Download Smallpox Vaccine - Northwest Center for Public Health Practice

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
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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
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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
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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
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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