Bioterrorism Infectious Agents Testing

Test Description

Among the health protection goals of the Centers for Disease Control and Prevention
(CDC) is to prepare people for emerging health threats, including those of bioterrorism.
The CDC website (http://www.bt.cdc.gov/bioterrorism/) provides access to
information on many biological agents. Biological agents are classified according to
three priority levels. The highest priority is Category A. According to the CDC, higher
priority agents include organisms that pose a risk to national security because they:
• can be easily disseminated or transmitted from person to person;
• result in high mortality rates and have the potential for major public health impact;
• might cause public panic and social disruption; and
• require special action for public health preparedness.
Currently, the agents classified as Category A include:

• Anthrax (Bacillus anthracis)

• Botulism (Clostridium botulinum toxin)
• Plague (Yersinia pestis)
• Smallpox (variola major)
• Tularemia (Francisella tularensis)
• Viral hemorrhagic fevers (filoviruses [e.g., Ebola, Marburg] and arenaviruses
[e.g., Lassa, Machupo])
Following is a compilation of information on the Category A agents, including a
description of the agent and how it is diagnosed.

Anthrax
Anthrax is caused by Bacillus anthracis, a bacterium that forms spores. People can
become infected through handling or breathing in the anthrax spores, or from ingesting
undercooked meat from infected animals. There are three types of anthrax: cutaneous,
gastrointestinal (GI), and inhalation. The cutaneous form begins with a papule
resembling an insect bite, which then progresses to development of a central vesicle.
This vesicle becomes a painless, necrotic ulcer. Lesions may be solitary or multiple
and are accompanied by regional lymphadenopathy, fatigue, fever, and/or chills. Even
without treatment, 80% of people with cutaneous anthrax survive. GI anthrax is more
serious, with 25% to 50% mortality. Symptoms include nausea, loss of appetite, bloody
diarrhea, fever, and abdominal pain. The most serious form is inhalation anthrax. It
first appears with cold or flu-like symptoms which progress to more severe respiratory
difficulty. Death can occur in 50% of the cases. Treatment involves antibiotic therapy
(ciprofloxacin or doxycycline) for 60 days. Survival depends on the type of anthrax
and how soon treatment is initiated.

Diagnostic Testing: Testing method depends on the type of anthrax suspected.
Cutaneous anthrax:
• Swabs of lesion for Gram stain, culture, and polymerase chain reaction (PCR)
• Biopsies for PCR
• Blood testing: acute and convalescent titers, blood culture

Gastrointestinal anthrax:
• Stool specimen
Inhalation anthrax:
• Blood for Gram stain, culture, and PCR.
• If pleural effusion present, pleural fluid can be obtained for Gram stain, culture, and
  PCR.
• Blood testing: acute and convalescent titers.
• If possible meningitis, cerebrospinal fluid (CSF) can be used for Gram stain, culture, and
  PCR.

Botulism
Botulism is a neuroparalytic illness caused by a toxin made by the bacterium Clostridium
botulinum. The disease is caused by ingestion of the toxin in food including vegetables,
meat, poultry, and milk products. Symptoms include dysphagia, dysarthria, progressive
weakness with paralysis, double vision, nausea, vomiting, abdominal pain, dry mouth, and
respiratory distress leading to possible respiratory failure. Treatment, involving respiratory
support and administration of botulinus antitoxin, is begun prior to laboratory results being
available.
Diagnostic Testing: Because botulism involves paralysis, it can easily be misdiagnosed as
Guillain-Barre, myasthenia gravis, or stroke. A normal Tensilon test can rule out myasthenia
gravis; normal neuroimaging studies rule out stroke. Confirmation of botulism is made
through identifying the toxin in serum, stool, or food or by culturing the bacterium from
stool, a wound, or food.

Plague

Plague is caused by the bacterium Yersinia pestis. It is usually transmitted by the bites of
infected fleas. However, it can also be spread through the handling of infected animals,
direct contact with contaminated tissue, or through inhalation of infectious droplets from
another person infected with plague pneumonia. Plague usually first appears as a tender
lymph gland (“bubo”) in the groin, axilla, or neck, followed by development of fever, chills,
headache, and fatigue. Pneumonic plague, characterized by fever, cough, hemoptysis, and
dyspnea, can also occur. Since the symptoms are not unlike many other illnesses, a thorough
history is needed to assess for exposure to infected animals or fleas. Without treatment
50% to 60% of the patients die; mortality is 14% with treatment. Treatment with antibiotics
(streptomycin, tetracyclines, or chloramphenicol) should begin immediately after laboratory
specimens are obtained.
Diagnostic Testing: Testing involves blood cultures for plague bacteria and microscopic
examination and culture of lymph gland, blood, and sputum samples, or bronchial
washings.

Smallpox

Smallpox is caused by the variola virus, usually the variola major virus. There are four
types of variola major including ordinary (most frequent type), modified, flat, and hemorrhagic.
Overall, the four types have a 30% mortality rate; however, the flat and hemorrhagic

types are usually fatal. Symptoms include high fever and a rash. During the prodromal
stage, fever, malaise, headache, body aches, and possibly vomiting occur. The rash begins
as red spots in the mouth and on the tongue which develop into lesions that break open. At
the same time, a rash appears on the skin, covering the body in 24 hours. Over the next
3 to 5 days, the rash progresses through becoming raised, umbilicating, becoming pustular,
crusting, scabbing, and then falling off, leaving pitted scars. There is no treatment for smallpox;
it is prevented through vaccination against the virus. There have been no cases of
smallpox in the world since 1977, however, since there are laboratory stockpiles of the
virus, the potential use for bioterrorism exists.
Diagnostic Testing: Diagnosis is confirmed through a viral culture conducted on the contents
of a skin vesicle.

Tularemia

Tularemia is caused by a coccobacillus, Francisella tularensis. This is one of the most
infectious pathogenic bacteria known because it takes so few (<10) of the organisms to
infect someone with the disease. Infection can occur through bites from infected insects
(tick, deerfly), handling of infected animal carcasses, eating or drinking contaminated food
or water, or through breathing in the bacteria (most likely route in the case of a bioterrorism
attack). Symptoms begin abruptly with fever, headache, chills, body aches, coryza, sore
throat, cough, and chest pain/tightness. If untreated, the bacilli multiply in the skin or
mucous membranes, spread to regional lymph nodes, and may disseminate to organs
throughout the body. With inhalational exposure, hemorrhagic inflammation of the airways
may progress to bronchopneumonia. Treatment involves antibiotics, typically parenteral
streptomycin or intravenous gentamicin. However, ciprofloxacin or doxycycline would be
used in case of a mass casualty situation.

Diagnostic Testing: The bacteria may be identified through direct examination of secretions,
exudates, or biopsy specimens using special staining techniques. Cultures can be
done on pharyngeal washings or sputum. There is also a blood test available to check for
the presence of Tularemia antibody formation.

Viral Hemorrhagic Fevers
Viral hemorrhagic fevers (VHFs) include illnesses caused by certain families of viruses
which typically cause multisystem damage. Symptoms vary, but may include high fever,
fatigue, dizziness, muscle aches, weakness, and exhaustion. Hemorrhage may occur in the
skin, in internal organs, or from body orifices. Death occurs in those who are severely ill
from shock, renal failure, and nervous system dysfunction, leading to delirium, seizures,
and coma. The various VHFs are similar in that humans are not the natural reservoir for
these viruses. Hosts include rats, mice, and other field rodents. Ticks and mosquitoes may
carry the virus from host to victim. Humans are infected when they come into contact with
infected hosts. However, with some of the viruses (such as Ebola), after accidental transmission
from the host, humans can transmit the virus to one another. Treatment is quite limited
at this time. It is preferable to prevent VHFs through controlling rodent populations. If
human infection does occur, it is essential that strict infection control techniques be used
when caring for the infected individual.

Diagnostic Testing: Testing can occur through serologic testing for viral antigens and culture

of biopsy material (lung, bone marrow) for virus isolation.
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Normal Values        
Negative for infectious agent
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Possible Meanings of Abnormal Values

Presence of infectious agent

Interventions/Implications

Pretest

• Explain to the patient the purpose of the test. Provide any written teaching materials
available on the subject.

Procedure

• See discussions of individual biological agents for type of testing to be done, and type of
  sample required.
• Appropriate personal protection is used throughout sample collection and delivery of
  specimen to testing facility.

Posttest

• Label the specimen and transport to laboratory as soon as possible.
• Notify the laboratory of suspected diagnosis so that special precautions can be taken
when handling the specimen(s), and to assist in determining the type of procedure/staining
to be used in the testing procedure.
• Gloves are worn when handling any specimen.
• Report abnormal findings to the primary care provider.
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clinical alert            

Confirmed cases of any of the above illnesses must be reported to local and state
authorities, as well as the CDC.