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Preparing for and Responding to Bioterrorism: Information for Primary Care Clinicians Northwest Center for Public Health Practice University of Washington School of Public Health and Community Medicine, December 2002 Acknowledgements This presentation, and the accompanying instructor’s manual (current as of 12/02), were prepared by Jennifer Brennan Braden, MD, MPH, at the Northwest Center for Public Health Practice in Seattle, Washington, and Jeff Duchin, MD with Public Health – Seattle & King County, and the Division of Allergy & Infectious Diseases, University of Washington, for the purpose of educating primary care clinicians in relevant 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 The Centers for Disease Control & Prevention Project Coordinator Judith Yarrow Health Policy & Analysis, University of WA Design and Editing UW Northwest Center for Public Health Practice Jane Koehler, DVM, MPH Communicable Disease Control, Epidemiology and Immunization section, Public Health - Seattle & King County Ed Walker, MD; University of WA Department of Psychiatry Diseases of Bioterrorist Potential Smallpox CDC, AFIP UW Northwest Center for Public Health Practice Diseases of BT Potential Learning Objectives Be familiar with the agents most likely to be used in a biological weapons attack and the most likely mode of dissemination Know the clinical presentation(s) of the Category A agents and features that may distinguish them from more common diseases Be familiar with diagnosis, treatment recommendations, infection control, and preventive therapy for management of infection with or exposure to Category A agents. UW Northwest Center for Public Health Practice Biological Agents of Highest Concern Category A Agents Easily disseminated, infectious via aerosol Susceptible civilian populations Cause high morbidity and mortality Person-to-person transmission Unfamiliar to physicians – difficult to diagnose/treat Cause panic and social disruption Previous development for BW Biological Agents of Highest Concern Category A Agents Variola major (Smallpox) Bacillus anthracis (Anthrax) Yersinia pestis (Plague) Francisella tularensis (Tularemia) Botulinum toxin (Botulism) Filoviruses & Arenaviruses (Viral hemorrhagic fevers) Report ANY suspected illness due to these agents to Public Health immediately. Biological Agents of 2nd Highest Concern Category B Agents Coxiella burnetti (Q-fever) Brucella species (brucellosis) Burkholderia mallei (glanders) Alphaviruses (Venezuelan, Western and Eastern encephalomyelitis viruses) Ricin toxin from Ricinus communis (castor bean) Epsilon toxin from Clostridium perfringens Staphlococcus enterotoxin B Biological Agents of 2nd Highest Concern Food- or Water-borne Category B Agents Salmonella species Shigella dysenteriae Escherichia coli 0157:H7 Vibrio cholera Cryptosporidium parvum Biological Agents of 3rd Highest Concern Category C Agents Emerging pathogens that could be engineered for mass dissemination in the future Nipah virus Hantaviruses Tick-borne hemorrhagic fever viruses Tickborne encephalitis viruses Yellow fever Multidrug-resistant tuberculosis UW Northwest Center for Public Health Practice Smallpox Overview Two strains: variola major and variola minor Variola minor – milder disease with case fatality typically 1% or less Variola major – more severe disease with average 30% mortality in unvaccinated Person-to-person transmission UW Northwest Center for Public Health Practice Smallpox Overview Killed approximately 300,000,000 persons in 20th century Routine smallpox vaccination in the U.S. stopped in 1972 WHO declared smallpox eradicated in 1980 Vaccine has significant adverse effects No effective treatment Smallpox Overview Person-to-person transmission Average 30% mortality from variola major in unvaccinated A single case is considered a global public health emergency Smallpox Pathogenesis Virus implants on oropharynx or respiratory mucosa and is transported to regional lymph nodes Day 3-4: asymptomatic viremia followed by viral multiplication in spleen, bone marrow, lymph nodes, lung Day 8: secondary viremia leads to fever and toxemia on day 12-14 Smallpox Pathogenesis Virus localizes in small blood vessels of respiratory and pharyngeal mucosa, then dermis = characteristic rash and case communicability Toxemia: circulating immune complexes and variola antigens Smallpox Transmission Infectious dose extremely low Spread primarily by droplet nuclei >aerosols > direct contact Maintains infectivity for prolonged periods out of host Contaminated clothing and bedding can be infectious Smallpox Transmission Transmission does not usually occur until after febrile prodrome Coincident with onset of rash Slower spread through the population than chickenpox or measles Large outbreaks in schools were uncommon Less transmissible than measles, chickenpox, influenza Smallpox Transmission Secondary cases primarily household, hospital, and other close contacts Secondary attack rate 37-87% among unvaccinated contacts Patients with severe disease or cough at highest risk for transmission Greatest infectivity from rash onset to day 7-10 of rash Infectivity decreases with scab formation and ceases with separation of scabs Smallpox Clinical Features Prodrome (incubation 7-19 days) Acute onset of fever, malaise, headache, backache, vomiting, occasional delirium Transient erythematous rash Exanthem (2-3 days later) CDC Preceded by enanthem on Synchronous progression: oropharyngeal mucosa macules vesicles Begins on face, hands, pustules scabs forearms Lesions most abundant Spread to lower extremities on face and extremities, then trunk over ~ 7 days including palms/soles Smallpox Clinical Course WHO UW Northwest Center for Public Health Practice Smallpox Clinical Presentation CDC Smallpox Clinical Presentation WHO This link will take you away from the educational site Smallpox Clinical Presentation WHO Smallpox Clinical Progression WHO Smallpox Clinical Progression Day 10 Day 14 Day 21 Thomas, D. UW Northwest Center for Public Health Practice Smallpox Clinical Progression UW Northwest Center for Public Health Practice Smallpox Clinical Types Ordinary smallpox: 90% of cases Case-fatality average 30% Occurs in non-immunized persons Modified smallpox Milder, rarely fatal Occurs in 25% of previously immunized persons and 2% of non-immunized persons Fewer, smaller,more superficial lesions that evolve more rapidly Smallpox Clinical Types Hemorrhagic smallpox: <3% of cases Immunocompromised persons and pregnant women at risk Shortened incubation period, severe prodrome Extensive viral multiplication, coagulopathy Dusky erythema followed by petechiae and hemorrhages into skin and mucous membranes Almost uniformly fatal within 7 days Smallpox Clinical Types Malignant, or flat-type smallpox: 7% of cases Slowly evolving lesions that coalesce without forming pustules Associated with cell-mediated immune deficiency Usually fatal Variola sine eruptione Occurs in previously vaccinated persons or infants with maternal antibodies Asymptomatic or mild illness Transmission from these cases has not been documented Malignant Smallpox Thomas, D. UW Northwest Center for Public Health Practice Smallpox Complications Encephalitis 1 in 500 cases Variola major 1 in 2,000 cases Variola minor Keratitis, corneal ulceration Blindness in 1% of cases Infection in pregnancy High perinatal fatality rate Congenital infection CDC Major Smallpox Criteria Febrile prodrome Occurring 1-4 days before rash onset: fever >102°F and at least one of the following: prostration, headache, backache, chills, vomiting or severe abdominal pain Classic smallpox lesions Deep, firm/hard, round, well-circumscribed; may be umbilicated or confluent Lesions in same stage of development on any one part of the body (e.g., face or arm) More on CDC's response plan... UW Northwest Center for Public Health Practice This link will take you away from the educational site CDC Minor Smallpox Criteria Centrifugal distribution: greatest concentration of lesions on face and distal extremities First lesions on oral mucosa or palate, face, forearms Patient appears toxic or moribund Slow evolution: lesions evolve from macules to papules to pustules over days Lesions on palms and soles (majority of cases) UW Northwest Center for Public Health Practice CDC Criteria for Determining Risk of Smallpox High risk: report immediately All three major criteria Moderate risk: urgent evaluation Febrile prodrome and 1 major or 4 minor criteria Low risk: manage as clinically indicated No viral prodrome or Febrile prodrome and <4 minor criteria (no major criteria) UW Northwest Center for Public Health Practice CDC Recommended Evaluation of Patients at High Risk of Smallpox Contact and airborne precautions Notify infection control Infectious disease and/or dermatology consult Notify local/state health dept immediately Response team advises on management and specimen collection Specimen testing at CDC UW Northwest Center for Public Health Practice CDC Recommended Evaluation of Patients at Moderate Risk of Smallpox Contact and airborne precautions Notify infection control Infectious disease and/or Dermatology consult VZV and/or other lab tests as indicated If cannot rule out smallpox, contact local/state health dept. immediately UW Northwest Center for Public Health Practice CDC Recommended Evaluation of Patients at Low Risk of Smallpox Contact and airborne precautions Notify infection control Evaluate clinically for VZV Test for VZV and other conditions, as indicated UW Northwest Center for Public Health Practice Differential Diagnosis of Smallpox Variola vs. Varicella Smallpox: clinical features Febrile prodrome 1-4d before rash onset Lesions deep, firm, wellcircumscribed Varicella: clinical features Short, mild or no prodrome Lesions typically superficial, appear delicate Rash concentrated on Rash concentrated on face & extremities, trunk and proximal lesions on palms & soles extremities, uncommon on palms & soles Source: CDC UW Northwest Center for Public Health Practice Differential Diagnosis of Smallpox Variola vs. Varicella Smallpox: clinical features Rash in same stage of evolution on any one part of body Rash evolves slowly, papules ->pustules over days Extremely ill Illness lasts 14-21 days Varicella: clinical features Rash appears in crops, lesions in different stages of evolution Rash evolves more quickly, some macules ->crusts in 1d Feel unwell, but not usually extremely ill Illness lasts 4-7 days, if uncomplicated Source: CDC UW Northwest Center for Public Health Practice Variola vs. Varicella Lesion Distribution Chickenpox Smallpox WHO This link will take you away from the educational site Variola vs. Varicella Lesion Distribution Smallpox Chickenpox WHO Differential Diagnosis of Smallpox Varicella Disseminated herpes zoster Drug eruptions and contact dermatitis Disseminated herpes simplex UW Northwest Center for Public Health Practice Impetigo Erythema multiforme Scabies, insect bites Bullous pemphigoid Secondary syphillis Molluscum contagiosum Enterovirus exanthem Smallpox Diagnosis Clinical diagnosis = public health emergency Laboratory confirmation: vesicular or pustular fluid on swab or biopsy Seal in vacutainer and overpack - transport to state public health laboratory Culture (BSL-4 Lab) followed by PCR and RFLP Smallpox Diagnosis EM: characteristic “brick shaped” morphology distinct from HSV and VZV Light microscopy: Giemsa stain aggregations of viral particles (Guarnieri bodies) Gel diffusion test: vesicular fluid + hyperimmune globulin Smallpox Specimen Collection Specimen collection by trained teams Only recently, successfully vaccinated personnel (within 3yrs) wearing appropriate barrier protection should be involved in specimen collection Respiratory and contact precautions Testing done by CDC; contact local HD before collecting clinical specimens More on CDC's response plan... UW Northwest Center for Public Health Practice This link will take you away from the educational site Smallpox Specimen Collection If necessary, unvaccinated personnel without contraindications to vaccination may collect specimens If smallpox confirmed, will need immediate vaccination UW Northwest Center for Public Health Practice Smallpox Medical Management Respiratory and contact isolation for hospitalized cases Negative pressure room; HEPA-filtered exhaust All health care workers employ aerosol and contact precautions regardless of immunization status No specific therapy available Supportive care: fluid and electrolyte, skin, nutritional Smallpox Medical Management Antibiotics for secondary infection Antiviral drugs under evaluation Notify Public Health and hospital epidemiology immediately for suspected case Smallpox Outbreak Management Case identification, isolation, and immunization Rapid identification of contacts Immediate vaccination or boosting of ALL potential contacts including health care workers Vaccination within 4 days of exposure may prevent or lessen disease Isolation with monitoring for fever or rash 18 days from last contact with case Respiratory isolation if possible for febrile contacts Passive immunization (VIG) Potential use for contacts at high risk for vaccine complications Smallpox Outbreak Management Strategy for outbreak containment: Ring vaccination Isolation of confirmed & suspected smallpox cases Tracing, vaccination & close surveillance of contacts Vaccination of contacts of contacts Isolation CDC Smallpox Response Plan Facility Categories Type C – Contagious Confirmed Type and probable cases X – Uncertain diagnosis Vaccinated Type febrile contacts without rash R – Asymptomatic Non-febrile UW Northwest Center for Public Health Practice contacts Smallpox Outbreak Management Priority Groups for Vaccination Persons exposed to an intentional release Direct (<6.5 feet) face-to-face contacts of case/suspect case Persons involved in direct medical or public health management or transport of case/suspect case Smallpox Outbreak Management Priority Groups for Vaccination Others at risk of contact with infectious materials Persons whose unhindered function is essential to support response activities Smallpox Outbreak Management Pre-release Vaccination Select individuals vaccinated to enhance smallpox response capacity Smallpox Response Teams Designated public health, law enforcement, and medical personnel in each state/territory Investigate, evaluate, and diagnose initial suspect cases of smallpox Select personnel at acute health care facilities (Smallpox Health Care Teams) UW Northwest Center for Public Health Practice ACIP, June 2002 Smallpox Vaccine Made from live Vaccinia virus ~ 200 million doses in U.S. stores Intradermal inoculation with bifurcated needle (scarification) Pustular lesion or induration surrounding central lesion (scab or ulcer) 6-8 days postvaccination Low grade fever, axillary lymphadenopathy Scar (permanent) demonstrates successful WHO vaccination (“take”) Immunity not life-long Smallpox Vaccine Administration JAMA 1999;281:1735-45 Vaccine admin instructions WHO This link will take you away from the educational site Smallpox Vaccine “Take” WHO Smallpox Complications Rates for Primary Vaccination Complication rates lower with revaccination Primary vaccination: ~1 death/million Revaccination: ~0.2 deaths/million Most common complication: Inadvertent auto- and secondary inoculation (skin, eye) 529/million (30% in one study were contacts) Sources: MMWR June 22, 2001 / 50(RR10);1-25. Vaccinia (Smallpox) Vaccine Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001 Vaccines 3rd Ed. Plotkin SA, Orenstein WA. W.B. Saunders, Phila. 1999 Smallpox Complication Rates for Primary Vaccination Less common Post-vaccination encephalopathy (7-42.3/million)* Post-vaccination encephalitis (12.3/million) 25% fatal; 23% neurological sequelae Progressive vaccinia/vaccinia necrosum (1.5/million) Generalized vaccinia (241.5/million): severe in 10% Eczema vaccinatum (38.5/million) Fetal vaccinia - rare Sourced: MMWR June 22, 2001 / 50(RR10);1-25. Vaccinia (Smallpox) Vaccine Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001 *Vaccines 3rd Ed. Plotkin SA, Orenstein WA. W.B. Saunders, Phila. 1999 Smallpox Vaccine Complications WHO Smallpox Vaccine Complications WHO Smallpox Vaccine Pre-exposure Contraindications Immunosuppression Agammaglobulinemia Leukemia, lymphoma, generalized malignancy Chemo- or other immunosuppressive therapy HIV infection History or evidence of eczema Household, sexual, or other close contact with person with one of the above conditions Life-threatening allergy to polymixin B, streptomycin, tetracycline, or neomycin Pregnancy Smallpox Vaccinia Immune Globulin (VIG) Treatment of adverse reactions (AR) Approximately 25 AR’s/100,000 vaccinations AR rate may be increased in immunocompromised populations Post-exposure prophylaxis (if available) Pregnant patients: VIG + vaccinia vaccine Eczema: VIG + vaccinia vaccine Immunocompromised patients: no consensus on VIG alone vs. VIG + vaccinia vaccine Current supplies very limited, but new lots are being produced that conform to IV standards Smallpox Summary of Key Points The clinical diagnosis of smallpox is a public health emergency; the local or state health department and hospital infection control should be notified immediately for suspected cases, including cases that meet criteria of the CDC smallpox case definition. CDC criteria for determining the risk of smallpox can help differentiate smallpox from varicella and other rash illnesses. UW Northwest Center for Public Health Practice Smallpox Summary of Key Points Smallpox is transmitted person to person; standard contact and airborne precautions should be initiated in all suspected cases until smallpox is ruled out. Vaccine-induced immunity wanes with time; therefore most people today are considered susceptible to infection. UW Northwest Center for Public Health Practice Smallpox Additional Images & Information Herron C. Smallpox — 26 Years Ago N Engl J Med 1996; 334:1304 Moses A. E. & Cohen-Poradosu R. Eczema vaccinatum — a timely reminder. N Engl J Med 2002; 346:1287. World Health Organization This link will take you away from the educational site UW Northwest Center for Public Health Practice Summary - Category A Critical Agents Disease Transmit Man to Man Infective Dose* (Aerosol) Incubation Period Duration of Illness Approx. case fatality rate Inhalation anthrax Pneumonic Plague No 8,000-50,000 spores 100-500 organisms 1-6 days 3-5 days (usually fatal if untreated) 1-6 days (usually fatal) High Tularemia No High 2-10 days (average 3-5) 7-17 days (average 12) > 2 weeks Smallpox Viral Hemorrhagic Fevers Moderate 10-50 organisms Assumed low (10-100 organisms) 1-10 organisms 2-21 days Death between 7-16 days Botulism No 0.001 g/kg is LD50 for type A 1-5 days Death in 24-72 hours; lasts months if not lethal High 2-3 days 4 weeks High unless treated within 1224 hours Moderate if untreated High to moderate High for Zaire strain, moderate with Sudan High without respiratory support *infectious dose may be less in certain circumstances Modified from: USAMRIID’s Medical Management of Biological Casualties Handbook UW Northwest Center for Public Health Practice This link will take you away from the educational site Summary Category A Critical Agents Decontamination of exposed persons Showering or washing thoroughly with soap and water adequate for most; bleach not necessary Infection control Standard precautions – all cases Airborne and contact precautions – smallpox and viral hemorrhagic fevers Droplet precautions – pneumonic plague UW Northwest Center for Public Health Practice Resources These links will take you away from the educational site Centers for Disease Control and Prevention Bioterrorism Web page: http://www.bt.cdc.gov/ CDC Office of Health and Safety Information System (personal protective equipment) http://www.cdc.gov/od/ohs/ USAMRIID – includes link to online version of Medical Management of Biological Casualties Handbook http://www.usamriid.army.mil/ Johns Hopkins Center for Civilian Biodefense Studies http://www.hopkins-biodefense.org fact sheets and links to other info, including JAMA series from Working Group on Civilian Biodefense and BTrelated anthrax case studies UW Northwest Center for Public Health Practice Resources These links will take you away from the educational site Office of the Surgeon General: Medical Nuclear, Biological and Chemical Information http://www.nbc-med.org St. Louis University Center for the Study of Bioterrorism and Emerging Infections – fact sheets and links http://bioterrorism.slu.edu Public Health - Seattle & King County http://www.metrokc.gov/health UW Northwest Center for Public Health Practice Resources These links will take you away from the educational site American College of Physicians – links to BT resources, including decision support tools and palm documents http://www.acponline.org Self-Assessment (case scenarios – chemical and biological) http://www.acponline.org/bioterro/self_assessment.htm MMWR Rec. and Rep. Case definitions under public health surveillance. 1997;46(RR-10):1-55 UW Northwest Center for Public Health Practice In Case of An Event… Web Sites with Up-to-Date Information and Instructions These links will take you away from the educational site Centers for Disease Control and Prevention http://www.bt.cdc.gov/EmContact/index.asp Saint Louis University, CSB & EI http://bioterrorism.slu.edu/hotline.htm WA State Local Health Departments/Districts http://www.doh.wa.gov/LHJMap/LHJMap.htm Level A Lab Protocols: Presumptive Agent ID http://www.bt.cdc.gov/LabIssues/index.asp UW Northwest Center for Public Health Practice In Case of An Event… Web Sites with Up-to-Date Information and Instructions These links will take you away from the educational site FBI Terrorism Web Page http://www.fbi.gov/terrorism/terrorism.htm WA State Emergency Mgt Division – Hazard Analysis Update http://www.wa.gov/wsem Mail Security http://www.usps.com/news/2001/press/serviceupdates.htm Links to your state health department http://www.astho.org/state.html NIOSH – Worker Safety and Use of PPE http://www.cdc.gov/niosh/emres01.html UW Northwest Center for Public Health Practice