Reported
by: National Center for Infectious Diseases; Epidemiology Program
Office; Public Health Practice Program Office; Office of the Director,
CDC.
Recognition of
Illness Associated with the Intentional Release of a Biologic Agent
On September 11,
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. 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
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 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, or
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); and 3) a large number of cases of acute
flaccid paralysis with prominent bulbar palsies, suggestive of a
release of botulinum toxin.
CDC defines three
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. 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.
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.
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.
Clinical
Laboratory Personnel
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 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.
Infection-Control
Professionals
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.
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
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.
