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Anthrax
CDC, AFIP
Diseases of Bioterrorist Potential
Learning Objectives
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Describe the epidemiology, mode of transmission
and presenting symptoms of disease caused by
the CDC-defined Category A agents
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Identify the infection control and prophylactic
measures to implement in the event of a
suspected or confirmed Category A case or
outbreak
Anthrax
Overview
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Primarily a disease of herbivores
Hardy spore exists in soil reservoir
Humans “naturally” infected 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
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Infectious dose in humans not precisely known
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Estimated 8-50,000 spores required for inhalation
anthrax
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May be less in the context of bioterrorism
May depend on host factors and bacterial strain
Inhalational Anthrax
Acquisition of Infection
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Infectious aerosol particles >5 in size fall from
atmosphere and bond to surfaces
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Secondary aerosolization unlikely
Particles 1-5 behave like a gas and are deposited
in small air sacs of the lungs
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No environmental residue
Anthrax
Case Definition
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An illness with acute onset characterized by
several distinct clinical forms
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Cutaneous: a skin lesion evolving during a period of
2-6 days from a papule, through a vesicular stage, to a
depressed black eschar
Inhalation*: a brief prodrome resembling a viral
respiratory illness, followed by development of
hypoxia and dyspnea, with radiographic evidence of
mediastinal widening
*Presentation may vary in the context of bioterrorism
MMWR 1997;46(RR-10)
Anthrax
Case Definition, cont.
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An illness with acute onset characterized by
several distinct clinical forms (continued)
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Intestinal: severe abdominal distress followed by a
fever and signs of septicemia
Oropharyngeal: mucosal lesion in the oral cavity or
oropharynx, cervical adenopathy & edema, & fever
Confirmed case: Clinically compatible with
laboratory confirmation
MMWR 1997;46(RR-10)
Anthrax
Laboratory Criteria for Diagnosis
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Isolation of B. anthracis from a clinical specimen
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Blood, lung fluid, spinal fluid, skin lesion OR
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Positive serology* (after symptom onset) OR
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Demonstration of B. anthracis in a clinical specimen by
immunofluorescence*
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Nasal swabs & serology – not useful for clinicians, but
can help determine the extent of exposure in an
epidemiologic investigation
*testing at state public health labs or CDC
MMWR 1997;46(RR-10)
Inhalational Anthrax
Clinical Features
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Incubation period: 1 to 43 days or longer; may be related to
dose and host factors
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Initial symptoms typically appear in 2-5 days
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Nonspecific: fever, dry cough, chest discomfort, muscle aches, malaise,
profound fatigue, sweats
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Gastrointestinal symptoms
Late symptoms
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Hemorrhagic mediastinitis, dyspnea
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Some cases develop meningitis
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Rapid progression to shock, death
Inhalational Anthrax
Clinical Features
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No person-to-person transmission of inhalational anthrax
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Mortality rate 100% despite aggressive Rx in “advanced
disease” but is lower with early treatment
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6/11 cases in the 2001 outbreak survived with early
aggressive therapy
Cutaneous Anthrax
Presentation and Course
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Most common form (95%) under
natural conditions
Portal of entry: break in skin
Incubation: hours - 12 days
Papule  vesicle  ulcer/painless
eschar
Significant edema surrounding the
lesion, and in nearby lymph nodes
Fever, malaise, headache may be
present
Death 20% untreated; rare if treated
CDC
Cutaneous Anthrax
Clinical Progression
Day 5
Day 10-12
Day 7
Day 15
CDC
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.
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)
BT-related Inhalational Anthrax
Distinguishing Anthrax from Other Influenza-Like Illnesses
MMWR. Nov 9, 2001;50(44)
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
Anthrax
Treatment
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Antibiotics are effective against germinating or vegetative
B. anthracis but not against the spore form
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Disease development can be prevented as long as
therapeutic levels of antibiotics are maintained to kill
germinating organisms, or until spores are cleared or
controlled by immune defenses (duration unclear)
Anthrax
Treatment and Prophylaxis
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Treatment of cases
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Antibiotics x 60 days
Can treat cutaneous disease for 7-10 days, if no potential aerosol
exposure
Standard precautions
Cover cutaneous lesions, treat dressings as biohazard waste
Prophylaxis for those exposed
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Antibiotics for 60 – 100 days
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Possible role for vaccine in combination with antibiotics
Anthrax
Post-exposure Prophylaxis Beyond 60 days?
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Rationale:
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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
Anthrax
Extension of PEP: CDC Options
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Earlier Recommendations – 60 days of antibiotics +
medical monitoring
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Additional Option 1 – 40 additional* days of
antibiotic treatment + medical monitoring
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Additional Option 2 – 40 additional* days of
antibiotic treatment + 3 doses of anthrax vaccine over
4 weeks + medical monitoring
*Total=100 days
CDC Responds, Dec 21, 2001
Anthrax Letters
Extension of PEP: CDC Options
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Both additional options investigational
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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
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Anthrax Vaccine
Current U.S. vaccine (FDA licensed): developed
from attenuated strain of virus
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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 postexposure, when given w/antibiotics
83% serologic response after 3 doses
100% after 5
Limited availability
Anthrax Vaccine
Adverse Effects
 Safety profile similar to other licensed
vaccines
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Up to 30% with mild discomfort (tenderness,
redness, swelling, or itching) at inoculation site
for up to 72 hours
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<2% with more severe local reactions,
potentially limiting use of the arm for 1-2 days
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Systemic reactions uncommon
Anthrax
Summary of Key Points
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The most likely presentation of anthrax in a BT attack is
inhalational disease; cutaneous disease is also possible.
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Early in the course of illness, inhalational anthrax is not
easily distinguished from an influenza-like illness due to
other causes.
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Antibiotic prophylaxis can be used to prevent
development of disease in infected persons.
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Anthrax is not transmitted person to person.
Case Reports
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Anthrax
AN EPIDEMIC OF INHALATION ANTHRAX:
THE FIRST IN THE TWENTIETH CENTURY
American Journal of Hygiene 72, 6-23, 1960
THE SVERDLOVSK ANTHRAX
OUTBREAK OF 1979
Science 266, 1202-1208, 1994
Anthrax Outbreak 2001 – UCLA SOPH website
Resources
 Centers for Disease Control & Prevention
http://www.bt.cdc.gov/
 Bioterrorism Web page:
 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 Medical Management of Biological Casualties
Handbook
http://www.usamriid.army.mil/
Resources
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Office of the Surgeon General: Medical
Nuclear, Biological and Chemical Information
http://www.nbc-med.org
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St. Louis University Center for the Study of
Bioterrorism and Emerging Infections
http://bioterrorism.slu.edu