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Bacillus anthracis is a gram-positive, sporulating rod. Anthrax infection occurs naturally after contact with contaminated animals or contaminated animal products. A biologic attack would likely involve the aerosol release of anthrax spores. Clinically, the disease occurs in three forms: inhalational, gastrointestinal, and cutaneous.
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Inhalational anthrax is the form of disease most likely expected after a terrorist attack. After spores are inhaled, an incubation period occurs, usually lasting 1–7 days. However, incubation periods of up to 60 days have been observed. Initially, nonspecific symptoms of fever, cough, headache, chills, vomiting, dyspnea, chest pain, abdominal pain, and weakness occur. This stage may last from a few hours to a few days. Following these nonspecific symptoms, a transient period of improvement may be seen. When the second stage of disease is reached, high fever, diaphoresis, cyanosis, hypotension, lymphadenopathy, shock, and death will occur. Often, death will occur within hours once the second stage is reached. The average time from onset of symptoms to death is 3 days. Once the initial symptoms of inhalational anthrax develop, the overall mortality rate may be as high as 95%. Early diagnosis of anthrax infection and rapid initiation of therapy may improve survival.
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Gastrointestinal Anthrax
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Gastrointestinal anthrax occurs when spores are ingested into the digestive tract. Two forms of the disease occur: oropharyngeal and abdominal. Oropharyngeal disease occurs when spores are deposited in the upper gastrointestinal tract. An oral or esophageal ulcer develops followed by regional lymphadenopathy and eventual sepsis. In abdominal anthrax, the spores are deposited in the lower gastrointestinal tract. Symptoms include nausea, vomiting, bloody diarrhea, and the development of an acute abdomen with sepsis. Mortality rates for gastrointestinal anthrax are in excess of 50%.
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Cutaneous anthrax is the most common naturally occurring form of the disease. It occurs when spores come in contact with open skin lesions. This usually occurs on the arms, hands, and face. Following exposure, a small, often pruritic, papule will develop. Eventually, this papule will turn into a small ulcer over 2 days, then progress to a small vesicle, and ultimately to a painless black eschar with surrounding edema. Then, over a period of 1–2 weeks, the eschar will dry and fall off. Regional lymphadenitis or lymphadenopathy may also occur. In some case, secondary sepsis may develop. Without treatment, cutaneous anthrax has a mortality rate of 20%; however, the mortality rate drops to 1% with treatment.
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Anthrax meningitis can occur as a complication of any other form of anthrax. Symptoms include headache and meningismus. Anthrax meningitis carries a mortality rate of nearly 100%.
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Laboratory and X-Ray Findings
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Multiple laboratory studies can be used to identify anthrax. In fulminant cases, the organism may be seen on routine Gram stain. Blood cultures, wound cultures, and nasal cultures may be obtained. Given the lack of an infiltrate, sputum cultures are rarely useful. Often Bacillus spp. are thought to be the contaminant; therefore, notify laboratory personnel of possible anthrax. Confirmatory enzyme-linked immunoassay (ELISA) and polymerase chain reaction (PCR) tests are available at some national reference laboratories. Patients with inhalational anthrax will display a wide mediastinum on chest x-ray without infiltrate.
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Treatment and Prophylaxis
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Because anthrax has a rapid and fulminant course, do not delay treatment while awaiting confirmatory tests. Delaying empiric treatment for even hours may significantly increase mortality.
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Most naturally occurring strains of anthrax are sensitive to penicillin. Some strains, however, are penicillin resistant. Weapons-grade anthrax is likely to be penicillin resistant. As a result, the first-line therapy is now ciprofloxacin; doxycycline is an acceptable alternative (see Table 3–1). Treatment should continue for 60 days. If cultures were obtained, later sensitivity testing may direct antibiotic use.
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Patients may require intensive medical support such as airway management, hemodynamic support, and various measures to manage multisystem organ failure.
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Individuals thought to be at high risk for anthrax exposure should receive treatment as though infection has occurred. Later, laboratory analysis may allow discontinuation of therapy. An anthrax vaccination is available and requires injections at 0, 2, and 4 weeks, followed by injections at 6, 12, and 18 months. An annual booster is also required. If a combination of vaccination and antibiotics is used during treatment, the course of antibiotics may be shortened to 30 days.
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No data indicate that anthrax is spread via person-to-person contact. Use standard precautions during patient care activities (Table 3–2).
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Yersinia pestis is a nonmotile, gram-negative bacillus. Plague occurs naturally after the bite of an infected arthropod vector. Biologic attack would most likely involve the aerosolized release of Y. pestis. Plague occurs in three clinical forms: bubonic plague, septicemic plague, and pneumonic plague.
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Bubonic plague is the most common naturally occurring form of the disease. Infection begins with the bite of a contaminated flea. A latent period then occurs and may last up to 1 week, followed by fevers, chills, and weakness. Eventually, the organism will migrate to the regional lymph nodes where it causes destruction and necrosis. A swollen and tender lymph node called a bubo will develop, which ranges from 1 to 10 cm. Some patients may develop secondary sepsis. Without treatment, bubonic plague has an estimated mortality rate of 50%; however, with antibiotic therapy the mortality rate falls to 10%.
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Septicemic plague may occur either as a complication of other forms of plague or as a primary entity. Symptoms include fever, dyspnea, hypotension, and purpuric skin lesions. Gangrene of the nose and extremities may occur, hence the name “black death.” Complications of disseminated intravascular coagulation may also be evident. Without treatment, septicemic plague has an estimated mortality rate of 100%; however, with antibiotic therapy the mortality rate falls to 40%.
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Pneumonic plague may occur either as a complication of other forms of plague or as a primary entity. It is the most likely form of the disease to result from a terrorist attack. A latent period of 1–6 days following exposure is likely. Patients will then develop signs and symptoms of severe pulmonary infection including fever, cough, dyspnea, hypoxia, and sputum production. Gastrointestinal symptoms of nausea, vomiting, and diarrhea may also occur. Pneumonic plague has an estimated mortality rate of 100% if antibiotic therapy is not begun within 24 hours.
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Laboratory and X-Ray Findings
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Y. pestis can be identified by several different staining techniques, including routine Gram, Wright, Giemsa, and Wayson stains. Blood cultures, sputum cultures, and cultures of lymph node aspirates may be useful. Specialized rapid confirmatory tests are available at some laboratories. In patients with pneumonic plague, chest x-ray will display a patchy or confluent infiltrate.
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Treatment and Prophylaxis
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Plague has a rapid disease progression, and any delay in empiric treatment will cause significant increases in mortality.
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Streptomycin or gentamicin is the drug of choice for the treatment of plague (see Table 3–1). Alternative antibiotics include doxycycline, ciprofloxacin, and chloramphenicol.
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Patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
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Patients in a community experiencing a pneumonic plague epidemic should receive antibiotic therapy if they develop a cough or a fever above 38.5°C (101.2°F). Any person who has been in close contact with an individual with plague should receive a 7-day course of antibiotics.
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Pneumonic plague can be spread from person to person by aerosol droplets. Use droplet precautions, and either the patient or the caregivers should wear masks (see Table 3–2). Once the patient has received 48 hours of antibiotics and has improved clinically, standard precautions may be used.
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Francisella tularensis is a nonmotile, aerobic, gram-negative coccobacillus. Two strains of tularemia are known to exist. F. tularensis biovar tularensis is considered highly virulent, whereas F. tularensis biovar palaearctiais more benign. Tularemia occurs naturally after the bite of an infected arthropod vector or after exposure to contaminated animal products. Biologic attack would most likely involve the release of aerosolized F. tularensis. Tularemia displays multiple clinical forms including ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, and typhoidal forms. The form of disease depends on the site and type of inoculation.
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Patients with any form of tularemia may present with the abrupt onset of fever, chills, headache, malaise, and myalgias. Often a maculopapular rash is seen.
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Ulceroglandular Tularemia
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Ulceroglandular tularemia usually occurs after handling infected animals or after the bite of an infected arthropod vector. At the inoculation site, a papule will form that will eventually become a pustule and then a tender ulcer. The ulcer may have a yellow exudate and will slowly develop a black base. Regional lymph nodes will become swollen and painful.
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Glandular tularemia displays signs and symptoms similar to ulceroglandular tularemia, except that no ulcer formation is noted.
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Oculoglandular Tularemia
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After ocular inoculation, a painful conjunctivitis will develop with regional lymphadenopathy. Lymphadenopathy may involve the cervical, submandibular, or preauricular chains. In some cases, ulcerations occur on the palpebral conjunctiva.
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Oropharyngeal Tularemia
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After inoculation of the pharynx, an exudative pharyngotonsillitis will develop with cervical lymphadenopathy.
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Pneumonic tularemia occurs after inhalation of F. tularensis or following secondary spread from other infectious foci. A terrorist attack will most likely cause this form of disease. The findings of pulmonary involvement are variable and include pharyngitis, bronchiolitis, hilar lymphadenitis, and pneumonia. Early in the course of disease, systemic symptoms may predominate over pulmonary symptoms. In some cases, however, pulmonary disease progresses rapidly to pneumonia, pulmonary failure, and death.
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In this form of tularemia, systemic signs and symptoms of disease are present without a clear infectious site. Signs and symptoms include fever, chills, headache, malaise, and myalgias.
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Any form of tularemia may be complicated by hematogenous spread leading to pneumonia, meningitis, or sepsis. The overall mortality rates for untreated tularemia range from 10% to 30%; however, with antibiotic therapy, mortality rates drop to less than 1%.
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Laboratory and X-Ray Findings
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F. tularensis requires special growth media. Notify laboratory personnel of a possible tularemia specimen so that proper plating can be performed. Cultures may be obtained from sputum, pharyngeal, or blood specimens. Specialized ELISA and PCR confirmatory tests are also available at some reference laboratories. In the case of pneumonic tularemia, chest x-ray may demonstrate peribronchial infiltrates, bronchopneumonia, or pleural effusions.
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Treatment and Prophylaxis
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Streptomycin and gentamicin are considered the drugs of choice for the treatment of tularemia (see Table 3–1). Ciprofloxacin has also displayed efficacy against tularemia. Second-line agents such as tetracycline and chloramphenicol may be used, but these agents are associated with higher rates of treatment failure. A 10-day course of antibiotics should be used. For second-line agents, a 14-day course should be used.
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Rarely, patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
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Some data suggest that a 14-day course of antibiotics begun during the incubation period may prevent disease. Antibiotic choices are the same as for treatment. A live attenuated vaccine for tularemia also exists and is often used for at-risk laboratory workers. Vaccination decreases the rate of inhalational tularemia but does not confer complete protection. Given tularemia's short incubation period, and the incomplete protection of the vaccine, postexposure vaccination is not recommended.
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Significant person-to-person transmission of tularemia does not occur. Standard precautions are sufficient during patient care activities (see Table 3–2).
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Brucellae are small aerobic, gram-negative, pleomorphic coccobacilli. Many Brucella spp. occur naturally; however, only four species are infectious to humans. Each species typically infects a particular host organism, and human infection follows contact with contaminated animal material. The Brucella spp. that are infectious to humans are B. melitensis (found in goats), B. suis (found in swine), B. abortus (found in cattle), and B. canis (found in dogs). B. suis has been weaponized in the past.
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The symptoms and signs of brucellosis are similar whether infection is contracted via oral, inhalational, or percutaneous routes. The usual incubation period following infection is 1–3 weeks. Because Brucella spp. infection can involve multiple body systems, a wide range of clinical findings is typical. Nonspecific symptoms are common and include fever, chills, malaise, and myalgias. Osteoarticular involvement may manifest as joint infections or vertebral osteomyelitis. Respiratory symptoms include cough, dyspnea, and pleuritic chest pain. Cardiovascular complications are numerous and include endocarditis, myocarditis, pericarditis, and mycotic aneurysms. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and hepatitis. Multiple types of genitourinary infections can also occur. Neurologic involvement may cause meningitis, encephalitis, cerebral abscesses, cranial nerve abnormalities, or Guillain–Barré syndrome. Patients may also develop anemia, thrombocytopenia, or neutropenia. Central nervous system and cardiac involvement, although infrequent, account for most fatalities. Brucella spp. are not known for their lethality, and infection has an estimated mortality rate of less than 2%. Its interest as a biologic weapon stems from the prolonged disease course and significant morbidity.
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Laboratory and X-Ray Findings
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Brucella spp. will grow on standard culture media. Because of their slow growth, cultures may need to be maintained for at least 6 weeks. Specialized biphasic culture techniques may improve isolation. A more common diagnostic modality is a serum tube agglutination test. ELISA and PCR studies are available at some reference laboratories. If vertebral involvement is suspected, spinal x-rays, magnetic resonance imaging, computed tomography scanning, or bone scintigraphy may be helpful.
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Treatment and Prophylaxis
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Because of the high rate of treatment failure, single-drug therapy is not recommended. A prolonged course of multiple antibiotics is now considered to be the standard of care. The most common regimen involves the use of rifampin and doxycycline given for a 6-week period (see Table 3–1). Other antibiotics that have displayed efficacy against Brucella spp. include gentamicin, streptomycin, trimethoprim–sulfamethoxazole, and ofloxacin. In patients with serious infections, a three-drug parenteral regimen is the norm.
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Rarely, patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
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No human vaccine against Brucella spp. currently exists. Some physicians recommend a 3- to 6-week course of antibiotics following a high-risk exposure such as a biologic attack.
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Person-to-person spread of brucellosis is thought to be uncommon. Standard precautions are sufficient during patient care activities (see Table 3–2).
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Q fever is caused by a rickettsial organism known as Coxiella burnetii. C. burnetii has a worldwide distribution and occurs naturally in many domesticated animals (dogs, cats, sheep, goats, cattle). The organism is shed in feces, urine, milk, and placental material. Much like anthrax, C. burnetii produces a sporelike form. Humans become infected by inhaling contaminated aerosols.
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After infection, a typical incubation period ranges from 5 to 30 days. The symptoms and signs of Q fever are nonspecific and may occur acutely or have an indolent course. Typical symptoms and signs include fever, chills, malaise, myalgias, headache, and anorexia. If cough occurs, it tends to occur late in the disease process and may or may not be associated with pneumonia. Various cardiac manifestations may occur and include endocarditis, myocarditis, and pericarditis. Gastrointestinal findings are common and include nausea, vomiting, diarrhea, and hepatitis. A nonspecific maculopapular rash may develop. Although not as common, various neurologic symptoms may also occur.
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In some patients, Q fever may become a chronic condition. Chronic Q fever is typically manifested as endocarditis and tends to affect previously diseased cardiac valves. Although Q fever can be debilitating, it is usually not fatal. Mortality rates are generally less than 2.5%.
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Laboratory and X-Ray Findings
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C. burnetii is difficult to grow in culture and sputum analysis is equally futile. Several serologic tests are available and include indirect fluorescent antibody staining, ELISA, and complement fixation. These tests often must be conducted at specialized reference laboratories. Elevated liver enzymes are also common in C. burnetii infection.
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Treatment and Prophylaxis
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Most cases of C. burnetii infection will resolve without antibiotic therapy. Regardless, antibiotics are recommended because treatment will lower the rate of complications. A 7-day course of either doxycycline or tetracycline is usually sufficient (see Table 3–1). Fluoroquinolones are an acceptable alternative.
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Rarely, patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
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Prophylactic antibiotics should be started 8–12 days after initial exposure. Antibiotics are ineffective if started sooner. A 7-day course of either doxycycline or tetracycline is usually sufficient. Fluoroquinolones are an acceptable alternative. An investigational vaccine exists but is not yet available to the general public.
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Person-to-person spread of the disease is unlikely. Standard precautions are sufficient while engaging in patient care activities (see Table 3–2).
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Smallpox is a disease caused by the variola virus, which is a DNA virus of the genus Orthopoxvirus. It occurs in two strains: the more severe variola major and a milder form, variola minor. Smallpox was essentially eradicated worldwide by an aggressive treatment and vaccination campaign conducted by the World Health Organization. The last naturally occurring case was in Somalia in 1977. Two stockpiles of the virus remain, one in the Centers for Disease Control and Prevention in Atlanta and the other in the Institute of Virus Preparations in Moscow.
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Disease begins with inhalation of the variola virus. After an initial exposure, a 7- to 17-day incubation period begins, during which the virus replicates in the lymph nodes, bone marrow, and spleen. A secondary viremia then develops leading to high fever, malaise, headache, backache, and in some cases delirium. After approximately 2 days, a characteristic rash will develop. The rash begins on the extremities and moves to the trunk. The palms and soles are not spared. The rash follows a typical progression beginning as macules, then papules, and eventually becoming pustular. Eventually, lesions will form scabs that separate, leaving small scars. The rash appears similar to chickenpox, except that all the lesions in smallpox will be in similar stages of development. In unvaccinated individuals, mortality rates associated with variola major are approximately 30%. Variola minor has a similar progression to variola major, but toxicity and rash are not as severe. In unvaccinated individuals, the mortality rates associated with variola minor are approximately 1%. In 10% of cases, a variant form of rash will develop. A hemorrhagic rash displaying petechiae and frank skin hemorrhage may occur. This variant of smallpox carries a mortality rate of nearly 100%. Likewise, a malignant form exists in which the pustules remain soft and velvety to the touch.
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Laboratory and X-Ray Findings
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Analysis of pustular fluid will yield virus particles. All samples should be sealed in two airtight containers. Variola can easily be recognized via electron microscopy. The virus itself can be grown in cell cultures or on chorioallantoic egg membranes. Further characterization of strains can be accomplished via biologic assays. PCR analysis is available at some reference laboratories.
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Treatment and Prophylaxis
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Currently there is no specific therapy for smallpox other than supportive care. Many investigational drugs are currently under study. Strict patient isolation, preferably at home, should be used. Any person having close contact with infected patients should be either quarantined or monitored for signs of infection. Antibiotics may be used if secondary bacterial infection occurs.
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Smallpox vaccination is very effective at preventing the disease and gives immunity for 5–10 years. Universal smallpox immunization of the general population was discontinued over 30 years ago when smallpox was eradicated. Because of the risk of possible terrorist attack, there has recently been a preemptive initiation of smallpox vaccination for selected health care workers. However, the smallpox vaccine has several rare complications. Postvaccinal encephalitis occurs in approximately 1 in 300,000 vaccinations and is fatal in 25% of patients. Immunocompromised patients who are vaccinated may develop a condition known as progressive vaccinia, which is often fatal. In this condition, the initial inoculation site failed to heal, became necrotic, and necrosis spread to adjacent tissues. In some patients with eczema, a postvaccination condition known as eczema vaccinatum may occur. Here, vaccinial lesions occur in areas previously involved with eczema. Fortunately, the eruptions are usually self-limited. In some patients, a secondary generalized vaccinia could develop. In others, inadvertent autoinoculation of eyes, mouth, or other areas may occur. Many of these complications are treated with vaccinia immune globulin. Data indicate that vaccination within 4 days of smallpox exposure may lessen subsequent illness. Cidofovir has also displayed some efficacy in preventing smallpox infection if given within 48 hours. However, cidofovir is not more effective than the vaccine and is associated with significant renal toxicity.
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Smallpox is highly infectious. Infection is spread by aerosol droplets. It is generally thought that each index case will subsequently infect 10–20 secondary individuals. The period of infectivity begins with the onset of rash and ends when all scabs separate. Use airborne precautions during patient care activities (see Table 3–2). Any material in contact with patients should be either autoclaved or washed in a bleach solution.
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Viral hemorrhagic fever represents a clinical syndrome caused by several RNA viruses. These viruses exist in four different families: the Arenaviridae, the Filoviridae, the Flaviviridae, and the Bunyaviridae. Numerous viruses in each family may cause slightly different forms of hemorrhagic fever. The different forms of hemorrhagic fever are often named by their geographic origin (Table 3–3). Human infection occurs after contact with infected animals or infected arthropod vectors. Many of these viruses are also highly infectious in the aerosol form. This characteristic makes these viruses potential biologic weapons.
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Several clinical aspects of hemorrhagic fever are unique to the individual forms (Table 3–3). Many symptoms and signs, however, are common to all types of hemorrhagic fever. Alterations in the vascular bed and increased vascular permeability lead to the dominant features of this disease. Early symptoms and signs include fever, conjunctival injection, mild hypotension, prostration, facial flushing, vomiting, diarrhea, and petechial hemorrhages. Eventually some patients may develop shock and mucous membrane hemorrhage. In some instances, evidence of hepatic, pulmonary, and neurologic involvement will be present. Secondary bacterial infection is also common.
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Laboratory and X-Ray Findings
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A number of nonspecific laboratory abnormalities may be seen, including leukopenia, thrombocytopenia, proteinuria, hematuria, and elevated liver enzymes. Definitive diagnosis is possible with various rapid enzyme immunoassays and with viral culture.
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Treatment and Prophylaxis
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Ribavirin is a nucleoside analog that has been shown to improve mortality in some forms of hemorrhagic fever. Dosing is as follows: 30 mg/kg IV as an initial dose, followed by 16 mg/kg IV every 6 hours for 4 days, and then 8 mg/kg IV every 8 hours for 6 days. Ribavirin is usually most effective if begun within 7 days. Unfortunately, ribavirin is thought to be ineffective against the filoviruses and the flaviviruses. Convalescent plasma containing neutralizing antibodies is also effective in some cases.
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Intravenous lines and other invasive procedures should be limited. Use fluid resuscitation with caution. Because of increases in vascular permeability, peripheral edema and pulmonary edema are frequent complications of volume replacement. If frank disseminated intravascular coagulopathy develops, consider heparin therapy.
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A vaccine against yellow fever is currently available. Many other investigational vaccines exist but are not currently available to the general public. Protocols also exist for the use of ribavirin in high-risk exposures.
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The causal agents of hemorrhagic fever are highly infectious. Use caution when using sharps or when coming into contact with the body fluids of the patients. Some forms are spread via aerosol, and patients with significant cough should be placed under airborne precautions. All laboratory specimens should be double sealed in airtight containers.
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Much like viral hemorrhagic fever, viral encephalitis represents a clinical syndrome caused by numerous viruses. Of the pathogens that cause viral encephalitis, members of the family Togaviridae are thought to have the potential as biologic weapons. The family Togaviridae includes the eastern equine encephalitis (EEE) virus, western equine encephalitis (WEE) virus, and Venezuelan equine encephalitis (VEE) virus. VEE virus has been weaponized in the past. In nature, these viruses are spread by infected arthropod vectors and they infect humans as well as equines. They are also infectious in aerosol form, hence their utility as biologic weapons.
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Nearly all forms of infection will cause nonspecific symptoms and signs of fever, chills, malaise, myalgias, sore throat, vomiting, and headache. A large number of associated equine deaths may lead one to suspect equine encephalitis. The degree to which encephalitis develops depends on the pathogen involved. Although nearly all cases of VEE are symptomatic, encephalitis occurs in less than 5% of cases. If encephalitis does develop, and the patient recovers, residual neurologic sequelae usually do not occur. Without encephalitis, VEE has an expected mortality rate of less than 1%. Although uncommon, if encephalitis develops, the mortality rate increases to approximately 20%. In contrast, EEE tends to progress to neurologic involvement. Encephalitis is usually severe and residual neurologic findings are common. With EEE, mortality rates range from 50% to 75%. WEE displays an intermediate degree of severity, with an overall estimated mortality rate of approximately 10%. If encephalitis develops, confusion, obtundation, seizures, ataxia, cranial nerve palsies, and coma may occur.
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Laboratory and X-Ray Findings
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Although nonspecific, leukopenia and lymphopenia are common. In cases of encephalitis, cerebral spinal fluid analysis will display a lymphocytic pleocytosis. A number of serologic studies such as ELISA, complement fixation, and hemagglutination inhibition may aid diagnosis. Although time consuming, the gold standard test for VEE involves viral isolation following inoculation of cell cultures of suckling mice. Additional specialized tests may be available only at regional reference laboratories.
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Treatment and Prophylaxis
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Unfortunately, no specific treatment for equine encephalitis exists. Supportive care is all that can be offered. Headache may be treated with typical analgesics. Seizures are treated with typical anticonvulsant medications.
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Patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
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An investigational vaccine against VEE virus exists. It does not provide protection against all strains of VEE virus, and some patients will not display an effective antibody response. In 20% of the patients receiving the vaccine, fever, malaise, and myalgias may develop.
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Infection is not spread by person-to-person contact. Standard precautions are sufficient during patient care activities. To limit the spread of disease, patient exposure to arthropod vectors should be prevented.
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Botulism is caused by a protein toxin produced by Clostridium botulinum. C. botulinum is a gram-positive, spore-forming, obligate anaerobe found naturally in the soil. Many authorities consider botulinum toxin to be among the most potent naturally occurring poisons. The toxin occurs in seven antigenic types, designated types A–G. Once absorbed, toxin will bind to motor neurons and prevent the release of acetylcholine, causing a flaccid muscle paralysis. Natural infection occurs in three forms: wound botulism, foodborne botulism, and intestinal botulism. Wound botulism occurs after C. botulinum contaminates an open wound, subsequently producing toxin. Foodborne botulism occurs after ingesting food already contaminated by the toxin. Intestinal botulism, typically seen in infants, occurs after ingesting food contaminated by C. botulinum, which in turn produces toxin. Although not occurring naturally, botulism can also be caused by inhalation of the toxin. This is the form of botulism that will likely occur following biologic attack. Contamination of food or water supplies also represents a possible terrorist threat. Food contamination, however, is unlikely to induce the large numbers of affected persons that would be seen following aerosol exposure. Water contamination would be difficult because current purification techniques are effective in neutralizing botulinum toxin.
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After initial exposure, an incubation period ranging from 12 to 80 hours will occur. The duration of the incubation period depends on the type and amount of exposure. After the incubation period, a flaccid symmetric muscle paralysis will affect the bulbar musculature. Patients often display ptosis, diplopia, dysphagia, dysarthria, and dysphonia. Dilated, poorly reactive pupils are common. Eventually the paralysis will extend to the lower muscle groups, leading to paralysis. Airway compromise is common and patients may lose respiratory function.
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If foodborne exposure is involved, gastrointestinal symptoms such as nausea, vomiting, and diarrhea may occur. Botulism does not cause altered sensorium, sensory changes, or fever.
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Laboratory and X-Ray Findings
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A mouse bioassay is the definitive test for botulism. Specimens for evaluation may be obtained from suspected food, blood, gastric contents, or possibly stool. This type of diagnostic testing is not widely available, and specimens may need to be sent to specialized laboratories. In addition to laboratory studies, electromyograms may display patterns consistent with botulism.
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Treatment and Prophylaxis
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A botulinum antitoxin can be obtained from many state health departments or from the Centers for Disease Control and Prevention. Antitoxin therapy is most effective when given early in the disease course. It acts by binding free toxin but will not restore nerve terminals that have already been compromised. The civilian antitoxin is effective in neutralizing the three most common types of botulinum toxin found to affect humans (types A, B, and E). If other forms of toxin are utilized, an investigational heptavalent antitoxin may be available from the military. The military antitoxin is effective against all types of toxin (types A–G). Because some patients may develop allergic reactions to the antitoxin, a test dose is recommended.
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Patients may require intensive medical support such as airway management and ventilator support. Parenteral or tube feedings may be required. Treat secondary bacterial infections with antibiotics. Avoid clindamycin and aminoglycoside antibiotics because they may worsen neurologic blockade.
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Some evidence suggests that initiation of antitoxin prior to the onset of symptoms may prevent disease. Unfortunately, large amounts of the antitoxin are not available. A more prudent course of action would be to institute antitoxin therapy at the first signs of illness.
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Person-to-person transmission of botulism does not occur. Standard precautions are sufficient during patient care activities (see Table 3–2). If food is suspected of being contaminated, thorough cooking will neutralize the toxin.
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Ricin is a polypeptide toxin that causes cell death by inhibiting protein synthesis. It occurs naturally as a component of the castor bean from the castor plant, Ricinus communis. Accidental ricin toxicity has occurred following ingestion of castor beans. Although ricin is less toxic than many other potential biologic agents, it is inexpensive, easy to produce, and can be aerosolized. These characteristics make it a potential biologic weapon. Ricin may be delivered by parenteral injection, ingestion, or inhalation. Ingestion and inhalation are the likely modes of biologic attack.
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The signs and symptoms of ricin intoxication depend on the type and amount of exposure. Parenteral exposure causes necrosis of local tissues and regional lymph nodes. As the toxin spreads, visceral organs become involved, manifested as a moderate to severe gastroenteritis. Parenteral exposure is an unlikely means of biologic attack. If ricin is ingested, symptoms of gastrointestinal exposure will occur and may include nausea, vomiting, hematemesis, bloody diarrhea, melena, or visceral organ necrosis. If death occurs following parenteral or gastrointestinal exposure, it is usually secondary to circulatory collapse.
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The most likely means of biologic attack involve aerosol exposure. Inhalation of ricin is manifested by direct pulmonary toxicity. Between 4 and 8 hours after exposure, the patient may develop fever, cough, chest pain, and dyspnea. Findings consistent with an aerosol exposure include bronchitis, bronchiolitis, interstitial pneumonia, and acute respiratory distress syndrome. If death occurs, it is usually secondary to respiratory failure and generally will occur within 36–72 hours.
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Laboratory and X-Ray Findings
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Various laboratory tests, including ELISA, PCR, and immunohistochemical staining, may aid in the diagnosis of ricin toxicity. In the event of pulmonary involvement, chest x-ray may display bilateral infiltrates or noncardiogenic pulmonary edema.
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Treatment and Prophylaxis
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The treatment of ricin toxicity depends largely on the mode of exposure.
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With parenteral exposure, treatment is largely supportive.
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Gastrointestinal Exposure
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The treatment of gastrointestinal exposure primarily involves the elimination of toxin. This can be accomplished by vigorous gastric lavage and by the use of cathartics such as magnesium citrate or whole bowel irrigation. Activated charcoal may be considered. Correct electrolyte abnormalities and maintain adequate volume status. Treat secondary bacterial infections with appropriate antibiotics.
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With pulmonary exposure, treatment involves providing adequate ventilatory support. Patients may require oxygen, intubation, and ventilator management. Treat secondary bacterial infections with appropriate antibiotics.
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Ricin vaccines are under development.
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Ricin intoxication is not spread by person-to-person contact. Standard precautions are sufficient during patient care activities (see Table 3–2).
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Like penicillin, mycotoxins are a diverse group of compounds produced by fungi for environmental protection. These compounds are frequently toxic to many animal species including humans. The T-2 mycotoxins are a particular group of compounds produced by fungi of the genus Fusarium. Although the actions of the T-2 mycotoxins are not completely understood, they are known to inhibit DNA and protein synthesis. They are most toxic to rapidly dividing cell lines.
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Many properties of these compounds make them attractive as biologic weapons. Specifically, they are resistant to destruction by ultraviolet radiation and are heat stabile. T-2 mycotoxins confer toxicity after ingestion, inhalation, or dermal exposure. Unlike most other biologic agents, they can be absorbed directly through the skin.
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With T-2 mycotoxin exposure, contamination via dermal, gastrointestinal, and pulmonary routes may occur simultaneously. The earliest symptoms and signs may begin within minutes to hours. Dermal exposure may manifest as skin pain, erythema, blistering, and skin necrosis. Toxin exposure to the eyes and upper airway may cause ocular pain, redness, tearing, sneezing, rhinorrhea, oral pain, blood-tinged mucus, and epistaxis. Patients with pulmonary involvement will display chest pain, cough, and dyspnea. Signs and symptoms of gastrointestinal toxicity include abdominal pain, nausea, vomiting, and a bloody diarrhea. With systemic toxicity, patients may develop weakness, dizziness, and ataxia. Similar to radiation exposure, these toxins may also cause bone marrow suppression resulting in thrombocytopenia and neutropenia.
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Laboratory and X-Ray Findings
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Two primary forms of laboratory testing may be used to identify T-2 mycotoxins. First, antigen detection can be performed on urine samples. The metabolites of the T-2 mycotoxins are eliminated primarily in the urine and feces. These metabolites are detectable in the urine up to 1 month after exposure. Second, mass spectrometric evaluation can be conducted on various body fluids. Appropriate samples include nasal secretions, pulmonary secretions, urine, blood, and stomach contents.
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Treatment and Prophylaxis
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The treatment of T-2 mycotoxin poisoning is essentially supportive care. Remove all contaminated clothing and wash the patient's skin with large amounts of soap and water. Treat dermal burns with standard therapy. Treat secondary bacterial infections with appropriate antibiotics. Ocular involvement requires irrigation with water or sterile saline. Activated charcoal may aid in gastrointestinal decontamination. Patients with pulmonary involvement may require advanced respiratory techniques such as intubation or ventilatory support.
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Vaccines against the T-2 mycotoxins are under study. The early use of soap and water may prevent skin toxicity.
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The T-2 mycotoxins are dispersed as an oily liquid. Contact with this liquid may cause cross-contamination. Therefore, remove all contaminated clothing and wash the patient's skin with soap and water. Standard precautions are sufficient during patient care activities (see Table 3–2).
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Staphylococcal Enterotoxin B
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Staphylococcal aureus produces a number of exotoxins that produce disease in humans. One such exotoxin, staphylococcal enterotoxin B (SEB), is a causal agent of the gastrointestinal symptoms seen in staphylococcal food poisoning. It is a heat-stabile toxin that belongs to a group of compounds known as super antigens. These compounds have the ability to activate certain cells in the immune system, causing a severe inflammatory response. This response causes injury to various host tissues. Aside from injury caused by SEB in natural infections, it can be aerosolized, making it a potential biologic weapon. Biologic attack could involve deliberate contamination of foodstuffs, although a more likely scenario would involve an aerosol release.
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After exposure to SEB, a variable incubation period occurs, ranging from 4 to 10 hours for gastrointestinal exposure and from 3 to 12 hours for inhalational exposure. Regardless of the type of exposure, nonspecific symptoms and signs will develop and include fever, chills, headache, malaise, and myalgias. If the exposure occurred via the gastrointestinal route, then patients will also develop nausea, vomiting, and diarrhea. Conversely, if the exposure occurred via an inhalational route, the patient will also develop chest pain, cough, and dyspnea. Death is rare but in severe cases may occur from respiratory failure. Patients generally recover from symptoms after 1–2 weeks.
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Laboratory and X-Ray Findings
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The presence of SEB can be confirmed by identifying specific antigens via ELISA testing. Obtain serum and urine samples. Urine samples are more productive because toxin tends to accumulate in the urine. In the case of aerosol exposure, respiratory and nasal swabs may also demonstrate toxin if samples are obtained within 1 day of exposure. With inhalational exposure, the chest x-ray is usually normal but in severe cases may demonstrate pulmonary edema.
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Treatment and Prophylaxis
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The treatment of SEB exposure is largely supportive. Correct electrolyte abnormalities and maintain volume status. If pulmonary edema develops, patients may benefit from diuretic therapy and in some cases may require intubation and ventilatory support. Steroids may be given to lessen the inflammatory response, but this approach is controversial. Treat secondary bacterial infections with appropriate antibiotics.
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Vaccines against SEB are under study.
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Person-to-person transmission of toxin is not a hazard. Standard precautions are sufficient during patient care activities (see Table 3–2).
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