Incubation: 2-8 days Sudden onset nonspecific symptoms: fever, chills, malaise, muscle aches, headache Regional lymphadenitis (buboes) Swollen, very painful lymph nodes Typically inguinal, femoral, axillary, or cervical Erythema overlying skin May have surrounding edema Concurrent with or shortly after onset of other symptoms Incubation: 2-8 days Sudden onset nonspecific symptoms: fever, chills, malaise, muscle aches, headache Regional lymphadenitis (buboes) Swollen, very painful lymph nodes Typically inguinal, femoral, axillary, or cervical Erythema overlying skin May have surrounding edema Concurrent with or shortly after onset of other symptoms

UW Northwest Center for Public Health Practice 15 Septicemic & Bubonic Plague Source: CDC NVBIDCDC NVBID

UW Northwest Center for Public Health Practice 16 Plague Infection Control Person-to-person transmission via respiratory droplets Standard respiratory droplet precautions Treatment = 10 days antibiotics Case isolation for at least the first 48 hrs of antibiotic treatment Bubonic plague - standard precautions Person-to-person transmission via respiratory droplets Standard respiratory droplet precautions Treatment = 10 days antibiotics Case isolation for at least the first 48 hrs of antibiotic treatment Bubonic plague - standard precautions

UW Northwest Center for Public Health Practice 17 Plague Infection Control Antibiotic prophylaxis for close contacts Duration: 7 days or duration of risk of exposure + 7 days Close contacts refusing prophylaxis: Observe 7 days after last exposure and treat if fever or cough develop Bubonic contacts: Observe 7d and treat if symptoms develop Antibiotic prophylaxis for close contacts Duration: 7 days or duration of risk of exposure + 7 days Close contacts refusing prophylaxis: Observe 7 days after last exposure and treat if fever or cough develop Bubonic contacts: Observe 7d and treat if symptoms develop

UW Northwest Center for Public Health Practice 18 Plague Summary of Key Points The most likely presentation in a BT attack is pneumonic plague. Unlike other forms of plague, pneumonic plague is transmitted person to person, and thus respiratory droplet precautions are indicated in suspected cases until 48 hours after the initiation of antibiotic therapy. The most likely presentation in a BT attack is pneumonic plague. Unlike other forms of plague, pneumonic plague is transmitted person to person, and thus respiratory droplet precautions are indicated in suspected cases until 48 hours after the initiation of antibiotic therapy.

UW Northwest Center for Public Health Practice 19 Case Reports PlaguePlague Plague Pneumonia - CA. MMWR 1984;33(34) Pneumonic Plague -- Arizona, MMWR 41(40)

UW Northwest Center for Public Health Practice 20 Clostridium Botulinum C. botulinum spores found in soil worldwide Toxin causative agent of botulism Types A-G; A,B&E most commonly associated with human disease Most potent toxin known (lethal dose 1ng/kg) Inactivated by chlorine (~20min) and sunlight (1-3hrs); destroyed by heat (5min at 85  C) Absorbed into circulation via mucosal surface or wound, not intact skin Interferes with nerve transmission  paralysis C. botulinum spores found in soil worldwide Toxin causative agent of botulism Types A-G; A,B&E most commonly associated with human disease Most potent toxin known (lethal dose 1ng/kg) Inactivated by chlorine (~20min) and sunlight (1-3hrs); destroyed by heat (5min at 85  C) Absorbed into circulation via mucosal surface or wound, not intact skin Interferes with nerve transmission  paralysis

UW Northwest Center for Public Health Practice 21 Clostridium Botulinum Epidemiology Approximately 100 reported cases botulism/year in the U.S. Infant most common (72%) Food-borne not common Incubation (food-borne): 12-72hrs (range 2hr- 8d) Dose dependent Could be less following a BT attack No person-to-person transmission Death 60% untreated; <5% treated Approximately 100 reported cases botulism/year in the U.S. Infant most common (72%) Food-borne not common Incubation (food-borne): 12-72hrs (range 2hr- 8d) Dose dependent Could be less following a BT attack No person-to-person transmission Death 60% untreated; <5% treated

UW Northwest Center for Public Health Practice 22 Botulism & Bioterrorism Weaponized by former U.S. and Soviet offensive BW programs Iran, Iraq, N. Korea, Syria believed to have developed/be developing toxin as a weapon Aerosol use or food supply sabotage most likely Weaponized by former U.S. and Soviet offensive BW programs Iran, Iraq, N. Korea, Syria believed to have developed/be developing toxin as a weapon Aerosol use or food supply sabotage most likely

UW Northwest Center for Public Health Practice 23 Botulism Clinical Forms Food-borne Toxin produced anaerobically in improperly processed or canned, low-acid foods contaminated by spores Wound Toxin produced by organisms contaminating wound Infant T oxin produced by organisms in intestinal tract T oxin produced by organisms in intestinal tract Inhalation botulism No natural* occurrence, developed as BW weapon Food-borne Toxin produced anaerobically in improperly processed or canned, low-acid foods contaminated by spores Wound Toxin produced by organisms contaminating wound Infant T oxin produced by organisms in intestinal tract T oxin produced by organisms in intestinal tract Inhalation botulism No natural* occurrence, developed as BW weapon *3 accidental cases in veterinary personnel, W. Germany, 1962

UW Northwest Center for Public Health Practice 24 Botulism: Case Definition Ingestion of botulinum toxin results in an illness of variable severity. Common symptoms are diplopia, blurred vision and bulbar weakness. Symmetric paralysis may progress rapidly. Laboratory* criteria for diagnosis: Detection of botulinum toxin in serum, stool or patient’s food (food-borne) or other clinical specimen (“botulism, other”) OR Isolation of Clostridium botulinum from stool (food-borne) or other clinical specimen Ingestion of botulinum toxin results in an illness of variable severity. Common symptoms are diplopia, blurred vision and bulbar weakness. Symmetric paralysis may progress rapidly. Laboratory* criteria for diagnosis: Detection of botulinum toxin in serum, stool or patient’s food (food-borne) or other clinical specimen (“botulism, other”) OR Isolation of Clostridium botulinum from stool (food-borne) or other clinical specimen MMWR 1997;46(RR-10) *Assay available at CDC & some state public health labs

UW Northwest Center for Public Health Practice 25 Botulism: Case Classification Botulism, Food-borne Probable: Clinically compatible with an epidemiologic link Confirmed: Clinically compatible case that is laboratory confirmed or that occurs among persons who ate the same food as persons who have laboratory-confirmed botulism Botulism, Other Confirmed: Clinically compatible case that is laboratory confirmed in a patient  1 yr* who has no history of ingestion of suspect food and has no wounds Botulism, Food-borne Probable: Clinically compatible with an epidemiologic link Confirmed: Clinically compatible case that is laboratory confirmed or that occurs among persons who ate the same food as persons who have laboratory-confirmed botulism Botulism, Other Confirmed: Clinically compatible case that is laboratory confirmed in a patient  1 yr* who has no history of ingestion of suspect food and has no wounds *age parameter may not apply in BT MMWR 1997;46(RR-10)

UW Northwest Center for Public Health Practice 26 Botulism Treatment Ventilatory assistance and supportive care Standard precautions Botulinum antitoxin Most effective if given early: does not reverse effect of toxin already bound to nerve receptor Trivalent equine product against types A,B, and E currently available from CDC Heptavalent (A-G) antitoxin - investigational Monovalent human anti-serum for infant botulism -investigational Ventilatory assistance and supportive care Standard precautions Botulinum antitoxin Most effective if given early: does not reverse effect of toxin already bound to nerve receptor Trivalent equine product against types A,B, and E currently available from CDC Heptavalent (A-G) antitoxin - investigational Monovalent human anti-serum for infant botulism -investigational

UW Northwest Center for Public Health Practice 27 Botulism Prophylaxis Pre-exposure Prophylaxis for at-risk lab workers and military with investigational vaccine No pre-exposure prophylaxis recommended for general public Post-exposure: close monitoring of those exposed; treat with antitoxin at first signs of illness Pre-exposure Prophylaxis for at-risk lab workers and military with investigational vaccine No pre-exposure prophylaxis recommended for general public Post-exposure: close monitoring of those exposed; treat with antitoxin at first signs of illness

UW Northwest Center for Public Health Practice 28 Botulism Summary of Key Points An outbreak of botulism occurring with a common geographic factor, but with no common food exposure, would suggest a deliberate aerosol exposure. Inhalational botulism does not occur naturally, and any potential cases suggest a deliberate source of infection. An outbreak of botulism occurring with a common geographic factor, but with no common food exposure, would suggest a deliberate aerosol exposure. Inhalational botulism does not occur naturally, and any potential cases suggest a deliberate source of infection.

UW Northwest Center for Public Health Practice 29 Botulism Summary of Key Points Gastrointestinal symptoms may not occur with inhalational botulism or with food-borne botulism (e.g., resulting from deliberate contamination of the food supply). Botulinum antitoxin must be administered as soon as possible for optimum results. Gastrointestinal symptoms may not occur with inhalational botulism or with food-borne botulism (e.g., resulting from deliberate contamination of the food supply). Botulinum antitoxin must be administered as soon as possible for optimum results.

UW Northwest Center for Public Health Practice 30 Botulism Case Reports MMWR Morb Mortal Wkly Rep 1995;44(48) MMWR Morb Mortal Wkly Rep 1999;48(21)

UW Northwest Center for Public Health Practice 31 ResourcesResources Centers for Disease Control & Prevention Bioterrorism Web page: CDC Office of Health and Safety Information System (personal protective equipment) USAMRIID -- includes link to on-line version of Medical Management of Biological Casualties Handbook Johns Hopkins Center for Civilian Biodefense Studies Centers for Disease Control & Prevention Bioterrorism Web page: CDC Office of Health and Safety Information System (personal protective equipment) USAMRIID -- includes link to on-line version of Medical Management of Biological Casualties Handbook Johns Hopkins Center for Civilian Biodefense Studies

UW Northwest Center for Public Health Practice 32 ResourcesResources Office of the Surgeon General: Medical Nuclear, Biological and Chemical Information St. Louis University Center for the Study of Bioterrorism and Emerging Infections Public Health - Seattle & King County Office of the Surgeon General: Medical Nuclear, Biological and Chemical Information St. Louis University Center for the Study of Bioterrorism and Emerging Infections Public Health - Seattle & King County

UW Northwest Center for Public Health Practice 33 ResourcesResources Washington State Department of Health Washington State Department of Health Communicable Disease Epidemiology Communicable Disease Epidemiology (206) OR (206) OR (877) (24 hour emergency) (877) (24 hour emergency) Association for Professionals in Infection Control Association for Professionals in Infection Control MMWR Rec & Rep. Case definitions under public health surveillance. MMWR Rec & Rep. Case definitions under public health surveillance. Washington State Department of Health Washington State Department of Health Communicable Disease Epidemiology Communicable Disease Epidemiology (206) OR (206) OR (877) (24 hour emergency) (877) (24 hour emergency) Association for Professionals in Infection Control Association for Professionals in Infection Control MMWR Rec & Rep. Case definitions under public health surveillance. MMWR Rec & Rep. Case definitions under public health surveillance. 1997;46(RR-10):