In the absence of a known release, the discovery of a patient with characteristic
findings of a disease caused by a Category A agent should prompt further
investigation, as well as the institution of appropriate infection control measures.
Perhaps an ED triage nurse discovers that within a short period of time two
separate infants arrive with complaints of floppiness and weakness, raising the
concern for infant botulism. Perhaps a pediatric resident becomes concerned
about a viral hemorrhagic fever after encountering a highly febrile and illappearing child with a purpuric rash who recently traveled to Africa. Although
not all of the Category A biologic agents are spread from person to person ( Table
132.3A ), in these cases it would be prudent to assume this mode of spread. The
staff member, after washing his hands, should put on a gown, gloves, and eye
protection. An N-95 respirator should be added if there is concern for smallpox or
viral hemorrhagic fever. The child should be covered with a sheet, provided a
mask, and escorted directly to a negative-pressure room for further evaluation and
treatment.

CLINICAL ASSESSMENT AND MANAGEMENT
Specific Agents
Anthrax
CLINICAL PEARLS AND PITFALLS
Inhalational anthrax should be suspected when there is fever with a
widened mediastinum on chest x-ray in the absence of trauma.
Inhalational anthrax is not contagious and therefore poses no risk to
healthcare workers.
Background. Anthrax is caused by infection with Bacillus anthracis, a grampositive spore-forming rod capable of surviving long periods in its spore form
without nutrients or moisture. Natural disease caused by B. anthracis manifests in
cutaneous, gastrointestinal (GI), and inhalational forms. Anthrax spores can be
formulated in a manner to enhance aerosolization. The resulting small particles
may drift long distances with air currents, produce lethal infection when inhaled,
and resist environmental degradation, making them a formidable terrorist
weapon.
The anthrax attacks of 2001 resulted in 22 confirmed cases (11 inhalational, 11

cutaneous), with five deaths, resulting from presumed or known exposure to


anthrax-contaminated mail. The attack resulted in enormous public anxiety, as
well as major demands for medical care and public health resources. Antibiotic
prophylaxis was prescribed for more than 30,000 persons, and decontamination of
the Hart Senate Office Building alone took months and was extremely costly.
Many bioterrorism defense experts, however, fear an even more widespread
aerosol release that could potentially sicken hundreds of thousands.
Inhalational anthrax is the disease form that poses the greatest threat.
Following the accidental release of anthrax spores from a Soviet military facility
at Sverdlovsk in 1979, 66 of 77 known victims of inhalational anthrax died. In the
recent U.S. attack, all 5 deaths occurred among the 11 patients with this form of
disease.
Pathophysiology/Common Manifestations. Inhalational anthrax results from
spore uptake in the alveoli by pulmonary macrophages, followed by bacterial
germination and toxin production in the mediastinal lymph nodes, leading to
hemorrhagic lymphadenitis, mediastinitis, and sepsis. Symptoms typically begin
1 to 5 days after exposure, although incubation periods up to several weeks in
length have been reported. The disease begins as a nonspecific influenza-like
illness, characterized by fever, headache, myalgia, and cough. The relative lack of
eye, nose, and throat findings such as red, watery eyes, rhinorrhea, or pharyngitis
helps to distinguish this phase from common viral infections. A brief intervening
period of improvement sometimes follows, but rapid deterioration then ensues
with high fever, dyspnea, cyanosis, and shock marking this second phase.
Hemorrhagic meningitis occurs in up to 50% of cases. Chest radiographs or
computed tomography scans may reveal a widened mediastinum or prominent
mediastinal lymphadenopathy; infiltrates and pleural effusions may also be seen.
Gram stains of peripheral blood smears at this stage may demonstrate grampositive rods. Prompt treatment is imperative as, historically, death occurred in as
many as 95% of inhalational anthrax cases if such treatment began more than 48

hours after symptom onset. Even with modern intensive care, in the 2001 anthrax
attack, all four patients with inhalational anthrax who exhibited signs of fulminant
disease prior to antibiotic administration died. Thus, in the context of a known
bioterrorism incident, a potential dilemma facing emergency care providers
involves deciding which patients presenting with nonspecific flu-like, febrile
illness are candidates for empiric antibiotic therapy.
Cutaneous anthrax occurs when organisms gain entry into skin, usually
through abrasions or cuts. It is characterized by the appearance of a papule at the
inoculum site, which then progresses over days to a vesicle, then to an ulcer, and


finally to a depressed, black eschar. The surrounding tissue becomes markedly
edematous, but not particularly tender, distinguishing this infection from typical
cellulitis. This form of anthrax is quite amenable to therapy with a variety of
antibiotics and, with timely institution of treatment, is rarely fatal. In the 2001
outbreak, all 11 patients with cutaneous anthrax survived. The one pediatric
victim of the 2001 attack was a 7-month-old boy with cutaneous anthrax on his
arm, presumably contracted after a brief visit to a New York City television news
studio that had received contaminated mail (a similar lesion is pictured on the
face of a child in Fig. 132.2 ). Of note, he also developed hemolysis,
thrombocytopenia, and renal insufficiency, features not usually observed in
otherwise uncomplicated cases of cutaneous disease, thus raising the possibility
of a particular vulnerability in infancy.

FIGURE 132.2 Cutaneous anthrax on the eyelids of a young child. (Courtesy of Dr. Larry
Schwab. Reprinted from Ostler HB, Maibach HI, Hoke AW, et al., eds. Diseases of the Eye and
Skin: A Color Atlas . Philadelphia, PA: Lippincott Williams Wilkins, 2004. With permission.)

The finding of gram-positive rods in skin biopsy material (in the case of
cutaneous disease) or in blood smears, pleural fluid, or spinal fluid should suggest

anthrax. Chest radiographs demonstrating a widened mediastinum in the context
of fever and constitutional signs should also lead one to consider the diagnosis.


Confirmation may be obtained by blood culture. State health laboratories,
USAMRIID, and the CDC can also confirm a diagnosis of anthrax by polymerase
chain reaction (PCR) and immunohistochemical assay.
Management. As anthrax has little potential for person to person transmission,
standard precautions are adequate for healthcare workers caring for anthrax
victims. Given the usual 1- to 5-day incubation period, decontamination of
victims presenting days after exposure is unwarranted. Aerosolization of
organisms from skin or clothing likewise poses little threat under typical
circumstances, but bathing and laundry with soap and water would seem prudent
soon after direct physical contact with a suspect substance.
Although naturally occurring strains of B. anthracis are usually quite sensitive
to penicillin G, penicillin-resistant strains of B. anthracis are known; thus, many
experts consider ciprofloxacin, levofloxacin, or doxycycline as essential
components of first-line treatment for victims of intentional anthrax. Infectious
Disease and Emergency Preparedness experts can provide advice regarding
postexposure prophylaxis. See Table 132.3B for detailed treatment
recommendations for children. Newer treatments include the recently licensed
monoclonal antibodies raxibacumab and obiltoxaximab, as well as investigational
anthrax immune globulin preparations.
Plague
Background. Plague, caused by infection with the gram-negative bipolar-staining
rod Yersinia pestis, is usually transmitted in nature via the bite of fleas. Endemic
disease is still seen in areas of the southwestern United States, South and
Southeast Asia, as well as in South America and Africa. Plague has long appeared
attractive as an agent of bioterrorism. Testimony to its extreme lethality and
infectivity can be obtained by considering that the “Black Death” eliminated onethird of the population of Europe during the Middle Ages.

Pathophysiology. Y. pestis is a facultative intracellular pathogen that is able to
survive temporarily within macrophages, thus aiding its dissemination to distant
sites following inoculation or inhalation. It is lymphotropic, and significantly
tender regional lymphadenopathy (e.g., in the distribution of a flea bite) is a
prominent feature of bubonic plague. Pneumonic plague (along with smallpox) is
one of the few bioterrorist threats readily transmissible from person to person via
the respiratory route, and coughing patients are often highly contagious.