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BIOTERRORISM
TABLE OF CONTENTS
(click
on the links below to view more details)
 Learning
Objectives
Introduction
Anthrax
as a Biological Weapon
History
of Current Threat
Epidemiology
of Anthrax
Microbiology
Pathogenesis
and Clinical Manifestations
Diagnosis
Vaccination
Therapy
Infection
Control
Decontamination
Smallpox
as a Biological Weapon
History
and Potential as a Bioweapon
Epidemiology
Microbiology
Pathongenesis
and Clinical Presentation
Diagnosis
Preexposure
Preventive Vaccination
Postexposure
Therapy
Postexposure
Infection Control
Hospital
Epidemiology and Infection Control
Vaccine
Administration and Complications
Decontamination
Research
Summary
Smallpox
Update
Botulism
as a Bioterror Weapon
History
of Current Threat
Microbiology
and Virulence Factors
Pathogenesis
and Clinical Manifestations
Epidemiology
Diagnosis
and Differential Diagnosis
Therapy
Special
Populations
Prophylaxis
Decontamination
Infection
Control
Research
Needs
Plague
as a Biological Weapon
History
and Potential as a Bioterrorist Agent
Epidemiology
Microbiology
and Virulence Factors
Pathogenesis
and Clinical Manifestations
Diagnosis
Vaccination
Therapy
Postexposure
Prophylaxis Recommendations
Infection
Control
Environmental
Decontamination
Appendix
Examination
Learning
Objectives
·
Upon successful completion of this continuing education module,
you will be able to:
· Identify and discuss the history, epidemiology, microbiology,
pathogenesis, clinical manifestations, diagnosis, treatment
and prevention of: Anthrax, Small Pox, Botulism and Plague
Introduction
Bioterrorism
has become a common household term ever since anthrax was
spread across a wide reach of the nation last fall. Now, it
almost appears everyone is involved in serious anti-terrorism
campaigns which are not as readily seen as flags attached
to cars, homes and clothing.
In the event of another bioterrorist attack, will you as a
caregiver be prepared?
RTs
and Nurses are in the first line of defense in combating biohazard
substances because inhalation is the major pathways for toxic
and biological agents to infect humans. The airway is one
of the primary routes infectious agents follow to enter the
body, and the harm caused by the agent would impact the respiratory
system first, so RTs and Nurses need to be alert.
Tom
Johnson, MS, RRT, program director of respiratory care and
professor at Long Island University in New York, was an officer
during the Vietnam era. He trained military personnel about
chemical warfare. Thirty years later, he teaches RTs and Nurses
about bioterrorism and how they need to be prepared in the
event of a biological disaster.
Johnson
urges all RTs and Nurses to recognize potential bioterrorist
agents. "During the Gulf War, biowarfare became an issue,
and I realized I was ignorant and did not know anthrax was
already weaponized." Bioterrorism is not a new idea.
"We have had the threat of bioterrorism for a long time
in history," he said.
Today's
need is different. Caregivers need to be prepared and knowledgeable
in bioterrorism in order to treat patients in the best manner
possible.
Knowledge
Is Power
In
the event of a bioterrorist attack, every second counts, especially
when caregivers are trying to determine whether, in fact,
a patient has symptoms of a bioterrorist agent. If health
care professionals are keen enough to know what symptoms to
look for, the impact of a potentially deadly bioterrorist
attack can be lessened.
"RTs
and nurses are the front line in an attack," Johnson
said. If they have a suspicion and knowledge of which tests
to run, the treatment can begin. "RTs and Nurses can
help in the epidemiological standpoint and help blunt the
attack," Johnson said. The key is to be alert in the
event a bioterrorist attack happens. "Therapists need
to be aware of which drugs to administer by IV and when to
begin intubation," he said.
Early
detection of an agent allows health care professionals more
time to treat the patient and yield a cured patient. "RTs
and Nurses need to be very quick thinking and detect early.
Also, RTs and Nurses should have strong airway control skills
and be very familiar with oxygenation ventilation issues with
biological warfare," he said.
The
goal is not to make experts of everyone; it's to heighten
awareness. "RTs and Nurses can be under-recognized and
underutilized, and we have to not only improve our skills
but get those skills recognized, maybe within our licensure
laws so if we have another disaster, natural or man-made,
we can adequately respond as part of the health care team,"
Johnson said.
September
11
As
Americans watched the events surrounding 9/11 unfold on national
television, their gasps and sobs could be heard around the
country. Little did they know it was just the beginning, a
foreshadowing to the anthrax scare.
"Never
before has the U.S. become so acutely aware of biological,
chemical and radiological threats," said Frank Rando,
MS, Ph, CRT, CVT, EMT-P, a certified hazardous materials specialist.
Rando is a special adviser on counter-terrorism and public
health preparedness and respiratory causality management.
"Respiratory therapists have never received detailed
instruction or reading materials on how to handle these types
of casualties," said Rando, who became a part of counter-terrorism
because he felt RTs and Nurses need to become more aware and
oriented about how to medically manage biological, chemical
and radiological casualties since they are first-line health
care providers. There is a one in 10 chance, he explained,
there would be casualties with some degree of respiratory
impairment.
Crisis
Plans
One
of the things that would help galvanize hospital staff is
to have them prepare response plans and enforce them. Response
plans are one key step in advancing a response system to alert
staff members and operationalize a plan.
Patrick
Libbey, director of Thurston County Public Health and Social
Service Department, Olympia, Wash., and the president of the
National Association of County and City Health Officials,
recognizes the importance of crisis management plans in the
event of natural or terrorism events.
"When you have an earthquake or a flood, you have a very
set geographic and time-specific event to respond to. Bioterrorism
may roll out very differently," he said.
As
a result of national campaigns, numerous agencies are creating
more concise and structured plans to augment earlier models.
Other agencies are creating disaster plans for the first time.
All emergency agencies need to be alerted in the event of
a disaster. If a hospital activates as a result of an existing
condition, it acts in conjunction with the emergency management
agency of that jurisdiction, Libbey explained.
Emergency
response systems must work cohesively with each other, he
added. "If any of the systems are acting independently,
that is where the troubles are. They need to work together
to make the earliest and most complete intervention,"
he said.
Crisis
drills help prepare individuals involved to have at least
a vague idea of what to expect when something does happen.
"The more you can think through a scenario, the needs
for accessing resources, and who needs to be involved, the
better prepared you will be when a situation does occur,"
Libbey said.
Public
Safety
September
11 was a wake up call, not only to public safety and law enforcement
officers but to the health care establishment as well because
the country discovered how vulnerable it is to terrorist attacks
and how devastating terrorist attacks can be.
We
have become more acutely aware of bioterrorism because of
the anthrax mailings, subsequent to the 9/11 attacks. The
events of September and beyond have lead health care facilities
to revamp and reevaluate their existing disaster response
capabilities. Everyone has become leery of planes passing
overhead and suspicious looking letters in the mailbox.
"The
tricky piece is that many biologic agents can be used, and
the initial presenting symptoms are very parallel to other
on-going ailments," Johnson said. One of the keys is
spotting unusual signs, "to notice if there is something
specific in the presenting characteristics of the individual."
Secondly, health care personnel should notice if there is
something unusual going on within the community. If there
are some out of the ordinary occurring, that merits broader
attention, Libbey said. When treating any patient today, clinicians
need to be more aware of things they have not thought of before.
"I think it's prudent that RTs and Nurses have a knowledge
of this," Johnson said. "We don't all have to be
experts in neonatal or geriatrics; we just need to know something
about bioterrorism."
Top Five Issues for RTs and Nurses In Bio-Terrorism Attacks
1.
Have some familiarity with the top seven biological weapons:
anthrax, smallpox, botulism, tularemia, bubonic/pneumonic
plague, viral encephalitis, and Staphylococcus enterotoxin
B. Therapists need to remembers terrorists get creative and
may not use traditional agents.
2.
Early warning: The therapist is a part of the early warning
system of an attack.
3.
Necessary Lab Tests: This will help determine which agent
was used and what antibiotic will help treat it.
4.
Personal protection: Health care professionals need to protect
themselves and their facility. There are bioagents which require
only standard precautions.
5.
Therapeutic Interventions: This may include oxygen and ventilation
as necessary, especially with a botulism attack.
Physicians
Urged to Learn ABCs Of Highly Infectious Q Fever
Q
fever, is not the most deadly agent to be used as a biological
weapon, but it could be one of the most effective because
of its ability to spread easily through the air and cause
widespread debilitating illness, according to a report in
the April 20 issue of Bioterror Medical Alert.
Q
fever typically occurs when the bacteria is passed from farm
animals to humans and can cause flu-like symptoms, in many
cases followed by pneumonia and hepatitis. In some cases,
infection leads to a particularly hard-to-treat form of endocarditis.
Public
health officials worry about the use of Q fever by bioterrorists
because it is already known to have been put into a weapon
form by Russia and possibly by Iraq. No licensed vaccine exists,
although the U.S. army is working rapidly to develop one.
FAQs
regarding Anthrax
What
is anthrax?
Anthrax is an infectious disease caused by a spore-forming
bacterium called Bacillus anthracis. Anthrax is most often
seen in hoofed mammals, but may also infect humans.
Are
there different types of anthrax?
Three different types of anthrax infections that can occur
in humans. These are: inhalation (breathing in spores), cutaneous
(deposit of spores into skin that has cuts or abrasions) and
intestinal (deposit of spores in intestinal tract due to the
eating of contaminated meat)
How
often is anthrax disease observed in the U.S?
Anthrax is primarily an occupational disease. It is occasionally
identified in individuals exposed to dead animals and animal
products or individuals who handle the hides of animals (e.g.
farmers) and has been called “wool sorter’s disease.”
In
the United States, the incidence of anthrax is extremely low.
In the U.S. between 1944-1994, 224 cases of cutaneous anthrax
were reported. Until this more recent exposure in Florida,
no cases of inhalation anthrax were reported in the U.S. since
1978. Gastrointestinal anthrax is uncommonly reported, although
outbreaks have occurred in Africa and Asia.
What
are the symptoms of anthrax?
The symptoms of anthrax are different depending on how the
disease was contracted Symptoms will generally occur within
seven days after exposure, however it may take as long as
sixty days.
Specific
symptoms are as follows:
-
Inhalation anthrax: initial symptoms may resemble the flu
and can include, cough, headache, vomiting, chills and general
weakness. This can last from a few hours to a few days.
The second stage of the illness may occur directly after
the first, or following a short recovery period. The second
stage develops with sudden fever, shortness of breath, perspiration
and shock.
- Cutaneous
anthrax: areas of exposed skin, such as arms, hands and
face are most frequently affected. Skin infection begins
as a raised itchy bump that resembles an insect bite but
within 1-2 days develops into a fluid filled bump and then
a painless ulcer, usually 1-3 cm in diameter, with a characteristic
black necrotic (dying) area in the center.
- Gastrointestinal
anthrax: Initial signs of the disease include nausea, loss
of appetite, vomiting, fever are followed by abdominal pain,
vomiting of blood, and severe diarrhea
How
is anthrax diagnosed?
For people who have been exposed to anthrax, laboratory testing
must be conducted to perform an accurate diagnosis.
These
lab tests may include:
- Examination
of tissue under a microscope
- Cultures
of a person’s blood or spinal fluid (must be done before
antibiotics are given)
- Cultures
of tissue or fluid from an affected area
- The
polymerase chain reaction (PCR) test can increase small
amounts of anthrax DNA to show that the anthrax bacteria
are present.
Nasal
swabs can be used to detect anthrax spores that may be resting
in the nose. Swabs may document exposure, but cannot rule
it out, even if they are negative. Nasal swabs are useful
to provide clues regarding exposure for investigative purposes,
but are not a definitive measure.
How
is anthrax spread?
The inhalation form of anthrax is contracted by breathing
in spores. The cutaneous form is spread by contact of spores
with a break in the skin, such as a scratch. The intestinal
form is by eating contaminated meat.
Person
to person transmission of anthrax is extremely rare and has
only been reported with cutaneous anthrax. Spread of the disease
is not a concern in managing or visiting patients with inhalation
anthrax.
What
is the treatment for anthrax?
The Food and Drug Administration has approved three antibiotics
to treat or prevent the development of anthrax in exposed
individuals: These are: penicillin, doxycycline, and cirprofloxacin.
Most
naturally occurring strains of anthrax are sensitive to these
antibiotics. Early antibiotic treatment of anthrax is essential
as delay reduces the chances for survival.
Persons
will exposure or contact with an environment known or suspected
to be contaminated with anthrax should be considered for antibiotic
treatment. Exposure or contact, not lab test results, should
be the deciding factor for beginning treatment.
I
don't have any reason to believe I've been exposed to anthrax
but I'm still worried. Should I get tested?
No.
People without symptoms are given antibiotics preventively
only if they were in the area where anthrax was present. Nasal
swabs can show that someone was exposed, but a negative swab
does not mean someone was not exposed. These tests are given
mostly to help authorities determine a pattern of exposure,
not to diagnose individuals.
Should
I get antibiotics from my doctor in case of an attack?
No, this is not a good idea. Taking antibiotics because you
are afraid of an attack can cause more harm that good. It
may lead to antibiotic resistance of other bacteria. People
who take antibiotics when they are not needed may develop
a resistance to the drugs, which may not be effective when
they are needed to treat an actual disease in the future.
And these drugs can have serious side effects, such as an
irregular heartbeat or digestive problems.
Should
I stock up on antibiotics just in case I need them later?
No. Federal officials say there are plenty available, and
they plan to stockpile even more. They also are advising doctors
against prescribing antibiotics to people who do not need
them.
Should
I buy a mask to protect myself from anthrax exposure?
It is strongly discouraged to purchase a gas mask for protection
against a biological agent. Gas masks are intended for short
term use and would only provide protection if worn at the
time of a known release. Additionally, gas masks are useless
unless properly fit tested. Unless a mask was worn all the
time, it would not protect against the covert release of anthrax.
Improper use of gas masks can cause serious injury or even
death by accidental suffocation. Masks are not effective post
exposure.
Can
my heating and ventilation system prevent anthrax exposure?
Information on the effectiveness of air cleaning devices is
dependent on many factors, including the air flow rate, the
proximity of the source, capture efficiency, filtration efficiency,
as well as other factors. For more information on HVAC systems
please review to the summary of the “Achieving
Healthy Indoor Air” Workshop.
The
following agencies may be of some help in answering questions
on heating, ventilation and air conditioning systems.
ASHRAE-American Society of Heating, Refrigerating and Air
Conditioning Engineers
1791 Tullie Circle, N.E.
Atlanta, GA 30329
Phone: (800) 527-4723 (U.S. and Canada only)
Fax: (404) 321-5478
Web Site: www.ashrae.org
NAFA-National
Air Filtration Association
1518 K Street, NW, Suite 503
Washington, DC 20005
Phone:(202) 628-5328
Web Site: www.nafahq.org/default.htm
View
American Lung Association Nationwide
Research Awardees for 2001-2002
Web
sites for additional info:
As
you can see from the introduction above, RTs and Nurses play
an important role in the defense against bio-terrorism. This
continuing education unit will present to you a “consensus
report” prepared by included 23 experts from academic
medical centers, research organizations, and governmental,
military, public health, and emergency management institutions
and agencies.
Anthrax
As A Biological Weapon, 2002
Updated
Recommendations for Management
Authors/Contributors:
Thomas V. Inglesby, MD; Tara O'Toole, MD, MPH;
Donald A. Henderson, MD, MPH; John G. Bartlett, MD;
Michael S. Ascher, MD; Edward Eitzen, MD, MPH; Arthur M. Friedlander,
MD; Julie Gerberding, MD, MPH; Jerome Hauer, MPH; James Hughes,
MD; Joseph McDade, PhD; Michael T. Osterholm, PhD, MPH; Gerald
Parker, PhD, DVM; Trish M. Perl, MD, MSc; Philip K. Russell,
MD; Kevin Tonat, DrPH, MPH; for the Working Group on Civilian
Biodefense
Objective
To review and update consensus-based recommendations for medical
and public health professionals following a Bacillus anthracis
attack against a civilian population.
Participants
The working group included 23 experts from academic medical
centers, research organizations, and governmental, military,
public health, and emergency management institutions and agencies.
Evidence
MEDLINE databases were searched from January 1966 to January
2002, using the Medical Subject Headings anthrax, Bacillus
anthracis, biological weapon, biological terrorism, biological
warfare, and biowarfare. Reference review identified work
published before 1966. Participants identified unpublished
sources.
Consensus
Process The first draft synthesized the gathered information.
Written comments were incorporated into subsequent drafts.
The final statement incorporated all relevant evidence from
the search along with consensus recommendations.
Conclusions
Specific recommendations include diagnosis of anthrax infection,
indications for vaccination, therapy, post-exposure prophylaxis,
decontamination of the environment, and suggested research.
This revised consensus statement presents new information
based on the analysis of the anthrax attacks of 2001, including
developments in the investigation of the anthrax attacks of
2001; important symptoms, signs, and laboratory studies; new
diagnostic clues that may help future recognition of this
disease; current anthrax vaccine information; updated antibiotic
therapeutic considerations; and judgments about environmental
surveillance and decontamination.
Of
the biological agents that may be used as weapons, the Working
Group on Civilian Biodefense identified a limited number of
organisms that, in worst-case scenarios, could cause disease
and deaths in sufficient numbers to gravely impact a city
or region. Bacillus anthracis, the bacterium
that causes anthrax, is one of the most serious of these.
Several
countries are believed to have offensive biological weapons
programs, and some independent terrorist groups have suggested
their intent to use biological weapons. Because the possibility
of a terrorist attack using bioweapons is especially difficult
to predict, detect, or prevent, it is among the most feared
terrorism scenarios.1 In September 2001, B anthracis spores
were sent to several locations via the US Postal Service.
Twenty-two confirmed or suspect cases of anthrax infection
resulted. Eleven of these were inhalational cases, of whom
5 died; 11 were cutaneous cases (7 confirmed, 4 suspected).2
In this article, these attacks are termed the anthrax attacks
of 2001. The consequences of these attacks substantiated many
findings and recommendations in the Working Group on Civilian
Biodefense's previous consensus statement published in 19993;
however, the new information from these attacks warrant updating
the previous statement.
Before
the anthrax attacks in 2001, modern experience with inhalational
anthrax was limited to an epidemic in Sverdlovsk, Russia,
in 1979 following an unintentional release of B anthracis
spores from a Soviet bioweapons factory and to 18 occupational
exposure cases in the United States during the 20th century.
Information about the potential impact of a large, covert
attack using B anthracis or the possible efficacy of postattack
vaccination or therapeutic measures remains limited. Policies
and strategies continue to rely partially on interpretation
and extrapolation from an incomplete and evolving knowledge
base.
Consensus
Methods
The
working group comprised 23 representatives from academic medical
centers; research organizations; and government, military,
public health, and emergency management institutions and agencies.
For the original consensus statement,3 we searched MEDLINE
databases from January 1966 to April 1998 using Medical Subject
Headings of anthrax, Bacillus anthracis, biological weapon,
biological terrorism, biological warfare, and biowarfare.
Reference review identified work published before 1966. Working
group members identified unpublished sources.
The
first consensus statement, published in 1999,3 followed a
synthesis of the information and revision of 3 drafts. We
reviewed anthrax literature again in January 2002, with special
attention to articles following the anthrax attacks of 2001.
Members commented on a revised document; proposed revisions
were incorporated with the working group's support for the
final consensus document.
The
assessment and recommendations provided herein represent our
best professional judgment based on current data and expertise.
The conclusions and recommendations need to be regularly reassessed
as new information develops.
HISTORY
OF CURRENT THREAT
For
centuries, B anthracis has caused disease in animals and serious
illness in humans.4 Research on anthrax as a biological weapon
began more than 80 years ago.5 Most national offensive bioweapons
programs were terminated following widespread ratification
or signing of the Biological Weapons Convention (BWC) in the
early 1970s6;
the US offensive bioweapons program was terminated after President
Nixon's 1969 and 1970 executive orders. However, some nations
continued offensive bioweapons development programs despite
ratification of the BWC. In 1995, Iraq acknowledged producing
and weaponizing B anthracis to the United Nations Special
Commission.7
The former Soviet Union is also known to have had a large
B anthracis production program as part of its offensive bioweapons
program.8
A recent analysis reports that there is clear evidence of
or widespread assertions from nongovernmental sources alleging
the existence of offensive biological weapons programs in
at least 13 countries.6
The
anthrax attacks of 2001 have heightened concern about the
feasibility of large-scale aerosol bioweapons attacks by terrorist
groups. It has been feared that independent, well-funded groups
could obtain a manufactured weapons product or acquire the
expertise and resources to produce the materials for an attack.
However, some analysts have questioned whether "weapons
grade" material such as that used in the 2001 attacks
(i.e., powders of B anthracis with characteristics such as
high spore concentration, uniform particle size, low electrostatic
charge, treated to reduce clumping) could be produced by those
not supported by the resources of a nation-state. The US Department
of Defense recently reported that 3 defense employees with
some technical skills but without expert knowledge of bioweapons
manufactured a simulant of B anthracis in less than a month
for $1 million.9
It is reported that Aum Shinrikyo, the cult responsible for
the 1995 release of sarin nerve gas in a Tokyo subway station,10
dispersed aerosols of anthrax and botulism throughout Tokyo
at least 8 times.11
Forensic analysis of the B anthracis strain used in these
attacks revealed that this isolate most closely matched the
Sterne 34F2 strain, which is used for animal vaccination programs
and is not a significant risk to humans.12
It is probable that the cult attacks produced no illnesses
for this and other technical reasons. Al Quaeda also has sought
to acquire bioweapons in its terrorist planning efforts although
the extent to which they have been successful is not reported.13
In
the anthrax attacks of 2001, B anthracis spores were sent
in at least 5 letters to Florida, New York City, and Washington,
DC. Twenty-two confirmed or suspected cases resulted. All
of the identified letters were mailed from Trenton, NJ. The
B anthracis spores in all the letters were identified as the
Ames strain. The specific source (provenance) of B anthracis
cultures used to create the spore-containing powder remains
unknown at time of this publication.
It
is now recognized that the original Ames strain of B anthracis
did not come from a laboratory in Ames, Iowa, rather from
a laboratory in College Station, Tex. Several distinct Ames
strains have been recognized by investigating scientists,
which are being compared with the Ames strain used in the
attack. At least 1 of these comparison Ames strains was recovered
from a goat that died in Texas in 1997.14
Sen.
Daschle's letter reportedly had 2 g of B anthracis containing
powder; the quantity in the other envelopes has not been disclosed.
The powder has been reported to contain between 100 billion
to 1 trillion spores per gram15
although no official analysis of the concentration of spores
or the chemical composition of the powder has been published.
The
anthrax attacks of 2001 used 1 of many possible methods of
attack. The use of aerosol-delivery technologies inside buildings
or over large outdoor areas is another method of attack that
has been studied. In 1970, the World Health Organization16
and in 1993 the Office of Technology Assessment17
analyzed the potential scope of larger attacks. The 1979 Sverdlovsk
accident provides data on the only known aerosol release of
B anthracis spores resulting in an epidemic.18
An
aerosol release of B anthracis would be odorless and invisible
and would have the potential to travel many kilometers before
dissipating.16,
19
Aerosol technologies for large-scale dissemination have been
developed and tested by Iraq17
and the former Soviet Union8 Few details of those tests are
available. The US military also conducted such trials over
the Pacific Ocean in the 1960s. A US study near Johnston Atoll
in the South Pacific reported a plane "sprayed a 32-mile
long line of agent that traveled for more then 60 miles before
it lost its infectiousness."20
In
1970, the World Health Organization estimated that 50 kg of
B anthracis released over an urban population of 5 million
would sicken 250 000 and kill 100 000.16
A US Congressional Office of Technology assessment analysis
from 1993 estimated that between 130 000 and 3 million deaths
would follow the release of 100 kg of B anthracis, a lethality
matching that of a hydrogen bomb.17
EPIDEMIOLOGY
OF ANTHRAX
Naturally
occurring anthrax in humans is a disease acquired from contact
with anthrax-infected animals or anthrax-contaminated animal
products. The disease most commonly occurs in herbivores,
which are infected after ingesting spores from the soil. Large
anthrax epizootics in herbivores have been reported.21 A published
report states that anthrax killed 1 million sheep in Iran
in 194522; this number is supported by an unpublished Iranian
governmental document.23 Animal vaccination programs have
reduced drastically the animal mortality from the disease.24
However, B anthracis spores remain prevalent in soil samples
throughout the world and cause anthrax cases among herbivores
annually.22, 25, 26
Anthrax
infection occurs in humans by 3 major routes: inhalational,
cutaneous, and gastrointestinal. Naturally occurring inhalational
anthrax is now rare. Eighteen cases of inhalational anthrax
were reported in the United States from 1900 to 1976; none
were identified or reported thereafter. Most of these cases
occurred in special-risk groups, including goat hair mill
or wool or tannery workers; 2 of them were laboratory associated.27
Cutaneous
anthrax is the most common naturally occurring form, with
an estimated 2000 cases reported annually worldwide.26 The
disease typically follows exposure to anthrax-infected animals.
In the United States, 224 cases of cutaneous anthrax were
reported between 1944 and 1994.28 One case was reported in
2000.29 The largest reported epidemic occurred in Zimbabwe
between 1979 and 1985, when more than 10 000 human cases of
anthrax were reported, nearly all of them cutaneous.30
Although
gastrointestinal anthrax is uncommon, outbreaks are continually
reported in Africa and Asia26, 31, 32 following ingestion
of insufficiently cooked contaminated meat. Two distinct syndromes
are oral-pharyngeal and abdominal.31, 33, 34 Little information
is available about the risks of direct contamination of food
or water with B anthracis spores. Experimental efforts to
infect primates by direct gastrointestinal instillation of
B anthracis spores have not been successful.35 Gastrointestinal
infection could occur only after consumption of large numbers
of vegetative cells, such as what might be found in raw or
undercooked meat from an infected herbivore, but experimental
data is lacking.
Inhalational
anthrax is expected to account for most serious morbidity
and most mortality following the use of B anthracis as an
aerosolized biological weapon. Given the absence of naturally
occurring cases of inhalational anthrax in the United States
since 1976, the occurrence of a single case is now cause for
alarm.
MICROBIOLOGY
B
anthracis derives from the Greek word for coal, anthrakis,
because of the black skin lesions it causes. B anthracis is
an aerobic, gram-positive, spore-forming, nonmotile Bacillus
species. The nonflagellated vegetative cell is large (1-8
µm long, 1-1.5 µm wide). Spore size is approximately
1 µm. Spores grow readily on all ordinary laboratory
media at 37°C, with a "jointed bamboo-rod" cellular
appearance and a unique "curled-hair" colonial appearance.
Experienced microbiologists should be able to identify this
cellular and colonial morphology; however, few practicing
microbiologists outside the veterinary community have seen
B anthracis colonies beyond what they may have seen in published
material.37 B anthracis spores germinate when they enter an
environment rich in amino acids, nucleosides, and glucose,
such as that found in the blood or tissues of an animal or
human host. The rapidly multiplying vegetative B anthracis
bacilli, on the contrary, will only form spores after local
nutrients are exhausted, such as when anthrax-infected body
fluids are exposed to ambient air.22 Vegetative bacteria have
poor survival outside of an animal or human host; colony counts
decline to being undetectable within 24 hours following inoculation
into water.22 This contrasts with the environmentally hardy
properties of the B anthracis spore, which can survive for
decades in ambient conditions.37
PATHOGENESIS
AND CLINICAL MANIFESTATIONS
Inhalational Anthrax
Inhalational anthrax follows deposition into alveolar spaces
of spore-bearing particles in the 1- to 5-µm range.38,
39 Macrophages then ingest the spores, some of which are lysed
and destroyed. Surviving spores are transported via lymphatics
to mediastinal lymph nodes, where germination occurs after
a period of spore dormancy of variable and possibly extended
duration.35, 40, 41 The trigger(s) responsible for the transformation
of B anthracis spores to vegetative cells is not fully understood.42
In Sverdlovsk, cases occurred from 2 to 43 days after exposure.18
In experimental infection of monkeys, fatal disease occurred
up to 58 days40 and 98 days43 after exposure. Viable spores
were demonstrated in the mediastinal lymph nodes of 1 monkey
100 days after exposure.44
Once
germination occurs, clinical symptoms follow rapidly. Replicating
B anthracis bacilli release toxins that lead to hemorrhage,
edema, and necrosis.32, 45 In experimental animals, once toxin
production has reached a critical threshold, death occurs
even if sterility of the bloodstream is achieved with antibiotics.27
Extrapolations from animal data suggest that the human LD50
(i.e., dose sufficient to kill 50% of persons exposed to it)
is 2500 to 55 000 inhaled B anthracis spores.46 The LD10 was
as low as 100 spores in 1 series of monkeys.43 Recently published
extrapolations from primate data suggest that as few as 1
to 3 spores may be sufficient to cause infection.47 The dose
of spores that caused infection in any of the 11 patients
with inhalational anthrax in 2001 could not be estimated although
the 2 cases of fatal inhalational anthrax in New York City
and Connecticut provoked speculation that the fatal dose,
at least in some individuals, may be quite low.
A
number of factors contribute to the pathogenesis of B anthracis,
which makes 3 toxins protective antigen, lethal factor, and
edema factor that combine to form 2 toxins: lethal toxin and
edema toxin. The protective antigen allows the binding of
lethal and edema factors to the affected cell membrane and
facilitates their subsequent transport across the cell membrane.
Edema toxin impairs neutrophil function in vivo and affects
water homeostasis leading to edema, and lethal toxin causes
release of tumor necrosis factor and interleukin 1 , factors
that are believed to be linked to the sudden death in severe
anthrax infection.48 The molecular target of lethal and edema
factors within the affected cell is not yet elucidated.49
In addition to these virulence factors, B anthracis has a
capsule that prevents phagocytosis. Full virulence requires
the presence of both an antiphagocytic capsule and the 3 toxin
components.37 An additional factor contributing to B anthracis
pathogenesis is the high concentration of bacteria occurring
in affected hosts.49
Inhalational
anthrax reflects the nature of acquisition of the disease.
The term anthrax pneumonia is misleading because typical bronchopneumonia
does not occur. Postmortem pathological studies of patients
from Sverdlovsk showed that all patients had hemorrhagic thoracic
lymphadenitis, hemorrhagic mediastinitis, and pleural effusions.
About half had hemorrhagic meningitis. None of these autopsies
showed evidence of a bronchoalveolar pneumonic process although
11 of 42 patient autopsies had evidence of a focal, hemorrhagic,
necrotizing pneumonic lesion analogous to the Ghon complex
associated with tuberculosis.50 These findings are consistent
with other human case series and experimentally induced inhalational
anthrax in animals.40, 51, 52 A recent reanalysis of pathology
specimens from 41 of the Sverdlovsk patients was notable primarily
for the presence of necrotizing hemorrhagic mediastinitis;
pleural effusions averaging 1700 mL in quantity; meningitis
in 50%; arteritis and arterial rupture in many; and the lack
of prominent pneumonitis. B anthracis was recovered in concentrations
of up to 100 million colony-forming units per milliliter in
blood and spinal fluid.53
In
animal models, physiological sequelae of severe anthrax infection
have included hypocalcemia, profound hypoglycemia, hyperkalemia,
depression and paralysis of respiratory center, hypotension,
anoxia, respiratory alkalosis, and terminal acidosis,54, 55
suggesting that besides the rapid administration of antibiotics,
survival might improve with vigilant correction of electrolyte
disturbances and acid-based imbalance, glucose infusion, and
early mechanical ventilation and vasopressor administration.
Historical
Data
Early
diagnosis of inhalational anthrax is difficult and requires
a high index of suspicion. Prior to the 2001 attacks, clinical
information was limited to a series of 18 cases reported in
the 20th century and the limited data from Sverdlovsk. The
clinical presentation of inhalational anthrax had been described
as a 2-stage illness. Patients reportedly first developed
a spectrum of nonspecific symptoms, including fever, dyspnea,
cough, headache, vomiting, chills, weakness, abdominal pain,
and chest pain.18, 27 Signs of illness and laboratory studies
were nonspecific. This stage of illness lasted from hours
to a few days. In some patients, a brief period of apparent
recovery followed. Other patients progressed directly to the
second, fulminant stage of illness.4, 27, 56
This
second stage was reported to have developed abruptly, with
sudden fever, dyspnea, diaphoresis, and shock. Massive lymphadenopathy
and expansion of the mediastinum led to stridor in some cases.57,
58 A chest radiograph most often showed a widened mediastinum
consistent with lymphadenopathy.57 Up to half of patients
developed hemorrhagic meningitis with concomitant meningismus,
delirium, and obtundation. In this second stage, cyanosis
and hypotension progressed rapidly; death sometimes occurred
within hours.4, 27, 56
In
the 20th-century series of US cases, the mortality rate of
occupationally acquired inhalational anthrax was 89%, but
the majority of these cases occurred before the development
of critical care units and, in most cases, before the advent
of antibiotics.27 At Sverdlovsk, it had been reported that
68 of the 79 patients with inhalational anthrax died.18 However
a separate report from a hospital physician recorded 358 ill
with 45 dead; another recorded 48 deaths among 110 patients.59
A recent analysis of available Sverdlovsk data suggests there
may have been as many as 250 cases with 100 deaths.60 Sverdlovsk
patients who had onset of disease 30 or more days after release
of organisms had a higher reported survival rate than those
with earlier disease onset. Antibiotics, antianthrax globulin,
corticosteroids, mechanical ventilation, and vaccine were
used to treat some residents in the affected area after the
accident, but how many were given vaccine and antibiotics
is unknown, nor is it known which patients received these
interventions or when. It is also uncertain if the B anthracis
strain (or strains) to which patients was exposed were susceptible
to the antibiotics used during the outbreak. However, a community-wide
intervention about the 15th day after exposure did appear
to diminish the projected attack rate.60 In fatal cases, the
interval between onset of symptoms and death averaged 3 days.
This is similar to the disease course and case fatality rate
in untreated experimental monkeys, which have developed rapidly
fatal disease even after a latency as long as 58 days.40
2001
Attacks Data
The
anthrax attacks of 2001 resulted in 11 cases of inhalational
anthrax, 5 of whom died. Several clinical findings from the
first 10 patients with inhalational anthrax deserve emphasis.36,
61-66 Malaise and fever were presenting symptoms in all 10
cases. Cough, nausea, and vomiting were also prominent. Drenching
sweats, dyspnea, chest pain, and headache were also seen in
a majority of patients. Fever and tachycardia were seen in
the majority of patients at presentation, as were hypoxemia
and elevations in transaminases.
Importantly,
all 10 patients had abnormal chest x-ray film results: 7 had
mediastinal widening; 7 had infiltrates; and 8 had pleural
effusions. Chest computed tomographic (CT) scans showed abnormal
results in all 8 patients who had this test: 7 had mediastinal
widening; 6, infiltrates; 8, pleural effusions.
Data
are insufficient to identify factors associated with survival
although early recognition and initiation of treatment and
use of more than 1 antibiotic have been suggested as possible
factors.61 For the 6 patients for whom such information is
known, the median period from presumed time of exposure to
the onset of symptoms was 4 days (range, 4-6 days). Patients
sought care a median of 3.5 days after symptom onset. All
4 patients exhibiting signs of fulminant illness prior to
antibiotic administration died.61 Of note, the incubation
period of the 2 fatal cases from New York City and Connecticut
is not known.
The
Anthrax threat as posed to the United States in 2001-2 was
focused on the use of the mail to deliver these dangerous
weapons. According to an article in September of 2002 entitled:
Can These Boxes Be Locked Against Terror? By Andrew C. Revkin:
U.S.
postal authorities scramble to strengthen security of the
mail, they face a daunting realization: the process will take
years, it will cost at least a billion dollars and until it
is finished the nation is probably even more vulnerable than
it was last fall, when anthrax-tainted letters killed five
people, sickened at least 17 more and caused widespread disruption
and fear.
Engineers
are rushing to devise steps to deter bioterrorist mailings,
or to speed detection of any such attacks. They are reconsidering
almost every step in the chain that moves 200 billion pieces
of mail a year — from the design of the 350,000 street-corner
mailboxes to the way postage stamps are printed and sold.
Meanwhile, though, the postal system stands revealed as a
potent tool for terrorism.
"We
cannot believe that whoever did this is the only one capable
or willing to do this," said Thomas G. Day, the Postal
Service's vice president for engineering. The attacks last
year served as a blueprint, he said. "Clearly anyone
who hadn't thought of it now fully understands it."
In
fact, despite their toll, some postal authorities view last
year's attacks as a close call, not a true disaster. For one
thing, the tainted letters were apparently designed to affect
only the mail recipients. Their seams were carefully taped
and they were precisely addressed. But as they passed through
high-speed machinery, they spewed a trail of spores that infected
postal workers and, apparently, people who received other
mail moving through the system at the same time.
"If
such an incident was repeated on a larger scale, the consequence
to the economic health of the entire nation could be truly
incalculable," said Patrick R. Donahoe, the Postal Service's
senior vice president for operations, in an August letter
to the General Accounting Office.
The
Postal Service, consulting with several federal agencies,
contractors, scientists, and the Royal Mail and other postal
agencies overseas, is proceeding with the first stages of
a long-term plan to secure its sprawling system, in which
almost every collection box is an unguarded portal.
Private
corporations and government agencies that are potential targets
or that handle floods of mail, among them Pitney Bowes and
the Internal Revenue Service, are also conducting their own
searches for ways to defuse biological threats without impeding
their work. The only mail being routinely irradiated with
bacteria-killing electron beams or X-rays is that bound for
government agencies in Washington, leaving other offices,
like the many addresses for paying tax bills, unsecured.
The
mail network — linking every address in America in a
chain of boxes, trucks, letter sorters, 750,000 letter carriers
and other postal workers — will never be immune to terror,
postal officials and experts say. But a number of steps could
reduce the threat.
Some
efforts focus on reducing the volume of anonymous mail, which
now constitutes about 17 percent of the daily flow of some
680 million items.
For
example, the Postal Service plans eventually to change most
stamps from uniform bits of sticky paper to personalized,
encrypted records that would provide the postal equivalent
of caller ID. This would make it harder for someone to send
a malicious letter anonymously.
Letters,
either the postage itself or a return address label, would
be imprinted with a box containing a dense checkered pattern
that encodes far more information than a conventional bar
code, according to the postal security plan.
Such
postage is already being sold over the Internet by companies
like Stamps.com to consumers seeking convenience. But the
Postal Service and private mail companies are considering
a vast expansion of this technology, even offering it door
to door.
Letter
carriers may eventually wield hand-held printers — somewhat
like those used by workers checking in rental cars —
that can spit out personalized postage for each outgoing letter.
Any
concerns about reduced privacy would most likely be outweighed,
officials and experts said, by the knowledge that such mail
would be in the fast lane — in the same way that proposed
special identification cards for frequent travelers might
someday allow them to pass airport checkpoints.
Besides
serving as a deterrent, the data-containing postage —
read by sorting machinery all along a letter's path —
would allow investigators of an attack to more easily trace
an envelope back to its point of origin or sender.
The
investigation of last fall's attacks remains hampered by a
lack of any data trail pointing to a perpetrator.
In
fact, the only recent lead in the 11-month-old investigation
is a chance trace of anthrax found on a single mailbox in
Princeton, N.J., after swabs were done of more than 600 collection
boxes in the central part of the state, where all the tainted
letters are thought by investigators to have originated.
The
tainted box was removed from a street corner and now sits
in a sealed enclosure at the Army's Edgewood center, undergoing
more analysis to see if its anthrax strain matches the deadly
Ames variant used in the attacks, investigators said. In another
effort to reduce the amount of potentially suspicious mail,
the Postal Service is also working on certifying as secure
the operations of the dominant users of its system: commercial
mailing houses sending electric bills, fashion catalogs and
the like.
With
adequate security and screening of employees, such mail could
be deemed "safe," postal officials say, cutting
the volume of mail bound for biohazard detection systems or
subject to irradiation.
The
number of blue mailboxes is likely to be reduced, and those
that remain may eventually be monitored by video cameras and
have replaceable plastic liners that will prevent any contamination
from spreading.
Other
efforts focus on detecting the presence of pathogens in the
mail.
At
two mail-sorting hubs in Virginia, postal engineers and the
National Institute for Occupational Safety and Health say
they successfully tested new systems that check the dust that
arises from sorting machinery as the mail moves through it.
The checks, performed hourly using a process called polymerase
chain reaction, would bathe dust samples in enzymes that cause
DNA to explosively replicate, allowing | 
