Ricin is a potent cytotoxin that can be easily extracted from the beans of the castor plant (Ricinus communis). Castor beans are processed worldwide in production of castor oil, and ricin-rich waste mash is a by-product. Ricin can be prepared in liquid, crystalline, or powder form; as an agent of terrorism, it could be disseminated as an aerosol, injected, or used to contaminate food or water. Symptoms depend on the route of exposure: respiratory, enteral, or parenteral. Compared with other biological toxins (e.g., botulinum toxin), ricin has low toxicity, and large quantities would be required to affect large numbers of people.
Ricin inhibits cellular protein synthesis. Aerosol exposure results in fever, chest tightness, cough, dyspnea, nausea, and arthralgias after a delay of 4-8 hours. Death after aerosol exposure has not been reported in people, but animals develop necrosis and severe alveolar fluid collection. Ingestion of ricin causes necrosis of the gastrointestinal (GI) epithelium with local necrosis of muscle and regional lymph nodes. Intravascular injection causes minimal pulmonary perivascular edema.
Ricin exposure should be suspected if a geographic cluster of individuals develop acute lung injury. Pulmonary edema develops 1-3 days after exposure (compared with about 12 hours after Staphylococcus enterotoxin B exposure and about 6 hours after phosgene exposure). Ricin provokes a specific antibody response, and acute and convalescent sera should be obtained for antibody titer. Tissue can also be stained using immunohistochemical methods.
Treatment involves supportive care, including appropriate respiratory support and treatment for pulmonary edema if required. Enteral exposure should be treated by vigorous gastric lavage and use of cathartics.
Protective masks are effective in preventing exposure. No vaccine is available.
If ricin exposure is suspected, contact your State and local health departments. If they are unavailable, contact the Centers for Disease Control and Prevention (CDC) at 770-488-7100.
Q fever is caused by Coxiella burnetti, a rickettsial organism that causes usually asymptomatic infection in farm animals (cattle, sheep, goats). It can also infect dogs, cats, rodents, and some birds. Natural infection in people is rare. When it does occur, it usually is transmitted by aerosolized organisms from the tissues, fluids, or excreta of infected animals. Exposure through terrorism would likely involve aerosolization, and resulting disease would likely be similar to naturally occurring disease.
The incubation period is 9-39 days after exposure. Initial symptoms include sudden onset of fever, chills, headache, weakness, lethargy, anorexia, and profuse sweating. Approximately 50% of infected individuals have pneumonia. Liver function tests are often abnormal—a result of granulomatous hepatitis—but jaundice is rare. Neuropathies sometimes develop. Transmission to the fetus is common when pregnant women are infected. The infection becomes chronic in approximately 1% of infected individuals and can manifest as endocarditis or hepatitis.
Clinically, Q fever is not easily distinguished from other causes of flu-like symptoms and pneumonia. Coxiella can be isolated from blood cultures; however, if Q fever is suspected, blood cultures are not recommended because of the risk of exposure of laboratory personnel. Polymerase chain reaction (PCR) assays can identify the organism in tissue or environmental samples. Acute and convalescent sera should be submitted for antibody titers; antibody concentration may rise only after 2-3 weeks of illness.
Most infections resolve without specific therapy. Treatment with doxycycline may hasten recovery in acute infection. Chronic infection may require prolonged or repeated treatment. Chloramphenicol and ciprofloxacin are alternate choices for children <8 years of age and for pregnant women, respectively. The same antibiotics may be used for prophylaxis after known or suspected exposure. Prophylaxis should be delayed for 8-12 days after exposure and should be given for 5-7 days. Earlier prophylactic treatment may delay but not prevent disease.
Person-to-person transmission is not known to occur, although transmission from contaminated clothing has been reported. Soap and water or a 0.5% chlorine solution can be used for decontamination.
If Q fever is suspected, contact your local and State health departments. If they are unavailable, contact the CDC at 770-488-7100.
Staphylococcus enterotoxin B (SEB) is an exotoxin that acts on the intestine to produce a brisk cascade of pro-inflammatory cytokines, resulting in an intense inflammatory response. Food poisoning due to SEB results from ingestion of improperly handled food that contains enterotoxin.
Natural disease is generally localized to the GI tract. After a brief incubation period (30 minutes to 8 hours, usually 2-4 hours), the exposed individual experiences abrupt and sometimes violent onset of severe nausea, abdominal cramps, vomiting, and prostration, often accompanied by diarrhea. There may be an associated low-grade fever or subnormal temperature. Symptoms typically last 1-2 days. Inhalational exposure, as might be expected in an incident of bioterrorism, results in predominantly respiratory symptoms, including nonproductive cough, retrosternal chest pain, and dyspnea. GI symptoms may be seen as well if toxin is inadvertently swallowed. Fever (103°-106° F) is likely and may last up to 5 days with chills and prostration. There may be conjunctival injection, and fluid losses may lead to postural hypotension. Chest radiographs are likely to be normal, but overt pulmonary edema can occur.
Clinically, symptoms of staphylococcal enterotoxin ingestion can be distinguished from other causes of food poisoning except those due to Bacillus cereus. Illness due to Clostridium perfringens has a shorter incubation period and rarely is accompanied by vomiting. Foodborne Salmonella or Shigella infection usually is accompanied by fever.
Symptoms of inhalation of SEB are similar to those caused by many other respiratory pathogens. However, the clinical condition of respiratory disease due to inhaled SEB would be expected to stabilize without specific therapy, unlike that caused by tularemia, anthrax, or pneumonic plague. The absence of infiltrates on chest radiographs should also help distinguish respiratory tract disease caused by SEB from that caused by other likely agents of bioterrorism.
SEB antigen can be detected in urine, serum, or respiratory secretions. In addition, acute and convalescent serum samples should be submitted for antibody titer.
Supportive care should include close attention to hydration and oxygenation.
SEB is not absorbed through intact skin, and secondary aerosolization from affected patients is not hazardous. Environmental surfaces may be decontaminated using soap and water. Contaminated foodstuffs should be destroyed.
If disease due to SEB is suspected, contact your local and State health departments. If they are unavailable, contact the CDC at 770-488-7100.
Brucella species that infect people include B. abortus, B. melitensis, B. suis, and rarely, B. canis. Brucella species are small, gram-negative coccobacilli. People contract disease naturally through direct contact with infected animals and their carcasses or secretions or by ingestion of unpasteurized milk or milk products. Brucella species, particularly B. melitensis and B. suis, are potential terrorist agents. Aerosolization also can result in human infection.
Most infected individuals become ill within 3-4 weeks of exposure, but the incubation period may vary from <1 week to several months. Clinical features after natural exposure are extremely variable and nonspecific. They include flu-like symptoms—i.e., fever, sweats, malaise, anorexia, headache, myalgia, and back pain. Disease in children is commonly mild and self-limited, but in adults the illness is more chronic. Physical findings may include lymphadenopathy, hepatosplenomegaly, and occasionally, arthritis. Serious complications include meningitis, endocarditis, and osteomyelitis.
Brucella can be recovered in culture from blood, bone marrow, or other tissues. Specimens should be incubated for a minimum of 4 weeks. Serum samples collected at least 2 weeks apart can confirm the diagnosis with a four-fold rise in antibody titers. A polymerase chain reaction (PCR) test has been developed but is available only in reference laboratories.
Oral doxycycline (2-4 mg/kg/day, max 200 mg/day, divided BID [twice a day]) should be administered for 4-6 weeks. For children younger than 8 years, trimethoprim-sulfamethoxazole may be used (trimethoprim, 10 mg/kg/day, max 480 mg/day; sulfamethoxazole 50 mg/kg/day, maximum 2.4 g/day) divided BID for 4-6 weeks. Rifampin (15-20 mg/kg/day, max 600-900 mg/day), divided BID, should be added to prevent relapse. For patients who have endocarditis, osteomyelitis, or meningitis, therapy is often extended for several months with streptomycin sulfate or gentamicin sulfate added to the above regimens.
Prophylaxis after suspected exposure should be provided using doxycycline and rifampin.
Standard precautions provide adequate protection from spread of infection, except that contact precautions should be added for patients with draining wounds.
Reporting suspected Brucella infection, regardless of mechanism of exposure, is mandated throughout the United States. You should contact your local and State health departments. If they are unavailable, contact the CDC at 770-488-7100.
Glanders is caused by the gram-negative bacillus Burkholderia mallei. Most cases occur in horses, mules, or donkeys, but people may become infected through handling infected animals. There have been no naturally acquired cases of glanders in people in the United States in more than half a century; most human cases occur in Asia, the Middle East, or South America. It is believed that this organism was used during WWI and WWII as a weapon of terrorism to infect horses, mules, and people. Human cases diagnosed in the absence of animal cases should raise suspicion of terrorism.
The incubation period after exposure ranges from 1 to 14 days. Acute and chronic presentation is possible, but acute illness is most likely after a bioterrorist event. Disease may be localized (e.g., pneumonia) or disseminated (fulminant sepsis). Most commonly, symptoms include high fever, mucositis, and abscesses in multiple organs, predominantly the lungs, liver, and spleen.
Symptoms and signs associated with acute septicemia include fever, rigors, headache, muscle pain, night sweats, pleuritic chest pain, jaundice, sensitivity to light, and diarrhea. Diffuse erythroderma may be accompanied by necrotizing lesions. Cervical adenopathy, tachycardia, and mild hepatomegaly or splenomegaly may be present.
Acute localized disease may involve the lungs (after inhalation of particles or through hematogenous spread). In addition to the signs and symptoms associated with acute septicemia (above), miliary lesions and/or bilateral upper lobe infiltrates with or without consolidation or cavitation may be noted on chest radiograph. Mucous membrane involvement begins with nasal ulcers and nodules that secrete bloody discharge and often lead to sepsis. A papular and/or pustular rash, similar in appearance to the smallpox rash, may develop. Liver and spleen abscesses may be present. Septic shock usually follows.
Small bacilli may be seen on methylene blue or Wright stain of exudates. Both B. mallei and B. pseudomallei can be grown and identified from standard cultures.
Without effective antibiotic therapy, mortality nears 100%. Localized disease may be treated successfully with oral therapy for 60-150 days, while systemic illness requires parenteral therapy. Definitive antibiotic therapy should be based on susceptibility testing. Presumptive therapy can be provided using amoxicillin/clavulanate (60 mg/kg/day, PO [by mouth], divided TID [three times a day]), tetracycline (40 mg/kg/day, PO, divided TID), or trimethoprim-sulfamethoxazole (trimethoprim 4 mg/kg/day; sulfamethoxazole 20 mg/kg/day, PO, divided BID) for localized disease.
The effectiveness of prophylactic, postexposure therapy is not known. Trimethoprim-sulfamethoxazole may be tried.
Person-to-person transmission is unlikely after inhalational exposure as would be expected in disease due to terrorism. Transmission from direct contact between nonintact skin or mucous membranes and infected animal tissue is the usual means of natural infection. Standard precautions are adequate for most patients, while contact precautions should be added for patients with skin lesions. Environmental decontamination using 0.5% hypochlorite solution (bleach) is effective.
If glanders is suspected, contact your local and State health departments. If they are unavailable, contact the CDC at 770-488-7100.
Arboviruses (arthropod-borne viruses) are spread by mosquitoes, ticks, or sand flies and produce four principal clinical syndromes:
Infection with some arboviruses results in perinatal illness. Alpha viruses, including Eastern equine encephalitis (EEE) virus, Western equine encephalitis (WEE) virus, and Venezuelan equine encephalitis (VEE) virus, and yellow fever virus, a member of the Flavivirus genus, have been included in the CDC's list of potential agents of bioterrorism. In nature, disease due to these viral agents is limited to the geographic areas in which their arthropod vectors live.
For many encephalitis viruses, asymptomatic infection is common. Clinical illness, when it occurs, ranges in severity from a self-limiting febrile illness with headache and vomiting to a syndrome of aseptic meningitis or acute encephalitis. EEE virus infection is typically a fulminant illness that leads to coma and death in one-third of cases and to serious neurologic sequelae in another third. The clinical severity of WEE virus infection is intermediate, with a case fatality rate of 5%; neurologic impairment is common in infants. VEE virus infection produces acute systemic febrile illness, with encephalitis developing in a small percentage (4% in children; <1% in adults). The incubation period for EEE and WEE encephalitis viruses is 2-10 days, while that for VEE virus infection is 1-4 days.
Yellow fever virus infection evolves through three periods from a nonspecific febrile illness (with headache, malaise, weakness, nausea, and vomiting) through a brief period of remission, to a hemorrhagic fever with GI tract bleeding and hematemesis, jaundice, hemorrhage, cardiovascular instability, albuminuria, oliguria, and myocarditis. The incubation period is 3-6 days, and 50% of cases are fatal.
Diagnosis is made by serologic testing of cerebrospinal fluid (CSF) or serum or by viral isolation. Detection of virus-specific IgM antibody in CSF is confirmatory, and its presence in a serum sample is presumptive evidence of recent infection in a patient with acute CNS infection. Greater than four-fold change in serum antibody titer in paired serum samples obtained 2-4 weeks apart is confirmatory. A single increased antibody titer defines a case as presumptive. During the acute phase of yellow fever and VEE virus infection, virus can be isolated from blood and, in Venezuelan encephalitis, from the throat.
Active clinical monitoring and supportive therapy may be life saving.
Respiratory precautions are recommended when caring for patients with VEE virus infection. Patients with yellow fever may have active virus circulating in the blood, so they should be kept away from potential vector mosquitoes that could feed on them and subsequently transmit infection to others. Standard precautions are recommended for patients with EEE and WEE virus infection. A live-attenuated yellow fever vaccine is available and is currently used for individuals traveling to countries where yellow fever is endemic (some parts of South America and Africa). The vaccine is currently available in the United States only at approved vaccination centers.
If viral encephalitis or yellow fever is suspected, contact your local and State health departments. If they are unavailable, contact the CDC at 770-488-7100.
Food poisoning may be caused by a heat-labile toxin produced in vivo by C. perfringens type A; type C causes enteritis necroticans. Spores of C. perfringens may survive cooking. Spores germinate and multiply during slow cooling and storage at temperatures of 20°-60° C (68°-140° F). Once ingested, an enterotoxin produced by the organisms in the lower intestine is responsible for symptoms. Beef, poultry, gravies, and dried or precooked foods are common sources. Infection usually is acquired when food is prepared in large quantities and kept warm for prolonged periods (e.g., at banquets or institutions or from food provided by caterers or restaurants).
Onset of watery diarrhea and moderate to severe, crampy, midepigastric pain is sudden. Vomiting and fever are uncommon. Symptoms usually resolve in 24 hours. The incubation period is usually 8-12 hours.
The short incubation, short duration, and absence of fever in most patients differentiates C. perfringens foodborne disease from shigellosis and salmonellosis. The infrequency of vomiting and longer incubation period contrast with the clinical features of foodborne disease associated with heavy metals, Staphylococcus aureus enterotoxins, and fish and shellfish toxins. Diarrheal disease caused by Bacillus cereus enterotoxin may be indistinguishable from that caused by C. perfringens. Enteritis necroticans is a cause of severe illness and death attributable to C. perfringens food poisoning among children in Papua, New Guinea (where it is also known as pigbel).
Because the fecal flora of healthy people commonly includes C. perfringens, counts of 106/gram of feces obtained within 48 hours of onset of illness are required to support the diagnosis. The diagnosis can be suggested by detection of C. perfringens enterotoxin in feces by commercially available kits. To confirm C. perfringens as the cause, the concentration of organisms should be at least 105/gram in the epidemiologically implicated source of infection (food). Although C. perfringens is an anaerobe, special transport conditions are unnecessary because the spores are durable. Fecal samples, rather than rectal swab specimens, should be obtained.
Oral rehydration or, occasionally, intravenous (IV) fluid and electrolyte replacement may be indicated to prevent or treat dehydration. Antimicrobial agents are not indicated.
Clostridium perfringens food poisoning is not transmissible from person to person.
If C. perfringens food poisoning is suspected, contact your local and State health departments. If they are unavailable, contact the CDC at 770-488-7100.