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Preparing for and Responding to Bioterrorism: Information for the Public Health Workforce. Acknowledgements. This presentation, and the accompanying instructor’s manual, were prepared by Jennifer Brennan Braden, MD, MPH, at the

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acknowledgements
Acknowledgements

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

diseases of bioterrorist potential learning objectives
Diseases of Bioterrorist PotentialLearning 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
smallpox overview
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
smallpox overview1
SmallpoxOverview
  • 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

6

smallpox overview2
SmallpoxOverview
  • Person-to-person transmission
  • Average 30% mortality from variola major in unvaccinated
  • A single case is considered a global public health emergency

7

smallpox transmission
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

8

smallpox transmission1
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

9

smallpox transmission2
SmallpoxTransmission
  • 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

10

smallpox case definition
SmallpoxCase Definition
  • Clinical case definition
    • An illness with acute onset of fever 101F followed by a rash characterized by vesicles or firm pustules in the same stage of development without other apparent cause
  • Laboratory criteria for confirmation (Level C/D* lab)
    • Isolation of smallpox virus from a clinical specimen, OR
    • Identification of variola in a clinical specimen by PCR or electronmicroscopy

*initial confirmation of outbreak requires testing in level D lab (I.e., CDC)

smallpox case classification
SmallpoxCase Classification
  • Case classification
    • Confirmed: laboratory confirmed
    • Probable: meets clinical case definition & has an epi link to another confirmed or probable case
    • Suspected:
      • Meets clinical case definition but is not laboratory-confirmed and does not have an epi link OR
      • Atypical presentation not lab confirmed but has an epi link to a confirmed or probable case
smallpox clinical features
SmallpoxClinical Features
  • Prodrome (incubation 7-19 days)
    • Acute onset of fever, malaise, headache, backache, vomiting, occasional delirium
    • Transient red rash
  • Exanthem(2-3 days later)
    • Preceded by enanthem on oropharyngeal mucosa
    • Begins on face, hands, forearms
    • Spread to lower extremities then trunk over ~ 7 days
    • Synchronous progression: flat lesions  vesicles  pustules  scabs

CDC

Lesions most abundant on

face and extremities,

including palms/soles

13

smallpox clinical progression1
SmallpoxClinical Progression

Day 10

Day 14

Day 21

Thomas, D.

smallpox clinical types
SmallpoxClinical 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

17

smallpox clinical types1
SmallpoxClinical Types
  • Hemorrhagic smallpox: <3% of cases
    • Immunocompromised persons and pregnant women at risk
    • Shortened incubation period, severe prodrome
    • Dusky erythema followed by petechiae & hemorrhages into skin and mucous membranes
    • Almost uniformly fatal within 7 days

18

smallpox clinical types2
SmallpoxClinical 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

19

smallpox complications
SmallpoxComplications
  • Encephalitis
    • 1 in 500 cases Variola major
    • 1 in 2,000 cases Variola minor
  • Corneal ulceration
    • Blindness in 1% of cases
  • Infection in pregnancy
    • High perinatal fatality rate
    • Congenital infection

21

smallpox medical management
SmallpoxMedical 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

22

smallpox medical management1
SmallpoxMedical Management
  • Antibiotics for secondary infection
  • Antiviral drugs under evaluation
  • Notify Public Health and hospital epidemiology immediately for suspected case

23

smallpox outbreak management
SmallpoxOutbreakManagement
  • Case identification, isolation, and immunization
  • Rapid identification of contacts
  • Immediate vaccination or boosting of ALL potential contacts including health care workers (ring vaccination)
    • 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

24

smallpox outbreak management1
SmallpoxOutbreakManagement
  • Priority groups for vaccination in a smallpox outbreak include persons involved in the direct medical or public health evaluation of confirmed, probable, or suspected smallpox patients
  • Passive immunization (VIG)
    • Potential use for contacts at high risk for vaccine complications
      • Pregnancy, skin disorders, immunosuppression
      • VIG not readily available

More on CDC's response plan...

smallpox definition of a contact
SmallpoxDefinition of a Contact
  • Contact: A person who has had contact with a suspected, probable or confirmed case of smallpox
    • Cases should be considered infectious from the onset of fever, until all scabs have separated
  • Close contact: Face-to-face contact (6ft) with a smallpox case
smallpox outbreak management pre release vaccination
Smallpox Outbreak ManagementPre-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 care health care facilities (Smallpox Health Care Teams)

ACIP, June 2002

smallpox vaccine
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 post-vaccination
    • Low grade fever, axillary lymphadenopathy
    • Scar (permanent) demonstrates successful vaccination (“take”)
    • Immunity not life-long

WHO

28

smallpox vaccine administration
Smallpox VaccineAdministration

Vaccine admin instructions

JAMA 1999;281:1735-45

WHO

29

smallpox vaccine complications
Smallpox Vaccine Complications
  • More common in children and primary vaccinees
  • Most common: secondary inoculation
    • Skin, eye, nose, genitalia
    • 50% of all complications
    • 529/million (30% in one study were contacts)
  • Severe reactions less common
  • Primary vaccination ~ 1 death/million
  • Revaccination ~ 0.2 deaths/million
smallpox complication rates for primary vaccination
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

32

smallpox vaccine pre exposure contraindications
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

33

distinguishing smallpox from chickenpox similar epidemiologic features
Distinguishing Smallpox from Chickenpox: SimilarEpidemiologic Features
  • Incubation period 14 (10-21) days
  • Person-to-person transmission
  • Seasonal transmission of disease highest during winter and early spring
distinguishing smallpox from chickenpox epi features that differ
Chickenpox (varicella)

Most cases occur in children

Expected case fatality rate 2-3/100,000

Secondary attack rate of 80% among susceptible household contacts

Smallpox (variola)

Most of the population expected to be susceptible

Expected case fatality rate averages 30%

Secondary attack rate ~60% in unvaccinated family contacts

Distinguishing Smallpox from Chickenpox: Epi Featuresthat Differ
distinguishing smallpox from chickenpox clinical features that differ
Chickenpox (varicella)

Lesions superficial

Rash concentrated on trunk

Lesions rarely on palms or soles

Lesions in different stages of development

Rash progresses more quickly

Smallpox (variola)

Lesions deep

Rash concentrated on face & extremities

Lesions on palms & soles

Lesions in same stage of evolution on any one area of body

Rash progresses slowly

Distinguishing Smallpox from Chickenpox: Clinical Featuresthat Differ

CDC

smallpox surveillance
Smallpox Surveillance
  • Pre-event
    • Development of a listing of surveillance partners, points of contact, and mechanisms for reporting
    • Establishing sentinel surveillance for generalized febrile vesicular-pustular rash in health care settings
  • Post-event:
    • Once a confirmed case of smallpox is identified in your jurisdiction, active surveillance for suspected, probable, and confirmed cases should be initiated
smallpox surveillance cont
Smallpox Surveillance, cont.
  • Contact tracing, interviewing, and vaccination
    • Monitored for vaccine “take”
    • Non-symptomatic contacts monitored for fever or rash
      • 18 days beyond last contact OR
      • 14 days beyond successful vaccination
  • Followup
    • Laboratory results & epi links
    • Case outcomes/complications
    • Vaccine adverse events (for VAERS)
smallpox summary of key points
Smallpox Summary of Key Points
  • Smallpox is transmitted person to person; standard and airborne precautions should be initiated in all suspected cases until smallpox is ruled out.
  • Smallpox cases should be considered infectious from the onset of fever until all scabs have separated.
smallpox summary of key points1
Smallpox Summary of Key Points
  • Vaccine-induced immunity wanes with time; therefore most people today are considered susceptible to smallpox infection.
  • In a smallpox outbreak, vaccination is indicated for all case contacts, including health care workers and case investigators.
  • Smallpox surveillance includes pre-event rash surveillance, post-event surveillance for active cases, and follow-up of cases, contacts, and vaccine recipients.
smallpox summary of key points2
Smallpox Summary of Key Points
  • Epidemiologic features that differentiate smallpox from chickenpox include a higher case fatality and a lower attack rate.
  • Clinical features differentiating smallpox from varicella include differences in lesion progression and distribution, illness course and presence of a febrile prodrome.
resources
Resources

http://www.bt.cdc.gov/

  • 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

http://www.cdc.gov/od/ohs/

http://www.usamriid.army.mil/

http://www.hopkins-biodefense.org

resources1
Resources
  • 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

http://www.nbc-med.org

http://bioterrorism.slu.edu

http://www.metrokc.gov/health

resources2
Resources

http://www.doh.wa.gov

  • Washington State Department of Health
    • Communicable Disease Epidemiology
      • (206) 361-2914 OR
      • (877) 539-4344 (24 hour emergency)
  • Association for Professionals in Infection Control
  • MMWR Rec & Rep. Case definitions under public health surveillance.

http://www.apic.org/bioterror

1997;46(RR-10):1-55