INTRODUCTION
In the past, injuries resulting from nuclear, biologic, and chemical attack were largely dealt with only in the military sector. Society as a whole, and specifically the civilian medical community, felt it unlikely that such weapons would be used against civilian populations. Recent changes in the global political environment have forced changes in this thinking. Many smaller nations, some of which are judged unstable, are attempting to develop weapons of mass destruction. Likewise, many terrorist organizations are now actively attempting to purchase or develop such weapons. In addition to the risk of an overt attack, other sources of exposure could come from accidents involving many nuclear, biologic, and chemical agents stored in facilities throughout the United States. An accident at any of these facilities could result in a large number of civilian casualties. As with most mass casualty situations, emergency physicians will be at the forefront of patient care. This chapter attempts to provide specific information regarding the management of nuclear, biologic, and chemical weapons injuries.
NUCLEAR WEAPONS
Several incidents in recent history, both military and civilian, have resulted in radiation injuries. The most notable, and in fact the only war-time use, involved the detonation of nuclear weapons over Hiroshima and Nagasaki, Japan. Unfortunately, many terrorist organizations have attempted to obtain nuclear weapons. A terrorist attack would most likely involve the detonation of a nuclear bomb or the detonation of a conventional explosive that also dispersed radioactive material (so-called dirty bomb).
General Considerations
Radiation-induced injury occurs when various types of ionizing radiation interact with body tissues. Radiation exposure may be external or internal. Internal contamination can occur via wound contamination or via inhalation or ingestion of contaminated particles. Four types of radioactive particles may cause damage:
1. Alpha particles—Alpha particles are large particles that are stopped by the epidermis. They cause no significant external damage. Internal contamination may cause local tissue injury.
2. Beta particles—Beta particles are small particles that can penetrate the superficial skin and cause mild burnlike injuries.
3. Gamma rays—Gamma rays are high-energy particles that can enter tissues easily and cause significant damage to multiple body systems.
4. Neutrons—Neutrons are large particles that are typically produced only during nuclear detonation. Like gamma rays, they cause significant tissue injury.
The effect that radiation will have on the body depends on the type of radiation, the amount of exposure, and the body system involved. Tissues that display higher rates of cellular mitosis, such as the gastrointestinal and hematopoietic systems, are more severely affected. At very high radiation doses, neurovascular effects will also be seen. Radiation injury may cause either abnormal cell function or cell death.
Clinical Findings
A. Symptoms and Signs
The symptoms and signs of radiation exposure occur in 3 phases: prodromal, latent, and symptomatic.
1. Prodromal phase—Patients will develop nonspecific symptoms of nausea, vomiting, weakness, and fatigue. Symptoms generally last no longer than 24-48 hours. With higher radiation exposures, symptoms will occur more rapidly and last longer.
2. Latent period—The length of the latent period depends on the dose of radiation and the body system involved (neurologic, several hours; gastrointestinal, 1-7 days; hematopoietic, 2-6 weeks).
3. Symptomatic phase—Symptoms will depend largely on the body system affected, which will depend on the radiation dose. At doses of 0.7-4 gray (Gy),1 the hematopoietic system will begin to manifest signs and symptoms of bone marrow suppression. Because of their long life span, erythrocytes are less severely affected than are the myeloid and platelet cell lines. Neutropenia and thrombocytopenia may be significant and lead to infectious and hemorrhagic complications. At doses of 6-8 Gy, gastrointestinal symptoms develop. Nausea, vomiting, diarrhea (bloody), and severe fluid and electrolyte imbalances will occur. The neurovascular system becomes affected at doses of 20-40 Gy. Symptoms include headache, mental status changes, hypotension, focal neurologic changes, convulsions, and coma. Exposures in this range are uniformly fatal. If an explosive device was used to disperse radioactive material, patients may also have thermal and blast injuries.
1The gray, a unit of measure for the dose of ionizing radiation, is equal to 1 J/kg of tissue. One gray is equal to 100 rad.
B. Laboratory and X-ray Findings
Obtain a complete blood count (CBC) with differential for all patients sustaining a radiation injury. Although symptomatic bone marrow suppression may not be evident for some weeks, a drop of the absolute lymphocyte count of 50% at 24-48 hours is indicative of significant exposure. Monitor electrolytes in patients with gastrointestinal symptoms.
Treatment
In the absence of aggressive medical therapy, the LD50 (the dose of radiation that will kill 50% of those exposed) is approximately 3.5 Gy. Aggressive medical care affords improved survival. Treat all life-threatening injuries associated with blast or thermal effects according to standard advanced trauma life support protocols. Perform surgical procedures early to avoid the electrolyte and hematopoietic effects that will occur. Clean wounds extensively and close them as soon as possible to prevent infection. Treat nausea and vomiting with standard antiemetic medications (prochlorperazine, promethazine, ondansetron). Treat fluid and electrolyte abnormalities with appropriate replacement. Anemia and thrombocytopenia can be treated with transfusion therapy. Leukopenia may be treated with hematopoietic growth factors such as sargramostim and filgrastim. In some instances bone marrow transplantation may be utilized. Follow neutropenic precautions at absolute neutrophil counts below 500. Some authors recommend prophylactic antibiotics at counts below 100. Use broad-spectrum antibiotics to treat infections. Infection is the most common cause of death in radiation patients. Despite aggressive medical care, radiation exposures above 10 Gy are usually fatal.
Decontamination
Remove all contaminated clothing. Change contaminated dressings and splints. Thoroughly clean the patient's skin with soap and water or a 0.5% hypochlorite solution. Hair should be washed and in some instances removed. Eyes may be washed with large amounts of water or sterile saline. All contaminated materials should be bagged if possible and sent for proper disposal.
Disposition
Patients who have been decontaminated and have only mild transient symptoms can be safely discharged. Because of the variable and lengthy latent period involved with this disorder, early admission is not indicated. Patients should be closely monitored and admitted when warranted.
Goans RE et al: Early dose assessment in criticality accidents. Health Phys 2001;81(4):446. [PMID: 11569639] (Describes techniques for estimating the severity of radiation exposure.)
Military Medical Operations Office, Armed Forces Radiobiology Research Institute: Medical Management of Radiological Casualties, 1st ed. Military Medical Operations Office, Armed Forces Radiobiology Research Institute, 1999. (Produced by the U.S. Army, this text provides general information regarding all aspects of radiologic injuries.)
BIOLOGIC WEAPONS
Many agents can be used as biologic weapons. The most likely pathogens are presented here. Biologic agents can be classified as bacterial agents (anthrax, plague, tularemia, brucellosis, Q fever, glanders), viral agents (smallpox, hemorrhagic fever, encephalitis), and biologic toxins (botulinum, ricin, T-2 mycotoxins, staphylococcal enterotoxin B). A high index of suspicion will be required in order to identify patients who have experienced a biologic attack. A large number of patients with severe febrile illnesses will be the most likely clue. Keep in mind the attack most likely occurred several days prior to patient presentation. Aerosol release of infectious material is the most common form of biologic attack.
BACTERIAL AGENTS
1. Anthrax
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. The spore form of anthrax causes infection. Clinically the disease occurs in 3 forms: inhalational anthrax, gastrointestinal anthrax, and cutaneous anthrax.
Clinical Findings
A. Symptoms and Signs
1. Inhalational anthrax—Inhalation anthrax is the form of disease most likely expected after a terrorist attack. After spores are inhaled, a variable incubation period occurs, usually lasting 1-7 days. Prolonged 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.
2. Gastrointestinal anthrax—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, diarrhea (bloody), and the development of an acute abdomen with sepsis. Mortality rates for gastrointestinal anthrax are in excess of 50%.
3. Cutaneous anthrax—Cutaneous anthrax is the most common naturally occurring form of the disease. Cutaneous anthrax 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.
4. Anthrax meningitis—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%.
B. Laboratory and X-ray Findings
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. Notify laboratory personnel of a possible anthrax exposure. Often Bacillus spp. are thought to be the contaminant and are not pursued further. Confirmatory enzyme-linked immunoassay (ELISA) and polymerase chain reaction (PCR) tests are available at some national reference laboratories. Chest X-ray may also be useful. Patients with inhalational anthrax will display a wide mediastinum on chest x-ray. No infiltrate is typically observed.
Treatment & Prophylaxis
Because anthrax has a rapid and fulminant course, do not delay treatment while awaiting confirmatory tests. Institute empiric therapy when the diagnosis is considered. Delaying treatment for even hours may significantly increase mortality.
A. Antibiotics
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.
B. Supportive Care
Patients may require intensive medical support such as airway management, hemodynamic support, and various measures to manage multisystem organ failure.
C. Prophylaxis
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.
Infection Control
No data indicate that anthrax is spread via person-to-person contact. Use standard precautions during patient care activities (Table 3-2).
2. Plague
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 3 clinical forms: bubonic plague, septicemic plague, and pneumonic plague.
Clinical Findings
A. Symptoms and Signs
1. Bubonic plague—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. Bubo size 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%.
2. Septicemic plague—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%.
3. Pneumonic plague—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.
B. Laboratory and X-ray Findings
Y pestis can be identified by several different staining techniques. Routine Gram stain may reveal the organism. Y pestis also has a characteristic bipolar staining pattern with Wright, Giemsa, and Wayson stains. Routine 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.
Treatment & Prophylaxis
Plague has a rapid disease progression, and any delay in treatment will cause significant increases in mortality. Institute treatment on empiric grounds, and do not delay treatment while awaiting confirmatory tests.
A. Antibiotics
Streptomycin is the drug of choice for the treatment of plague. Gentamicin may also be used and is thought to have equal efficacy (see Table 3-1). Alternative antibiotics include doxycycline, ciprofloxacin, and chloramphenicol.
B. Supportive Care
Patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
C. Prophylaxis
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. Antibiotic choices are the same as for treatment.
Infection Control
Pneumonic plague can be spread from person to person by aerosol droplets. Use droplet precautions, and either the patient or 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.
3. Tularemia
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 palaearctica is 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.
Clinical Findings
A. Symptoms and Signs
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.
1. Ulceroglandular tularemia—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.
2. Glandular tularemia—Glandular tularemia displays signs and symptoms similar to ulceroglandular tularemia, except that no ulcer formation is noted.
3. Oculoglandular tularemia—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.
4. Oropharyngeal tularemia—After inoculation of the pharynx, an exudative pharyngotonsillitis will develop with cervical lymphadenopathy.
5. Pneumonic tularemia—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.
6. Typhoidal tularemia—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.
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%.
B. Laboratory and X-ray Findings
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 to bronchopneumonia. Pleural effusions are often present.
Treatment & Prophylaxis
A. Antibiotics
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.
B. Supportive Care
Rarely patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
C. Prophylaxis
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.
Infection Control
Significant person-to-person transmission of tularemia does not occur. Standard precautions are sufficient during patient care activities (see Table 3-2).
4. Brucellosis
Brucellae are small aerobic, gram-negative, pleomorphic coccobacilli. Many Brucella spp. occur naturally; however, only 4 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.
Clinical Findings
A. Symptoms and Signs
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-Barre syndrome. Patients may also develop anemia, thrombocytopenia, or neutropenia. Central nervous system and cardiac involvement, although infrequent, accounts 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 biological weapon stems from the prolonged disease course and significant morbidity.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Antibiotics
Because of the high rate of treatment failure, single drug therapy is no longer 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. Regardless of the antibiotics chosen, combination drug therapy should be used. In patients with serious infections, a 3-drug parenteral regimen is the norm.
B. Supportive Care
Rarely patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
C. Prophylaxis
No human vaccine against Brucella spp. currently exists. Some authors recommend a 3- to 6-week course of antibiotics following a high-risk exposure such as a biologic attack.
Infection Control
Person-to-person spread of brucellosis is thought to be uncommon. Standard precautions are sufficient during patient care activities (see Table 3-2).
5. Q Fever
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.
Clinical Findings
A. Symptoms and Signs
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.
In some patients, Q fever may become a chronic condition. Chronic Q fever is typically manifest 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%.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Antibiotics
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.
B. Supportive Care
Rarely patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
C. Prophylaxis
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.
Infection Control
Person-to-person spread of the disease is unlikely. Standard precautions are sufficient while engaging in patient care activities (see Table 3-2).
6. Glanders & Melioidosis
Glanders and melioidosis are similar diseases caused by related bacteria. The causal agent of glanders is Burkholderia mallei; the causal agent of melioidosis is Burkholderia pseudomallei. Both organisms are gram-negative bacilli. Glanders and melioidosis occur naturally. Glanders is a rare disease in humans; horses and other domesticated animals are often infected. Melioidosis occurs more commonly in humans and is endemic to Southeast Asia. Infection with either organism occurs via contact with open wounds or mucous membranes or by inhalation.
Clinical Findings
A. Symptoms and Signs
Both glanders and melioidosis can cause multiple clinical syndromes.
1. Localized disease—A localized disease may be seen and typically occurs after wound contamination or mucous membrane exposure. With wound contamination, patients develop a small ulcer with associated cellulitis. Regional lymphadenopathy or lymphangitis is also common. If mucous membrane exposure occurs, patients develop a bloody purulent discharge from the infected area (eyes, nose, or mouth). If secondary systemic infection occurs, a pustular rash similar to smallpox may develop.
2. Pulmonary disease—A pulmonary form of disease may also be seen. Pulmonary disease may occur after inhalation of aerosols or after hematogenous spread. An incubation period of 1-2 weeks occurs initially. Symptoms of pulmonary disease, including fever, chills, cough, chest pain, and dyspnea, develop eventually.
3. Septicemic disease—The most severe form of infection is the septicemic form. Patients present with nonspecific symptoms and signs of fever, chills, malaise, myalgias, photophobia, rigors, diffuse body abscesses, pustular rash, and headache. This condition is usually fatal; death occurs in 7-10 days.
B. Laboratory and X-ray Findings
Both organisms can be identified by routine Gram stain and culture. Special staining with methylene blue or Wright stain may facilitate diagnosis. Growth may be enhanced by the addition of meat nutrient agar or glucose to the growth media. Specialized agglutination and complement fixation tests may also be used. If pulmonary involvement is suspected, chest x-ray may demonstrate lung abscesses, miliary nodules, or pneumonia.
Treatment & Prophylaxis
A. Antibiotics
Both glanders and melioidosis respond to various antibiotics. Appropriate antibiotic choices include amoxicillin-clavulanate, tetracycline, trimethoprim-sulfamethoxazole, rifampin, ciprofloxacin, and ceftazidime (see Table 3-1). Various combinations of antibiotics have been recommended depending on the type and severity of infection.
B. Supportive Care
Rarely patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
C. Prophylaxis
According to some authorities, a course of trimethoprim-sulfamethoxazole may prevent the onset of disease.
Infection Control
Person-to-person spread of the disease is uncommon but can occur with improper handling of body fluids. Standard precautions are sufficient during patient care activities (see Table 3-2).
VIRAL AGENTS
1. Smallpox
Smallpox is a disease caused by the variola virus. The variola virus is a DNA virus of the genus orthopoxvirus. It occurs in 2 strains: the more severe variola major and a milder form, variola minor. Smallpox was essentially eradicated 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. Concern now exists that the Russian stockpile may have been compromised.
Clinical Findings
A. Symptoms and Signs
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. Unlike chickenpox, 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.
B. Laboratory and X-ray Findings
Analysis of pustular fluid will yield virus particles. All samples should be sealed in 2 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.
Treatment & Prophylaxis
A. Specific Therapy
Currently there is no specific therapy for smallpox. Treatment is essentially supportive care. Many investigational drugs are currently under study. Strict patient isolation, preferably in the 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.
B. Prophylaxis
Data indicate that vaccination within 4 days of smallpox exposure may lessen subsequent illness. Because of the risk of possible terrorist attack, some authorities are recommending a preemptive initiation of smallpox vaccination. This would be problematic for several reasons. First, the current supply of smallpox vaccine is inadequate to protect a large populace. Second, many complications were known to occur with smallpox vaccination. Postvaccinial encephalitis occurred in approximately 1 in 300,000 vaccinations and was fatal in 25% of patients. Immunocompromised patients may develop a condition known as progressive vaccinia. In this condition, the initial inoculation site failed to heal, became necrotic, and necrosis spread to adjacent tissues. This complication was often fatal. In some patients with eczema, a condition known as eczema vaccinatum could occur. Here, vaccinial lesions would occur in areas previously involved with eczema. Fortunately, the eruption was usually self-limited. In some patients, a secondary generalized vaccinia could develop. In others, inadvertent autoinoculation of eyes, mouth, or other areas occurred. Many of these complications could be treated with vaccinia immune globulin. Unfortunately, vaccinia immune globulin is also in short supply.
Cidofovir has also displayed some efficacy in preventing smallpox infection if given within 48 hours. There is no evidence to suggest that cidofovir is more effective than vaccine. Further, cidofovir is associated with significant renal toxicity.
Individuals vaccinated prior to 1972 are likely no longer protected, given that immunity lapses over a 5- to 10-year period.
Infection Control
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.
2. Hemorrhagic Fever
Viral hemorrhagic fever represents a clinical syndrome caused by several RNA viruses. These viruses exist in 4 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 them potential biological weapons.
Clinical Findings
A. Symptoms and Signs
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.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Specific Therapy
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 intravenously as an initial dose, followed by 16 mg/kg intravenously every 6 hours for 4 days and then 8 mg/kg intravenously 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.
B. Supportive Care
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.
C. Prophylaxis
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.
Infection Control
The causal agents of hemorrhagic fever are highly infectious. Use caution when using sharps or when coming into contact with body fluids. 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.
3. Viral Encephalitis
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 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.
Clinical Findings
A. Symptoms and Signs
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.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Specific Therapy
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.
B. Supportive Care
Patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
C. Prophylaxis
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 patients receiving the vaccine, fever, malaise, and myalgias may develop.
Infection Control
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.
BIOLOGIC TOXINS
1. Botulinum Toxin
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 7 antigenic types, designated types A through G. Once absorbed, toxin will bind to motor neurons and prevent the release of acetylcholine, causing a flaccid muscle paralysis. Natural infection occurs in 3 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.
Clinical Findings
A. Symptoms and Signs
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.
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.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Specific Therapy
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 3 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 through G). Because some patients may develop allergic reactions to the antitoxin, a test dose is recommended.
B. Supportive Care
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.
C. Prophylaxis
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.
Infection Control
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.
2. Ricin
Ricin is a polypeptide toxin that causes cell death by inhibiting protein synthesis. Ricin 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.
Clinical Findings
A. Symptoms and Signs
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.
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.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
The treatment of ricin toxicity depends largely on the mode of exposure.
A. Parenteral Exposure
With parenteral exposure, treatment is largely supportive.
B. Gastrointestinal Exposure
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.
C. Pulmonary Exposure
With pulmonary exposure, treatment involves providing adequate ventilatory support. Patients may require oxygen, intubation, and ventilator management. Treat secondary bacterial infections with appropriate antibiotics.
D. Prophylaxis
Ricin vaccines are under development.
Infection Control
Ricin intoxication is not spread by person-to-person contact. Standard precautions are sufficient during patient care activities (see Table 3-2).
3. T-2 Mycotoxins
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 in 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.
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 though the skin.
Clinical Findings
A. Symptoms and Signs
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 be 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.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Specific Therapy
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.
B. Prophylaxis
Vaccines against the T-2 mycotoxins are under study. The early use of soap and water may prevent skin toxicity.
Infection Control
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).
4. Staphylococcal Enterotoxin B
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.
Clinical Findings
A. Symptoms and Signs
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.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Specific Therapy
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.
B. Prophylaxis
Vaccines against SEB are under study.
Infection Control
Person-to-person transmission of toxin is not a hazard. Standard precautions are sufficient during patient care activities (see Table 3-2).
CHEMICAL WEAPONS
Like radiation and biologic agents, many chemicals can be developed into weapons of mass destruction. Chemical weapons are particularly attractive to rogue governments and terrorist organizations because of their low cost, stability, and ease of production. In fact, chemical agents have already been used by terrorist organizations. The terrorist group Aum Shinrikyo released sarin gas in a Japan subway in 1995. Chemical agents can be delivered as liquids, vapors, or as components of explosive devices. Chemical agents are generally categorized as nerve agents, pulmonary agents, vesicants, and cyanide agents.
NERVE AGENTS
The nerve agents are a diverse group of compounds that were developed by the Germans prior to World War II. An agent known as GA (tabun) was the first nerve agent produced, followed by several others including GB (sarin), GD (soman), GF, and VX. Each of these agents has different physical characteristics, of which volatility is the most critical. The G agents are more volatile than VX; as a result, the G agents form a vapor more readily.
These agents are classified as organophosphates and induce toxicity by binding to and inhibiting various forms of the acetylcholine esterase enzyme. This causes increased levels of acetylcholine, leading to hyperstimulation of both central and peripheral muscarinic and nicotinic receptors. The stimulation of these receptors causes the clinical syndromes consistent with nerve agent toxicity. Toxicity can occur either from skin contact or from vapor exposure. Given their increased volatility, the G agents are more prone to cause vapor exposure.
Clinical Findings
A. Symptoms and Signs
1. Latent period—When nerve agent exposure occurs as a vapor, there is generally no significant latent period and symptoms will develop within minutes. Likewise, the clinical effects of vapor exposure do not tend to progress over time. In contrast, liquid contamination may have a significant latent period depending on the amount of skin exposure. With small exposures, latent periods of up to 18 hours may be seen. Further, with liquid contact, symptoms and signs may progress over a period of time.
2. Clinical syndromes—The findings that will develop following nerve agent poisoning depend on the amount and type of exposure. As the degree of exposure increases, so does the severity of symptoms. The general clinical syndromes of nerve agent toxicity are as follows:
a. Central nervous system—The effects on the central nervous system may range from mild to severe depending on the degree of exposure. Mild symptoms and signs include mood swings, difficulty concentrating, poor judgment, and sleep disturbances. With more significant exposures, coma, convulsions, and apnea may occur.
b. Peripheral nicotinic stimulation—The symptoms and signs of peripheral nicotinic receptor stimulation are manifest primarily as alterations in skeletal muscle functioning. The degree of involvement depends on the degree of exposure. Initially muscle fasciculations or weakness will occur and may eventually progress to paralysis.
c. Peripheral muscarinic stimulation—The symptoms and signs of peripheral muscarinic receptor stimulation are manifest primarily as increased exocrine gland and smooth muscle activity. Typical symptoms and signs of exocrine gland stimulation include rhinorrhea, salivation, sweating, increased gastrointestinal secretions, and increased pulmonary secretions. Increased pulmonary secretions may be severe enough to compromise the patient's airway. Increased smooth muscle activity will cause vomiting, diarrhea, increased urination, and abdominal pain.
B. Laboratory and X-ray Findings
Acetylcholine esterase exists in various tissues within the body. Two important subpopulations of acetylcholine esterase are the plasma cholinesterase and the erythrocyte cholinesterase. Decreased activity within either population may indicate nerve agent exposure. Of the two forms, the erythrocyte cholinesterase is the more sensitive indicator of exposure.
Treatment
A. Specific Therapy
The treatment of nerve agent toxicity involves the use of 3 primary medications. The first, atropine, is an anticholinergic medication used to counteract the hyperstimulation of peripheral muscarinic receptors. Atropine (1-2 mg intravenously; if no effect, double dose every 5 minutes until secretions dry) should generally be given until secretions begin to dry. Atropine will not prevent central nervous system or nicotinic toxicity. In contrast, pralidoxime chloride (2-PAM), 1-2 g intravenously given over 15-30 minutes, ameliorates nicotinic toxicity by breaking the bond formed between the nerve agent and the esterase enzyme. The nerve agent-esterase bond may be broken as long as the compound has not aged, a process by which the bond becomes irreversible. For most of the nerve agents, the aging process is not clinically significant. One notable exception is GD (soman), which ages after only 2 minutes and is refractory to 2-PAM therapy. Finally, a common complication of severe intoxication is seizure activity. Seizures may be treated with benzodiazepines.
B. Supportive Care
Patients may require intensive medical support such as airway management and ventilatory support. Frequent suctioning of secretions may also be required.
Decontamination
For more specific information on decontamination, see Chemical Decontamination, below.
PULMONARY AGENTS
Many different chemicals can be classified as pulmonary or lung agents. All have a similar mechanism of toxicity, producing delayed onset of pulmonary edema. Of these agents, carbonyl chloride (phosgene) has been the most studied. Because phosgene is the prototypical lung agent, most of the discussion here relates to phosgene; however, the principles of management can be applied to all lung agents. As a military agent, phosgene was first used during World War I and today can be found in numerous industrial applications. Because of its high volatility, phosgene forms a gas readily, often with the faint scent of freshly cut hay. It is not absorbed through the skin, but when inhaled, it causes toxicity. After inhalation, phosgene is deposited in the peripheral airways, where it undergoes acetylation reactions. Subsequent damage to the alveolar-capillary membrane will occur, resulting in pulmonary edema. Phosgene may also interact with mucous membranes, causing local irritation.
Clinical Findings
A. Symptoms and Signs
As noted previously, the primary effect of phosgene involves lung toxicity, although with some exposures, patients may have transient irritation to the eyes, nose, and mouth. In some cases, rhinorrhea and oral secretions may be significant. Patients may also complain of mild chest discomfort and cough secondary to bronchial irritation. In significant exposures, early death may occur secondary to laryngeal spasm. Despite these early effects, most of the toxicity of phosgene exposure is delayed. After inhalation, a variable latent period of up to 24 hours will ensue. The length of the latent period depends on the dose of phosgene delivered and will be shorter with higher exposures. Eventually the patient may develop symptoms and signs consistent with pulmonary edema, including dyspnea, hypoxia, chest pain, and cough. In some cases, pulmonary edema may be severe enough to cause hypotension. The degree to which each patient is affected depends on the severity of exposure. In severe exposures, death may occur.
B. Laboratory and X-ray Findings
No clinical test exists for the diagnosis of phosgene exposure. Appropriate studies such as arterial blood gas measurements and chest x-ray should be used to manage pulmonary edema. Hemoconcentration secondary to pulmonary edema may also be evident.
Treatment
A. Bed Rest
Any activity, even walking, may increase the severity of pulmonary edema. As a result, discourage patients from any physical activity.
B. Upper Respiratory Symptoms
In some cases, upper airway secretions may be significant. Nasal, oral, or bronchial secretions should be suctioned, if needed. If bronchospasm develops, it may be treated with intravenous steroids and inhaled bronchodilators. Treat secondary bacterial infections with appropriate antibiotics.
C. Lower Airway Symptoms
If pulmonary edema develops, it should be managed with standard medical interventions including supplemental oxygen, intubation, and ventilator management. Positive end-expiratory pressure is a useful ventilator adjunct. Treat secondary bacterial infection with antibiotics.
D. Hypotension
Secondary hypotension may develop in the event of severe pulmonary edema. Treatment of hypotension is problematic, given the increased permeability of the alveolar-capillary membrane. Supplemental crystalloid or colloid solutions can be used but may worsen pulmonary edema. Vasopressor agents such as dopamine may also be used.
Decontamination
No specific decontamination is required except removing the patient from the phosgene gas.
VESICANTS
Vesicants are a group of related compounds known to cause skin lesions, primarily blisters. Despite their predilection for skin involvement, multiple systemic effects are also seen. Although multiple agents may be used as vesicants, sulfur mustard and lewisite are the most common.
1. Sulfur Mustard
Sulfur mustard (mustard) was first used as a chemical weapon during World War I. Mustard is a lipophilic compound that is readily absorbed through intact skin. It causes significant dermal toxicity and after systemic absorption will affect various body systems. Exposure can occur after contact with mustard vapor or liquid. At different ambient temperatures, mustard may exist in either form. It displays a characteristic odor of garlic or mustard, hence, its name. The exact mechanism of mustard toxicity is not known but appears to involve DNA alkylation. Mustard also displays mild cholinergic activity. After systemic absorption, cell lines undergoing active mitosis are affected the most.
Clinical Findings
A. Symptoms and Signs
The symptoms and signs of mustard toxicity depend on the dose and mechanism of exposure. Unfortunately, initial mustard exposure is not symptomatic, and the patient may be unaware of contamination. Given the initial lack of symptoms, patients may not decontaminate, thus increasing toxicity. Depending on the dose, the latent period after exposure may range from 2 to 48 hours. In mild exposures, patients may display only mild dermal injury; in severe exposures, death may occur within hours. The specific symptoms and signs of mustard toxicity depend on the body areas exposed and the degree of systemic absorption. As noted, the skin is typically affected and will display areas of erythema, burning, and blister formation. The blisters may become large and express a clear to straw-colored fluid. The fluid does not contain mustard agent.
The eyes are one of the organs most sensitive to mustard exposure and may develop symptoms and signs first. Following ocular exposure, ocular pain, photophobia, conjunctivitis, and blepharospasm may occur. The superficial layers of the cornea may be denuded, leading to corneal clouding with visual changes.
With injury to the respiratory tree, patients may develop oronasal burning, rhinorrhea, sore throat, or epistaxis. In more severe exposures, findings of cough, dyspnea, mucous membrane necrosis, airway muscular damage, pulmonary edema, and respiratory failure may be seen. Symptoms and signs of gastrointestinal exposure may result either from the direct toxicity of mustard exposure or from mustard's cholinergic affects. Nausea, vomiting, diarrhea, and constipation are common findings.
Severe mustard exposure may also affect the central nervous system; mental status changes and seizure activity are the most common findings. Given mustard's interference with DNA activity, delayed findings of bone marrow suppression may also occur.
B. Laboratory and X-ray Findings
With exposure to mustard, an early leukocytosis is typical. If bone marrow suppression develops, later findings of anemia, leukopenia, and thrombocytopenia may be seen. If wound or pulmonary secretions become more purulent, a secondary bacterial infection should be suspected and Gram stain and culture obtained. Gastrointestinal symptoms may require electrolyte monitoring. The primary metabolite of mustard agent thiodiglycol may be detected in the urine in contaminated patients. Such specialized testing usually can be conducted only at reference or military laboratories. In the event of pulmonary involvement, chest x-ray may demonstrate a focal or diffuse pneumonitis and occasionally pulmonary edema.
Treatment
A. Decontamination
The most critical aspect in the treatment of mustard toxicity is removal of the chemical agent. This is problematic given the initial lack of symptoms. Even delayed decontamination, however, may lessen subsequent toxicity. Washing contaminated areas with either large amounts of soapy water or 0.5% hypochlorite solution is the preferred method of decontamination. For more specific information on decontamination, see Chemical Decontamination, below.
B. Specific Therapy
With skin injuries, leave small blisters intact and unroof larger lesions. Clean unroofed areas frequently and cover them with antibiotic cream (Polysporin, silver sulfadiazine). Treat other irritated areas of skin with systemic analgesics or topical lotions. With ocular exposure, use topical antibiotics to prevent secondary bacterial infections. Topical anticholinergics may prevent the discomfort of ciliary spasm. With pulmonary involvement, treat associated cough with typical antitussive medications. Treat episodes of bronchospasm with systemic steroids and inhaled bronchodilators. Treat secondary bacterial infection with appropriate antibiotics. Supplemental oxygen, intubation, or ventilator management may be required in some patients. Typical gastrointestinal antispasmodics may ameliorate the symptoms of gastrointestinal exposure. Bone marrow transplant, growth factor utilization, or factor replacement are alternatives for the treatment of bone marrow suppression.
Decontamination
As noted above, toxin can be removed by washing contaminated surfaces with large amounts of soapy water or 0.5% hypochlorite solution. For more specific information on decontamination, see Chemical Decontamination, below.
2. Lewisite
Much like sulfur mustard, exposure to lewisite causes injury to contaminated body surfaces and may lead to systemic symptoms. Unlike mustard, however, lewisite exposure causes symptoms and signs without a significant latent period. Lewisite is a volatile agent with the odor of geraniums. Its exact mechanism of action is unknown, but it is thought that the arsenic component of lewisite may inhibit various enzymes.
Clinical Findings
A. Symptoms and Signs
As noted above, the symptoms and signs of lewisite exposure begin without a significant latent period. Even though findings of exposure begin early, it may take several hours for symptoms to fully develop. The severity of clinical findings depends on the degree and method of exposure. Shortly after skin exposure, an area of dead skin will develop that will subsequently blister. These lesions may take up to 18 hours to fully develop. Skin necrosis may also be evident. Symptoms and signs of ocular exposure are similar to those associated with mustard toxicity and include conjunctivitis, iritis, edema, ocular pain, and corneal injury. If pulmonary toxicity develops, findings of cough, dyspnea, and pulmonary edema may occur. Lewisite causes increases in vascular permeability that may lead to third spacing of fluid with subsequent hypotension. In some cases, gastrointestinal, renal, and liver involvement may be seen.
B. Laboratory and X-ray Findings
No specific test for lewisite exposure is currently available.
Treatment
A. Decontamination
As with mustard exposure, the cornerstone of treatment involves early decontamination. Compared with mustard exposure, decontamination is usually more successful with lewisite exposure, given the early onset of symptoms. Standard washing with soap and water or 0.5% hypochlorite solution is sufficient.
B. Supportive Care
Patients may require intensive medical support such as airway management, hemodynamic support, and various measures to manage multisystem organ failure.
C. Specific Therapy
British anti-lewisite (dimercaprol), 2-3 mg/kg every 4 hours, is a compound that can be given intramuscularly to decrease the effects of lewisite exposure.
Decontamination
As noted above, the toxin can be removed by washing contaminated surfaces with large amounts of soapy water or 0.5% hypochlorite solution. For more specific information on decontamination, see Chemical Decontamination, below.
CYANIDE AGENTS
Historically, cyanide was classified as a blood agent. This classification is somewhat inappropriate because many other chemical agents exert their effects after being distributed within the vascular system. Nevertheless, this classification is still used occasionally. Once cyanide is absorbed, it distributes rapidly throughout the body. It has a high affinity for trivalent iron compounds and will bond to the cytochrome a3 complex within the mitochondria. The cytochrome a3-cyanide bond effectively blocks aerobic cellular respiration, and anaerobic metabolism ensues. Cyanide exposure most often occurs naturally after inhalation of smoke from burning synthetic materials. In a biologic attack, cyanide exposure would likely follow an aerosol release. Cyanide gas is known to exhibit the scent of bitter almonds.
Clinical Findings
A. Symptoms and Signs
After inhalation of cyanide gas, the cytochrome a3 enzyme is effectively blocked. Because cells can no longer utilize oxygen, they will convert to anaerobic metabolism, leading to a lactic acidosis. This inability to utilize oxygen effectively smothers the patient. Tachycardia, hypertension, and tachypnea will be seen initially. As symptoms and signs progress, anxiety, mental status changes, coma, seizures, cardiac arrest, and death will occur. Because cyanide does not alter oxygen-hemoglobin saturation, cyanosis will not develop. In fact, the inability to utilize oxygen increases the venous oxygen saturation, leading to a cherry red appearance to the skin. It generally takes 6-8 minutes for death to occur following cyanide exposure.
B. Laboratory and X-ray Findings
An elevated blood cyanide concentration confirms the diagnosis. Given the short time interval to death, such testing is not useful in the acute setting but may later confirm the diagnosis. Two rapid tests, an elevated venous blood oxygen saturation and an increased lactic acid level, are characteristic of cyanide poisoning.
Treatment
A. Specific Therapy
In addition to cyanide's affinity for certain iron compounds, it also has a high affinity for sulfhydryl groups and for the methemoglobin complex. These 2 characteristics are the basis of the cyanide antidote kit. The kit contains 3 components: amyl nitrite (used if no vascular access is available), sodium nitrite, and sodium thiosulfate. First, the patient is given a nitrite compound (inhalation of an amyl nitrate ampule or sodium nitrite), which will cause the formation of methemoglobin. The dose of sodium nitrite is based on the patient's weight and hemoglobin concentration although 300 mg IV is the usual dose for non-anemic adults. Given the high affinity of methemoglobin for cyanide, it will preferentially bind the compound and help to remove it from the cytochrome a3 complex. Second, the patient is given sodium thiosulfate, (typically 12.5 g IV for an adult), which interacts with cyanide, forming thiocyanate. Thiocyanate is then excreted in the urine.
B. Supportive Measures
Severe lactic acidosis may be treated with bicarbonate administration. Seizures may be treated with benzodiazepines. In many cases, patients require intubation and ventilator support.
Decontamination
The only effective mode of decontamination involves removing the patient from the cyanide gas.
CHEMICAL DECONTAMINATION
Because of the risk of cross contamination to health care workers, the need for patient decontamination should be emphasized. All patients suspected of experiencing a chemical weapons attack should be decontaminated as soon as possible. Optimally, patient decontamination should be conducted in the field. Often this is not practical, and a decontamination station should be established in a secure location adjacent to the health care facility. All persons conducting decontamination duties should be provided adequate protective clothing and should receive specialized training.
Decontamination involves physical removal of toxin and chemical deactivation of toxin. The physical removal of toxin is usually the most effective means of decontamination in the acute setting. Remove all clothing, jewelry, dressings, and splints. Wash the patient with copious amounts of soap and water. Avoid vigorous scrubbing because this may facilitate toxin absorption.
After physical removal of toxin, any remaining toxin can be chemically deactivated. This may take some time and thus is considered secondary to physical removal of toxin. The most common neutralizing solution is 0.5% hypochlorite solution, which detoxifies many chemical agents via oxidation reactions. Hypochlorite solution should not be used to decontaminate open peritoneal wounds, open chest wounds, exposed neural tissue, or ocular tissue. Irrigate these areas with copious amounts of normal saline. All contaminated materials should be bagged and sent for proper disposal.
In the past, injuries resulting from nuclear, biologic, and chemical attack were largely dealt with only in the military sector. Society as a whole, and specifically the civilian medical community, felt it unlikely that such weapons would be used against civilian populations. Recent changes in the global political environment have forced changes in this thinking. Many smaller nations, some of which are judged unstable, are attempting to develop weapons of mass destruction. Likewise, many terrorist organizations are now actively attempting to purchase or develop such weapons. In addition to the risk of an overt attack, other sources of exposure could come from accidents involving many nuclear, biologic, and chemical agents stored in facilities throughout the United States. An accident at any of these facilities could result in a large number of civilian casualties. As with most mass casualty situations, emergency physicians will be at the forefront of patient care. This chapter attempts to provide specific information regarding the management of nuclear, biologic, and chemical weapons injuries.
NUCLEAR WEAPONS
Several incidents in recent history, both military and civilian, have resulted in radiation injuries. The most notable, and in fact the only war-time use, involved the detonation of nuclear weapons over Hiroshima and Nagasaki, Japan. Unfortunately, many terrorist organizations have attempted to obtain nuclear weapons. A terrorist attack would most likely involve the detonation of a nuclear bomb or the detonation of a conventional explosive that also dispersed radioactive material (so-called dirty bomb).
General Considerations
Radiation-induced injury occurs when various types of ionizing radiation interact with body tissues. Radiation exposure may be external or internal. Internal contamination can occur via wound contamination or via inhalation or ingestion of contaminated particles. Four types of radioactive particles may cause damage:
1. Alpha particles—Alpha particles are large particles that are stopped by the epidermis. They cause no significant external damage. Internal contamination may cause local tissue injury.
2. Beta particles—Beta particles are small particles that can penetrate the superficial skin and cause mild burnlike injuries.
3. Gamma rays—Gamma rays are high-energy particles that can enter tissues easily and cause significant damage to multiple body systems.
4. Neutrons—Neutrons are large particles that are typically produced only during nuclear detonation. Like gamma rays, they cause significant tissue injury.
The effect that radiation will have on the body depends on the type of radiation, the amount of exposure, and the body system involved. Tissues that display higher rates of cellular mitosis, such as the gastrointestinal and hematopoietic systems, are more severely affected. At very high radiation doses, neurovascular effects will also be seen. Radiation injury may cause either abnormal cell function or cell death.
Clinical Findings
A. Symptoms and Signs
The symptoms and signs of radiation exposure occur in 3 phases: prodromal, latent, and symptomatic.
1. Prodromal phase—Patients will develop nonspecific symptoms of nausea, vomiting, weakness, and fatigue. Symptoms generally last no longer than 24-48 hours. With higher radiation exposures, symptoms will occur more rapidly and last longer.
2. Latent period—The length of the latent period depends on the dose of radiation and the body system involved (neurologic, several hours; gastrointestinal, 1-7 days; hematopoietic, 2-6 weeks).
3. Symptomatic phase—Symptoms will depend largely on the body system affected, which will depend on the radiation dose. At doses of 0.7-4 gray (Gy),1 the hematopoietic system will begin to manifest signs and symptoms of bone marrow suppression. Because of their long life span, erythrocytes are less severely affected than are the myeloid and platelet cell lines. Neutropenia and thrombocytopenia may be significant and lead to infectious and hemorrhagic complications. At doses of 6-8 Gy, gastrointestinal symptoms develop. Nausea, vomiting, diarrhea (bloody), and severe fluid and electrolyte imbalances will occur. The neurovascular system becomes affected at doses of 20-40 Gy. Symptoms include headache, mental status changes, hypotension, focal neurologic changes, convulsions, and coma. Exposures in this range are uniformly fatal. If an explosive device was used to disperse radioactive material, patients may also have thermal and blast injuries.
1The gray, a unit of measure for the dose of ionizing radiation, is equal to 1 J/kg of tissue. One gray is equal to 100 rad.
B. Laboratory and X-ray Findings
Obtain a complete blood count (CBC) with differential for all patients sustaining a radiation injury. Although symptomatic bone marrow suppression may not be evident for some weeks, a drop of the absolute lymphocyte count of 50% at 24-48 hours is indicative of significant exposure. Monitor electrolytes in patients with gastrointestinal symptoms.
Treatment
In the absence of aggressive medical therapy, the LD50 (the dose of radiation that will kill 50% of those exposed) is approximately 3.5 Gy. Aggressive medical care affords improved survival. Treat all life-threatening injuries associated with blast or thermal effects according to standard advanced trauma life support protocols. Perform surgical procedures early to avoid the electrolyte and hematopoietic effects that will occur. Clean wounds extensively and close them as soon as possible to prevent infection. Treat nausea and vomiting with standard antiemetic medications (prochlorperazine, promethazine, ondansetron). Treat fluid and electrolyte abnormalities with appropriate replacement. Anemia and thrombocytopenia can be treated with transfusion therapy. Leukopenia may be treated with hematopoietic growth factors such as sargramostim and filgrastim. In some instances bone marrow transplantation may be utilized. Follow neutropenic precautions at absolute neutrophil counts below 500. Some authors recommend prophylactic antibiotics at counts below 100. Use broad-spectrum antibiotics to treat infections. Infection is the most common cause of death in radiation patients. Despite aggressive medical care, radiation exposures above 10 Gy are usually fatal.
Decontamination
Remove all contaminated clothing. Change contaminated dressings and splints. Thoroughly clean the patient's skin with soap and water or a 0.5% hypochlorite solution. Hair should be washed and in some instances removed. Eyes may be washed with large amounts of water or sterile saline. All contaminated materials should be bagged if possible and sent for proper disposal.
Disposition
Patients who have been decontaminated and have only mild transient symptoms can be safely discharged. Because of the variable and lengthy latent period involved with this disorder, early admission is not indicated. Patients should be closely monitored and admitted when warranted.
Goans RE et al: Early dose assessment in criticality accidents. Health Phys 2001;81(4):446. [PMID: 11569639] (Describes techniques for estimating the severity of radiation exposure.)
Military Medical Operations Office, Armed Forces Radiobiology Research Institute: Medical Management of Radiological Casualties, 1st ed. Military Medical Operations Office, Armed Forces Radiobiology Research Institute, 1999. (Produced by the U.S. Army, this text provides general information regarding all aspects of radiologic injuries.)
BIOLOGIC WEAPONS
Many agents can be used as biologic weapons. The most likely pathogens are presented here. Biologic agents can be classified as bacterial agents (anthrax, plague, tularemia, brucellosis, Q fever, glanders), viral agents (smallpox, hemorrhagic fever, encephalitis), and biologic toxins (botulinum, ricin, T-2 mycotoxins, staphylococcal enterotoxin B). A high index of suspicion will be required in order to identify patients who have experienced a biologic attack. A large number of patients with severe febrile illnesses will be the most likely clue. Keep in mind the attack most likely occurred several days prior to patient presentation. Aerosol release of infectious material is the most common form of biologic attack.
BACTERIAL AGENTS
1. Anthrax
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. The spore form of anthrax causes infection. Clinically the disease occurs in 3 forms: inhalational anthrax, gastrointestinal anthrax, and cutaneous anthrax.
Clinical Findings
A. Symptoms and Signs
1. Inhalational anthrax—Inhalation anthrax is the form of disease most likely expected after a terrorist attack. After spores are inhaled, a variable incubation period occurs, usually lasting 1-7 days. Prolonged 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.
2. Gastrointestinal anthrax—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, diarrhea (bloody), and the development of an acute abdomen with sepsis. Mortality rates for gastrointestinal anthrax are in excess of 50%.
3. Cutaneous anthrax—Cutaneous anthrax is the most common naturally occurring form of the disease. Cutaneous anthrax 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.
4. Anthrax meningitis—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%.
B. Laboratory and X-ray Findings
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. Notify laboratory personnel of a possible anthrax exposure. Often Bacillus spp. are thought to be the contaminant and are not pursued further. Confirmatory enzyme-linked immunoassay (ELISA) and polymerase chain reaction (PCR) tests are available at some national reference laboratories. Chest X-ray may also be useful. Patients with inhalational anthrax will display a wide mediastinum on chest x-ray. No infiltrate is typically observed.
Treatment & Prophylaxis
Because anthrax has a rapid and fulminant course, do not delay treatment while awaiting confirmatory tests. Institute empiric therapy when the diagnosis is considered. Delaying treatment for even hours may significantly increase mortality.
A. Antibiotics
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.
B. Supportive Care
Patients may require intensive medical support such as airway management, hemodynamic support, and various measures to manage multisystem organ failure.
C. Prophylaxis
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.
Infection Control
No data indicate that anthrax is spread via person-to-person contact. Use standard precautions during patient care activities (Table 3-2).
2. Plague
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 3 clinical forms: bubonic plague, septicemic plague, and pneumonic plague.
Clinical Findings
A. Symptoms and Signs
1. Bubonic plague—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. Bubo size 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%.
2. Septicemic plague—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%.
3. Pneumonic plague—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.
B. Laboratory and X-ray Findings
Y pestis can be identified by several different staining techniques. Routine Gram stain may reveal the organism. Y pestis also has a characteristic bipolar staining pattern with Wright, Giemsa, and Wayson stains. Routine 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.
Treatment & Prophylaxis
Plague has a rapid disease progression, and any delay in treatment will cause significant increases in mortality. Institute treatment on empiric grounds, and do not delay treatment while awaiting confirmatory tests.
A. Antibiotics
Streptomycin is the drug of choice for the treatment of plague. Gentamicin may also be used and is thought to have equal efficacy (see Table 3-1). Alternative antibiotics include doxycycline, ciprofloxacin, and chloramphenicol.
B. Supportive Care
Patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
C. Prophylaxis
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. Antibiotic choices are the same as for treatment.
Infection Control
Pneumonic plague can be spread from person to person by aerosol droplets. Use droplet precautions, and either the patient or 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.
3. Tularemia
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 palaearctica is 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.
Clinical Findings
A. Symptoms and Signs
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.
1. Ulceroglandular tularemia—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.
2. Glandular tularemia—Glandular tularemia displays signs and symptoms similar to ulceroglandular tularemia, except that no ulcer formation is noted.
3. Oculoglandular tularemia—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.
4. Oropharyngeal tularemia—After inoculation of the pharynx, an exudative pharyngotonsillitis will develop with cervical lymphadenopathy.
5. Pneumonic tularemia—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.
6. Typhoidal tularemia—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.
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%.
B. Laboratory and X-ray Findings
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 to bronchopneumonia. Pleural effusions are often present.
Treatment & Prophylaxis
A. Antibiotics
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.
B. Supportive Care
Rarely patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
C. Prophylaxis
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.
Infection Control
Significant person-to-person transmission of tularemia does not occur. Standard precautions are sufficient during patient care activities (see Table 3-2).
4. Brucellosis
Brucellae are small aerobic, gram-negative, pleomorphic coccobacilli. Many Brucella spp. occur naturally; however, only 4 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.
Clinical Findings
A. Symptoms and Signs
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-Barre syndrome. Patients may also develop anemia, thrombocytopenia, or neutropenia. Central nervous system and cardiac involvement, although infrequent, accounts 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 biological weapon stems from the prolonged disease course and significant morbidity.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Antibiotics
Because of the high rate of treatment failure, single drug therapy is no longer 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. Regardless of the antibiotics chosen, combination drug therapy should be used. In patients with serious infections, a 3-drug parenteral regimen is the norm.
B. Supportive Care
Rarely patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
C. Prophylaxis
No human vaccine against Brucella spp. currently exists. Some authors recommend a 3- to 6-week course of antibiotics following a high-risk exposure such as a biologic attack.
Infection Control
Person-to-person spread of brucellosis is thought to be uncommon. Standard precautions are sufficient during patient care activities (see Table 3-2).
5. Q Fever
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.
Clinical Findings
A. Symptoms and Signs
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.
In some patients, Q fever may become a chronic condition. Chronic Q fever is typically manifest 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%.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Antibiotics
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.
B. Supportive Care
Rarely patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
C. Prophylaxis
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.
Infection Control
Person-to-person spread of the disease is unlikely. Standard precautions are sufficient while engaging in patient care activities (see Table 3-2).
6. Glanders & Melioidosis
Glanders and melioidosis are similar diseases caused by related bacteria. The causal agent of glanders is Burkholderia mallei; the causal agent of melioidosis is Burkholderia pseudomallei. Both organisms are gram-negative bacilli. Glanders and melioidosis occur naturally. Glanders is a rare disease in humans; horses and other domesticated animals are often infected. Melioidosis occurs more commonly in humans and is endemic to Southeast Asia. Infection with either organism occurs via contact with open wounds or mucous membranes or by inhalation.
Clinical Findings
A. Symptoms and Signs
Both glanders and melioidosis can cause multiple clinical syndromes.
1. Localized disease—A localized disease may be seen and typically occurs after wound contamination or mucous membrane exposure. With wound contamination, patients develop a small ulcer with associated cellulitis. Regional lymphadenopathy or lymphangitis is also common. If mucous membrane exposure occurs, patients develop a bloody purulent discharge from the infected area (eyes, nose, or mouth). If secondary systemic infection occurs, a pustular rash similar to smallpox may develop.
2. Pulmonary disease—A pulmonary form of disease may also be seen. Pulmonary disease may occur after inhalation of aerosols or after hematogenous spread. An incubation period of 1-2 weeks occurs initially. Symptoms of pulmonary disease, including fever, chills, cough, chest pain, and dyspnea, develop eventually.
3. Septicemic disease—The most severe form of infection is the septicemic form. Patients present with nonspecific symptoms and signs of fever, chills, malaise, myalgias, photophobia, rigors, diffuse body abscesses, pustular rash, and headache. This condition is usually fatal; death occurs in 7-10 days.
B. Laboratory and X-ray Findings
Both organisms can be identified by routine Gram stain and culture. Special staining with methylene blue or Wright stain may facilitate diagnosis. Growth may be enhanced by the addition of meat nutrient agar or glucose to the growth media. Specialized agglutination and complement fixation tests may also be used. If pulmonary involvement is suspected, chest x-ray may demonstrate lung abscesses, miliary nodules, or pneumonia.
Treatment & Prophylaxis
A. Antibiotics
Both glanders and melioidosis respond to various antibiotics. Appropriate antibiotic choices include amoxicillin-clavulanate, tetracycline, trimethoprim-sulfamethoxazole, rifampin, ciprofloxacin, and ceftazidime (see Table 3-1). Various combinations of antibiotics have been recommended depending on the type and severity of infection.
B. Supportive Care
Rarely patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
C. Prophylaxis
According to some authorities, a course of trimethoprim-sulfamethoxazole may prevent the onset of disease.
Infection Control
Person-to-person spread of the disease is uncommon but can occur with improper handling of body fluids. Standard precautions are sufficient during patient care activities (see Table 3-2).
VIRAL AGENTS
1. Smallpox
Smallpox is a disease caused by the variola virus. The variola virus is a DNA virus of the genus orthopoxvirus. It occurs in 2 strains: the more severe variola major and a milder form, variola minor. Smallpox was essentially eradicated 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. Concern now exists that the Russian stockpile may have been compromised.
Clinical Findings
A. Symptoms and Signs
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. Unlike chickenpox, 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.
B. Laboratory and X-ray Findings
Analysis of pustular fluid will yield virus particles. All samples should be sealed in 2 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.
Treatment & Prophylaxis
A. Specific Therapy
Currently there is no specific therapy for smallpox. Treatment is essentially supportive care. Many investigational drugs are currently under study. Strict patient isolation, preferably in the 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.
B. Prophylaxis
Data indicate that vaccination within 4 days of smallpox exposure may lessen subsequent illness. Because of the risk of possible terrorist attack, some authorities are recommending a preemptive initiation of smallpox vaccination. This would be problematic for several reasons. First, the current supply of smallpox vaccine is inadequate to protect a large populace. Second, many complications were known to occur with smallpox vaccination. Postvaccinial encephalitis occurred in approximately 1 in 300,000 vaccinations and was fatal in 25% of patients. Immunocompromised patients may develop a condition known as progressive vaccinia. In this condition, the initial inoculation site failed to heal, became necrotic, and necrosis spread to adjacent tissues. This complication was often fatal. In some patients with eczema, a condition known as eczema vaccinatum could occur. Here, vaccinial lesions would occur in areas previously involved with eczema. Fortunately, the eruption was usually self-limited. In some patients, a secondary generalized vaccinia could develop. In others, inadvertent autoinoculation of eyes, mouth, or other areas occurred. Many of these complications could be treated with vaccinia immune globulin. Unfortunately, vaccinia immune globulin is also in short supply.
Cidofovir has also displayed some efficacy in preventing smallpox infection if given within 48 hours. There is no evidence to suggest that cidofovir is more effective than vaccine. Further, cidofovir is associated with significant renal toxicity.
Individuals vaccinated prior to 1972 are likely no longer protected, given that immunity lapses over a 5- to 10-year period.
Infection Control
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.
2. Hemorrhagic Fever
Viral hemorrhagic fever represents a clinical syndrome caused by several RNA viruses. These viruses exist in 4 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 them potential biological weapons.
Clinical Findings
A. Symptoms and Signs
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.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Specific Therapy
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 intravenously as an initial dose, followed by 16 mg/kg intravenously every 6 hours for 4 days and then 8 mg/kg intravenously 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.
B. Supportive Care
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.
C. Prophylaxis
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.
Infection Control
The causal agents of hemorrhagic fever are highly infectious. Use caution when using sharps or when coming into contact with body fluids. 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.
3. Viral Encephalitis
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 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.
Clinical Findings
A. Symptoms and Signs
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.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Specific Therapy
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.
B. Supportive Care
Patients may require intensive medical support such as airway management, hemodynamic support, and other measures to manage multisystem organ failure.
C. Prophylaxis
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 patients receiving the vaccine, fever, malaise, and myalgias may develop.
Infection Control
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.
BIOLOGIC TOXINS
1. Botulinum Toxin
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 7 antigenic types, designated types A through G. Once absorbed, toxin will bind to motor neurons and prevent the release of acetylcholine, causing a flaccid muscle paralysis. Natural infection occurs in 3 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.
Clinical Findings
A. Symptoms and Signs
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.
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.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Specific Therapy
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 3 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 through G). Because some patients may develop allergic reactions to the antitoxin, a test dose is recommended.
B. Supportive Care
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.
C. Prophylaxis
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.
Infection Control
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.
2. Ricin
Ricin is a polypeptide toxin that causes cell death by inhibiting protein synthesis. Ricin 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.
Clinical Findings
A. Symptoms and Signs
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.
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.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
The treatment of ricin toxicity depends largely on the mode of exposure.
A. Parenteral Exposure
With parenteral exposure, treatment is largely supportive.
B. Gastrointestinal Exposure
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.
C. Pulmonary Exposure
With pulmonary exposure, treatment involves providing adequate ventilatory support. Patients may require oxygen, intubation, and ventilator management. Treat secondary bacterial infections with appropriate antibiotics.
D. Prophylaxis
Ricin vaccines are under development.
Infection Control
Ricin intoxication is not spread by person-to-person contact. Standard precautions are sufficient during patient care activities (see Table 3-2).
3. T-2 Mycotoxins
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 in 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.
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 though the skin.
Clinical Findings
A. Symptoms and Signs
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 be 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.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Specific Therapy
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.
B. Prophylaxis
Vaccines against the T-2 mycotoxins are under study. The early use of soap and water may prevent skin toxicity.
Infection Control
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).
4. Staphylococcal Enterotoxin B
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.
Clinical Findings
A. Symptoms and Signs
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.
B. Laboratory and X-ray Findings
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.
Treatment & Prophylaxis
A. Specific Therapy
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.
B. Prophylaxis
Vaccines against SEB are under study.
Infection Control
Person-to-person transmission of toxin is not a hazard. Standard precautions are sufficient during patient care activities (see Table 3-2).
CHEMICAL WEAPONS
Like radiation and biologic agents, many chemicals can be developed into weapons of mass destruction. Chemical weapons are particularly attractive to rogue governments and terrorist organizations because of their low cost, stability, and ease of production. In fact, chemical agents have already been used by terrorist organizations. The terrorist group Aum Shinrikyo released sarin gas in a Japan subway in 1995. Chemical agents can be delivered as liquids, vapors, or as components of explosive devices. Chemical agents are generally categorized as nerve agents, pulmonary agents, vesicants, and cyanide agents.
NERVE AGENTS
The nerve agents are a diverse group of compounds that were developed by the Germans prior to World War II. An agent known as GA (tabun) was the first nerve agent produced, followed by several others including GB (sarin), GD (soman), GF, and VX. Each of these agents has different physical characteristics, of which volatility is the most critical. The G agents are more volatile than VX; as a result, the G agents form a vapor more readily.
These agents are classified as organophosphates and induce toxicity by binding to and inhibiting various forms of the acetylcholine esterase enzyme. This causes increased levels of acetylcholine, leading to hyperstimulation of both central and peripheral muscarinic and nicotinic receptors. The stimulation of these receptors causes the clinical syndromes consistent with nerve agent toxicity. Toxicity can occur either from skin contact or from vapor exposure. Given their increased volatility, the G agents are more prone to cause vapor exposure.
Clinical Findings
A. Symptoms and Signs
1. Latent period—When nerve agent exposure occurs as a vapor, there is generally no significant latent period and symptoms will develop within minutes. Likewise, the clinical effects of vapor exposure do not tend to progress over time. In contrast, liquid contamination may have a significant latent period depending on the amount of skin exposure. With small exposures, latent periods of up to 18 hours may be seen. Further, with liquid contact, symptoms and signs may progress over a period of time.
2. Clinical syndromes—The findings that will develop following nerve agent poisoning depend on the amount and type of exposure. As the degree of exposure increases, so does the severity of symptoms. The general clinical syndromes of nerve agent toxicity are as follows:
a. Central nervous system—The effects on the central nervous system may range from mild to severe depending on the degree of exposure. Mild symptoms and signs include mood swings, difficulty concentrating, poor judgment, and sleep disturbances. With more significant exposures, coma, convulsions, and apnea may occur.
b. Peripheral nicotinic stimulation—The symptoms and signs of peripheral nicotinic receptor stimulation are manifest primarily as alterations in skeletal muscle functioning. The degree of involvement depends on the degree of exposure. Initially muscle fasciculations or weakness will occur and may eventually progress to paralysis.
c. Peripheral muscarinic stimulation—The symptoms and signs of peripheral muscarinic receptor stimulation are manifest primarily as increased exocrine gland and smooth muscle activity. Typical symptoms and signs of exocrine gland stimulation include rhinorrhea, salivation, sweating, increased gastrointestinal secretions, and increased pulmonary secretions. Increased pulmonary secretions may be severe enough to compromise the patient's airway. Increased smooth muscle activity will cause vomiting, diarrhea, increased urination, and abdominal pain.
B. Laboratory and X-ray Findings
Acetylcholine esterase exists in various tissues within the body. Two important subpopulations of acetylcholine esterase are the plasma cholinesterase and the erythrocyte cholinesterase. Decreased activity within either population may indicate nerve agent exposure. Of the two forms, the erythrocyte cholinesterase is the more sensitive indicator of exposure.
Treatment
A. Specific Therapy
The treatment of nerve agent toxicity involves the use of 3 primary medications. The first, atropine, is an anticholinergic medication used to counteract the hyperstimulation of peripheral muscarinic receptors. Atropine (1-2 mg intravenously; if no effect, double dose every 5 minutes until secretions dry) should generally be given until secretions begin to dry. Atropine will not prevent central nervous system or nicotinic toxicity. In contrast, pralidoxime chloride (2-PAM), 1-2 g intravenously given over 15-30 minutes, ameliorates nicotinic toxicity by breaking the bond formed between the nerve agent and the esterase enzyme. The nerve agent-esterase bond may be broken as long as the compound has not aged, a process by which the bond becomes irreversible. For most of the nerve agents, the aging process is not clinically significant. One notable exception is GD (soman), which ages after only 2 minutes and is refractory to 2-PAM therapy. Finally, a common complication of severe intoxication is seizure activity. Seizures may be treated with benzodiazepines.
B. Supportive Care
Patients may require intensive medical support such as airway management and ventilatory support. Frequent suctioning of secretions may also be required.
Decontamination
For more specific information on decontamination, see Chemical Decontamination, below.
PULMONARY AGENTS
Many different chemicals can be classified as pulmonary or lung agents. All have a similar mechanism of toxicity, producing delayed onset of pulmonary edema. Of these agents, carbonyl chloride (phosgene) has been the most studied. Because phosgene is the prototypical lung agent, most of the discussion here relates to phosgene; however, the principles of management can be applied to all lung agents. As a military agent, phosgene was first used during World War I and today can be found in numerous industrial applications. Because of its high volatility, phosgene forms a gas readily, often with the faint scent of freshly cut hay. It is not absorbed through the skin, but when inhaled, it causes toxicity. After inhalation, phosgene is deposited in the peripheral airways, where it undergoes acetylation reactions. Subsequent damage to the alveolar-capillary membrane will occur, resulting in pulmonary edema. Phosgene may also interact with mucous membranes, causing local irritation.
Clinical Findings
A. Symptoms and Signs
As noted previously, the primary effect of phosgene involves lung toxicity, although with some exposures, patients may have transient irritation to the eyes, nose, and mouth. In some cases, rhinorrhea and oral secretions may be significant. Patients may also complain of mild chest discomfort and cough secondary to bronchial irritation. In significant exposures, early death may occur secondary to laryngeal spasm. Despite these early effects, most of the toxicity of phosgene exposure is delayed. After inhalation, a variable latent period of up to 24 hours will ensue. The length of the latent period depends on the dose of phosgene delivered and will be shorter with higher exposures. Eventually the patient may develop symptoms and signs consistent with pulmonary edema, including dyspnea, hypoxia, chest pain, and cough. In some cases, pulmonary edema may be severe enough to cause hypotension. The degree to which each patient is affected depends on the severity of exposure. In severe exposures, death may occur.
B. Laboratory and X-ray Findings
No clinical test exists for the diagnosis of phosgene exposure. Appropriate studies such as arterial blood gas measurements and chest x-ray should be used to manage pulmonary edema. Hemoconcentration secondary to pulmonary edema may also be evident.
Treatment
A. Bed Rest
Any activity, even walking, may increase the severity of pulmonary edema. As a result, discourage patients from any physical activity.
B. Upper Respiratory Symptoms
In some cases, upper airway secretions may be significant. Nasal, oral, or bronchial secretions should be suctioned, if needed. If bronchospasm develops, it may be treated with intravenous steroids and inhaled bronchodilators. Treat secondary bacterial infections with appropriate antibiotics.
C. Lower Airway Symptoms
If pulmonary edema develops, it should be managed with standard medical interventions including supplemental oxygen, intubation, and ventilator management. Positive end-expiratory pressure is a useful ventilator adjunct. Treat secondary bacterial infection with antibiotics.
D. Hypotension
Secondary hypotension may develop in the event of severe pulmonary edema. Treatment of hypotension is problematic, given the increased permeability of the alveolar-capillary membrane. Supplemental crystalloid or colloid solutions can be used but may worsen pulmonary edema. Vasopressor agents such as dopamine may also be used.
Decontamination
No specific decontamination is required except removing the patient from the phosgene gas.
VESICANTS
Vesicants are a group of related compounds known to cause skin lesions, primarily blisters. Despite their predilection for skin involvement, multiple systemic effects are also seen. Although multiple agents may be used as vesicants, sulfur mustard and lewisite are the most common.
1. Sulfur Mustard
Sulfur mustard (mustard) was first used as a chemical weapon during World War I. Mustard is a lipophilic compound that is readily absorbed through intact skin. It causes significant dermal toxicity and after systemic absorption will affect various body systems. Exposure can occur after contact with mustard vapor or liquid. At different ambient temperatures, mustard may exist in either form. It displays a characteristic odor of garlic or mustard, hence, its name. The exact mechanism of mustard toxicity is not known but appears to involve DNA alkylation. Mustard also displays mild cholinergic activity. After systemic absorption, cell lines undergoing active mitosis are affected the most.
Clinical Findings
A. Symptoms and Signs
The symptoms and signs of mustard toxicity depend on the dose and mechanism of exposure. Unfortunately, initial mustard exposure is not symptomatic, and the patient may be unaware of contamination. Given the initial lack of symptoms, patients may not decontaminate, thus increasing toxicity. Depending on the dose, the latent period after exposure may range from 2 to 48 hours. In mild exposures, patients may display only mild dermal injury; in severe exposures, death may occur within hours. The specific symptoms and signs of mustard toxicity depend on the body areas exposed and the degree of systemic absorption. As noted, the skin is typically affected and will display areas of erythema, burning, and blister formation. The blisters may become large and express a clear to straw-colored fluid. The fluid does not contain mustard agent.
The eyes are one of the organs most sensitive to mustard exposure and may develop symptoms and signs first. Following ocular exposure, ocular pain, photophobia, conjunctivitis, and blepharospasm may occur. The superficial layers of the cornea may be denuded, leading to corneal clouding with visual changes.
With injury to the respiratory tree, patients may develop oronasal burning, rhinorrhea, sore throat, or epistaxis. In more severe exposures, findings of cough, dyspnea, mucous membrane necrosis, airway muscular damage, pulmonary edema, and respiratory failure may be seen. Symptoms and signs of gastrointestinal exposure may result either from the direct toxicity of mustard exposure or from mustard's cholinergic affects. Nausea, vomiting, diarrhea, and constipation are common findings.
Severe mustard exposure may also affect the central nervous system; mental status changes and seizure activity are the most common findings. Given mustard's interference with DNA activity, delayed findings of bone marrow suppression may also occur.
B. Laboratory and X-ray Findings
With exposure to mustard, an early leukocytosis is typical. If bone marrow suppression develops, later findings of anemia, leukopenia, and thrombocytopenia may be seen. If wound or pulmonary secretions become more purulent, a secondary bacterial infection should be suspected and Gram stain and culture obtained. Gastrointestinal symptoms may require electrolyte monitoring. The primary metabolite of mustard agent thiodiglycol may be detected in the urine in contaminated patients. Such specialized testing usually can be conducted only at reference or military laboratories. In the event of pulmonary involvement, chest x-ray may demonstrate a focal or diffuse pneumonitis and occasionally pulmonary edema.
Treatment
A. Decontamination
The most critical aspect in the treatment of mustard toxicity is removal of the chemical agent. This is problematic given the initial lack of symptoms. Even delayed decontamination, however, may lessen subsequent toxicity. Washing contaminated areas with either large amounts of soapy water or 0.5% hypochlorite solution is the preferred method of decontamination. For more specific information on decontamination, see Chemical Decontamination, below.
B. Specific Therapy
With skin injuries, leave small blisters intact and unroof larger lesions. Clean unroofed areas frequently and cover them with antibiotic cream (Polysporin, silver sulfadiazine). Treat other irritated areas of skin with systemic analgesics or topical lotions. With ocular exposure, use topical antibiotics to prevent secondary bacterial infections. Topical anticholinergics may prevent the discomfort of ciliary spasm. With pulmonary involvement, treat associated cough with typical antitussive medications. Treat episodes of bronchospasm with systemic steroids and inhaled bronchodilators. Treat secondary bacterial infection with appropriate antibiotics. Supplemental oxygen, intubation, or ventilator management may be required in some patients. Typical gastrointestinal antispasmodics may ameliorate the symptoms of gastrointestinal exposure. Bone marrow transplant, growth factor utilization, or factor replacement are alternatives for the treatment of bone marrow suppression.
Decontamination
As noted above, toxin can be removed by washing contaminated surfaces with large amounts of soapy water or 0.5% hypochlorite solution. For more specific information on decontamination, see Chemical Decontamination, below.
2. Lewisite
Much like sulfur mustard, exposure to lewisite causes injury to contaminated body surfaces and may lead to systemic symptoms. Unlike mustard, however, lewisite exposure causes symptoms and signs without a significant latent period. Lewisite is a volatile agent with the odor of geraniums. Its exact mechanism of action is unknown, but it is thought that the arsenic component of lewisite may inhibit various enzymes.
Clinical Findings
A. Symptoms and Signs
As noted above, the symptoms and signs of lewisite exposure begin without a significant latent period. Even though findings of exposure begin early, it may take several hours for symptoms to fully develop. The severity of clinical findings depends on the degree and method of exposure. Shortly after skin exposure, an area of dead skin will develop that will subsequently blister. These lesions may take up to 18 hours to fully develop. Skin necrosis may also be evident. Symptoms and signs of ocular exposure are similar to those associated with mustard toxicity and include conjunctivitis, iritis, edema, ocular pain, and corneal injury. If pulmonary toxicity develops, findings of cough, dyspnea, and pulmonary edema may occur. Lewisite causes increases in vascular permeability that may lead to third spacing of fluid with subsequent hypotension. In some cases, gastrointestinal, renal, and liver involvement may be seen.
B. Laboratory and X-ray Findings
No specific test for lewisite exposure is currently available.
Treatment
A. Decontamination
As with mustard exposure, the cornerstone of treatment involves early decontamination. Compared with mustard exposure, decontamination is usually more successful with lewisite exposure, given the early onset of symptoms. Standard washing with soap and water or 0.5% hypochlorite solution is sufficient.
B. Supportive Care
Patients may require intensive medical support such as airway management, hemodynamic support, and various measures to manage multisystem organ failure.
C. Specific Therapy
British anti-lewisite (dimercaprol), 2-3 mg/kg every 4 hours, is a compound that can be given intramuscularly to decrease the effects of lewisite exposure.
Decontamination
As noted above, the toxin can be removed by washing contaminated surfaces with large amounts of soapy water or 0.5% hypochlorite solution. For more specific information on decontamination, see Chemical Decontamination, below.
CYANIDE AGENTS
Historically, cyanide was classified as a blood agent. This classification is somewhat inappropriate because many other chemical agents exert their effects after being distributed within the vascular system. Nevertheless, this classification is still used occasionally. Once cyanide is absorbed, it distributes rapidly throughout the body. It has a high affinity for trivalent iron compounds and will bond to the cytochrome a3 complex within the mitochondria. The cytochrome a3-cyanide bond effectively blocks aerobic cellular respiration, and anaerobic metabolism ensues. Cyanide exposure most often occurs naturally after inhalation of smoke from burning synthetic materials. In a biologic attack, cyanide exposure would likely follow an aerosol release. Cyanide gas is known to exhibit the scent of bitter almonds.
Clinical Findings
A. Symptoms and Signs
After inhalation of cyanide gas, the cytochrome a3 enzyme is effectively blocked. Because cells can no longer utilize oxygen, they will convert to anaerobic metabolism, leading to a lactic acidosis. This inability to utilize oxygen effectively smothers the patient. Tachycardia, hypertension, and tachypnea will be seen initially. As symptoms and signs progress, anxiety, mental status changes, coma, seizures, cardiac arrest, and death will occur. Because cyanide does not alter oxygen-hemoglobin saturation, cyanosis will not develop. In fact, the inability to utilize oxygen increases the venous oxygen saturation, leading to a cherry red appearance to the skin. It generally takes 6-8 minutes for death to occur following cyanide exposure.
B. Laboratory and X-ray Findings
An elevated blood cyanide concentration confirms the diagnosis. Given the short time interval to death, such testing is not useful in the acute setting but may later confirm the diagnosis. Two rapid tests, an elevated venous blood oxygen saturation and an increased lactic acid level, are characteristic of cyanide poisoning.
Treatment
A. Specific Therapy
In addition to cyanide's affinity for certain iron compounds, it also has a high affinity for sulfhydryl groups and for the methemoglobin complex. These 2 characteristics are the basis of the cyanide antidote kit. The kit contains 3 components: amyl nitrite (used if no vascular access is available), sodium nitrite, and sodium thiosulfate. First, the patient is given a nitrite compound (inhalation of an amyl nitrate ampule or sodium nitrite), which will cause the formation of methemoglobin. The dose of sodium nitrite is based on the patient's weight and hemoglobin concentration although 300 mg IV is the usual dose for non-anemic adults. Given the high affinity of methemoglobin for cyanide, it will preferentially bind the compound and help to remove it from the cytochrome a3 complex. Second, the patient is given sodium thiosulfate, (typically 12.5 g IV for an adult), which interacts with cyanide, forming thiocyanate. Thiocyanate is then excreted in the urine.
B. Supportive Measures
Severe lactic acidosis may be treated with bicarbonate administration. Seizures may be treated with benzodiazepines. In many cases, patients require intubation and ventilator support.
Decontamination
The only effective mode of decontamination involves removing the patient from the cyanide gas.
CHEMICAL DECONTAMINATION
Because of the risk of cross contamination to health care workers, the need for patient decontamination should be emphasized. All patients suspected of experiencing a chemical weapons attack should be decontaminated as soon as possible. Optimally, patient decontamination should be conducted in the field. Often this is not practical, and a decontamination station should be established in a secure location adjacent to the health care facility. All persons conducting decontamination duties should be provided adequate protective clothing and should receive specialized training.
Decontamination involves physical removal of toxin and chemical deactivation of toxin. The physical removal of toxin is usually the most effective means of decontamination in the acute setting. Remove all clothing, jewelry, dressings, and splints. Wash the patient with copious amounts of soap and water. Avoid vigorous scrubbing because this may facilitate toxin absorption.
After physical removal of toxin, any remaining toxin can be chemically deactivated. This may take some time and thus is considered secondary to physical removal of toxin. The most common neutralizing solution is 0.5% hypochlorite solution, which detoxifies many chemical agents via oxidation reactions. Hypochlorite solution should not be used to decontaminate open peritoneal wounds, open chest wounds, exposed neural tissue, or ocular tissue. Irrigate these areas with copious amounts of normal saline. All contaminated materials should be bagged and sent for proper disposal.
