On 11 Sep 2001, following the terrorist incidents in New York City and
Washington, D.C., CDC recommended heightened surveillance for any unusual
disease occurrence or increased numbers of illnesses that might be
associated with the terrorist attacks. Subsequently, cases of anthrax in
Florida and New York City have demonstrated the risks associated with
intentional release of biologic agents (1). This report provides guidance
for health-care providers and public health personnel about recognizing
illnesses or patterns of illness that might be associated with intentional
release of biologic agents.
Health-care providers should be alert to illness patterns and diagnostic
clues that might indicate an unusual infectious disease outbreak associated
with intentional release of a biologic agent and should report any clusters
or findings to their local or state health department. The covert release
of a biologic agent may not have an immediate impact because of the delay
between exposure and illness onset, and outbreaks associated with
intentional releases might closely resemble naturally occurring outbreaks.
Indications of intentional release of a biologic agent include:
Indications
(1) an unusual temporal or geographic clustering of illness (e.g., persons who attended the same public event or gathering) or patients presenting
with clinical signs and symptoms that suggest an infectious disease
outbreak (e.g., >2 patients presenting with an unexplained febrile illness
associated with sepsis, pneumonia, respiratory failure, rash, or a
botulism-like syndrome with flaccid muscle paralysis, especially if
occurring in otherwise healthy persons
(2) an unusual age distribution for common diseases (e.g., an increase in
what appears to be a chickenpox-like illness among adult patients, but which might be smallpox)
(3) a large number of cases of acute flaccid paralysis with prominent bulbar palsies, suggestive of a release of botulinum toxin.
CDC defines 3 categories of biologic agents with potential to be used
as weapons, based on ease of dissemination or transmission, potential for
major public health impact (e.g., high mortality), potential for public
panic and social disruption, and requirements for public health
preparedness (2). Agents of highest concern are _Bacillus anthracis_
(anthrax), _Yersinia pestis_ (plague), _variola major_ (smallpox),
_Clostridium botulinum_ toxin (botulism), _Francisella tularensis_
(tularemia), filoviruses (Ebola hemorrhagic fever, Marburg hemorrhagic
fever); and arenaviruses (Lassa [Lassa fever], Junin [Argentine hemorrhagic
fever], and related viruses). The following summarizes the clinical
features of these agents (3--6).
Anthrax
A nonspecific prodrome (i.e., fever, dyspnea, cough, and chest
discomfort) follows inhalation of infectious spores. Approximately 2--4
days after initial symptoms, sometimes after a brief period of improvement,
respiratory failure and hemodynamic collapse ensue. Inhalational anthrax
also might include thoracic edema and a widened mediastinum on chest
radiograph. Gram-positive bacilli can grow on blood culture, usually 2--3
days after onset of illness. Cutaneous anthrax follows deposition of the
organism onto the skin, occurring particularly on exposed areas of the
hands, arms, or face. An area of local edema becomes a pruritic macule or
papule, which enlarges and ulcerates after 1-2 days. Small, 1-3 mm vesicles
may surround the ulcer. A painless, depressed, black eschar usually with
surrounding local edema subsequently develops. The syndrome also may
include lymphangitis and painful lymphadenopathy.
Plague
Clinical features of pneumonic plague include fever, cough with
muco-purulent sputum (gram-negative rods may be seen on gram stain),
hemoptysis, and chest pain. A chest radiograph will show evidence of
bronchopneumonia.
Botulism
Clinical features include symmetric cranial neuropathies (i.e., drooping eyelids, weakened jaw clench, and difficulty swallowing or
speaking), blurred vision or diplopia, symmetric descending weakness in a
proximal-to-distal pattern, and respiratory dysfunction from respiratory
muscle paralysis or upper airway obstruction without sensory deficits.
Inhalational botulism would have a similar clinical presentation as
foodborne botulism; however, the gastrointestinal symptoms that accompany
foodborne botulism may be absent.
Smallpox (variola)
The acute clinical symptoms of smallpox resemble other
acute viral illnesses, such as influenza, beginning with a 2-4 day
nonspecific prodrome of fever and myalgias before rash onset. Several
clinical features can help clinicians differentiate varicella (chickenpox)
from smallpox. The rash of varicella is most prominent on the trunk and
develops in successive groups of lesions over several days, resulting in
lesions in various stages of development and resolution. In comparison, the
vesicular/pustular rash of smallpox is typically most prominent on the face
and extremities, and lesions develop at the same time.
Inhalational tularemia
Inhalation of _F. tularensis_ causes an abrupt
onset of an acute, nonspecific febrile illness beginning 3--5 days after
exposure, with pleuropneumonitis developing in a substantial proportion of
cases during subsequent days (7).
Hemorrhagic fever (such as would be caused by Ebola or Marburg viruses)
After an incubation period of usually 5-10 days (range: 2-19 days), illness
is characterized by abrupt onset of fever, myalgia, and headache. Other
signs and symptoms include nausea and vomiting, abdominal pain, diarrhea,
chest pain, cough, and pharyngitis. A maculopapular rash, prominent on the
trunk, develops in most patients approximately 5 days after onset of
illness. Bleeding manifestations, such as petechiae, ecchymoses, and
hemorrhages, occur as the disease progresses (8).
Although unidentified gram-positive bacilli growing on agar may be
considered as contaminants and discarded, CDC recommends that these bacilli
be treated as a "finding" when they occur in a suspicious clinical setting
(e.g., febrile illness in a previously healthy person). The laboratory
should attempt to characterize the organism, such as by motility testing,
inhibition by penicillin, absence of hemolysis on sheep blood agar, and
further biochemical testing or species determination.
An unusually high number of samples, particularly from the same biologic
medium (e.g., blood and stool cultures), may alert laboratory personnel to
an outbreak. In addition, central laboratories that receive clinical
specimens from several sources should be alert to increases in demand or
unusual requests for culturing (e.g., uncommon biologic specimens such as
cerebrospinal fluid or pulmonary aspirates).
When collecting or handling clinical specimens, laboratory personnel should
1) use Biological Safety Level II (BSL-2) or Level III (BSL-3) facilities
and practices when working with clinical samples considered potentially
infectious; 2) handle all specimens in a BSL-2 laminar flow hood with
protective eyewear (e.g., safety glasses or eye shields), use closed-front
laboratory coats with cuffed sleeves, and stretch the gloves over the
cuffed sleeves; 3) avoid any activity that places persons at risk for
infectious exposure, especially activities that might create aerosols or
droplet dispersal; 4) decontaminate laboratory benches after each use and
dispose of supplies and equipment in proper receptacles; 5) avoid touching
mucosal surfaces with their hands (gloved or ungloved), and never eat or
drink in the laboratory; and 6) remove and reverse their gloves before leaving the laboratory and dispose of them in a biohazard container, and
wash their hands and remove their laboratory coat.
When a laboratory is unable to identify an organism in a clinical specimen,
it should be sent to a laboratory where the agent can be characterized,
such as the state public health laboratory or, in some large metropolitan
areas, the local health department laboratory. Any clinical specimens
suspected to contain variola (smallpox) should be reported to local and
state health authorities and then transported to CDC. All variola
diagnostics should be conducted at CDC laboratories. Clinical laboratories
should report any clusters or findings that could indicate intentional
release of a biologic agent to their state and local health departments.
Heightened awareness by infection-control professionals (ICPs) facilitates
recognition of the release of a biologic agent. ICPs are involved with many
aspects of hospital operations and several departments and with
counterparts in other hospitals. As a result, ICPs may recognize changing
patterns or clusters in a hospital or in a community that might otherwise
go unrecognized.
ICPs should ensure that hospitals have current telephone numbers for
notification of both internal (ICPs, epidemiologists, infectious diseases
specialists, administrators, and public affairs officials) and external
(state and local health departments, Federal Bureau of Investigation field
office, and CDC Emergency Response office) contacts and that they are
distributed to the appropriate personnel (9). ICPs should work with
clinical microbiology laboratories, on- or off-site, that receive specimens
for testing from their facility to ensure that cultures from suspicious
cases are evaluated appropriately.
State health departments should implement plans for educating and reminding
health-care providers about how to recognize unusual illnesses that might
indicate intentional release of a biologic agent. Strategies for responding
to potential bioterrorism include 1) providing information or reminders to
health-care providers and clinical laboratories about how to report events
to the appropriate public health authorities; 2) implementing a
24-hour-a-day, 7-day-a-week capacity to receive and act on any positive
report of events that suggest intentional release of a biologic agent; 3)
investigating immediately any report of a cluster of illnesses or other
event that suggests an intentional release of a biologic agent and
requesting CDC's assistance when necessary; 4) implementing a plan,
including accessing the Laboratory Response Network for Bioterrorism, to
collect and transport specimens and to store them appropriately before
laboratory analysis; and 5) reporting immediately to CDC if the results of
an investigation suggest release of a biologic agent.
Reported by: National Center for Infectious Diseases; Epidemiology Program
Office; Public Health Practice Program Office; Office of the Director, CDC.
Health-care providers, clinical laboratory personnel, infection control
professionals, and health departments play critical and complementary roles
in recognizing and responding to illnesses caused by intentional release of
biologic agents. The syndrome descriptions, epidemiologic clues, and
laboratory recommendations in this report provide basic guidance that can
be implemented immediately to improve recognition of these events.
After the terrorist attacks of September 11, state and local health
departments initiated various activities to improve surveillance and
response, ranging from enhancing communications (between state and local
health departments and between public health agencies and health-care
providers) to conducting special surveillance projects. These special
projects have included active surveillance for changes in the number of
hospital admissions, emergency department visits, and occurrence of
specific syndromes. Activities in bioterrorism preparedness and emerging
infections over the past few years have better positioned public health
agencies to detect and respond to the intentional release of a biologic
agent. Immediate review of these activities to identify the most useful and
practical approaches will help refine syndrome surveillance efforts in
various clinical situations.
Information about clinical diagnosis and management can be found elsewhere
(1--9). Additional information about responding to bioterrorism is
available from:
Center for Disease Control and Prevention