Bioterrorism and Public Health Safety Concerns

Bioterrorism and Public Health Safety Concerns: Testing for Toxins and Infectious Agents

Synonym/acronym: N/A.

Common use

To assist in confirming the diagnosis of infection or poisoning in cases of accidental or intentional exposure to agents of high risk to public health safety.

Specimen

The facility or testing laboratory should be contacted regarding specimen collection requirements.

Normal findings

(Method: Disease specific) Negative findings for the organism or toxin of interest; negative serology; negative PCR.

Description

All local and state health departments and the Centers for Disease Control and Prevention (CDC) require health-care providers (HCPs) to report specific diseases/pathogens when they are identified by the requesting HCP or the testing laboratory. Information regarding reportable diseases for each agency can be accessed on their official Web site. This monograph will address some of the pathogens and toxins of biological origin that pose a national security risk through unintended exposure or transmission, use in a military action, or to perpetrate terrorist attacks against civilians. The CDC has grouped biological agents of concern into three categories based on the types of impact to public health that include ease of transmission, high mortality or morbidity rates, and level of action required for intervention by public health services. A selected sampling from categories A and B are presented in the table below. The full listing can be viewed at the CDC Web site (www.bt.cdc.bov/agent/agentlist-category.asp). Category A includes infectious organisms and toxins that pose the highest risk, Category B includes the next highest risk group, and Category C includes emerging infectious diseases.

The subspecialty of microbiology has been revolutionized by molecular diagnostics. Molecular diagnostics involves the identification of specific sequences of DNA. The application of molecular diagnostics techniques, such as PCR, has led to the development of automated instruments that can identify a single infectious agent or multiple pathogens from a small amount of specimen in less than 2 hr.

Infectious Organism/Toxin	Disease	Mode of Transmission and Site of Entry	Incubation Period, Signs, Symptoms, and Treatment	Specimen Required and Test Method
Category A
Bacillus anthracis is a gram-positive, aerobic, rod-shaped, spore-forming bacteria; spores are a dormant form of the bacteria. The composition of the spore confers resistance to unfavorable conditions for growth until a suitable environment is attained.	Anthrax	Bacillus anthracis is found naturally in soil and causes disease in humans when spores from the bacteria are ingested into the GI system in contaminated water, undercooked meat, or cutaneously by handling meat, wool, or hides from infected animals (usually hoofed animals in close contact with humans); by inhalation of spores or introduction of spores through breaks in the skin from contaminated animal products; or by an intentional and targeted release of spores in a bioterrorist attack. Infected individuals are not contagious; the disease is not transmitted directly from person to person.	The incubation period for anthrax infection is between 1 and 7 days and may vary according to the site of entry with inhalation anthrax having the most rapid progression of symptoms. Symptoms may also vary according to the site of entry. General symptoms include fever, malaise, and vomiting. Papules escalating to skin ulceration and eschar formation are associated with cutaneous anthrax; bloody diarrhea is associated with gastrointestinal (GI) anthrax; severe respiratory distress, pulmonary edema, and development of pleural effusions are associated with inhalation anthrax, advancing to shock, coma, nd possible death within 1–3 days after inhalation. Treatment for all forms of anthrax with antibiotics (penicillin, doxycycline, and ciprofloxacin) is usually successful, especially if administered early in the course of the disease. Untreated anthrax of any type or late stage inhaled anthrax may be fatal. Prevention can be enhanced through a veterinary vaccine used for periodic immunization of livestock, where appropriate. A cell free culture filtrate vaccine prepared from a non-encapsulated strain of Bacillus anthracis is available to individuals in high risk groups (military personnel and other individuals with high exposure risk due to the nature of their jobs). The vaccine is given in a series of five doses over 18 months (three primary doses and two boosters), the effectiveness is not well established, and there is a possibility of significant side effects.	Specimens considered for testing include blood, stool, skin lesions, sputum, throat culture, body fluids (sputum, ascites, cerebrospinal fluid (CSF), pleural fluid), tissue biopsy, and contaminated food (in the original container if possible). Test methods include culture and gram stain; polymerase chain reaction (PCR); immunochemical techniques (tissue samples); serology; enzyme-linked immunosorbent assays (ELISA). Specimen handling, testing, and culture handling should be performed in a Biosafety Level (BSL) 2 environment.
Clostridium botulinum is a gram-positive, anaerobic, rod-shaped, spore-forming bacteria that produces a potent neurotoxin; spores are a dormant form of the bacteria. The composition of the spore confers resistance to unfavorable conditions for growth until a suitable environment is attained	Botulism	Clostridium botulinum is found naturally in soil and other types of environments, including the human intestine. There are four forms of botulism. The food-borne disease occurs when the bacteria, toxin, or spores are ingested into the GI system in undercooked, contaminated meat, fish, vegetables, sauces, and home-canned foods especially when kept at room temperature after cooking. Infants under 1 year of age are susceptible to a type of botulism linked to ingestion of spores in honey. Wound botulism occurs when the bacteria, toxin, or spores are introduced through breaks in the skin. Botulism can also occur by inhalation of spores from a contaminated source or by an intentional and targeted release of spores in a bioterrorist attack. Infected individuals are not contagious; the disease is not transmitted directly from person to person. There are seven distinct botulism neurotoxin types known to affect humans, identified as A, B, C, D, E, F, and G.	The most common type of botulism is food borne, and the incubation period is a few hours to 3 days. Incubation periods for other types of botulism may vary according to the site of entry and can extend up to 1 wk for exposure by wound. Neuromuscular symptoms are the hallmark of how the toxin achieves its effect on the body and include blurred vision, difficulty swallowing, and muscle weakness that progresses to paralysis. Irreversible binding of the toxin to sites where neuromuscular activity is normally initiated prevent the release of a neurotransmitter called acetylcholine. Normal neuromuscular function halts as the body’s muscles are irreversibly paralyzed. Respiratory symptoms may also occur with inhalation botulism. Additional symptoms of infant botulism include other indications of altered neuromuscular function such as poor feeding (due to loss of muscle function related to sucking), constipation (due to loss of muscle function related to elimination), pooled oral secretions (due to loss of muscle function related to swallowing), and loss of head control related to loss of neck muscle strength and function. There is no prescribed treatment for botulism other than palliative care. As the paralysis advances and organ function diminishes, mechanical support is required for breathing and nutrition. A heptavalent vaccine is available for individuals identified as high risk and is effective for clostridial toxin strains A through G. An IV botulism immune globulin is available for infant botulism and is approved for the treatment of botulism types A and B. More information can be obtained from http://www.infantbotulism.org/.	Specimens considered for testing include blood, stool, vomitus, and contaminated food (in the original container if possible). Test methods include mouse neutralization test (to detect the toxin), culture. Specimen handling, testing, and culture handling should be performed in a BSL2 environment.
Francisella tularensis is a gram-negative, aerobic, coccobacillus.	Tularemia	Tularemia can be contracted in a number of different ways: ingestion of the bacteria into the GI system from contaminated water or plants; cutaneously through a break in the skin when handling infected animal products or from the bite of an infected insect, such as a tick or deerfly; or breathing the bacteria into the lungs. Infected individuals are not contagious; the disease is not transmitted directly from person to person.	The incubation period for tularemia averages 3 to 5 days but can take as long as 2 wk, depending on the site of entry. Symptoms may also vary according to the site of entry; the general symptoms of which include fever, chills, headache, diarrhea, weakness, muscle aches, and joint pain. Ingestion of the bacteria can cause symptoms that affect the entire alimentary canal including mouth ulcers, sore throat, swollen and painful lymph glands, intestinal pain, vomiting, and diarrhea. Inhalation of the bacteria can cause symptoms that resemble influenza or pneumonia, such as chest pain from difficulty breathing or bloody sputum. When the infection is introduced cutaneously, skin ulcers and swelling of the associated lymph nodes are evident. The disease can be fatal if it is not treated in a timely manner. Treatment for infection is a 2-wk course of the antibiotic doxycycline or ciprofloxacin. Currently there is no vaccine available in the United States; there is ongoing research to identify an effective vaccine.	Specimens considered for testing include serum, blood, sputum/throat swab, bronchial/tracheal wash, and stool. Test methods include serology, gram stain, and culture. Specimen handling and testing should be performed in a BSL2 environment; culture handling should be performed in a BSL3 environment.
Variola major is a severe and potentially lethal strain of the variola DNA virus.	Smallpox	The smallpox virus is transmitted by an infected human through the respiratory system in droplets that become aerosolized and are inhaled by another person in very close proximity. The smallpox virus can also be transmitted by direct contact with contaminated fomites or direct contact with body fluids from an infected person (secretions from rashes, pustules, or scabs), or by an intentional and targeted bioterrorist attack. The disease can be directly transmitted from person to person.	The incubation period for smallpox averages 12 to 14 days after which general symptoms develop to include fever, headache, and body aches followed by the development of a rash in the mouth and on the skin; the most infectious period is during the first 7 to 10 days following development of the rash. In the next stage of the infection the rash becomes pustular. Eventually the pustules dry up and scab formation occurs. Viable viral particles are present in the scabs; therefore, a person is considered contagious until after the last scab has fallen off. There is no specified treatment for smallpox, and the only prevention is by vaccination. Routine vaccination in the United States ended in 1972 after the disease was eradicated.	Specimens considered for testing include culture, vesicular fluid, skin scraping, and biopsy specimens. Test methods include viral culture or identification from a sample using electron microscopy. Specimen handling, testing, and culture handling should be performed in a BSL4 environment.
Filoviruses (e.g., Ebola, Marburg), arenaviruses (e.g., Lassa, Machupo), flaviviruses (including the virus that causes yellow fever), and bunyaviridae (e.g., Haantan). The viruses responsible for viral hemorrhagic fevers (VHFs) are RNA viruses.	VHF	VHFs are a group of severe infections caused by different RNA viruses. The viruses are transmitted to humans cutaneously by way of a bite from an infected reservoir host (e.g., rodent) or infected arthropod vector (e.g., mosquito or tick that has bitten an infected host). Some viruses (e.g., Ebola, Marburg, Lassa) can be directly transmitted from person to person by way of contact with contaminated blood or body fluids. The infection is significant; it can result in multisystem failure and death. Because some viruses have the potential to cause massive numbers of deaths through contagious infection they are considered possible weapons for use in an intentional and targeted bioterrorist attack.	The incubation period for VHFs varies from 3 to 21 days. Beginning symptoms include fever, headache, body aches, fatigue, jaundice, and vomiting; some cases progress with bleeding, shock, and multiorgan failure. There is no prescribed treatment for VHFs, and patients are given supportive treatment for their symptoms. Care should be taken in the selection of medications to reduce fever and pain, avoiding those medications known to increase the risk of bleeding (e.g., salicylates and NSAIDs). Yellow fever is the only VHF for which an effective vaccine is available. Additional preventive measures for yellow fever include avoidance of further exposure to mosquitos by staying indoors during hours when they are most active and using repellents and mosquito netting. Preventive measures decrease the opportunity for uninfected mosquitoes to feed on infected blood, which in turn decreases the spread of the disease.	Specimens considered for testing include serum, blood, sputum, and tissue. Test methods include viral isolation, PCR, ELISA, immunohistochemistry of tissue, and serology. Specimen handling, testing, and culture handling for yellow fever should be performed in a BSL3; for dengue should be performed in a BSL2; for others should be performed in a BSL4 environment.
Yersinia pestis is a gram-negative, facultatively anaerobic, obligate intracellular coccobacillus.	Plague	There are three forms of plague. The first and probably best known is bubonic plague. The reservoir host (usually a rodent) carries infected fleas; the fleas spread the disease cutaneously to humans through a bite. The bacteria multiply in the lymph node closest to the site of the flea bite. Septicemic plague occurs when the bacteria is inoculated into the bloodstream by flea bite or by the bite of an infected animal. Pneumonic plague is the most lethal form of plague. It occurs when the infection from either untreated bubonic or septicemic plague spreads to the lungs. Pneumonic is the only form of plague that can be transmitted person to person from inhalation of aerosolized droplets of contaminated fluid, direct contact with contaminated fomites (for short periods of time), or by an intentional and targeted bioterrorist attack.	The average incubation period for plague is 1 to 6 days depending on the site of entry; generally pneumonic plague has a shorter incubation period. General symptoms include fever, chills, enlarged lymph nodes, malaise, septicemia, hemorrhagic skin changes, pneumonia (pneumonic plague), shock, and death. Early identification and administration of antibiotics (tetracycline or fluoroquinolone) for 7 days, with supportive care is the most effective treatment for plague. Currently there is no FDA-approved vaccine available.	Specimens considered for testing include serum, blood, sputum/throat swab, bronchial/tracheal wash, and lymph node aspirate. Test methods include serology, gram stain, and culture. Specimen and culture handling should be performed in a BSL2 environment.
Category B
Brucella abortus, B. suis, B. melitensis, or B. canis; the species are gram-negative, aerobic, coccobacilli	Brucellosis	Infection occurs after ingestion into the GI system from infected meats and contaminated milk products (especially goat’s milk), direct puncture of the skin (by butchers and farmers), or by inhalation. It is not a contagious disease that is transmitted from person to person.	The average incubation period for brucellosis infection is 1 to 2 mo. General symptoms include fever, chills, headache, night sweats, back pain, joint pain, and malaise. The disease is systemic, affecting multiple organs and body systems. Brucellosis can be effectively treated with antibiotics (e.g., doxycycline, tetracycline, streptomycin, bactrim, rifampin, ciprofloxicin, or gentamicin). Currently there is no vaccine available for use in humans.	Specimens considered for testing include serum, blood, bone marrow, spleen or liver tissue, sputum, and food. Test methods include serology, gram stain, culture, and immunofluorescence. Specimen handling should be performed in a BSL2 environment; culture handling should be performed in a BSL3 environment.
Ricinus communis is the name for the castor oil plant. The plant’s seeds contain an oil composed mostly of the lipid ricinolein and smaller amounts of ricin, a powerful toxin.	Ricin poisoning. The toxin is released after ingestion of castor beans. It can also be purposely made from a waste product generated in the normal production of castor oil. The manufactured toxin can then be used in an intentional and targeted bioterrorist attack.	Ricin poisoning occurs by ingestion into the GI system or by inhalation into the respiratory system. It is not a contagious disease that is transmitted from person to person, and the likelihood of accidental poisoning is very low. The manufactured toxin can be released as a powder into the air or dissolved in water supplies. Very small amounts could sicken and kill large numbers of people and for this reason it is considered as a potential weapon for use in an intentional and targeted bioterrorist attack.	Symptoms of ricin poisoning vary based on the site of entry and concentration of the dose. If the toxin is ingested, GI symptoms such as nausea, pain, and vomiting appear in 6 to 12 hr; if the toxin is inhaled, respiratory symptoms such as difficulty breathing, coughing, and chest pain appear in 4 to 6 hr. Over the next 12 to 24 hr the symptoms will rapidly escalate toward organ failure. Ricin affects the body at the cellular level by preventing the production of proteins, an essential process for every living cell, tissue, and organ. Presently there are no methods available for the detection of ricin in biological fluids. Diagnosis of ricin poisoning is made using general laboratory tests for evidence of the effects of the toxin on the body and is arrived at within the context of high suspicion of exposure. Lab results of interest might include elevated liver function results, elevated renal function results, abnormal urinalysis findings such as blood in the urine, and moderate to very increased WBC count (two to five times normal levels).	Environmental samples can be tested for the presence of ricin by time-resolved fluorescence immunoassay and PCR. Specimen handling should be performed in a BSL2 or BSL3 environment depending on the possibility of aerosolization and concentration of toxin submitted for testing.

This procedure is contraindicated for

N/A

Indications

Suspected infection by high-risk pathogen (demonstrated by associated signs and symptoms or known exposure)

Potential diagnosis

Positive findings in:

Positive findings for the organism or toxin of interest; positive serology. Refer to the table in the Description section for details.

Critical findings

Positive findings for a disease listed in Description section leads to a high likelihood of being required for reporting to local, state, and/or federal health departments.

Interfering factors

Failure to follow the appropriate specimen collection and transport procedures may affect the validity of the results.

Nursing Implications and Procedure

Pretest

Positively identify the patient using at least two unique identifiers before providing care, treatment, or services.
Patient Teaching: Inform the patient this test can assist in assessing for infection or poisoning.
Obtain a history of the patient’s complaints, including a list of known allergens, especially allergies or sensitivities to latex.
Obtain a history of exposure, including all possible sources (e.g., environmental, other individuals who are ill with similar symptoms, food, animals, etc.).
Obtain a history of the patient’s immune system, a history of other potential sources of exposure, symptoms, and results of previously performed laboratory tests and diagnostic and surgical procedures.
Obtain a list of the patient’s current medications, including herbs, nutritional supplements, and nutraceuticals (see Effects of Natural Products on Laboratory Values online at DavisPlus).
Review the procedure with the patient. Inform the patient that several tests may be necessary to confirm the diagnosis. Any individual positive serology result may be repeated in 3 wk to monitor a change in detectable level of antibody, as appropriate. Inform the patient that specimen collection takes approximately 5 to 10 min. Address concerns about pain, and explain that there may be some discomfort during the venipuncture.
Sensitivity to social and cultural issues, as well as concern for modesty, is important in providing psychological support before, during, and after the procedure.
Note that there are no food or fluid restrictions unless by medical direction; as a general rule specimens should be collected prior to administration of antibiotics whenever possible. Chain of custody policies may be required in cases of intentional exposure.

Intratest

Potential complications: N/A
Avoid the use of equipment containing latex if the patient has a history of allergic reaction to latex.
Instruct the patient to cooperate fully and to follow directions. Direct the patient to breathe normally and to avoid unnecessary movement.
Contact the testing laboratory prior to specimen collection in order to obtain accurate information regarding specimen collection containers, sample volumes, and specific transport instructions.
Observe standard precautions, and follow the general guidelines in Patient Preparation and Specimen Collection. Positively identify the patient, and label the appropriate specimen container with the corresponding patient demographics, initials of the person collecting the specimen, date, and time of collection. Collect the appropriate specimen as described in the related body fluid analysis or culture monograph. The facility or testing laboratory should be contacted for guidelines regarding chain of custody, specimen collection requirements, and specimen packaging and shipping instructions.
Perform a venipuncture if blood is the specimen required for testing. Remove the needle and apply direct pressure with dry gauze to stop bleeding. Observe/assess venipuncture site for bleeding or hematoma formation and secure gauze with adhesive bandage.
Promptly transport the specimen to the laboratory for processing and analysis.

Post-Test

Inform the patient that a report of the results will be made available to the requesting health-care provider (HCP), who will discuss the results with the patient.
Recognize anxiety related to test results, and provide emotional support if results are positive. Discuss the implications of abnormal test results on the patient’s lifestyle. Provide teaching and information regarding the clinical implications of the test results, as appropriate. Educate the patient regarding access to counseling services.
Reinforce information given by the patient’s HCP regarding further testing, treatment, or referral to another HCP. Instruct the patient in isolation precautions during time of communicability or contagion, as appropriate. Instruct the patient in the proper way to decontaminate solid surfaces with a 1:10 dilution of household bleach; to decontaminate clothing; to “cover a cough;” and to perform good hand hygiene.
Depending on the results of this procedure, additional testing may be performed to evaluate or monitor progression of the disease process and determine the need for a change in therapy. Evaluate test results in relation to the patient’s symptoms and other tests performed. Emphasize the need to return to have a convalescent blood sample taken in 3 wk, if ordered. Answer any questions or address any concerns voiced by the patient or family.

Related Monographs

Related tests include acetylcholine receptor antibodies, basic metabolic panel, biopsy lung, biopsy lymph node, bronchoscopy, chest x-ray, CSF analysis, comprehensive metabolic panel, CT chest, culture throat, culture blood, culture sputum, culture stool, liver function tests, peritoneal fluid analysis, pleural fluid analysis, and renal function tests.
Refer to the Gastrointestinal, Genitourinary, Hematopoietic, Hepatobiliary, Immune, Musculoskeletal, and Respiratory System tables at the end of the book for related tests by body system.