TABLE 8–2.

AGENTS MOST LIKELY TO BE USED FOR BIOLOGIC TERRORISM (CATEGORY A AGENTS)

AGENT MODE OF TRANSMISSION	CLINICAL SYNDROME	PATHOLOGIC FINDINGS	AVAILABLE TESTSa/APPEARANCE OF ORGANISM	TREATMENT/PROPHYLAXIS
Smallpox virus (variola major) Inhalation – aerosols Direct contact with lesions or contaminated surfaces Person to person spread	Diffuse rash (including palms and soles): deep-seated, firm/hard, round well circumscribed vesicles or pustules, all in same stage of development Hemorrhage into skin and GI tract	Early vesicles are multilocular (but coalesce in later stages), ballooning degeneration of epithelial cells (not multinucleated), eosinophilic intracytoplasmic viral inclusions (Guarnieri bodies)	IHC EM: fluid from vesicles can be used to detect viral particles PCR: viral DNA.	Vaccine availableb. Routine vaccination in the US ended in 1972. Persons with remote vaccination probably have some, but not complete, immunity.
Bacillus anthracis (anthrax) Direct contact with spores (skin or ingestion) Inhalation of spores No person-to-person spread	Cutaneous – eschar with hemorrhage, edema, necrosis, perivascular infiltrate, vasculitis Gastrointestinal – hemorrhagic enteritis, hemorrhagic lymphadenitis, mucosal ulcers with necrosis in the terminal ileum and cecum, peritonitis Inhalational - hemorrhagic mediastinitis, hemorrhagic lymphadenitis, hemorrhagic pleural effusion CNS – hemorrhagic meningitis	Skin: edema, focal necrosis, vasculitis, acute inflammation, ulceration. Organisms only rarely seen by H&E. Lymph nodes: hemorrhage, necrosis After antibiotic treatment, organisms may only be visible by silver stains and IHC	Gram, silver stains: Large broad (3 × 5 μm × 1 × 1.5 μm) encapsulated Gram pos bacilli with flattened ends in short chains India ink: shows capsule in blood and CSF IHC – sensitive and specific DFA (but cannot be used on formalin fixed tissue) PCR: formalin or fresh tissue	Vaccine availableb Antibiotic prophylaxis available
Yersinia pestis (plague) Flea bites Inhalation – aerosols Person-to-person spread	Bubonic – acute lymphadenitis with surrounding edema (a bubo is a local painful swelling) Pneumonic – severe, hemorrhagic bronchopneumonia, often with fibrinous pleuritis, diffuse alveolar damage (ARDS), sepsis with DIC CNS - meningitis	Lung: severe, confluent, hemorrhagic, necrotizing bronchopneumonia, often with fibrinous pleuritis Lymph nodes: necrosis – preferred for histologic examination and culture	Gram, silver, Giemsa stains: Short fat Gram neg bacilli IHC DFA	Vaccine available (but does not protect against pneumonia)b Antibiotic prophylaxis available
Clostridium botulinum toxin (botulism) Ingestion or inhalation of preformed neurotoxin No person-to-person spread	CNS – hyperemia and microthrombosis of small vessels associated with symmetrical, descending pattern of weakness and paralysis of cranial nerves, limbs, and trunk	No specific findings for cases due to ingestion or inhalation of preformed toxin Swabs of mucosal surfaces or serum may be used for the botulinum toxin mouse bioassay Samples should be taken prior to the use of antitoxin	Gram-positive bacteria – however organisms unlikely to be present in a terror attack	Antitoxin available
Francisella tularensis (tularemia) Tick bite Direct contact with infected fluids or tissues Ingestion of infected meat No person-to-person spread	Ulceroglandular – skin ulcer with associated suppurative lymphadenitis Glandular – suppurative necrotizing lymphadenitis without associated skin ulcer Oculoglandular – eyelid edema, acute conjunctivitis and edema, small conjunctival ulcers, regional lymphadenitis Pharyngeal – exudative pharyngitis or tonsillitis with ulceration, pharyngeal membrane formation, regional lymphadenitis Typhoidal – systemic involvement, DIC, focal necrosis of major organs Pneumonic – acute inflammation, diffuse alveolar damage	Ulcer with a nonspecific inflammatory infiltrate and a granulomatous reaction. In some cases, large necrotizing granulomas with giant cells may be present. Lymph nodes: extensive necrosis, irregular microabscesses and multiple granulomas with caseous necrosis. Lung: necrotizing pneumonia with abundant fibrin, acute inflammation	Small encapsulated Gram-negative coccobacilli - difficult to see with histochemical stains IHC DFA	Antibiotic prophylaxis available
Hemorrhagic fever viruses, including: -Filoviruses (including Ebola and Marburg viruses) -Arenaviruses (e.g., Lassa fever) Close personal contact with infected person, blood, tissue, or body fluids	Diffuse rash, massive hepatocellular necrosis, extensive necrosis in other major organs, diffuse alveolar damage	Massive hepatic necrosis with filamentous viral inclusions in hepatocytes, extensive necrosis of other organs	IHC EM: viral inclusions PCR	No specific treatment

ARDS: acute respiratory distress syndrome, DIC: disseminated intravascular coagulopathy, IHC: immunohistochemistry; DFA: direct fluorescent assay.

^aIHC and DFA tests for each of these organisms are available at the CDC. Consult their website to determine how to decide if a specimen is appropriate for testing and how to send such a sample: call the CDC at 404-639-3133 or fax the CDC at 404-639-3043, for more information.

^bVaccination is not currently recommended for individuals without a known exposure. Vaccination for smallpox may be considered for selected personnel who would be a first responder for the examination of the remains or specimens from patients dying of smallpox.