As part of a Congressional initiative begun in 1999 to upgrade national public health
capabilities for response to acts of biological terrorism, the Centers for Disease
Control and Prevention (CDC) was designated the lead agency for overall public health
planning. A Bioterrorism Preparedness and Response Office has been formed to help
target several areas for initial preparedness activities, including planning, improved
surveillance and epidemiologic capabilities, rapid laboratory diagnostics, enhanced
communications, and medical therapeutics stockpiling (1). To focus these preparedness
efforts, however, the biological agents towards which the efforts should be targeted
had to first be formally identified and placed in priority order. Many biological
agents can cause illness in humans, but not all are capable of affecting public health
and medical infrastructures on a large scale.
The military has formally assessed multiple agents for their strategic usefulness
on the battlefield (2). In addition, the Working Group on Civilian Biodefense, using
an expert panel consensus-based process, has identified several biological agents
as potential high-impact agents against civilian populations (
3
–
7
). To guide national public health bioterrorism preparedness and response efforts,
a method was sought for assessing potential biological threat agents that would provide
a reviewable, reproducible means for standardized evaluations of these threats.
In June 1999, a meeting of national experts was convened to 1) review potential general
criteria for selecting the biological agents that pose the greatest threats to civilians
and 2) review lists of previously identified biological threat agents and apply these
criteria to identify which should be evaluated further and prioritized for public
health preparedness efforts. This report outlines the overall selection and prioritization
process used to determine the biological agents for public health preparedness activities.
Identifying these priority agents will help facilitate coordinated planning efforts
among federal agencies, state and local emergency response and public health agencies,
and the medical community.
Overview of Agent Selection and Prioritization Process
On June 3-4, 1999, academic infectious disease experts, national public health experts,
Department of Health and Human Services agency representatives, civilian and military
intelligence experts, and law enforcement officials (see footnote) met to review and
comment on the threat potential of various agents to civilian populations. The following
general areas were used as criteria: 1) public health impact based on illness and
death; 2) delivery potential to large populations based on stability of the agent,
ability to mass produce and distribute a virulent agent, and potential for person-to-person
transmission of the agent; 3) public perception as related to public fear and potential
civil disruption; and 4) special public health preparedness needs based on stockpile
requirements, enhanced surveillance, or diagnostic needs. Participants reviewed lists
of biological warfare or potential biological threat agents and selected those they
felt posed the greatest threat to civilian populations.
The following unclassified documents containing potential biological threat agents
were reviewed: 1) the Select Agent Rule list, 2) the Australian Group List for Biological
Agents for Export Control, 3) the unclassified military list of biological warfare
agents, 4) the Biological Weapons Convention list, and 5) the World Health Organization
Biological Weapons list (
8
–
12
). Participants with appropriate clearance levels reviewed intelligence information
regarding classified suspected biological agent threats to civilian populations. Genetically
engineered or recombinant biological agents were considered but not included for final
prioritization because of the inability to predict the nature of these agents and
thus identify specific preparedness activities for public health and medical response
to them. In addition, no information was available about the likelihood for use of
one biological agent over another. This aspect, therefore, could not be considered
in the final evaluation of the potential biological threat agents.
Participants discussed and identified agents they felt had the potential for high
impact based on subjective assessments in the four general categories. After the meeting,
CDC personnel then attempted to identify objective indicators in each category that
could be used to further define and prioritize the identified high-impact agents and
provide a framework for an objective risk-matrix analysis process for any potential
agent. The agents were evaluated in each of the general areas according to the objective
parameters and were characterized by the rating schemes outlined in the Appendix.
Final category assignments (A, B, or C) of agents for public health preparedness efforts
were then based on an overall evaluation of the ratings the agents received in each
of the four areas.
Results
Based on the overall criteria and weighting, agents were placed in one of three priority
categories for initial public health preparedness efforts: A, B, or C (Table 1). Agents
in Category A have the greatest potential for adverse public health impact with mass
casualties, and most require broad-based public health preparedness efforts (e.g.,
improved surveillance and laboratory diagnosis and stockpiling of specific medications).
Category A agents also have a moderate to high potential for large-scale dissemination
or a heightened general public awareness that could cause mass public fear and civil
disruption.
Table 1
Critical biological agent categories for public health preparedness
Biological agent(s)
Disease
Category A
Variola major
Smallpox
Bacillus anthracis
Anthrax
Yersinia pestis
Plague
Clostridium botulinum (botulinum toxins)
Botulism
Francisella tularensis
Tularemia
Filoviruses and Arenaviruses (e.g., Ebola virus, Lassa virus)
Viral hemorrhagic fevers
Category B
Coxiella burnetii
Q fever
Brucella spp.
Brucellosis
Burkholderia mallei
Glanders
Burkholderia pseudomallei
Melioidosis
Alphaviruses (VEE, EEE, WEEa)
Encephalitis
Rickettsia prowazekii
Typhus fever
Toxins (e.g., Ricin, Staphylococcal enterotoxin B)
Toxic syndromes
Chlamydia psittaci
Psittacosis
Food safety threats (e.g., Salmonella spp., Escherichia coli O157:H7)
Water safety threats (e.g., Vibrio cholerae, Cryptosporidium parvum)
Category C
Emerging threat agents (e.g., Nipah virus, hantavirus)
aVenezuelan equine (VEE), eastern equine (EEE), and western equine encephalomyelitis
(WEE) viruses
Most Category B agents also have some potential for large-scale dissemination with
resultant illness, but generally cause less illness and death and therefore would
be expected to have lower medical and public health impact. These agents also have
lower general public awareness than Category A agents and require fewer special public
health preparedness efforts. Agents in this category require some improvement in public
health and medical awareness, surveillance, or laboratory diagnostic capabilities,
but presented limited additional requirements for stockpiled therapeutics beyond those
identified for Category A agents. Biological agents that have undergone some development
for widespread dissemination but do not otherwise meet the criteria for Category A,
as well as several biological agents of concern for food and water safety, are included
in this category.
Biological agents that are currently not believed to present a high bioterrorism risk
to public health but which could emerge as future threats (as scientific understanding
of these agents improves) were placed in Category C. These agents will be addressed
nonspecifically through overall bioterrorism preparedness efforts to improve the detection
of unexplained illnesses and ongoing public health infrastructure development for
detecting and addressing emerging infectious diseases (13).
Agents were categorized based on the overall evaluation of the different areas considered.
Table 2 shows the evaluation schemes as applied to agents in Categories A and B. For
example, smallpox would rank higher than brucellosis in the public health impact criterion
because of its higher untreated mortality (approximately 30% for smallpox and ≤2%
for brucellosis); smallpox has a higher dissemination potential because of its capability
for person-to-person transmission. Smallpox also ranks higher for special public health
preparedness needs, as additional vaccine must be manufactured and enhanced surveillance,
educational, and diagnostic efforts must be undertaken. Inhalational anthrax and plague
also have higher public health impact ratings than brucellosis because of their higher
morbidity and mortality. Although mass production of Vibrio cholera (the biological
cause of cholera) and Shigella spp. (the cause of shigellosis) would be easier than
the mass production of anthrax spores, the public health impact of widespread dissemination
would be less because of the lower morbidity and mortality associated with these agents.
Although the infectious doses of these bacteria are generally low, the total amount
of bacteria that would be required and current water purification and food-processing
methods would limit the effectiveness of intentional large-scale water or food contamination
with these agents.
Table 2
Criteria and weightinga used to evaluate potential biological threat agents
Disease
Public health impact
Dissemination
potential
Public
perception
Special preparation
Category
Disease
Death
P-Db
P - Pc
Smallpox
+
++
+
+++
+++
+++
A
Anthrax
++
+++
+++
0
+++
+++
A
Plagued
++
+++
++
++
++
+++
A
Botulism
++
+++
++
0
++
+++
A
Tularemia
++
++
++
0
+
+++
A
VHFe
++
+++
+
+
+++
++
A
VEf
++
+
+
0
++
++
B
Q Fever
+
+
++
0
+
++
B
Brucellosis
+
+
++
0
+
++
B
Glanders
++
+++
++
0
0
++
B
Melioidosis
+
+
++
0
0
++
B
Psittacosis
+
+
++
0
0
+
B
Ricin toxin
++
++
++
0
0
++
B
Typhus
+
+
++
0
0
+
B
Cholerag
+
+
++
+/-
+++
+
B
Shigellosisg
+
+
++
+
+
+
B
aAgents were ranked from highest threat (+++) to lowest (0).
bPotential for production
and dissemination in quantities that would affect a large population, based on availability,
BSL requirements, most effective route of infection, and environmental stability.
cPerson-to-person
transmissibility.
dPneumonic plague.
eViral hemorrhagic fevers due to Filoviruses
(Ebola, Marburg) or Arenaviruses (e.g., Lassa, Machupo).
fViral encephalitis.
gExamples
of food- and waterborne diseases.
Discussion
Although use of conventional weapons such as explosives or firearms is still considered
the most likely means by which terrorists could harm civilians (14), multiple recent
reports cite an increasing risk and probability for the use of biological or chemical
weapons (
15
–
18
). Indeed, the use of biological and chemical agents as small- and large-scale weapons
has been actively explored by many nations and terrorist groups (
19
,
20
). Although small-scale bioterrorism events may actually be more likely in light of
the lesser degrees of complexity to be overcome, public health agencies must prepare
for the still-possible large-scale incident that would undoubtedly lead to catastrophic
public health consequences. The selection and prioritization of the potential biological
terrorism agents described in this report were not based on the likelihood of their
use, but on the probability that their use would result in an overwhelming adverse
impact on public health.
Most evaluations of potential risk agents for biological warfare or terrorism have
historically been based on military concerns and criteria for troop protection. However,
several characteristics of civilian populations differ from those of military populations,
including a wider range of age groups and health conditions, so that lists of military
biological threats cannot simply be adopted for civilian use. These differences and
others may greatly increase the consequences of a biological attack on a civilian
population. Civilians may also be more vulnerable to food- or waterborne terrorism,
as was seen in the intentional Salmonella contamination of salad bars in The Dalles,
Oregon, in 1984 (21). Although food and water systems in the United States are among
the safest in the world, the occurrence of nationwide outbreaks due to unintentional
food or water contamination demonstrates the ongoing need for vigilance in protecting
food and water supplies (
22
,
23
). Overall, many other factors must be considered in defining and focusing multiagency
efforts to protect civilian populations against bioterrorism.
Category A agents are being given the highest priority for preparedness. For Category
B, public health preparedness efforts will focus on identified deficiencies, such
as improving awareness and enhancing surveillance or laboratory diagnostic capabilities.
Category C agents will be further assessed for their potential to threaten large populations
as additional information becomes available on the epidemiology and pathogenicity
of these agents. In addition, special epidemiologic and laboratory surge capacity
will be maintained to assist in the investigation of naturally occurring outbreaks
due to Category C “emerging” agents. Linkages established with established programs
for food safety, emerging infections diseases, and unexplained illnesses will augment
the overall bioterrorism preparedness efforts for many Category B and C agents.
The above categories of agents should not be considered definitive. The prioritization
of biological agents for preparedness efforts should continue. Agents in each category
may change as new information is obtained or new assessment methods are established.
Disease elimination and eradication efforts may result in new agents being added to
the list as populations lose their natural or vaccine-induced immunity to these agents.
Conversely, the priority status of certain agents may be reduced as the identified
public health and medical deficiencies related to these agents are addressed (e.g.,
once adequate stores of smallpox vaccine and improved diagnostic capabilities are
established, its rating within the special preparedness needs category would be reduced,
as would its overall rating within the risk-matrix evaluation process). To meet the
ever-changing response and preparedness challenges presented by bioterrorism, a standardized
and reproducible evaluation process similar to the one outlined above will continue
to be used to evaluate and prioritize currently identified biological critical agents,
as well as new agents that may emerge as threats to civilian populations or national
security.
Supplementary Material
Appendix
Risk-Matrix Analysis Process Used to Evaluate Potential Biological Threat Agents