Bioterrorism
Robert J. Leggiadro
The intentional delivery of Bacillus anthracis spores through mailed letters or packages established the clinical reality of bioterrorism in the United States in late 2001. An understanding of the epidemiology, clinical manifestations, and management of the more credible biologic agents is critical to limiting morbidity and mortality from a bioterrorism attack.
The implementation of an effective response to a deliberate release of biologic agents by terrorists requires the detection and reporting of cases as soon as possible. A prompt recognition of unusual clinical syndromes and increases above seasonal levels in the incidence of common syndromes or deaths caused by infectious agents is critical to launching an effective response.
EPIDEMIOLOGY
Potential biologic weapons share several characteristics. Ease of acquisition and production is a primary consideration. Other ideal properties include the potential to be aerosolized (particle sizes of 1 to 10 μm) and dispersed over a wide geographic area, as well as resistance to sunlight, dessication, and heat. The potential to cause lethal or debilitating disease and person-to-person transmission are important features, as is lack of effective therapy or prophylaxis.
Any small or large outbreak of disease merits evaluation as a potential biologic event. Unusually high rates of disease, as well as unusual clinical syndromes (e.g., a cluster of life-threatening pneumonia in otherwise healthy adults), should signal a warning. Once the case definition and attack rate have been determined, an epidemic curve can be calculated based on the number of cases over the course of time. The epidemic curve in a biologic event triggered by a point-source exposure most likely would be compressed, with a peak reached in a matter of hours or days. The occurrence of a second curve peak is possible with contagious agents, as a result of person-to-person transmission. The steep epidemic curve expected in a bioterrorism attack is similar to that seen with other point-source exposures, such as foodborne outbreaks.
Several epidemiologic clues may be helpful in determining whether further investigation into an outbreak as a potential biologic attack is warranted. A large epidemic, especially one occurring in a discrete population; more severe disease than expected for a given pathogen; and a disease unusual for a given geographic area (e.g., pulmonic tularemia in an urban setting) represent major indicators. Multiple simultaneous epidemics of different diseases, outbreaks with both human and zoonotic consequences, and unusual strains or susceptibility profiles are additional helpful parameters. Variable attack rates as a function of an agent released relative to the interior or exterior of a building also are useful. Although most bioterrorism attacks will be covert, intelligence revealing plans for an attack, terrorist claims of a deliberate release, or direct physical evidence of an attack obviously point to such an event.
The emergence of mosquito-borne West Nile (WN) virus encephalitis in New York City in the summer of 1999 is an example of a naturally occurring outbreak that had elements of a potential bioterrorist attack. This outbreak represented a disease occurring in an unusual (previously nonendemic) area as well as one with zoonotic (birds) in addition to human consequences. It marked the first documented appearance of WN virus in the Western hemisphere and the first arboviral outbreak in New York City since the yellow fever epidemics of the nineteenth century. A large avian die-off, affecting primarily crows, preceded the outbreak in humans by at least several weeks.
CRITICAL BIOLOGIC AGENTS
In addition to anthrax, critical biologic agents include plague, tularemia, smallpox, viral hemorrhagic fever, and botulinum toxin (Table 138.1). These credible biologic agents are discussed further.
Anthrax
B. anthracis is a large, sporulatory gram-positive rod with three distinct life cycles featuring multiplication of spores in soil,
animal (herbivore) infection, and human infection. Anthrax continues to occur in developing countries where the organism is highly endemic and the use of animal anthrax vaccine is not comprehensive (e.g., Iran, Iraq, Turkey, Pakistan, and sub-Saharan Africa). Human cases may be classified as either agricultural or industrial. Herders, butchers, and slaughterhouse workers in direct contact with infected animals are susceptible to acquisition of agricultural infection, whereas workers in animal-hair processing mills and those handling bone meal may acquire industrial infection.
animal (herbivore) infection, and human infection. Anthrax continues to occur in developing countries where the organism is highly endemic and the use of animal anthrax vaccine is not comprehensive (e.g., Iran, Iraq, Turkey, Pakistan, and sub-Saharan Africa). Human cases may be classified as either agricultural or industrial. Herders, butchers, and slaughterhouse workers in direct contact with infected animals are susceptible to acquisition of agricultural infection, whereas workers in animal-hair processing mills and those handling bone meal may acquire industrial infection.
TABLE 138.1. CRITICAL BIOLOGIC AGENTS | |||
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The three forms of human anthrax are cutaneous, inhalational, and gastrointestinal. The most common form is cutaneous, which is acquired through contact with an infected animal or animal products. The much less common inhalational form results from deposition of spores in the lungs, and gastrointestinal anthrax occurs after ingestion of infected meat. Because human-to-human transmission of anthrax has not been reported, standard precautions are recommended for hospitalized patients with all forms of anthrax infection. In the United States, 224 cases of cutaneous anthrax were reported between 1944 and 1994. Most cases in recent decades were a result of exposure to wool or animal hair.
The clinical presentation and course of the first ten confirmed cases of inhalational anthrax associated with bioterrorism in the United States were reported in late 2001. Epidemiologic investigation indicated that the outbreak was a result of the intentional delivery of B. anthracis spores through mailed letters or packages. The median incubation period was 4 days, ranging from 4 to 6 days. Several clinical features of these patients were not emphasized in earlier reports of inhalational anthrax, a previously rare disease. Drenching sweating, nausea, and vomiting were frequent symptoms of the initial phase of illness in this outbreak. Pleural effusions were a remarkably consistent clinical feature. No predominant underlying diseases or conditions were noted.
None of the ten patients had an initially normal chest radiograph. In addition to characteristic mediastinal widening, paratracheal or hilar fullness, pleural effusions, and parenchymal infiltrates were noted. Computed tomography (CT) of the chest was more sensitive than was chest radiography in revealing mediastinal lymphadenopathy, and an elevation in the proportion of neutrophils or band forms represented an early diagnostic clue.
Inhalational anthrax previously was reported to be a biphasic illness with influenza-like symptoms (i.e., fever, cough, malaise, fatigue, and chest discomfort) manifesting in the first phase, followed briefly by 1 to 2 days of improvement before development of the acute phase 2 to 5 days later. However, this brief period of improvement between initial and fulminant phases of illness was not observed in the first intentional outbreak associated with mail.
The 55% survival rate in these patients was higher than previously reported (less than 15%). Limited data on the treatment of survivors suggest that early treatment with a fluoroquinolone and at least one other active drug (e.g., rifampin, clindamycin, or vancomycin) may improve survival.
Nasal congestion, rhinorrhea, and sore throat, infrequently seen in this series, might help to distinguish influenza-like illness from inhalational anthrax. Newer diagnostic methods for B. anthracis include polymerase chain reaction (PCR), immunohistochemistry, and sensitive serologic tests. Optimal management, including combination antimicrobial regimens, as well as adjunctive therapies (e.g., immunoglobulin antitoxin and corticosteroids), remains to be defined.
Cutaneous anthrax is characterized by a skin lesion evolving from a papule, through a vesicular stage, to a depressed black eschar, often surrounded by significant edema and erythema (Fig. 138.1). The lesion, which may mimic a spider bite, usually is painless and located on exposed parts of the body such as the face, neck, and arms. The incubation period ranges from 1 to 12 days but often is less than 7 days. Fatalities seldom occur (less than 1%) with the administration of effective antimicrobial therapy. Cutaneous anthrax occurred in a 7-month old infant who was exposed at his mother’s workplace as a result of the 2001 attack. This infant displayed severe microangiopathic hemolytic anemia with renal involvement, coagulopathy, and hyponatremia, unusual findings with cutaneous anthrax.