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 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 to 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 ... 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,... 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... 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