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1
Introduction
Rapid access to antibiotics is critical for preventing and treating illness
and death due to a bioterrorism attack with a bacterial agent such as Bacil-
lus anthracis (anthrax). Yet the logistics of effectively delivering antibiotics
to prevent anthrax infection pose a tremendous challenge because such
an attack could potentially expose a large number of people who would
require antibiotics within a relatively brief time window. For example, if
aerosolized anthrax were released over a large, densely populated area,
hundreds of thousands of people could need prophylactic antibiotics to
prevent deadly inhalational anthrax (Danzig, 2003; U.S. Congress, 1993).
The goal of current planning efforts is to be able to dispense prophylactic
antibiotics to all exposed and potentially exposed individuals within 48
hours of the decision to dispense (CDC, 2011a). Although the nation has
made much progress in developing plans for the delivery of antibiotics
over the last decade, this public health goal continues to be recognized as
difficult to achieve because of the challenges involved in implementing and
executing these plans.
STUDY CHARGE
Given the challenges noted above, interest currently is focused on
supplementing existing centralized strategies for the delivery of prophylactic
antibiotics with so-called prepositioning strategies, whereby antibiotics
are stored at or near locations in which they are anticipated to be needed.
Accordingly, the Office of the Assistant Secretary for Preparedness and
Response (ASPR), Department of Health and Human Services (HHS), com-
21
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22 PREPOSITIONING ANTIBIOTICS FOR ANTHRAX
missioned the Institute of Medicine (IOM) to undertake a study that would
inform the use of prepositioned antibiotics for the public for protection
against an anthrax attack (Box 1-1).
To respond to this charge, the IOM appointed the Committee on
Prepositioned Medical Countermeasures for the Public, bringing together
16 experts with a broad spectrum of expertise, including state and local
public health preparedness, emergency medicine and response, infectious
disease, pediatrics, toxicology, systems analysis and operations research,
materials management and supply chains, economics, health systems, the
B OX 1-1
Statement of Task
In response to a request from the Department of Health and Human
Services (HHS) Office of the Assistant Secretary for Preparedness and
Response (ASPR), the Institute of Medicine will convene an ad hoc
committee of subject matter experts to inform the use of prepositioned
medical countermeasures (MCM) for the public. The committee will
focus on prepositioning antibiotics for protection against a terrorist
attack using Bacillus anthracis or a similar pathogen. More specifically,
the ad hoc committee will produce a report that will:
• C
onsider the role of prepositioned medical countermeasures for
the public (e.g., prepositioning at home, local stockpiles, and work-
place caches) within an overall MCM dispensing strategy that in-
cludes traditional MCM dispensing and distribution strategies such
as points of dispensing (PODs), taking into account both logistical
and non-logistical factors (e.g., safety and ethics).
• I
dentify and describe key factors and variables that should be
included in a strategy for prepositioning MCM for the public (e.g.,
population demographics, threat status, proximity to high-value
targets, proximity to healthcare facilities).
• D
iscuss preliminary considerations for the development of an incre-
mental and phased MCM prepositioning strategy.
• B
ased on available evidence, describe economic advantages and
disadvantages of various MCM prepositioning strategies for the
public.
The committee will develop scenarios, as needed, to illustrate the
interaction of the strategic considerations, key factors, and variables
in different situations and environments. The committee will base its
recommendations on currently available published literature and other
available guidance documents and evidence, expert testimony, as well
as its expert judgment.
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23
INTRODUCTION
private sector, the social sciences, risk management and communication,
bioethics, pharmacy, and faith and civic organizations. Biosketches of the
committee members are included in Appendix E. The committee developed
this report to assist federal policy makers and state, local, and tribal public
health officials, as well as their private-sector and community partners, in
evaluating the potential health benefits, health risks, costs, and practical
considerations of implementing strategies for prepositioning antibiotics in
their communities as a complement to existing, more centralized dispens-
ing strategies.
STUDY CONTEXT
In the fall of 2001, the United States experienced its first—and thus far
only—bioterrorism attack involving B. anthracis, in which the bacterium
spores were spread via mail sent through the U.S. postal system. These at-
tacks resulted in 22 cases of documented anthrax; 11 of these cases were
inhalational anthrax—the most deadly form of the disease—and resulted
in 5 deaths (Jernigan et al., 2002).
Despite relatively limited experience with anthrax in the United States,
it is considered one of the most serious threats to national security and the
health of the nation for a variety of reasons, including the following:
B. anthracis occurs in nature and is relatively inexpensive and easy
•
to obtain and grow (CDC, 2009a; Inglesby et al., 2002).
Inhalational anthrax can result from exposure to a relatively small
•
number of spores and typically is lethal without effective treatment,
and prophylaxis or treatment must be initiated within a relatively
brief window of time following exposure (Inglesby et al., 2002;
Turnbull, 2008).
Although no nation publicly acknowledges having an offensive
•
biological weapons program, it is estimated that a dozen countries
have such programs (Kerr, 2008). The largest anthrax outbreak in
history, the Sverdlovsk accident in 1979, is believed to have been
the result of an accidental release of aerosolized anthrax from a
Soviet Union biological weapons program (e.g., Meselson, 1988).
There is also evidence that some terrorist groups have attempted
to develop the capability to use anthrax, including the unsuccess-
ful attempts by Japanese cult group Aum Shinrikyo to release an-
thrax in Tokyo in 1993 and evidence that Al Qaeda has pursued
the development of anthrax as a biological weapon (Carus, 2002;
Danzig et al., 2011; Mowatt-Larssen, 2010). The actual capability
to conduct an attack using anthrax as a weapon is unknown for
both national programs and terrorist groups.
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24 PREPOSITIONING ANTIBIOTICS FOR ANTHRAX
Among terrorist attacks, those involving anthrax may be among
•
the easiest to carry out simultaneously in multiple locations or
repeatedly over time (Danzig, 2003).
Naturally occurring B. anthracis strains sometimes are resistant
•
to certain antibiotics, and B. anthracis can be engineered to be
resistant to multiple available antibiotics (Athamna et al., 2004;
Brouillard et al., 2006; Inglesby et al., 2002; Price et al., 2003).
In 2004, the Secretary of the Department of Homeland Security (DHS)
determined that anthrax presents a threat to the U.S. population of suf-
ficient severity to affect national security (GAO, 2009). In 2006, the Sec-
retary of DHS also determined that multi-drug-resistant anthrax was a
material threat to the nation (DHS, 2008; GAO, 2009). The Centers for
Disease Control and Prevention (CDC) classifies anthrax as a Category A
bioterrorism agent/disease, a designation that indicates the greatest poten-
tial to adversely impact public health and result in mass casualties (CDC,
2011b; Rotz et al., 2002).
Concerns About the Current Dispensing System for
Medical Countermeasures
All levels of government—federal, state, and local—and the private
sector are involved in plans to distribute and dispense antibiotics to the
public for protection against an anthrax attack. The backbone of current
distribution plans is the Strategic National Stockpile (SNS), a national
repository of medicine and medical supplies that can be deployed rapidly
around the country to supplement state and local stockpiles (CDC, 2011c).
Once medical countermeasures (MCM) from the SNS arrive, state and local
public health authorities assume responsibility for distributing and dispens-
ing them to their population.
Because of the scope of the challenge and the resources required, many
public health authorities and other policy experts fear that most commu-
nities still lack adequate mechanisms and capacity to dispense antibiotics
rapidly to all exposed and potentially exposed populations following a large
anthrax attack (HSPD-21, 2007). This concern is driven by several factors,
briefly outlined in the remainder of this section.
First, the anthrax attack of 2001 represents the nation’s only domestic
experience with response to an anthrax attack; the available real-world evi-
dence with which to assess the nation’s ability to dispense MCM following
an anthrax attack is limited. Similarly, the number of exposed individuals
in 2001 was small compared with estimates of the number of people who
could potentially be exposed and infected in a large multicity aerosolized
release of B. anthracis. Danzig (2003) predicts 200,000 expected infections
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25
INTRODUCTION
within a 40-mile radius of a small commercial sprayer from a single point
source; DHS Planning Scenario 2 uses 328,484 infections from a concealed
improvised spraying device in a densely populated urban city (DHS, 2006).
Even though the scope of the attack in 2001 was much smaller than these
estimates, the response to that event highlighted the challenges and time
pressure associated with responding to anthrax and revealed “an unaccept-
able level of fragility in systems now properly recognized as vital to national
defense” (Gursky et al., 2003, p. 97).
Second, there are sparse data from large-scale exercises and few mea-
sures of dispensing performance (not just planning), making it difficult to
assess the system’s capacity to dispense antibiotics to all potentially exposed
individuals within the required time window after a large attack. CDC and
other entities have developed criteria and metrics with which to evaluate the
development of state and local preparedness plans for the distribution and
dispensing of MCM, including CDC’s Technical Assistance Review (TAR)
tool and the recently published Public Health Preparedness Capabilities
(CDC, 2009b, 2010, 2011d). However, there are few criteria and metrics
with which to assess the actual implementation of dispensing plans (TFAH,
2010; Willis et al., 2009).
Third, concerns were fueled by the challenges encountered during
efforts to dispense vaccine in response to the 2009 H1N1 influenza pan-
demic. Lessons learned from response to the influenza pandemic do not
transfer directly to an anthrax response because of differences in geographic
scope, time window for response, and required countermeasures. However,
the distribution, dispensing, and communications challenges that occurred,
particularly in the early months of the vaccine program, made concrete for
many the immense difficulties of conducting a large antibiotic-dispensing
campaign within a time window of approximately 48 hours, as would be
required to respond to an anthrax attack (IOM, 2010a).
Finally, observation of responses to other, non-bioterrorism-related
disasters have highlighted the tremendous challenges of responding to
disasters. Recent examples include the earthquakes in Haiti and Japan
and Hurricane Katrina. The aftermath of these disasters underscored the
challenges of disaster response, the catastrophic consequences of gaps in
preparedness, and the many areas in which improvements could be made.
There is little evidence to suggest that mounting a mass MCM dispensing
campaign after a major bioterrorism attack would not reveal challenges of
a similar magnitude.
Prepositioning and Other Novel Dispensing Strategies
In response to the concerns outlined above, the past few years have seen
a burgeoning interest in exploring novel dispensing strategies to complement
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26 PREPOSITIONING ANTIBIOTICS FOR ANTHRAX
the existing system. In 2004, the U.S. Postal Service (USPS) began working
with selected large cities to develop plans to use the postal service to distrib-
ute antibiotics to residents in their homes after an attack. Drills of the plan
were conducted in Boston, Philadelphia, and Seattle in 2006 and 2007, and
a pilot program of this model has been developed in Minneapolis-St. Paul
(IOM, 2010b). A Presidential Executive Order issued in 2009 instructed
the federal government to pursue the development of a national postal
model in which postal carriers would distribute antibiotics to residents in
their homes for self-administration (Obama, 2010). In response, a National
Postal Model was developed by HHS, DHS, the Department of Defense, the
Department of Justice, and the USPS (HHS et al., 2011).
Another strategy under exploration is user-managed inventory, in which
materials are stockpiled in hospitals, to be used regularly for routine health
care purposes and continually replaced to maintain the quantity of stock-
piled materials but to avoid expiry (HHS, 2011). In addition, the response
to the 2009 H1N1 influenza pandemic saw a great increase in private-sector
mechanisms for dispensing of MCM, particularly via pharmacies and pri-
vate practices (ASTHO, 2010; Merchant Medicine, 2010; ORISE, 2009).
As a supplement to established strategies, federal, state, and local pub-
lic health authorities and the private sector also are interested in strategies
that would preposition MCM closer to their intended users prior to an
incident—the topic of the current report (see, for example, Kadlec [2011]
for results of a survey of opinions on prepositioning among editors and
readers of the journal DomPrep). Prepositioning strategies are being con-
sidered because they could potentially help ensure access to MCM for more
people within an appropriate time window, decrease stress on the existing
dispensing and health care systems, and help ensure fair and equitable ac-
cess to MCM. Despite the promise of prepositioning strategies, however,
prepositioning involves many complex issues that need to be carefully
considered before decisions are made about the wide implementation of
these strategies (IDSA, 2008; NBSB, 2008). These issues include questions
about effectiveness, cost-effectiveness, logistics, the legal and regulatory
framework, safety, equity, and sustainability.
Prepositioning and other novel dispensing strategies, as described
above, are just one potential component of a larger endeavor to enhance
the nation’s capability to prevent illness and death from an anthrax attack.
Other components include national security efforts to prevent an attack or
mitigate its effects, efforts to enhance detection and surveillance capability,
further development of anthrax vaccine and antitoxin strategies, continu-
ous refinement of the current MCM distribution and dispensing system,
and efforts to engage the private sector in both the development and the
delivery of MCM.
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27
INTRODUCTION
METHODS AND DEFINITIONS
The committee’s work was accomplished over a 12-month period com-
mencing in October 2010. The committee held four meetings between
January and June 2011 that included both closed-session deliberations and
open-session information-gathering dialogues with subject matter experts
and stakeholders. The second committee meeting was held in conjunction
with a 2-day public workshop whose objectives were to identify gaps and
challenges in current dispensing systems; assess current prepositioning ef-
forts; discuss a range of potential prepositioning strategies; examine ethical,
legal, regulatory, and safety issues; and discuss methods, metrics, and avail-
able data for evaluating the cost and effectiveness of prepositioning strategies.
A shorter open session also was held at the third committee meeting; this
open session focused specifically on vulnerable populations, ethical issues,
and public engagement. The agendas for both the workshop and the shorter
open session are available in Appendix B. Box 1-2 presents a glossary of key
terms used in this report.
In addition to the workshop and other information-gathering sessions,
the committee surveyed the relevant peer-reviewed literature and other avail-
able guidance documents and publications, gathered information through
personal contacts, and commissioned a paper on the economic costs and
time savings associated with prepositioning strategies (Appendix D). During
the study period, the committee also was able to garner relevant insights
into public behavior relevant to MCM stockpiling in response to the earth-
quake, tsunami, and resulting nuclear disaster in Japan in March 2011.
The committee did not review any classified information, including classi-
fied information about the risk of an anthrax attack. The committee’s recom-
mendations were informed by the members’ overall understanding of the
threat and risk of anthrax today, 10 years after the 2001 anthrax attack.
In its approach to this study and the formulation of its recommendations,
however, the committee focused on how public health officials should use
assessment of the current risk of an anthrax attack in their individual com-
munities to inform decisions about prepositioning.
Strategies for positioning MCM lie along a continuum based on prox-
imity to the location of the anticipated event. At one extreme, for example,
MCM from the SNS and commercial stockpiles may be centrally located
and distributed postevent to locations throughout the nation; at the other
extreme, stockpiles are kept in individual homes for use immediately post-
event. This continuum is depicted in Figure 1-1.
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28 PREPOSITIONING ANTIBIOTICS FOR ANTHRAX
BOX 1-2
Glossary of Key Terms
Critical infrastructure personnel, first responders: For this report, the
committee broadly defines critical infrastructure personnel and first
responders as including those persons who will be expected to report
to and stay at work during an attack in order to respond and maintain
critical functions within the community. This definition is not meant to
counter or supersede definitions of critical infrastructure personnel or
first responders used by federal, state, and local planners.
Dispensing: The act of providing medical countermeasures (MCM) to
individuals who will take them immediately or at some future defined/
declared time of need. Dispensing also includes providing MCM to
heads of households or other nonmedical caregivers for use by those
in their care.
Dispensing capacity: The number of individuals to whom a public health
dispensing system can dispense MCM per day, whether the MCM are
provided directly to individuals or via heads of households or other
nonmedical caregivers.
Distribution: The delivery of MCM from stockpiles to receiving, staging,
and storage (RSS) sites, as well as delivery from RSS sites to dispensing
sites. Distribution may be triggered by an event, or MCM may be distrib-
uted to a local storage site or point of dispensing (POD) in anticipation
of a potential future need.
Emergency Use Authorization (EUA): An authorization by the Com-
missioner of the Food and Drug Administration (FDA) for “the use of
an unapproved medical product or an unapproved use of an approved
medical product during a declared emergency involving a heightened
risk of attack on the public or U.S. military forces, or a significant po-
tential to affect national security” (FDA, 2010).
Jurisdiction, community: For this report, the committee uses jurisdic-
tion to refer to state, local, and tribal governments. The committee uses
community to refer to these governmental entities in conjunction with
private-sector entities, community organizations, and members of the
public within the jurisdictional boundaries.
Medical countermeasures (MCM): A drug, biological product, or device
that diagnoses, mitigates, prevents, or treats harm resulting from a
biological, chemical, radiological, or nuclear agent that causes a public
health emergency (PAHPA, Public Law 109-417, Sec403a2(Aii), 2006).
Points of dispensing (PODS): Locations where MCM are dispensed to
potentially exposed individuals. PODs may be open or closed, depend-
ing on the populations served:
• O
pen PODs: Locations where MCM are dispensed to all potentially
exposed members of the public.
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29
INTRODUCTION
• C
losed PODs: Locations where MCM are dispensed to a predefined
population, such as employees of a company and their family mem-
bers. Closed PODs may dispense MCM from a variety of sources,
including the Strategic National Stockpile (SNS), state stockpiles,
commercial supplies, and on-site workplace caches.
Prepositioning: The storage of MCM at or near the anticipated event
location where they will be needed so as to reduce the time required
to distribute and dispense initial doses. The placement of MCM lies on
a continuum with respect to their physical proximity to the anticipated
event location. Prepositioning refers to all potential placements of MCM
along this continuum, from forward deployment of MCM through place-
ment of stockpiles in the hands of individuals, as described below.
Prepositioned MCM may remain in the control of federal, state, and local
governments or may be managed by others, such as health systems,
businesses, and individuals.
• F
orwardDeployed MCM: MCM stored near the locations from which
they will be dispensed.
ached MCMa: MCM stored at the locations from which they will be
• C
dispensed.
• P
redispensed MCM: MCM stored by the intended users or by heads
of households or other nonmedical caregivers for use by those
in their care. Example strategies include personal stockpiles and
MedKits:
— Personal Stockpile: MCM dispensed to individuals pre-event via
normal prescribing routes for use during a public health emer-
gency. Individuals may store the MCM in the home, workplace,
or other personal location.
— MedKit: A medical kit containing prescription pharmaceuticals
that is dispensed pre-event to families or individuals for use only
as directed during a public health emergency.
– EUA MedKit: A medical kit allowed by the FDA for off-label use
under conditions specified in an Emergency Use Authorization
(EUA).
– FDA-approved MedKit: A medical kit approved by the FDA and
labeled for use as a predispensed MCM. (Note that an FDA-
approved MedKit does not currently exist.)
Prepositioning strategy: The specification of locations where MCM will
be stored, and for each location, the amount of antibiotics stored and
dispensing methods and protocols for their use in the event of a con-
firmed or suspected attack (e.g., for general use at public PODs, for use
at a specific closed POD, for home use).
Public: All members of a community who are not already adequately
covered by separate specialized programs, such as programs for federal
mission-essential personnel.
continued
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30 PREPOSITIONING ANTIBIOTICS FOR ANTHRAX
BOX 1-2 Continued
Strategic National Stockpile (SNS): “A national repository of antibiotics,
chemical antidotes, antitoxins, life-support medications, IV administra-
tion, airway maintenance supplies, and medical/surgical items. The SNS
is designed to supplement and re-supply state and local public health
agencies in the event of a national emergency anywhere and at anytime
within the U.S. or its territories” (CDC, 2011c).
Subpopulation: “An identifiable fraction or subdivision of a population”
(Merriam-Webster, 2011).
aThe term cache is often used broadly to describe stockpiles of MCM, whether
held by state or local jurisdictions, healthcare facilities, private sector organiza-
tions, among others. For the purposes of this report, and to enable clear discus-
sion of the different properties associated with different types of prepositioning,
the committee defines cache more specifically as storage in the location from
which they will be dispensed, and uses the term stockpile to cover federal, state,
and local stockpiles.
STUDY APPROACH AND SCOPE
Focus on Anthrax
ASPR asked the IOM committee to focus specifically on the dispensing
of antibiotics for anthrax because (1) as noted above, the threat of anthrax
currently is considered to be among the highest-priority threats; and (2) the
brief time window within which antibiotics must be dispensed to protect
effectively against anthrax infection is among the greatest challenges facing
the MCM distribution and dispensing system as a whole. In accordance
with the committee’s charge, then, the decision-aiding framework, analy-
sis, findings, and recommendations presented in this report are specific to
prepositioning of antibiotics for anthrax. The committee hopes that this
report will provide a starting point and potential model for evaluating
whether and how to preposition MCM to prevent, mitigate, and treat
illness and death caused by other biological, chemical, and radiological/
nuclear threats. The committee cautions, however, that the analysis pre-
sented herein does not translate directly to such other situations because
of differences in the nature of the threat, the time course of the threat, the
time within which the MCM must be taken to be effective, and whether
the MCM require administration by a health care professional. The find-
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31
INTRODUCTION
SNS and Other
Federal Stockpiles
Continuum of
MCM Placement
NO
PREPOSITIONING
Commercial
Stockpiles
FORWARD-
DEPLOYED
Potential
CACHED
Time/Distance
to End-user PREDISPENSED
MORE LESS
MCM
State
Stockpiles
MedKits
and
Personal
Stockpiles
Local
Stockpiles
Workplace
Caches
Hospital and
Pharmacy Caches
FIGURE 1-1
Strategies for positioning medical countermeasures:
Centralized stockpiles distribute medical countermeasures
(MCM) to a wider area but may take longer to reach people.
Workplace caches and personal stockpiles may allow for
more immediate access, but far more MCM are needed.
NOTE: The Strategic National Stockpile (SNS) and other entities may use
a mix of placements along this continuum—for example, some forward-
deployed stockpiles near areas of high risk combined with some centrally
located stockpiles to serve remaining areas.
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32 PREPOSITIONING ANTIBIOTICS FOR ANTHRAX
ings and recommendations presented here will be more closely applicable
to other threats in which the characteristics of the threat and the associ-
ated MCM are similar to those for anthrax (e.g., another noncontagious
disease with a similar time course that is prevented by an MCM that does
not require administration by a health care professional). It is important to
emphasize, however, that additional analysis will be needed for each threat
and associated MCM.
The committee was asked to focus primarily on the response to an
attack using a strain of anthrax that is susceptible to the antibiotics cur-
rently approved by the Food and Drug Administration (FDA) for anthrax
prophylaxis. An attack using a strain of anthrax that is resistant to one or
more antibiotics would, however, further challenge all aspects of current
dispensing strategies because the majority of stockpiled antibiotics would
be ineffective regardless of how early they were administered. In this event,
jurisdictions and U.S. Government leaders would need to communicate
with the public about alternative treatments, if any, and a massive surge
of patients into the health care system would be difficult to avoid. The
implications for prepositioning are discussed in more detail in Chapter 2.
Anthrax Vaccine and Anthrax Antitoxin
The committee recognizes two major issues that would significantly
affect decisions about prepositioning: widespread use of anthrax vaccine,
and the further development and stockpiling of anthrax antitoxin. These
issues are briefly discussed here, but because the committee’s charge focused
specifically on the distribution and dispensing of antibiotics, they were not
a primary emphasis of its deliberations.
Widespread pre-event anthrax vaccination could potentially impact
the selection and design of strategies for postexposure prophylaxis using
antibiotics, including strategies for prepositioning the antibiotics, because
it could decrease the size of the population needing postexposure pro-
phylaxis with antibiotics. Currently, the use of anthrax vaccine adsorbed
(AVA) is limited. CDC’s Advisory Committee on Immunization Practices
has said that pre-exposure vaccination for emergency responders is not
routinely recommended, but “may be offered on a voluntary basis under
the direction of a comprehensive occupational health and safety program”
(CDC/ACIP, 2010, p. 20). AVA is commercially available in certain travel
clinics (Passport Health, 2010). Vaccination of potentially exposed people
is recommended after an attack, in conjunction with a 60-day course
of antibiotics (CDC/ACIP, 2010). However, pre-event vaccination is not
recommended for the general public, and it is impractical for widespread
use because it requires multiple initial doses followed by annual boosters
(CDC, 2009c; CDC/ACIP, 2010; Roos, 2011).
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33
INTRODUCTION
The second issue is the development and stockpiling of anthrax anti-
toxin. Toxins produced by B. anthracis bacteria, not the bacteria them-
selves, cause death (Inglesby et al., 2002). Antibiotics kill the bacteria
before they can produce lethal quantities of toxins but are unable to prevent
death once the toxins, and the systemic damage they cause, accumulate.
Anthrax antitoxin, on the other hand, functionally inhibits one or both of
the toxins produced by anthrax, although debate remains as to whether the
antitoxin would be as effective when given in a later (fulminant) stage of
symptomatic disease, compared with early- or intermediate-stage symptom-
atic disease (FDA, 2009; Migone et al., 2009). The SNS stockpiles anthrax
antitoxin, but not in a quantity sufficient to treat the population that could
be exposed in a large anthrax attack, and the drug is not approved by the
FDA for the treatment or prophylaxis of anthrax (FDA, 2011; HHS, 2010).
In the future, should antitoxin be approved by the FDA and available in
sufficient quantities, this MCM could assume a greater role in plans to
protect the health of the potentially exposed population. The use of either
vaccine or antitoxin also avoids concerns about antibiotic-resistant anthrax,
discussed in Chapter 2.
Populations Considered
The committee defined the public to be all members of a community
who are not already adequately covered by separate specialized programs,
such as those for federal mission-essential personnel (Box 1-2). The com-
mittee was prompted to make this distinction because Section 4 of the
Executive Order on providing MCM, issued in 2009, identifies federal
mission-essential personnel as a specialized group whose work ensures the
continuity of operations, and it mandates the specific provision of MCM
to these individuals (Obama, 2010). State and local first responders and
critical infrastructure personnel are not included in the Executive Order,
since it focuses on federal mission-essential personnel. In its second infor-
mation-gathering session (agenda included in Appendix B), the committee
heard testimony about DHS’s internal plan to stockpile and dispense MCM
to its employees around the country (Brinsfield, 2011). This information
provided context for the committee’s definition of the public (Box 1-2).
Some communities should take into account that federal mission-essential
personnel stationed in their area will not be part of the public MCM dis-
pensing system.
The committee’s interpretation of the term public in this report includes
consideration of entities that are perhaps not perceived as part of the public,
such as civic entities and corporations. The committee, however, found that
it was impossible in practice, and potentially inadvisable, to draw clear lines
separating the public from civic entities and corporations. For example,
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34 PREPOSITIONING ANTIBIOTICS FOR ANTHRAX
most plans to dispense MCM to first responders also include sufficient
quantities for their families, the latter being considered members of the gen-
eral public. Similarly, employees of corporations are most likely to be con-
sidered members of the public, especially if they are not directly involved
in emergency response activities (e.g., employees of large retail stores).
Therefore, most plans to dispense MCM via civic entities or corporations
would also entail dispensing to “the public” and, moreover, would impact
the capacity needed to dispense MCM via more standard public strategies
such as open points of dispensing (PODs). A major benefit of dispensing
through corporations, for example, is alleviating the burden on public
PODs by reaching concentrated populations who would otherwise use these
traditional PODs. For this reason, the committee defined the public broadly
as “all members of a community who are not already adequately covered
by separate specialized programs, such as those for federal mission-essential
personnel.” This usage recognizes the interrelated nature of all programs
to dispense MCM within a community while avoiding interfering with any
specialized dispensing programs that a jurisdiction may already have.
Additionally, the committee wishes to highlight the importance of giv-
ing specific attention to the needs of children and other vulnerable or at-risk
populations, including those who, by virtue of socioeconomic status and/
or demographic characteristics, may be at systemically increased risk for
lower access to disaster mitigation response. These populations would in-
clude, for example, people with low incomes/limited transportation, people
with no or limited English proficiency, historically underserved ethnic/racial
groups, people with disabilities (especially the vision impaired, hearing im-
paired, or mobility impaired), people who are homeless, and people who
are homebound.
Limitations of the Data
During the course of this study, the committee noted gaps in the avail-
able evidence in three particular areas that are critical to its charge. These
gaps are introduced briefly here because of their importance to the com-
mittee’s overall approach to the study; they are discussed in greater detail
in subsequent chapters.
First, the committee found that reliable evidence on human inhalational
anthrax, particularly on the incubation period and the relationship of dose
to that period, is limited and uncertain. Data come from two primary
sources: the accidental release in 1979 of B. anthracis spores from a mili-
tary microbiology facility in Sverdlovsk, Union of Soviet Socialist Republics
(now Yekaterinburg, Russia), and the anthrax attack in the United States in
2001 (Jernigan et al., 2002; Meselson et al., 1994). The committee’s review
of the Sverdlovsk data revealed sufficient uncertainties and problems with
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35
INTRODUCTION
data quality to make the data of limited utility. The data and their implica-
tions for MCM distribution and dispensing, including prepositioning, are
discussed in Chapter 2.
Second, knowledge is insufficient as to the period of time that would
likely lapse between the release of anthrax spores and the start of dispens-
ing of MCM. This period includes the time to detection and the time to
decision. The former depends on how the attack is detected: environmental
detection through a BioWatch sensor, for instance, could take a minimum
of 24 hours, while clinical identification of a sick patient could occur days
after the release as a result of both the incubation period of the bacteria and
the time required for clinical recognition and definitive laboratory testing
(Jernigan et al., 2002; Shea, 2003). No data exist to support predictions of
the length of time that would lapse prior to the decision to dispense once
detection had occurred; this period likely would be somewhat dependent
on the U.S. government’s and the jurisdiction’s level of confidence that the
detection was not a false positive.
Third, the committee found a dearth of data, and even sparser publicly
available data from realistic exercises, on the performance and implemen-
tation of current state, local, and tribal dispensing plans. This lack of data
made it difficult for the committee to identify gaps in the current system.
In addition, the committee recognizes that tremendous variability exists in
state and local dispensing plans and capabilities and in the specific charac-
teristics and needs of communities across the nation.
Development of a Decision-Aiding Framework for State,
Local, and Tribal Jurisdictions
Many factors associated with decision making vary significantly across
communities, including the risk of attack, capabilities, resources, and cur-
rent public health infrastructure. Therefore, the committee concluded that
it would not be possible, or advisable, for it to prescribe a specific set of
prepositioning strategies to complement the traditional POD system. Simi-
larly, it was infeasible to attempt to categorize, identify, or address specific
gaps present in individual communities across the nation. Instead, the com-
mittee has outlined a decision-aiding framework for jurisdictions to use in
assessing their existing capabilities to meet the 48-hour goal for completion
of MCM dispensing to the population. This approach is intended to provide
state, local, and tribal jurisdictions with the framework and knowledge
required to select and develop the most effective prepositioning strategies
given their current capabilities and the specific needs of their communities.
In the report, the committee presents a qualitative exploration of the
potential effects of each of the key elements of the decision-aiding frame-
work on the incremental effectiveness of prepositioning strategies. The com-
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36 PREPOSITIONING ANTIBIOTICS FOR ANTHRAX
mittee also presents a first-order quantitative model for estimating health
benefits associated with different prepositioning strategies, a discussion
and case study of the estimation of likely economic costs, and a suggested
method for using estimates of health benefits and economic costs to explore
trade-offs associated with alternative prepositioning strategies and thereby
inform decision making.
Identification of Federal/National-Level Actions
Beyond a decision-aiding framework for individual jurisdictions, the
committee’s recommendations identify federal/national-level actions that
would facilitate the evaluation and development of prepositioning strate-
gies. While all preparedness and response is ultimately local, the federal
government has the unique ability to help coordinate regional and national
dispensing strategies and provide resources, research, and technical exper-
tise to enhance preparedness. Recognizing that implementation of the ac-
tions recommended by the committee should involve partnerships among
all levels of government and nongovernmental stakeholders, the committee
divides its recommendations into those aimed at the state/local/tribal level
and those aimed at the federal/national level to indicate the entity or entities
recommended to take the leading role, not the sole actor(s).
ORGANIZATION OF THE REPORT
Chapter 2 provides an overview of the use of antibiotics for post-
exposure anthrax prophylaxis, with particular focus on the uncertainties
associated with the time window within which antibiotics must be taken
to prevent the deadly inhalational form of the disease. Chapter 3 gives an
overview of current distribution and dispensing strategies for MCM for
anthrax. Chapter 4 presents an overview of the three categories of preposi-
tioning strategies for anthrax antibiotics: forward-deployed MCM, cached
MCM, and predispensed MCM. These chapters provide the foundation for
Chapter 5, which sets forth a decision-aiding framework to assist federal,
state, and local policy makers and public health officials in evaluating the
potential benefits and costs of implementing prepositioning strategies to
complement existing dispensing strategies and to address specific gaps or
overall capacity limitations. This framework encompasses the assessments
that jurisdictions should perform to provide the evidence base to inform de-
cision making about prepositioning, the need for ethical principles and pub-
lic engagement, and a modeling approach that can be used to weigh health
benefits and economic costs associated with the alternative prepositioning
strategies. Chapter 5 also presents the committee’s findings and recommen-
dations on the costs, benefits, and suitability of alternative prepositioning
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37
INTRODUCTION
strategies. Finally, Chapter 6 presents a summary of the recommended ac-
tions for moving forward that includes actions at the state, local, and tribal
levels and at the federal/national level, as well as areas in which additional
research is needed to provide a more solid evidence base to inform decisions
about prepositioning strategies.
The report also includes five appendixes: Appendix A is a list of acro-
nyms used in the report; Appendix B contains agendas for the committee’s
public meetings; Appendix C presents a first-order model developed by
the committee to estimate health outcomes for any prepositioning strat-
egy; Appendix D is a paper commissioned for this study containing a cost
and speed analysis of prepositioning strategies; and Appendix E provides
biosketches of the committee members.
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