Transcript Preparing and Responding to Bioterrorism: Information for

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, July 2002
Acknowledgements
This presentation, and the accompanying instructor’s manual
(current as of 7/02), were prepared by Jennifer Brennan Braden, MD,
MPH, at the Northwest Center for Public Health Practice in Seattle, WA,
and Jeff Duchin, MD with Public Health – Seattle & King County and
the Division of Allergy & Infectious Diseases, University of WA, 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 and 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
Anthrax
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
Anthrax
Overview







Primarily a disease of herbivores
Hardy spore exists in soil reservoir
Humans infected naturally by
contact with infected animals or
contaminated animal products
In the early 1900s ~130 cases/yr in
U.S.
Woolsorter’s disease: inhalation
anthrax
Until 2001, 18 U.S. cases of
inhalation anthrax reported in the
20th century
Last naturally occurring U.S. case
of inhalation anthrax in 1976
CDC
Inhalational Anthrax
Acquisition of Infection

Infectious dose in humans not precisely known

Estimated 8-50,000 spores required for
inhalation anthrax


May be less in the context of bioterrorism
May depend on host factors and bacterial strain
Inhalational Anthrax
Acquisition of Infection

Infectious aerosol particles >5 in size fall from
atmosphere and bond to surfaces


Secondary aerosolization unlikely
Particles 1-5 behave like a gas and are
deposited in alveoli

No environmental residue
Inhalational Anthrax
Pathogenesis

Once deposited, the inert spores reside within
alveoli, potentially for weeks

Inhaled spores taken up by alveolar macrophages
 regional (mediastinal, hilar, peribronchial) lymph
nodes

Spores germinate, producing vegetative cells that
proliferate within macrophages and gain access to
the bloodstream
Inhalational Anthrax
Pathogenesis

Vegetative cells produce toxins
Lethal factor (LF): protease inhibits protein
synthesis  tissue necrosis
 Edema factor (EF): adenylate cyclase  extensive
edema
 Protective antigen: combines with LF and EF to
produce functional toxins


Spores continue to vegetate within host for several
weeks

Antibiotics can prolong the incubation period by
killing the germinating cells while spores remain
viable
Inhalational Anthrax
Clinical Features

Incubation period: 1 to 43 days or longer; may be
related to dose and host factors

Initial symptoms typically appear in 2-5 days
Nonspecific: fever, dry cough, chest discomfort,
myalgia, malaise, profound fatigue, sweats
 GI symptoms


Late symptoms
Hemorrhagic mediastinitis, pleural effusions lead to
dyspnea, cyanosis
 CNS symptoms: hemorrhagic meningitis
 Toxemia leads to rapid progression to shock, death

Inhalational Anthrax
Clinical Features

No person-to-person transmission of inhalational
anthrax

Mortality rate 100% despite aggressive Rx in
“advanced disease” but is lower with early
treatment

6/11 cases in the 2001 outbreak survived with
early aggressive therapy
BT-Related Inhalational Anthrax
Symptoms
Symptoms
Fever, chills
Fatigue, malaise, lethargy
Cough (often nonproductive)
Nausea or vomiting
Dyspnea
Sweats, often drenching
Chest discomfort or
pleuritic pain
Myalgias
Headache
Confusion
Abdominal pain
Sore throat
Rhinorrhea
n=10
10
10
9
9
8
7
7
6
5
4
3
2
1
Jernigan, et al.
Emerg Infect Dis,
NOV 2001
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BT-Related Inhalational Anthrax
CXR & CT Scan Findings
CXR Findings
n=10
Any abnormality
10/10
Mediastinal widening
7/10
Infiltrates/consolidation
7/10
Pleural effusion
8/10
CT Scan Findings
Any abnormality
8/8
Mediastinal lymphadenopathy
or widening
7/8
Pleural effusion
8/8
Infiltrates/consolidation
6/8
Jernigan, et al.
Emerg Infect Dis, NOV 2001
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Inhalational Anthrax
CXR of Case
CDC
AFIP
BT-Related Inhalational Anthrax
CXR of Case
Jernigan, et al. Emerg Infect Dis, NOV 2001
BT-Related Inhalational Anthrax
Chest CT of Case
Jernigan, et al. Emerg Infect Dis, NOV 2001
BT-Related Inhalational Anthrax
CXR of Case
Jernigan, et al. Emerg Infect Dis, NOV 2001
BT-Related Inhalational Anthrax
Chest CT of Case
Jernigan, et al. Emerg Infect Dis, NOV 2001
2001 Anthrax Outbreak
Outcome
Anthrax Letter Cases
22 Anthrax Cases
11 Confirmed inhalational anthrax
11 cutaneous anthrax cases
(7 confirmed, 4 suspected)
5 deaths
(45% mortality rate)
No deaths
MMWR Weekly 50(48);1077-9
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UW Northwest Center for Public Health Practice
When to Think Inhalational Anthrax
History/Epi Clues

Other recent cases of inhalational anthrax
(i.e., outbreak occurring) in your community

Claims* by a terrorist or aggressor of a
release of anthrax in your practice area

Illness in persons with common ventilation
system or other exposure
*a ‘credible threat’ as determined by law enforcement or public health officials
UW Northwest Center for Public Health Practice
When to Think Inhalational Anthrax
History/Epi Clues

Cluster of cases with a similar or unusual
syndrome consistent with anthrax

More severe respiratory disease than expected,
or failure to respond to standard therapy

Increase in persons with respiratory illness
outside of the “flu season”
UW Northwest Center for Public Health Practice
Bioterrorism-Associated Anthrax
Epidemiologic Curve
Inhalation Case
NYC
FL
NJ*
DC
Cases
CT
5
4
3
2
NYC
letters*
Senate
letters*
1
0
9/17
9/21
9/25
9/29
*Postmarked date of known
contaminated letters.
UW Northwest Center for Public Health Practice
10/3
10/7
10/11
10/15
10/19 10/23 10/27 11/14
Date of Onset
*10/19 susp cutaneous case later removed
Modified from: MMWR Nov 2, 2001; 50(43)
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Differential Diagnosis
Anthrax vs. Influenza-Like Illness
MMWR. Nov 9, 2001;50(44)
UW Northwest Center for Public Health Practice
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Inhalational Anthrax
Diagnosis
 Nondescript
prodrome followed by an
overwhelming respiratory or systemic illness
 CXR/CT:
widened mediastinum, pleural
effusion, infiltrates/consolidation
 CT
scan may show pulmonary abnormalities not
seen on CXR
 Mediastinal/hilar adenopathy with increased
density on CT suggests hemorrhagic mediastinitis
 Blood
culture and Gram stain
 Blood
cultures may be positive in initial phase of
illness
 Likely to be negative shortly after initiation of
antibiotic therapy
Inhalational Anthrax
Diagnosis
 CSF
culture and Gram stain if CNS disease
present
 Pleural
fluid culture, cytology for
immunohistochemistry, biopsy
 Hemorrhagic
fluid, few WBC, high protein
 No
clinically useful test to detect exposure to
anthrax
 Nasal
swabs and serology not useful in clinical
case management
B. anthracis in CSF
Jernigan, et al. Emerg Infect Dis, NOV 2001
This link will take you away from the educational site
Cutaneous Anthrax
Presentation and Course
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





Most common form (95%)
under natural conditions
Inoculation of spores under skin
Incubation: hours - 12 days
Pruritic papule  vesicle 
ulcer/painless eschar with
edema, may be surrounded by
vesicles
Regional lymphadenitis
Fever, malaise, headache may
be present
Death 20% untreated; rare if
treated
CDC
Cutaneous Anthrax
Clinical Progression
CDC
Cutaneous Anthrax
Clinical Progression
Day 5
Day 10-12
Day 7
Day 15
UW Northwest Center for Public Health Practice
CDC
Cutaneous Anthrax
© 2001, Universidad Peruana Cayetano
Heredia
Cutaneous Anthrax
© 2001, Universidad Peruana Cayetano
Heredia
Cutaneous Anthrax
© 2001, Universidad Peruana Cayetano
Heredia
Cutaneous Anthrax
© 2001, Universidad Peruana Cayetano
Heredia
Cutaneous Anthrax
© 2001, Universidad Peruana Cayetano
Cutaneous Anthrax
Diagnosis
 Low
suspicion
Vesicular fluid for Gram stain and culture
 Synthetic swab of exudate or most actively
inflamed area
 Punch biopsy for Gram stain and culture
 Specimen in sterile saline

 High
suspicion
2 punch biopsies for culture, PCR and IHC at CDC
 One sample in formalin for IHC and
histopathology
 One sample at -70C or on dry ice for culture and
PCR
 Blood culture
 Acute and convalescent sera

Anthrax
Treatment

Antibiotics are effective against germinating or
vegetative B. anthracis but not against the spore
form

Disease development can be prevented as long
as therapeutic levels of antibiotics are
maintained to kill germinating organisms, or until
remaining spores are cleared or controlled by
immune defenses (duration unclear)
Inhalational Anthrax
Treatment Recommendations, 2001 Outbreak

Initial IV followed by PO for a total of 60 days
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
Ciprofloxacin
 Adults 400mg IV q12 hs
 Children 10-15 mg/kg q12 hs not to exceed 1g/d
OR, If susceptible

Doxycycline
 Adults and children >8 yrs & >45kg: 100mg IV q12 hs
 Children >8 yrs and <45kg: 2.2mg/kg/dose IV q12 hs
 Children <8 yrs: 2.2mg/kg/dose IV Q 12 hs
 And 1-2 other antimicrobials (e.g.,clindamycin, rifampin)

CDC. Update: Investigation of Bioterrorism-Related Anthrax and
Interim Guidelines for Exposure Management and Antimicrobial
Therapy, Octonber 2001.
MMWR 2001; 50:909
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Inhalational Anthrax
Treatment

Supportive care
 ICU
management
 Drainage of pleural effusions

Standard precautions, no need for isolation
Cutaneous Anthrax
Treatment

Cutaneous anthrax without potential aerosol
exposure can be treated with 7-10 days of
antibiotic therapy

In the context of bioterrorism, usually treat for 60
days because of potential aerosol exposure

Cover lesions – treat dressings as biohazard
waste

IV treatment indicated for systemic involvement,
extensive edema, or head and neck lesions
Anthrax
Post-Exposure Prophylaxis (PEP)

Oral antibiotics x 60 days
 Ciprofloxacin
 Adults: 500mg PO Q 12 hs
 Children 10-15mg/kg/dose Q
1g/d

12 hs not to exceed
If susceptible:
 Doxycycline
 Adults
and children >8 yrs and >45kg: 100mg PO
Q 12 hs
 Children >8 yrs and <45kg: 2.2mg/kg/dose BID
 Children <8 yrs: 2.2mg/kg/dose BID
 Amoxicillin
 Adults and children >20Kg:
 Children <20kg: 40mg/kg/d
Q 8 hs
500 mg PO Q 8 hs
divided in 3 doses
MMWR Weekly 50(42)
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Anthrax
Post-exposure Prophylaxis Beyond 60 days?

Rationale:
 Viable spores demonstrated in mediastinal
lymph nodes of monkeys 100d post-exposure
 ACIP Recommendations (December, 2000):
If anthrax vaccine is available, antibiotics can
be discontinued after 3 doses of vaccine (0,
2, and 4 weeks) MMWR 49(RR-15)
Link to Webcast
UW Northwest Center for Public Health Practice
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Anthrax
Extension of PEP: CDC Options

Earlier Recommendations – 60 days of
antibiotics + medical monitoring

Additional Option 1 – 40 additional* days of
antibiotic treatment + medical monitoring

Additional Option 2 – 40 additional* days of
antibiotic treatment + 3 doses of anthrax
vaccine over 4 weeks + medical monitoring
*Total=100days
UW Northwest Center for Public Health Practice
CDC Responds, Dec 21, 2001
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Anthrax Letters
Extension of PEP: CDC Options

Both additional options investigational
 PEP approved by FDA for only 60 days
 Anthrax vaccine, 3-dose schedule and lot
number not approved for this particular use
Link to Webcast
UW Northwest Center for Public Health Practice
This link will take you away from the educational site
Anthrax Vaccine

Current U.S. vaccine (FDA Licensed): culture
supernatant (protective antigen) of attenuated,
non-encapsulated strain
 Protective against cutaneous (human data)
and possibly inhalational anthrax (animal
data)
 Injections at 0, 2, 4 wks & 6, 12, 18 mos;
yearly boosters
 3-dose schedule (0, 2, 4 wks) may be
effective post-exposure, when given with
antibiotics
 83% serologic response after 3 doses,
 100% after 5
 Limited availability
Anthrax Vaccine
Adverse Effects

Safety profile similar to other licensed
vaccines

Up to 30% with mild discomfort (tenderness,
redness, swelling, or itching) at inoculation
site for up to 72 hours

<2% with more severe local reactions,
potentially limiting use of the arm for 1-2 days

Systemic reactions uncommon
Anthrax
Summary of Key Points

The most likely presentation of anthrax in a BT
attack is inhalational disease; cutaneous
disease is also possible.

Early in the course of illness, inhalational
anthrax is not easily distinguished from an
influenza-like illness due to other causes.

Symptoms suggestive of inhalational anthrax
include a febrile respiratory illness with profound
fatigue, drenching sweats, GI involvement, or
chest pressure or pain.
UW Northwest Center for Public Health Practice
Anthrax
Summary of Key Points

There are no specific chest x-ray findings for
inhalational anthrax. CXR is usually abnormal
and may demonstrate mediastinal
widening/hilar adenopathy, infiltrates/
consolidation, or pleural effusions.

CT scan of the chest is a more sensitive test
and may show these abnormalities before they
appear on CXR. Hyperdense lymphadenopathy
on a non-enhanced CT of the chest is
suggestive of anthrax.
UW Northwest Center for Public Health Practice
Anthrax
Summary of Key Points

Antibiotic prophylaxis and possibly anthrax
vaccine can be used to prevent development of
disease in infected persons.

Anthrax is not transmitted person to person.
UW Northwest Center for Public Health Practice
Anthrax
Case Studies and Reports
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JAMA 286(20) and 287(7)
Jernigan et al., Emerging Infect Dis 7(6):933-44
The Sverdlovsk anthrax outbreak of 1979.
Science. 1994;266:1202-1208
Roche et al. New Engl J Med 345:1611
Bush et al. New Engl J Med 345:1607-1610
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
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
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 on-line version of

Johns Hopkins Center for Civilian Biodefense
Studies http://www.hopkins-biodefense.org fact
Medical Management of Biological Casualties
Handbook
http://www.usamriid.army.mil/
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
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
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
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
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
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FBI Terrorism Web Page
http://www.fbi.gov/terrorism/terrorism.htm
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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