Public Health Emergency Preparedness
This resource was part of AHRQ's Public Health Emergency Preparedness program, which was discontinued on June 30, 2011, in a realignment of Federal efforts.
This information is for reference purposes only. It was current when produced and may now be outdated. Archive material is no longer maintained, and some links may not work. Persons with disabilities having difficulty accessing this information should contact us at: https://info.ahrq.gov. Let us know the nature of the problem, the Web address of what you want, and your contact information.
Please go to www.ahrq.gov for current information.
Chapter 4. Biological Terrorism (continued)
Category A Agents
Select Table 4.3 for Diagnostic Procedures, Isolation Precautions, Treatment, and Postexposure Prophylaxis for Selected Bioterrorist Agents in Children.
Bacillus anthracis, the etiologic agent of anthrax, is a gram-positive, anaerobic, spore-forming, bacterial rod. The three virulence factors of B. anthracis are edema toxin, lethal toxin and a capsular antigen. Human anthrax has three major clinical forms:
If untreated, anthrax in all forms can lead to septicemia and death. Anthrax generally is not contagious, but person-to-person transmission from cutaneous lesions has been reported rarely. For more information, go to: http://www.bt.cdc.gov/agent/anthrax/index.asp.
Signs and Symptoms
Symptoms usually occur within 2 weeks of exposure; however, the incubation period for inhalational anthrax may be as long as several months because of spore dormancy and delayed clearance from the lungs.
Cutaneous anthrax. Cutaneous anthrax is the most common type of infection (>95%). It usually develops after skin contact with contaminated meat, wool, hides, or leather from infected animals. The incubation period ranges from 1 to 12 days. The skin infection begins as a small papule and progresses to a vesicle in 1 to 2 days, followed by a painless, necrotic ulcer with a black eschar, usually 1-3 cm in diameter (Figure 4.3, 28 KB). Patients may have fever, malaise, headache, and regional lymphadenopathy.
Inhalational anthrax. Inhalational disease is the most lethal form of anthrax. The incubation time of inhalational anthrax in people is unclear, but it is reported to range from 1 to 7 days, possibly up to 60 days. Initial symptoms resemble common respiratory infections and include mild fever, muscle aches, and malaise. Some patients also complain of sore throat. These symptoms progress to nonproductive cough, pleuritic chest pain, shortness of breath, respiratory failure, and frequently, meningitis. Upper respiratory symptoms such as rhinorrhea are generally not seen with inhalational anthrax.
Gastrointestinal anthrax. Gastrointestinal disease is the least common form of anthrax. It usually follows the consumption of raw or undercooked contaminated meat and has an incubation period of 1 to 7 days. Severe abdominal distress is followed by fever and signs of septicemia. The disease can take an oropharyngeal or abdominal form. Lesions at the base of the tongue, sore throat, dysphagia, fever, and regional lymphadenopathy usually characterize involvement of the oropharynx. Lower bowel inflammation usually causes nausea, loss of appetite, vomiting, and fever, followed by abdominal pain, hematemesis, and bloody diarrhea.
The clinical evaluation of patients suspected of having inhalational anthrax should include a chest radiograph and/or computer tomography (CT) scan to evaluate for widened mediastinum and pleural effusion. (Figure 4.1, 20 KB).
Anthrax is not spread by person-to-person contact except in rare cases of transmission from cutaneous lesions. If the history does not reveal possible environmental exposure, anthrax is not a likely diagnosis. Depending on the clinical presentation, Gram stain and culture should be performed on specimens of blood, pleural fluid, cerebrospinal fluid (CSF), and tissue biopsy or discharge from cutaneous lesions; however, previous treatment with antimicrobial agents can result in false negatives. Isolates can be definitely identified through the Laboratory Response Network (LRN) in each State. Additional diagnostic tests, including immunohistochemistry, real-time polymerase chain reaction (PCR), time-resolved fluorescence, and an enzyme immunoassay that measures immunoglobulin-G (IgG) antibodies against B. anthracis protective antigen, are performed at the Centers for Disease Control and Prevention (CDC) and can be accessed through State health departments.
Nasal swabs for detection of B. anthracis may assist in epidemiologic investigations but should not be relied on as a guide for prophylaxis or treatment of individual patients. Epidemiologic investigation in response to threats of exposure to B. anthracis may use nasal swabs of potentially exposed individuals as an adjunct to environmental sampling to determine the extent of exposure. (Tables 4.4a and 4.4b).
A high index of clinical suspicion and rapid administration of effective antimicrobial therapy are essential for prompt diagnosis and effective treatment. No controlled trials have been performed in people to validate current treatment recommendations, and clinical experience is limited. For bioterrorism-associated cutaneous disease in adults or children, ciprofloxacin (500 mg, PO [by mouth], BID [twice a day], or 10-15 mg/kg/day for children, PO, divided BID) or doxycycline (100 mg, PO, BID, or 5 mg/kg/day, PO, divided BID for children younger than 8 years of age) are recommended for initial treatment until antimicrobial susceptibility data are available. Because of the risk of concomitant inhalational exposure, consideration should be given to continuing an appropriate antimicrobial regimen for postexposure prophylaxis.
Ciprofloxacin (400 mg, intravenously [IV], every 8-12 hours) or doxycycline (200 mg, IV, every 8-12 hours) should be used initially as part of a multidrug regimen for treating inhalational anthrax, anthrax meningitis, cutaneous anthrax with systemic signs, and gastrointestinal (GI) anthrax until results of antimicrobial susceptibility testing are known. Other agents with in vitro activity suggested for use in conjunction with ciprofloxacin or doxycycline include rifampin, vancomycin hydrochloride, imipenem, chloramphenicol, penicillin, ampicillin, clindamycin, and clarithromycin. Cephalosporins and trimethoprim-sulfamethoxazole should not be used. Treatment should continue for at least 60 days. Neither ciprofloxacin nor tetracycline is routinely used in children or pregnant women because of safety concerns. However, ciprofloxacin or tetracycline should be used for treatment of anthrax in children who have life-threatening infections until antimicrobial susceptibility patterns are known.
About 20% of untreated cases of cutaneous anthrax result in death, but deaths are rare if patients receive appropriate antimicrobial therapy. The case fatality rate of inhalational anthrax is estimated to be 50% to 75%, even with early treatment. The case fatality rate of GI anthrax is estimated to be between 25% and 60%. The impact of antibiotic treatment on the case fatality rate of GI anthrax is unknown.
Standard precautions are recommended for hospitalized patients. Contaminated dressings and bed linens should be incinerated or steam sterilized to destroy spores. Autopsies performed on patients with systemic anthrax require special precautions.
BioThrax (formerly known as Anthrax Vaccine Adsorbed [manufactured by BioPort Corp, Lansing, MI]) is the only vaccine licensed in the United States for prevention of anthrax in people. This vaccine is prepared from a cell-free culture filtrate. Immunization consists of six SC injections at 0, 2, and 4 weeks and at 6, 12, and 18 months, followed by annual boosters. The vaccine is currently recommended for people at risk of repeated exposures to B. anthracis spores, including select laboratory workers and military personnel. The vaccine is effective for preventing cutaneous anthrax in adults. Protection against inhalational anthrax has not been evaluated in people, but the vaccine has been effective in studies in nonhuman primates. Adverse events are mainly local injection site reactions; systemic symptoms, including fever, chills, muscle aches, and hypersensitivity are rare. No data on vaccine effectiveness or safety in children are available, and the vaccine is not licensed for use in children or pregnant women. Anthrax vaccine is not licensed for postexposure use in preventing anthrax.
Based on the limited available data, the best means of preventing inhalational anthrax after exposure to B. anthracis spores is prolonged antimicrobial therapy in conjunction with a three-dose regimen (at 0, 2, and 4 weeks) of anthrax immunization. However, because BioThrax is not licensed for postexposure prophylaxis or for use as a three-dose regimen or for use in children, it can be used only under an investigational new drug application as part of an emergency public health intervention. When no information is available about the antimicrobial susceptibility of the implicated strain of B. anthracis, initial postexposure prophylaxis for adults or children with ciprofloxacin or doxycycline is recommended.
Although fluoroquinolones and tetracyclines are not recommended as first-choice drugs in children because of adverse effects, these concerns may be outweighed by the need for early treatment of pregnant women and children exposed to B. anthracis after a terrorist attack. As soon as susceptibility of the organism to penicillin has been confirmed, prophylactic therapy for children should be changed to oral amoxicillin, 80 mg/kg/day, divided TID (three times a day; not to exceed 500 mg, TID). Bacillus anthracis is not susceptible to cephalosporins and trimethoprim-sulfamethoxazole; therefore, these agents should not be used for prophylaxis (Table 4.5).
For more information, go to: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5045a5.htm.
If a case of anthrax is suspected, immediately contact the local and State health departments and hospital infection control practitioner. If they are unavailable, contact the CDC at 770-488-7100.
For a quick fact sheet, go to http://www.bioterrorism.slu.edu/botulism/quick/botulism01.pdf.
For additional information, go to http://jama.ama-assn.org/cgi/content/full/285/8/1059?.
Botulism is a rare disease caused by ingestion of the anaerobic, spore-forming bacillus Clostridium botulinum. Botulism neurotoxins are the most potent toxins known. There are three forms of naturally occurring botulism:
- Infant (intestinal).
In addition, inhalational disease could occur if aerosolized botulinum toxin were used, such as in a bioterrorist incident. A thorough history may help determine the mode of infection. If no common food source is identified during an outbreak or cluster of cases, bioterrorism should be suspected.
Signs and Symptoms
The incubation period varies according to the type of botulism and the extent of exposure to the toxin:
- Foodborne: 12-36 hours (range 6 hours to 10 days).
- Wound: 7-8 days (range 4-18 days) after injury.
- Infant: 18-36 hours after ingestion.
- Inhalational: The true incubation period for aerosolized botulism is unknown. In the three known inhalational cases, onset was approximately 72 hours. In laboratory studies, monkeys developed disease 12-18 hours after exposure.
Regardless of the means of exposure, botulinum toxin causes permanent nerve damage by irreversibly binding to nerve synapses and interfering with the release of acetylcholine. Botulinum toxin cannot cross the blood-brain barrier and does not affect the central nervous system (CNS). Sensory systems remain intact while the peripheral cholinergic synapses are damaged, resulting in flaccid paralysis in a patient who remains mentally alert and afebrile.
The toxin first affects the muscles connected to the cranial nerves. Early symptoms of all forms of the disease include double or blurred vision, difficulty with speaking and swallowing, dry mouth, and fatigue. As the disease progresses, symmetrical muscle weakness develops, starting at the trunk and descending to the extremities; deep tendon reflexes generally remain intact.
Without ventilatory support, death results when the toxin attacks the respiratory system, resulting in airway obstruction and respiratory paralysis. Recovery may occur if paralyzed muscles are reinnervated, but this process requires weeks to months of intensive supportive therapy.
Foodborne. Infants may develop disease after ingestion of C. botulinum organisms and subsequent GI absorption of toxin. Among babies older than 6-12 months, disease results only from ingestion or inhalation of preformed toxin. Initial symptoms include vomiting, constipation, GI upset, and rarely diarrhea, followed by symptoms listed above. These GI symptoms are thought to be caused by other bacterial metabolites also present in the food and may not occur if purified botulinum toxin is intentionally placed in foods or aerosols. Respiratory support is required in 57% to 81% of patients.
Wound. This form of the disease most closely resembles tetanus. Neurotoxins produced by the contaminating organisms in the affected wound disseminate throughout the body and destroy the nerve endings. Symptoms are similar to those of foodborne illness, except that there are no GI symptoms.
Infants. The initial symptom is generally constipation, although lethargy, lack of appetite, drooling, and weakness also occur. Descending symmetrical paralysis follows, evidenced by bulbar palsies: poor head and muscle control; flat affect; ptosis; impaired gag, suck, and swallow reflexes; dilated or sluggish pupillary reaction; and a weak cry. Respiratory failure is common. Intubation is required in >80% of cases, and ventilatory support is necessary (Figure 4.2, 24 KB).
A presumptive diagnosis can be made based on signs and symptoms. Laboratory confirmation is needed for definitive diagnosis. Obtaining a history that focuses on food intake and potential exposure to the organism is imperative.
Signs and symptoms of botulism that help distinguish it from other causes of weakness include the following:
- Disproportionate involvement of cranial nerves.
- Involvement of facial muscles to a greater extent than more distal weakness.
- The lack of sensory changes that usually accompany other disorders that result in flaccid paralysis.
Confirmatory tests include detection of toxin through mouse bioassay using the following specimen(s): blood and feces (foodborne), blood and wound (wound), and feces (intestinal). Toxin can also be detected in gastric secretions, which might be the most useful specimen in a case of inhalational disease. For results of the bioassay to be accurate, all specimens should be refrigerated during storage, serum samples should be obtained before antitoxin treatment, and the laboratory should be notified if the patient has taken anticholinesterase medications. Definitive diagnosis may be made through monovalent and polyvalent diagnostic antitoxins available from the CDC and a limited number of public health departments.
Rapid diagnosis and initiation of treatment and supportive care provide the best opportunity for survival. Treatment should begin as soon as the diagnosis is suspected without waiting for laboratory confirmation. Antitoxin, available from the CDC by calling 770-488-7100, should be administered to all patients with known or suspected disease. Antitoxin cannot reverse the effects of toxin bound to nerve receptors, but it does prevent further progression of nerve damage. Because the antitoxin is derived from horse serum, serious complications (including anaphylaxis and serum sickness) can develop. Supportive care generally includes intensive care, tube feedings or total parenteral nutrition (TPN), and ventilator support (in 29% of foodborne cases and 80% of infant cases).
Recommendations for safe and effective administration of antitoxin have changed over time; package insert materials should be reviewed before initiation.
Foodborne and inhalational botulism. Trivalent equine botulinum antitoxin (types A, B, and E) and bivalent antitoxin (types A and B) are available from the CDC at 770-488-7100 or through State health departments for treatment of foodborne or wound botulism. Patients should be tested for hypersensitivity to equine sera before administration. Approximately 9% of treated people experience some degree of hypersensitivity to equine serum, but severe reactions are rare.
Infant botulism. A 5-year, randomized, double-blind, placebo-controlled treatment trial of human-derived botulinum antitoxin (formally known as botulism immune globulin intravenous [BIGIV]) in infants with botulism showed a significant decrease in hospital days, mechanical ventilation, tube feedings, and cost associated with BIGIV administration ($70,000 less per case). The California Department of Health Services (24-hour telephone number, 510-540-2646) should be contacted to procure BIGIV. Treatment with BIGIV should begin as early in the illness as possible. BIGIV is available only for treatment of infant botulism. Approximately 9% of treated people experience some degree of hypersensitivity reaction to equine serum, but severe reactions are rare.
Antimicrobial agents should be avoided in infant botulism because lysis of intraluminal C. botulinum could increase the amount of toxin available for absorption. Aminoglycosides can potentiate the paralytic effects of the toxin and should be avoided.
Standard precautions should be used in the care of hospitalized patients with botulism. Person-to-person transmission does not occur.
Individuals known to be exposed or suspected of having been exposed to aerosolized botulinum toxin should be closely monitored and treated with antitoxin at the first sign of disease. Prophylactic equine antitoxin for asymptomatic people who have ingested a food known to contain botulinum toxin is not recommended. Because of the danger of hypersensitivity reactions, the decision to administer antitoxin requires careful consideration. Consultation about antitoxin use may be obtained from the State health department or the CDC.
Elimination of recently ingested toxin may be facilitated by induction of vomiting, gastric lavage, rapid purgation, and high enemas. These measures should not be used in infant botulism. Enemas should not be administered to people with illness except to obtain a fecal specimen for diagnostic purposes. Exposed people should be observed closely.
Clostridium botulinum is a hardy spore that is highly heat resistant, but botulism toxin in food is easily destroyed through the normal cooking process (heating >85º C for 5 minutes). Weather conditions and size of the aerosolized particles determine how long the toxin can remain airborne, but it is estimated that most toxin would be inactive within 2 days of aerosol release. If a warning is issued before a release, some protection can be achieved by covering the mouth with cloth or a mask; toxin may be absorbed through mucous membranes but cannot penetrate intact skin. After a known exposure, patients and their clothing should be washed with soap and water. Surfaces exposed to the initial release should be cleaned with a 1:10 hypochlorite (bleach) solution.
If you suspect a case of botulism, immediately contact your hospital epidemiologist or infection control practitioner and local and State health departments. If local and State health departments are unavailable, contact the CDC at 770-488-7100.
For further information and fact sheets, go to: http://www.bt.cdc.gov/agent/botulism/index.asp.
Plague is caused by Yersinia pestis, a pleomorphic, bipolar-staining, gram-negative
coccobacillus. In nature, plague is a zoonotic infection of rodents, carnivores, and their fleas that
are found in many areas of the world. Plague has been reported throughout the Western United
States, but most human cases occur in New Mexico, Arizona, California, and Colorado as
isolated cases or in small clusters.
- Bubonic plague usually is transmitted by bites of infected rodent fleas and uncommonly by direct contact with tissues and fluids of infected rodents or other mammals, including domestic cats.
- Septicemic plague occurs most often as a complication of bubonic plague but may result from direct contact with infectious materials or the bite of an infected flea.
- Primary pneumonic plague is acquired by inhalation of respiratory droplets from a human or animal with respiratory plague or from exposure to laboratory aerosols.
- Secondary pneumonic plague arises from hematogenous seeding of the lungs with Y. pestis in patients with bubonic or septicemic plague.
The incubation period is 2-6 days for bubonic
plague and 2-4 days for primary pneumonic plague.
Signs and Symptoms
A bioterrorist incident involving plague would most likely occur through aerosolization and result in pneumonic involvement. The incubation period after flea-borne transmission is 2-8 days. Incubation after aerosolization would be expected to be shorter (1-3 days). Clinical features of pneumonic plague include fever, cough with mucopurulent sputum (gram-negative rods may be seen on Gram stain), hemoptysis, and chest pain. A chest radiograph will show evidence of bronchopneumonia.
Plague is characterized by massive growth of Y. pestis in affected tissues, especially lymph nodes, spleen, and liver. The organism has a bipolar (safety-pin) appearance when viewed with Wayson or Gram stains. If plague organisms are suspected, the laboratory examining the specimens should be informed to minimize risks of transmission to laboratory personnel. Handling of specimens should be coordinated with local or State health departments and undertaken in Biosafety Level 2 or Level 3 laboratories.
A positive fluorescent antibody test result for the presence of Y. pestis in direct smears or cultures of a bubo aspirate, sputum, CSF, or blood specimen provides presumptive evidence of Y. pestis infection. A single seropositive result by passive hemagglutination assay or enzyme immunoassay in an unimmunized patient who has not had plague previously also provides presumptive evidence of infection. Seroconversion and/or a four-fold difference in antibody titer between two serum specimens obtained 1 to 3 months apart provides serologic confirmation. The diagnosis of plague usually is confirmed by culture of Y. pestis from blood, bubo aspirate, or another clinical specimen. PCR assay or immunohistochemical staining for rapid diagnosis of Y pestis is available in some reference or public health laboratories. Isolates suspected as Y. pestis should be reported immediately to the State health department and submitted to the Division of Vector-Borne Infectious Diseases of the CDC. For additional information, go to: http://www.cdc.gov/ncidod/dvbid/plague/diagnosis.htm
Streptomycin sulfate (30 mg/kg/day, IM [intramuscular], divided BID-TID) is the treatment of choice for most children. Gentamicin sulfate in standard dosages for age given IM or IV is an equally effective alternative to streptomycin. Tetracycline, doxycycline, or chloramphenicol is also effective. Tetracycline or doxycycline should not be given to children younger than age 8 unless the benefits of use outweigh the risks of dental staining. Chloramphenicol is the preferred treatment for plague meningitis. Antimicrobial treatment should be continued for 7-10 days or until several days after fever breaks. Drainage of abscessed buboes may be necessary; drainage material is infectious until effective antimicrobial therapy has been given.
In addition to standard precautions, droplet precautions are indicated for all patients with suspected plague until pneumonia is excluded and appropriate therapy has been started. Special air handling is not indicated. In patients with pneumonic plague , droplet precautions should be continued for 48 hours after appropriate treatment has been started.
Postexposure prophylaxis should begin after confirmed or suspected exposure to Y. pestis and for postexposure management of health care workers and others who have had unprotected face-to-face contact with symptomatic patients. In children, prophylactic treatment with doxycycline (5 mg/kg/day, divided BID) or ciprofloxacin (20-30 mg/kg/day divided BID) is recommended and should be continued for 7 days after exposure or until exposure can be excluded. Household members and other people with intimate exposure to a patient with plague should report any fever or other illness to their physician.
Currently, no vaccine for plague is commercially available in the United States. Information concerning the availability of plague vaccines is available from the Division of Vector-Borne Infectious Diseases of the CDC.
State public health authorities should be notified immediately of any suspected cases of plague in people. Initial suspicion of a bioterrorist event involving Y. pestis will likely involve identification of more than one case in a nonendemic area. If this occurs, immediately contact your local and State health departments and hospital infection control practitioner. If they are unavailable, contact the CDC at 770-488-7100.
Variola, the virus that causes smallpox, is a member of the Poxviridae family (genus
Orthopoxvirus). These DNA viruses are among the largest and most complex viruses known, and
they differ from most other DNA viruses by multiplying in the cytoplasm. Monkeypox, vaccinia,
and cowpox are other members of the genus and can cause zoonotic infection of people, but they
usually do not spread from person to person. People are the only natural reservoir for variola
virus. For additional information, go to http://www.bt.cdc.gov/agent/smallpox/.
In 1980, the World Health Organization (WHO) declared that
smallpox (variola) had been successfully eradicated
worldwide. The last naturally occurring case of smallpox occurred
in Somalia in 1977, followed by two cases attributable to laboratory exposure in
1978. The United States discontinued routine childhood immunization against smallpox in
1971 and routine immunization of health care workers in 1976. The U.S. military
continued to immunize military personnel until 1990. Since 1980, the vaccine
has been recommended only for people working with nonvariola orthopoxviruses.
Two WHO reference laboratories were authorized to maintain stocks
of variola virus. There is increasing concern that the virus and the expertise
to use it as a weapon of bioterrorism may have been misappropriated.
Signs and Symptoms
An individual infected with variola major develops a severe prodromal illness characterized by high fever (102°-104° F [38.9°-40.0° C]) and constitutional symptoms, including malaise, severe headache, backache, abdominal pain, and prostration, lasting 2-5 days. Infected children may have vomiting and seizures during this prodromal period. Most patients with smallpox tend to be severely ill and bedridden during the febrile prodrome. The prodromal period is followed by enanthemas that may not be noticed by the patient. This stage occurs <24 hr before the onset of rash, which is usually the first recognized manifestation of infectiousness. With the onset of enanthemas, the patient becomes infectious and remains so until all skin crust lesions have separated. The rash, or exanthem, typically begins on the face and rapidly progresses to involve the forearms, trunk, and legs in a centrifugal distribution (greatest concentration of lesions on the face and distal extremities). Many patients have lesions on the palms and soles of their feet. With rash onset, fever decreases, but the patient does not fully defervesce. Lesions begin as maculas that progress to papules, then firm vesicles, and then deep-seated, hard pustules described as "pearls of pus," with each stage lasting 1-2 days. By day 6 or 7 of the rash, lesions may begin to umbilicate or become confluent. Lesions increase in size for approximately 8-10 days, after which they begin to crust. Once all the lesions have separated, 3-4 weeks after the onset of rash, the patient is no longer infectious. Infected people sustain significant scarring after the crusts have separated. Because of the relatively slow and steady evolution of the rash lesions, all lesions on any one part of the body are in the same stage of development (Figure 4.5 [26 KB], smallpox lesions).
Varicella (chickenpox) is the condition most likely to be mistaken for smallpox. Generally, children with varicella do not have a febrile prodrome; adults may have a brief, mild prodrome. Although the two diseases can be easily confused in the first few days of the rash, smallpox lesions develop into pustules that are firm and deeply embedded in the dermis, whereas varicella lesions develop into superficial vesicles. Because varicella erupts in crops of lesions that evolve quickly, lesions on any one part of the body are in different stages of development (papules, vesicles, and crusts; Figure 4.6 [40 KB], varicella lesions). The distribution of the rash in the two diseases differs. Varicella most commonly affects the face and trunk with relative sparing of the extremities, and lesions on the palms or soles are rare (Figure 4.4 [33 KB], distribution of smallpox lesions vs. varicella lesions).
In addition to the typical presentation of smallpox (≥90% of cases), there are two uncommon forms of variola major:
- Hemorrhagic, characterized by hemorrhage into skin lesions and disseminated intravascular coagulation.
- Malignant or flat type, in which the skin lesions do not progress to the pustular stage but remain flat and soft.
In the past, each variant occurred in approximately 5% of cases and was associated with a 95%-100% mortality rate. Hemorrhagic smallpox rash commonly was confused with meningococcemia. Flat-type (velvety) smallpox occurred more commonly in children. By contrast, variola minor, or alastrim, was associated with fewer lesions, more rapid progression of rash, and a much lower mortality rate (approximately 1%) than variola major, or typical smallpox.
Smallpox is spread most commonly in droplets from the oropharynx of infected individuals, although infrequent transmission from aerosol and direct contact with infected lesions, clothing, or bedding has been reported. Patients are not infectious during the incubation period or febrile prodrome but become infectious with the onset of mucosal lesions (enanthemas), which occur within hours of the rash. The first week of rash illness is regarded as the most infectious period, although patients remain infectious until all scabs have separated. Because most smallpox patients are extremely ill and bedridden, spread generally is limited to household contacts, hospital workers, and other health care professionals. Secondary household attack rates for smallpox were considerably lower than for measles and similar to or lower than rates for varicella. The incubation period is 7-17 days (mean 12 days).
Variola major in unimmunized people was associated with case fatality rates of approximately 30% during epidemics of smallpox. The mortality rate was highest in children younger than 1 year and adults older than 30. The potential for modern supportive therapy in improving outcome is not known. Death was most likely to occur during the second week of illness and was attributed to overwhelming viremia. Secondary bacterial infections occurred but were a less significant cause of mortality.
For help in evaluating a rash illness suspicious of smallpox, go to: http://www.bt.cdc.gov/agent/smallpox/diagnosis/riskalgorithm/index.asp.
Variola virus can be detected in vesicular or pustular fluid by culture or by PCR assay. Electron microscopy can detect orthopoxvirus infection but cannot distinguish between viruses. Currently, variola diagnostic testing is conducted only at the CDC. Reports of patients classified by the CDC as at high risk of having smallpox will trigger a rapid response, with a team deployed to obtain specimens and advise on clinical management.
There is no effective antiviral therapy available to treat smallpox. Infected patients should receive supportive care. Cidofovir, currently licensed for cytomegalovirus retinitis, has been suggested as having a role in smallpox therapy, but data to support its use in smallpox are not available. The drug must be given IV and is associated with significant renal toxicity. Vaccinia immune globulin (VIG) is reserved for certain complications of immunization and has no role in treatment of smallpox.
If a patient is suspected of having smallpox, standard, contact, and airborne precautions should be implemented immediately, and the State and local health departments should be alerted at once. Hospital infection control personnel should be notified when the patient is admitted, and the patient should be placed in a private, airborne infection isolation room equipped with negative-pressure ventilation with high-efficiency particulate air filtration. Anyone entering the room must wear an N95 or higher-quality respirator, gloves, and gown, even if there is a history of recent successful immunization. If the patient is moved from the room, he or she should wear a mask and be covered with sheets or gowns to decrease the risk of fomite transmission. Rooms vacated by patients should be decontaminated using standard hospital disinfectants, such as sodium hypochlorite or quaternary ammonia solutions. Laundry and waste should be discarded into biohazard bags and autoclaved, and bedding and clothing should be washed in hot water with laundry detergent followed by hot-air drying or incinerated.
Vaccination. Postexposure immunization (within 3-4 days of exposure) provides some protection against disease and significant protection against a fatal outcome. Any person who has had significant exposure to a patient with confirmed smallpox during the infectious stage of illness should be immunized as soon after exposure as possible, but within 4 days of first exposure. Because infected individuals are not contagious until the rash (and/or enanthema) appears, individuals exposed only during the prodromal period are not at risk.
Vaccinia immune globulin. Vaccinia immune globulin (VIG) prepared from plasma of immunized individuals was used in the past to prevent or modify smallpox when administered within 24 hours of a known exposure. Current supplies of VIG are used in the treatment of complications of smallpox immunization. The CDC is the only source of VIG in the United States. Supplies may be obtained by calling the CDC Smallpox Vaccine Adverse Events Clinical Information Line at 877-554-4625 for physicians in civilian medical facilities.
Cases of febrile rash illness for which smallpox is being considered in the differential diagnosis should be reported immediately to local or State health departments. After evaluation by the State or local health department, if smallpox laboratory diagnostic testing is considered necessary, the CDC Rash Illness Evaluation Team should be consulted at 770-488-7100. Laboratory confirmation of smallpox is available only from the CDC. (Figure 4.8, evaluating febrile rash illness in patients suspected of having smallpox [algorithm]; 22 KB).
Tularemia is caused by Francisella tularensis, a small, nonmotile, aerobic, gram-negative
coccobacillus. Francisella tularensis is one of the most infectious pathogens known; inoculation
with or inhalation of as few as 10 organisms can cause disease. It is found in diverse animal
hosts and can be recovered from contaminated water, soil, and vegetation. Small mammals,
including voles, mice, water rats, squirrels, rabbits, and hares, are natural reservoirs. They
acquire infection through tick, fly, or mosquito bites and by contact with contaminated
environments. Natural infection in people occurs through bites of infected arthropods; handling
infectious animal tissues or fluids; direct contact with or ingestion of contaminated food, water
or soil; or inhalation of infective aerosols. Person-to-person transmission does not occur.
Aerosol release of F. tularensis as a bioterrorist
event would be expected to cause primarily pleuropneumonitis, but some
exposures might result in ocular tularemia, ulceroglandular or glandular
disease, or oropharyngeal disease with cervical lymphadenitis. Release in a
densely populated area would be expected to result in an abrupt onset of large
numbers of people with acute, nonspecific febrile illness beginning 3-5 days
later (incubation period is 1-14 days), with pleuropneumonitis developing in a
significant proportion of cases during the ensuing days and weeks.
Signs and Symptoms
Francisella tularensis is a facultative intracellular bacterium that multiplies within macrophages. Major target organs are the lymph nodes, lungs and pleura, spleen, liver, and kidney. Bacteremia may be common in early stages. Initial tissue reaction is a focal, intensely suppurative necrosis that becomes granulomatous. After inhalational exposure, hemorrhagic inflammation of the airways develops and progresses to bronchopneumonia. Pleuritis with adhesions, and effusion and hilar lymphadenopathy are common.
Illness begins with fever, headache, chills and rigors, generalized body aches, coryza, and sore throat. There may be a dry or slightly productive cough and substernal pain or tightness with or without objective signs of pneumonia. These findings are followed by sweats, fever, chills, progressive weakness, malaise, anorexia, and weight loss. These signs and symptoms would be similar to those caused by Q fever, but the progression of illness would be expected to be slower and the case-fatality rate lower than in inhalational plague or anthrax.
Francisella tularensis can be isolated from respiratory secretions and, sometimes, from blood in cases of inhalational infection. Gram stain, fluorescent antibody, or immunohistochemical stains (performed in designated reference laboratories in the National Public Health Laboratory Network) may demonstrate the organism in secretions, exudates, or biopsy specimens. If tularemia is suspected, the laboratory should be informed to minimize risks of transmission to laboratory personnel. Routine diagnostic procedures can be performed in Biosafety Level 2 conditions. Cultures in which F. tularensis is suspected should be examined in a biological safety cabinet. Manipulation of cultures and other procedures that might produce aerosols or droplets (e.g., grinding, centrifuging, vigorous shaking, animal studies) should be conducted under Biosafety Level 3 conditions. Bodies of patients who die of tularemia should be handled using standard precautions. Autopsy procedures likely to produce aerosols or droplets should be avoided. Clothing or linens contaminated with body fluids of patients with tularemia should be disinfected per standard hospital procedure.
In case of a bioterrorist event, antimicrobial susceptibility testing of isolates should be conducted quickly and treatment altered according to test results and clinical response. For treatment recommendations in children before test results are known, go to Table 4.6.
Treatment with streptomycin, gentamicin, doxycycline, or ciprofloxacin started during the incubation period of tularemia and continued daily for 14 days can protect against symptomatic infection. Therefore, if an attack is discovered before individuals become ill, those who have been exposed should be treated prophylactically with oral doxycycline or ciprofloxacin for 14 days. If an attack is discovered only after individuals become ill, a fever watch should begin for those who potentially have been exposed. Treatment (as outlined above) should begin in those who develop an otherwise unexplained fever or flu-like illness within 14 days of presumed exposure.
Postexposure prophylactic treatment of those in close contact with tularemia patients is not recommended because person-to-person transmission is not known to occur. Standard precautions should be used in caring for hospitalized patients.
Initial suspicion of a bioterrorist event involving F. tularensis will likely involve identification of more than one case in a nonendemic area. If this happens, immediately contact the local and State health departments and hospital infection control practitioner. If they are unavailable, contact the CDC at 770-488-7100.
For additional information, go to: http://www.bt.cdc.gov/agent/tularemia/facts.asp and
Viral Hemorrhagic Fevers
The term "viral hemorrhagic fevers" (VHFs) refers to a group of illnesses that are caused by
several distinct families of viruses. In general, the term "viral hemorrhagic fever" is used to
describe a severe multisystemic syndrome. Characteristically, the overall vascular system is
damaged, and the body's ability to regulate itself is impaired. Although some types of
hemorrhagic fever viruses cause relatively mild illnesses, many of these viruses cause severe,
VHFs are caused by RNA viruses of four distinct families:
- Arenaviruses (including Lassa fever).
- Filoviruses (including Rift Valley fever and hantavirus).
- Bunyaviruses (including Ebola and Marburg hemorrhagic fever).
- Flaviviruses (including tick-borne encephalitis).
In nature, the survival of these viruses depends on an animal or insect host called the natural reservoir. They are geographically restricted to the areas where their host species lives, and people are not the natural reservoir for any of these viruses. People may become infected when they come into contact with infected hosts, and in some cases, people can transmit the virus to one another. With a few exceptions, there is no cure or established drug treatment for VHFs.
Signs and Symptoms
Specific signs and symptoms vary by the type of VHF, but initial signs and symptoms often include marked fever, fatigue, dizziness, muscle aches, loss of strength, and exhaustion. Other signs and symptoms can include vomiting, diarrhea, abdominal pain, chest pain, cough, and pharyngitis. A maculopapular rash, predominantly on the trunk, develops in many patients about 5 days after the onset of symptoms. Patients with severe VHF often show signs of bleeding under the skin, in internal organs, or from body orifices like the mouth, eyes, or ears. However, although they may bleed from many sites around the body, patients rarely die because of blood loss. Severely ill patients may go into shock with nervous system malfunction, coma, delirium, and seizures. Some types of VHF are associated with renal failure.
The incubation period is 4-21 days. The mortality rate varies depending on the specific virus involved.
Diagnosis of VHF introduced through bioterrorism is likely to be recognized only after a cluster of patients present with similar, severe illness. Clinical suspicion should prompt notification of infection control and State health officials. Serum for antibody testing and tissue samples should be sent through your State health department to the CDC.
In general, there is no specific treatment or established cure for VHFs. Treatment is supportive. Ribavirin has been effective in treating some individuals with Lassa fever or hemorrhagic fever with renal syndrome. Treatment with convalescent-phase plasma has been used with success in some patients with Argentinean hemorrhagic fever.
Some viruses that cause hemorrhagic fever—including Ebola, Marburg, Lassa fever, and Crimean-Congo hemorrhagic fever viruses—can spread from one person to another (once an initial person has become infected). This type of secondary transmission of the virus can occur directly through close contact with infected people or their blood or other body fluids. Contaminated syringes and needles have been involved in the spread of infection in outbreaks of Ebola hemorrhagic fever and Lassa fever.
Both standard precautions and contact precautions should be used in caring for patients with suspected or confirmed VHF. A surgical mask and eye protection should also be worn by those coming within 3 feet of a patient with suspected or confirmed Lassa fever, Crimean-Congo hemorrhagic fever, or filovirus infections. Airborne isolation, including use of a HEPA-filtered respirator, should be used if patients with these conditions have prominent cough, vomiting, diarrhea, or hemorrhage. Decontamination should be performed using hypochlorite or phenolic disinfectants.
There are no vaccines to protect against these diseases, except for yellow fever and Argentinean hemorrhagic fever. For more information about specific VHF illnesses and their management, go to: http://www.cdc.gov/ncidod/dvrd/spb/mnpages/vhfmanual/anx2.pdf. PDF Help.)
These viruses are highly pathogenic and require handling in special laboratory facilities designed to contain them (Biosafety Level 4 facilities). If VHF is suspected, contact your State and local health departments immediately. If local and State health departments are unavailable, contact the CDC at 770-488-7100.
Return to Contents
Proceed to Next Section