Biological Agents

Biological Agents
 Biological Agents

Objectives

● Analyze facts and principles of biological agents

● Identify the indicators, signs, and symptoms of exposure to
biological agents
● Apply principles of diagnosis and treatment of bacterial agent
casualties.
● Evaluate conditions and make proper decisions regarding the
diagnosis and treatment of biological agent casualties
● Apply principles of diagnosis and treatment of biological agent
casualties

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 Biological Agents

Diseases cause by Biological Agents

Bacteria Virus

• Anthrax • Smallpox
• Plague • Hemorrhagic Fever
• Tularemia Viruses
• Q Fever • Encephalitis Viruses
• Brucellosis
Toxin

• Botulinum toxin
• Ricin
• Staphylococcal
Enterotoxin B (SEB)
• T-2 Mycotoxins
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Biological Agents

Bacteria

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 Biological Agents

Anthrax: Clinical Forms

• Cutaneous

• Inhalational

• Gastrointestinal

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 Biological Agents

Anthrax: Behavior and Risk

Behavior
• Initial symptoms are flu-like in nature and progress to severe
respiratory distress/difficulty breathing.
• Death typically occurs within 24 to 36 hours after onset of
severe symptoms.

Risk
• Although it is not transmittable person-to-person, if not
recognized and treated, anthrax can have a high mortality rate.
• Spores are hardy and may necessitate decontamination.
• Treatment should ideally occur prior to onset of symptoms.

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 Biological Agents

Anthrax: Signs and Symptoms

Cutaneous

Incubation Period: Initial lesions develop within 1 to 5 days.

Signs and Symptoms: Local edema followed by:

● Macule, or papule progressing to a vesicle, which then ulcerates
over several days.
● Painless black eschar.
● Eschar drying, loosening, and falling off
within 1 to 2 weeks.
● Lymphangitis and painful lymphadenopathy
occurring with associated systemic symptoms.
● Local infection in some cases disseminating
into a fatal systemic infection.
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 Biological Agents

Anthrax: Signs and Symptoms

Inhalational

Incubation Period: Incubation period of 1 to 6 days

Signs and Symptoms: Begin gradually and nonspecifically:

● Fever
● Malaise
● Fatigue
● Nonproductive cough
● Mild chest discomfort

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 Biological Agents

Anthrax: Signs and Symptoms

Inhalational

May be followed by a short period of improvement, then:

● Abrupt onset development of severe respiratory distress

● Dyspnea
● Diaphoresis
● Stridor
● Cyanosis

Septicemia, shock, and death usually follow within 24 to 36 hours.

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 Biological Agents

Anthrax: Signs and Symptoms

Gastrointestinal

Incubation Period: Unknown, but thought to be days.

Signs and Symptoms:

● May affect the upper or lower Gastrointestinal (GI) tract
● Oral-pharyngeal form begins with an oral or esophageal ulcer leading
to regional lymphadenopathy, edema, and sepsis
● Adenopathy may develop rapidly leading to acute airway compromise
and asphyxiation before the development of sepsis
● Disease in the lower GI tract
● Massive ascites have occurred in some cases.
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 Biological Agents

Anthrax: Laboratory Diagnosis

Cutaneous

• Presents with vesicles that discharge clear or serosanguinous

fluid revealing gram-positive bacilli with few neutrophils.
• Lesions may be confused with Staph infections or ulcerated
spider bites.
• Culture of the fluid or a skin biopsy may yield B. anthracis within
24hours. Identification of cultured bacteria can be confirmed
with gram stain, gamma phage, and fatty acid analysis.
• Polymerase Chain Reaction (PCR) of the lesion fluid or a biopsy
may also be used to confirm the diagnosis, as well as Enzyme
Link Immunosorbent Assay (ELISA) and
Electrochemiluminescence (ECL).
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 Biological Agents

Anthrax: Laboratory Diagnosis

Inhalational

• Pathology resembles that of a Ghon complex similar to that seen in

pulmonary tuberculosis.
• Chest x-ray or CT scan may reveal a widened mediastinum, with or
without pleural effusions, in about half the cases.
• Not typically seen in the sputum until there is overwhelming infection.
• Gram stain and culture of pleural fluid commonly reveal Bacillus
anthracis.
• Identification of cultured bacteria can be confirmed with gamma phage
and fatty acid analysis.
• PCR, ELISA, and ECL can also reveal the presence of Bacillus anthracis.
• Tests to rapidly detect the toxin are available at research centers and
the Centers for Disease Control and Prevention (CDC).
• About 50% of cases are accompanied by hemorrhagic meningitis.
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 Biological Agents

Anthrax: Treatment

Early use of appropriate antibiotics is key to the effective treatment of

all three clinical forms of anthrax.

Cutaneous

• Treat orally with a quinolone (ciprofloxacin, levofloxacin,

gatifloxacin), doxycycline, or penicillin and adjust accordingly as
sensitivities become available.

• No antibiotic therapy may result in mortality as high as 20%.

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 Biological Agents

Anthrax: Treatment

Inhalational/Gastrointestinal

Treat using Ciprofloxacin or Doxycycline plus one or two of the

following:
Rifampin Vancomycin Penicillin
Ampicillin Clindamycin Imipenem
Chloramphenicol Clarithromycin

CDC recommends the following guidelines:

● Treat empirically first as noted above.

● Adjust treatment accordingly as sensitivities become available.
● Switch to oral antibiotics when appropriate.
● Total treatment may require 60 days therapy or longer.
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 Biological Agents

Plague: Clinical Forms

• Bubonic

• Pneumonic

• Septicemic

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 Biological Agents

Plague: Behavior and Risk

Behavior
• Exposure via inhalation of aerosols of Yersinia pestis results in
pneumonic plague, the most severe and transmissible form.
• Cutaneous exposure, such as through plague-carrying vectors
(fleas) results in bubonic plague.

Risk
•Pneumonic plague is highly contagious, which puts close
contacts and healthcare workers at increased risk of infection.

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 Biological Agents

Bubonic Plague: Signs and Symptoms

Etiology: Contracted from infected fleas

Signs and Symptoms:

● Sudden onset of fever, chills and weakness.
● Exquisitely swollen, tender lymph nodes of bubo soon after initial
systemic symptoms appear.
● Bubo typically develops in the groin, axilla,or cervical region and is
often so painful that it prevents patients from moving the affected area.
● Buboes are 1 to 10 cm in diameter, exquisitely tender, nonfluctuant, and
warm; often associated with considerable edema, but seldom
lymphadenitis. The overlying skin is warm and erythematous.
● Buboes rarely become fluctuant and suppurate. Skin ulcerations may
occur at the site of the fleabite in a minority of patients.

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 Biological Agents

Pneumonic Plague: Signs and Symptoms

Etiology: Results secondarily from the bubonic or pneumonic forms.

Can also occur primarily. (Septicemia without adenopathy)

Signs and Symptoms:

● Fever, chills, vomiting, abdominal pain
● DIC
● Necrosis of small blood vessels leading to gangrene of affected
extremities
● Purpuric skin lesions

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 Biological Agents

Septicemic Plague: Signs and Symptoms

Etiology: Results secondarily from bubonic or pneumonic forms. It

can also occur primarily.

Signs and Symptoms:

● Fever
● Cough
● Dyspnea, sometimes with the production of bloody, watery, or, less
commonly, purulent sputum
● Prominent Gastrointestinal (GI) symptoms such as:
- Nausea - Vomiting
- Abdominal pain - Diarrhea
● Absence of buboes (In rare cases, cervical buboes may be present.)

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 Biological Agents

Plague: Laboratory Diagnosis

• Presumptive diagnosis can be made microscopically by

identification of the coccobacillus in Gram, Wright, Giemsa, or
Wayson‘ stained smears from lymph node needle aspirate, sputum,
blood, or Cerebrospinal Fluid (CSF) samples.
• Immunofluorescent staining and fatty acid
analysis can be used to identify cultured
Yersinia pestis.
• Definitive diagnosis relies on culturing the
organism from blood, sputum, CSF, or bubo
aspirates.
• Can be identified using ECL, ELISA, or PCR.

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 Biological Agents

Plague: Treatment

● Streptomycin, gentamicin or doxycycline.

● Duration of therapy should be 10 to 14 days to prevent relapses.
● If secondary plague meningitis develops, treatment requires the
addition of chloramphenicol since other antibiotics do not penetrate
the CSF.
● Aggressive supportive therapy with use of hemodynamic monitoring
and pressors may be necessary if patient develops secondary
septicemic or pneumonic plague.
● Watch for the development of DIC.
● Buboes should almost never be I&D'd (incision and drainage) since it
greatly increases the risk of nosocomial infection. However, buboes
may be aspirated for diagnostic purposes and pain relief.

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 Biological Agents

Tularemia: Behavior and Risk

Behavior
• May produce pneumonia but may affect
other tissues as well, including various
glands and the eyes.

Risk
• Has a lower, but still significant, mortality
rate compared with pneumonic plague.

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 Biological Agents

Tularemia: Signs and Symptoms

● Fever from 100°F (38°C) to 104°F (40°C)

● Headache, chills, and rigors
● Generalized body aches, prominent in the low back
● Watery eyes
● Sore throat
● Dry or slightly productive cough
● Substernal pain or tightness frequently occurs with or without signs
of pneumonia, such as purulent sputum, dyspnea, tachypnea,
pleuritic pain, or hemoptysis
● Nausea and vomiting
● Diarrhea
● Malaise
● Anorexia and weight loss
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 Biological Agents

Tularemia: Clinical Forms

• Oculoglandular

• Pneumonic

• Oropharyngeal

• Glandular

• Typhoidal

• Ulceroglandular

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 Biological Agents

Tularemia: Signs and Symptoms

Oculoglandular

Ulceration occurs on the conjunctiva, accompanied by pronounced

chemosis, vasculitis, and regional lymphadenitis.

Pneumonic

Results as one or more of the following, accompanied by

various manifestations of systemic illness:

● Pharyngitis
● Bronchiolitis
● Pleuropneumonitis
● Hilar lymphadenitis
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 Biological Agents

Tularemia: Signs and Symptoms

Oropharyngeal

Affected persons may develop:

• Stomatitis
• Exudative pharyngitis
• Tonsillitis, sometimes with ulceration
• Pronounced cervical or retropharyngeal lymphadenopathy may
occur.

Glandular

• Characterized by fever and tender lymphadenopathy without an

ulcer.
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 Biological Agents

Tularemia: Signs and Symptoms

Typhoidal

● Fever ● Chills
● Malaise and weakness ● Myalgias
● Gastrointestinal symptoms: ● Arthralgias
- Watery, non-bloody diarrhea ● Prostration
- Vomiting ● Dehydration
- Abdominal pain
● Skin lesions may appear on hands, arms, or legs
- Erythema nodosum
- Erythema multiform
- Maculopapular rash
- Acneiform lesions
- Urticaria
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 Biological Agents

Tularemia: Signs and Symptoms

Ulceroglandular

● Local cutaneous papule appears at the inoculation site at the

onset of generalized symptoms, becomes pustular, and ulcerates
within a few days of its appearance.

● Initially the ulcer will be tender. Over the next few days it will be
covered by an eschar. Typically, one or more regional afferent
lymph nodes may become enlarged and tender within several
days of the appearance of the papule.

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 Biological Agents

Tularemia: Laboratory Diagnosis

Cultures

● May be identified by direct examination of secretions, exudates, or

biopsy specimens using direct fluorescent antibody or
immunohistochemical stains.

● Gram-stain will reveal gram-negative rod.

● Light microscopy will reveal the organism's small size (0.2 μm X 0.2-
0.7 μm), pleomorphism, and faint staining.

● Antigen detection assays, PCR, ELISAs, immunoblotting, pulsed-field

gel electrophoresis, and other specialized techniques may be used to
identify Francisella tularensis and to characterize strains.
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 Biological Agents

Tularemia: Treatment

Appropriate therapy includes one of the following antibiotics:

● Gentamicin
● Ciprofloxacin
● Streptomycin

Standard precautions should be taken.

For decontamination, mild heat

(55° Celsius for 10 minutes) and
standard disinfectants will render the
organism harmless.

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 Biological Agents

Q Fever: Behavior and Risk

Behavior
•Produces nonspecific illnesses that may be incapacitating or
require prolonged recuperation.

Risk
•Rarely causes death, but may be incapacitating or require
prolonged recuperation.

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 Biological Agents

Q Fever: Signs and Symptoms

● Headaches

● Fatigue

● Myalgias

Uncommon complications include chronic hepatitis, endocarditis,

aseptic meningitis, encephalitis, and osteomyelitis.

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 Biological Agents

Q Fever: Laboratory Diagnosis

● Chest radiographs are usually nonspecific. Findings may include:
patchy infiltrates, rounded opacities and adenopathy.

● Nonspecific leukocytosis may be present in one-third of patients.

● Most patients with Q fever have a mild elevation of hepatic

transaminase levels.

● Serological tests for Q fever include Indirect Fluorescent Antibody

(IFA), ELISA, ECL, and Complement Fixation (CF).

● PCR can also identify the bacteria's DNA.

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 Biological Agents

Q Fever: Treatment

To shorten the duration of the illness and reduce the risk of

complications, administer:

● Tetracycline 500 mg every 6 hours

● Doxycycline 100 mg every 12 hours for 5 to 7 days

Standard precautions are recommended.

Person-to-person transmission is rare.

Decontamination is achieved using soap and water or 0.5%

hypochlorite.

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 Biological Agents

Brucellosis: Behavior and Risk

Brucellosis:

Behavior
• Brucellosis typically presents as a nonspecific febrile illness
resembling influenza.
• Fever is usually intermittent and can assume an undulant
pattern.

Risk
• Highly infectious via aerosol exposure, but a low mortality rate.
• In naturally occurring infections only 5% of untreated cases
result in death.

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 Biological Agents

Brucellosis: Signs and Symptoms

General

• Fever
• Headache
• Myalgias
• Arthralgias
• Back pain
• Sweats and chills
• Generalized weakness and malaise

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 Biological Agents

Brucellosis: Signs and Symptoms/Diagnosis

Neurological

• Encephalitis.
• Peripheral neuropathy.
• Radiculoneuropathy.
• Meningovascular syndromes have also been observed in rare
instances.
• Behavioral disturbances and psychoses appear to occur out of
proportion to the height of fever, or to the amount of overt Central
Nervous System (CNS) disease.

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 Biological Agents

Brucellosis: Signs and Symptoms/Diagnosis

Pulmonary

• Pulmonary symptoms may not correlate with radiographic findings.

• Cough and pleuritic chest pain occur in up to 20% of cases.
• Acute pneumonitis is unusual.

Gastrointestinal

• Symptoms such as anorexia, nausea, vomiting, diarrhea, and

constipation occur in up to 70% of adult cases, but less frequently
in children.
• Ileitis, colitis, and granulomatous or mononuclear infiltrative
hepatitis may occur, with hepato- and spleno-megaly present in 45
to 63% of cases.
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 Biological Agents

Brucellosis: Signs and Symptoms/Diagnosis

Lumbar

• Lumbar pain and tenderness can occur in up to 60% of cases and

are sometimes due to various osteoarticular infections of the axial
skeleton.

Joint

• Joint involvement may vary from pain to joint immobility and

effusion.

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 Biological Agents

Brucellosis: Laboratory Diagnosis

● Chest x-rays are often normal, but may show lung abscesses, single
or miliary nodules, bronchopneumonia, enlarged hilar lymph nodes,
or pleural effusions

● Leukocyte count is usually normal but may be low; anemia and

thrombocytopenia may also occur

● During the acute febrile phase of illness, blood cultures yield the
organism in 15 to 70% of cases, and bone marrow cultures detect it
in 92%

● Serum Agglutination Test (SAT) is available. ELISA, ECL, and PCR

methods are becoming more widely utilized
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 Biological Agents

Brucellosis: Treatment

• Oral antibiotic therapy alone is sufficient

• Combination of doxycycline 200 mg/day orally and rifampin 600

mg/day orally is generally recommended

- Administered for 6 weeks

- Doxycycline 200 mg/day orally for 6 weeks in combination with 2
weeks of streptomycin (1 g/day IM) is an acceptable alternative

• Standard precautions are adequate in managing brucellosis

patients, as the disease is not generally transmissible from person-
to-person.

• Decontamination is achieved using a 0.5% hypochlorite solution.

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Biological Agents

Viruses

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 Biological Agents

Smallpox: Behavior and Risk

Behavior
• Is a serious, communicable, and sometimes fatal disease.
• Treatment is supportive care.
• The only licensed prevention is vaccination.

Risk
• Up to thirty percent of those infected may die, usually from
overwhelming sepsis, dehydration, or secondary bacterial
infections.

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 Biological Agents

Smallpox: Signs & Symptoms

• High fever

• Chills

• Weakness

• Muscle and backaches

• Painful rash beginning on the hands, feet, and face and spreading
over time toward the trunk, back, and chest (2 to 3 days after onset
of fever)

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 Biological Agents

Smallpox: Clinical Forms

• Variola major (classic)

• Variola minor (alastrim)

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 Biological Agents

Smallpox and Chickenpox Comparison

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 Biological Agents

Smallpox: Laboratory Diagnosis

Differentiation classically requires isolation of the virus and

characterization of its growth on chorioallantoic membrane.

• Electron Microscopy

• Gispen's Modified Silver Stain

• Polymerase Chain Reaction (PCR)

• Immunoassay

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 Biological Agents

Smallpox: Treatment

• Adequate hydration and nutrition, with treatment of secondary

bacterial infections.

• No antiviral approved by the FDA for treatment of clinical smallpox

disease.

• In the event of an epidemic, drugs like cidofovir may be made

available on an experimental basis.

• Post Exposure Prophylaxis Vaccine:

- Protective if given within 3-4 days exposure
- Reduces incidence 2-3 fold
- Decreases mortality by ~50%
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 Biological Agents

Equine Encephalitis Viruses: Clinical Forms

• Venezuelan Equine Encephalitis (VEE)

• Eastern Equine Encephalitis (EEE)

• Western Equine Encephalitis (WEE)

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 Biological Agents

Encephalitis Viruses: Behavior and Risk

Behavior
•After exposure, the tissues of the Central Nervous System
(CNS) and other organ systems are affected in both humans and
animals.

Risk
• Highly infectious.
• No antiviral drugs are effective for treatment, and vaccine
availability is very limited.
• Not transmittable from person to person.

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 Biological Agents

VEE: Diagnosis and Treatment

• Onset of disease is usually sudden and is manifested by:

- generalized malaise - sore throat
- spiking high fevers 100 °F-105 °F - rigors
- myalgias in the legs and lumbosacral area - chills
- photophobia - nausea
- vomiting - cough
- severe headache - diarrhea

• No specific antiviral therapy exists. Treat uncomplicated VEE with

analgesics.

• Treat encephalitis with anticonvulsants and intensive supportive

care.

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 Biological Agents

EEE: Diagnosis and Treatment

• EEE in humans is characterized by an acute onset of fever and

flu-like symptoms, such as:
- Headache
- Sore throat
- Abdominal pain
- Lethargy
• May progress rapidly to:
- Delirium
- Coma
- Possibly death
• There is no vaccine or specific therapy other than supportive care

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 Biological Agents

WEE: Diagnosis and Treatment

• There is a lack of specificity of symptoms, making it difficult to

diagnose

• Onset of illness is sudden, especially in adults

• Infection can cause a range of illnesses, from no symptoms to fatal

disease

• Management consists of treatment of symptoms and complications

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 Biological Agents

VEE: Laboratory Diagnosis

• Serelogy – IgM, ELISA indirect FA, hemagglutination inhibition,

Complement-fixation, and IgG.

• Isolation – VEE should be isolated only in a Biosafety Level-3

(BSL-3) laboratory.

• PCR – RNA PCR test available.

• Biochemical Assay – WBC count shows a striking leukopenia and

lymphpenia.

• Culture – Can be cultured.

• ECL – ECL test available.

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 Biological Agents

EEE: Laboratory Diagnosis

• Serology - Viral titers, IgM, and complement-fixation.

• Isolation - Viral isolation from the Cerebrospinal Fluid (CSF), blood,

or tissue is often difficult due to low levels of virus associated with
EEE.

• PCR - There is an RNA PCR test for this virus.

• Culture - The virus can be cultured.

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 Biological Agents

WEE: Laboratory Diagnosis

• Blood cultures – Unlikely to be helpful.

• Isolation – Difficult.
• Biochemical Assays – ELISA detects IgM and may detect
antiarboviral IgG.
• CSF Findings
- Lumbar puncture indicated if suspicion is high.
- Elevated CSF RBCs.
- Elevated CSF WBCs.
• PCR - There is an RNA PCR test for this virus.
• Culture - The virus can be cultured.

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 Biological Agents

Viral Hemorrhagic Fevers (VHFs): Families

There are four distinct VHF families:

• Arenaviridae (e.g. Lassa virus)

• Bunyviridae (e.g. Hantavirus)

• Filoviridae (e.g. Marburg HF)

• Flaviviridae (e.g. yellow fever)

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 Biological Agents

VHFs: Behavior and Risk

Behavior
• Includes approximately 20 different viruses such as Ebola that
attack the endothelium (lining) of blood vessels.

Risk
• Mortality rates range from less than 10% to close to 100%,
depending on the virus involved, host factors, and the
aggressiveness of supportive therapy.
• Are also transmissible person-to-person, and pose an increased
risk to healthcare workers and close contacts.

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 Biological Agents

VHFs: Signs and Symptoms

Common

• Fever • Conjunctival injection

• Myalgia • Mild hypotension
• Prostration • Flushing
• Abdominal pain
• Petechial hemorrhages

Full-blown VHF typically includes:

• Rash
• Shock
• Generalized mucous membrane hemorrhage, often accompanied
by pulmonary hematopoietic and neurologic involvement.

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 Biological Agents

VHFs: Diagnosis

• Biphasic form of this illness will include CNS manifestations.

• Renal insufficiency is proportional to cardiovascular compromise.

• While hepatic involvement is common among the VHFs, a clinical

picture involving jaundice and other
features of hepatitis are only seen in
some cases.

• Pulmonary hemorrhage often

accompanies full-blown VHFs.

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 Biological Agents

VHFs: Laboratory Diagnosis

• Specialized microbiologic containment is required.

• Electron micrographs have been used to identify these viruses.

• Many of these viruses can be cultured or identified by RNA, PCR,

or various immunoassays

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 Biological Agents

VHFs: Laboratory Diagnosis

• Specific virology studies are necessary for definitive diagnosis.

• Thrombocytopenia and leukopenia are the rule in VHFs.

• ELISA can detect viral antigens in acute sera.

• Proteinuria and/or hematuria are common.

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 Biological Agents

VHFs: Treatment

• Supportive care includes managing fluids and bleeding problems

• Restlessness, confusion, myalgia, and hyperesthesia should be

managed by conservative measures and the judicious use of
sedatives and analgesics

• Severely ill patients require intensive care, including:

- Vigorous fluid resuscitation

- Pressor agents
- Intravascular devices
- Invasive hemodynamic monitoring

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 Biological Agents

VHFs: Prophylaxis

• Licensed vaccine exists for yellow fever.

• Prophylactic ribavirin may be effective for Lassa fever, Rift Valley

fever, Congo-Crimean Hemorrhagic Fever (CCHF), and hemorrhagic
fever with renal syndrome as an IND.

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Biological Agents

Toxins

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 Biological Agents

Ricin: Behavior and Risk

Behavior
• Poison made from castor bean extract.
• Can be in the form of powder, mist, or pellet.
• Causes toxicity by inhibition of DNA replication and protein
synthesis and leading to cell death.

Risk
• May cause severe allergic reactions.
• No effective treatment and supportive
care will depend on route of exposure.

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 Biological Agents

Ricin: Signs & Symptoms

Inhalation

Acute onset of the following symptoms appears in 4 to 8 hours:

- Fever - Cough
- Chest tightness - Dyspnea
- Nausea - Arthralgias

Within 36 to 72 hours this may be followed by:

- Cyanosis
- Pulmonary edema
- Death from ARDS and respiratory failure

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 Biological Agents

Ricin: Signs and Symptoms

Ingestion

● Necrosis of the Gastrointestinal (GI) epithelium

● Local hemorrhage
● Hepatic, splenic, and renal necrosis
● Hematuria
● Jaundice

Injection

● Severe local necrosis of muscle and regional lymph nodes with

moderate to severe visceral organ involvement.

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 Biological Agents

Ricin: Treatment

Inhalation

• Appropriate respiratory support

- Oxygen - Intubation
- Ventilation - PEEP
- Hemodynamic monitoring

• Treatment for pulmonary edema, as indicated

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 Biological Agents

Ricin: Treatment

Ingestion

● Vigorous gastric lavage, followed by use of cathartics such as

magnesium citrate, if within one hour of ingestion, activated
charcoal (if not counterindication).

● Volume replacement of GI fluid losses is important.

Injection

● Treatment is primarily supportive.

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 Biological Agents

Ricin: Diagnosis

• Aerosolized ricin supported by clinical and epidemiological

evidence
• Supportive clinical or diagnostic features may include:
- Bilateral infiltrates on chest radiographs
- Arterial hypoxemia
- Neutrophilic leukocytosis
- Bronchial aspirate rich in protein compared to plasma,
which is characteristic of high permeability pulmonary edema

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 Biological Agents

Staphylococcal Enterotoxin B (SEB): Behavior and Risk

Behavior
• SEB is an exotoxin excreted by Staphylococcus aureus.
• Toxins are produced in unrefrigerated meats, daily, and bakery
products.
• Ingested SEB can cause a form of food poisoning.
• Causes symptoms at a very low doses.

Risk
• SEB may not make many people critically ill, but it can
incapacitate large numbers of individuals.
• Those with an underlying disease process reaction more severely.

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 Biological Agents

SEB: Signs & Symptoms

When ingested, causes a self-limited form of "food poisoning" with:

● Severe nausea
● Vomiting
● Diarrhea

When inhaled it causes sudden onset of:

● High fever
● Chills
● Muscle aches
● Headache
● Dry cough

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 Biological Agents

SEB: Laboratory Diagnosis

• Respiratory secretions and nasal swabs may show the toxin early
(within 24 hours of exposure).

• ELISA and ECL may be used to confirm the diagnosis.

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 Biological Agents

Botulinum Toxin: Behavior and Risk

Behavior
• Several toxins produced by the bacterium Clostridium botulinum
which causes a muscle paralyzing disease.
• Environmental conditions easily denature these toxins.
• When inhaled, these toxins produce a clinical picture very similar
to foodborne intoxication.
• Hallmark of disease is a progressive, descending, flaccid paralysis

Risk
• Mortality from untreated cases is approximately 60%.
• Cases treated with supportive care have a mortality rate of less
than 5%.
• Most will survive with supportive care alone, although the care
may be prolonged.
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 Biological Agents

Botulinum Toxins: Signs and Symptoms

Physical exam usually reveals an afebrile, alert, and oriented patient.

Central Nervous System (CNS)

Cranial nerve palsies are prominent early and

are often first manifested by the following:

- Dysarthria
- Dysphonia
- Dysphagia

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 Biological Agents

Botulinum Toxins: Signs and Symptoms

Ocular

● Blurred vision due to mydriasis; seen in approximately 50% of cases.

● Diplopia
● Photophobia
● Pupils may be dilated and even fixed
● Possibly Ptosis and extraocular muscle palsies

Mucous Membranes

● Mucous membranes may be dry and crusted and the patient may
complain of dry mouth or sore throat.
● There may be difficulty with speaking and swallowing.
● Gag reflex may be absent.
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 Biological Agents

Botulinum Toxins: Signs and Symptoms

Muscle
● Variable degrees of skeletal muscle weakness may be observed,
depending on the degree of progression in the patient.
● Flaccid skeletal muscle paralysis follows early symptoms in a
symmetrical, descending, and progressive manner.
● Collapse of the upper airway may occur due to weakness of the
oropharyngeal musculature.
● Progression from onset of symptoms to respiratory failure has
occurred in as little as 24 hours in cases of severe foodborne
botulism.
● Deep tendon reflexes may be present or absent

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 Biological Agents

Botulinum Toxins: Treatment

• Supportive care, including prompt respiratory support, can be

lifesaving.

• Prevention of nosocomial infections is a primary

concern.

• Intensive and prolonged nursing care may be

required for recovery, which may take up to 3
months for initial signs of improvement and up
to a year for complete resolution of symptoms.

• Early administration of botulinum antitoxin is

critical.
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 Biological Agents

Botulinum Toxins: Laboratory Diagnosis

Laboratory testing is generally not helpful to the diagnosis of botulism.

● Mouse neutralization (bioassay) remains

the most sensitive test.

● PCR might detect Clostridium botulinum

genes in an environmental sample in impure
preparations.

● Detection of toxin in clinical or

environmental samples is sometimes possible
using an ELISA or ECL test.

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Trichothecene (T-2) Mycotoxins: An Overview

• Are a group of over 40 compounds produced by fungus of

the genus Fusarium, a common grain mold.

• Have low molecular weight and are very stable.

• Can adhere to and penetrate the skin, be inhaled, or be ingested.

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T-2 Mycotoxin: Behavior and Risk

Behavior
• Are very stable, even when autoclaved, and have multiple
mechanisms of action.
• Cause pain within minutes of contact with human skin similar to
the chemical warfare agent Lewisite.

Risk
• Can penetrate the skin, be inhaled, or be ingested.
• Systemic toxicity and death may occur.

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T-2 Mycotoxins: Clinical Picture

• Most common symptoms are:

- Vomiting
- Diarrhea
- Dyspnea
- Skin involvement with burning pain, redness,
and pruritus; rash or blisters; bleeding

• Systemic toxicity can occur via any route of exposure, resulting in:
- Weakness - Prostration
- Ataxia - Loss of coordination
- Dizziness
• Tachycardia, hypothermia, and hypotension follow in fatal cases
• Death may occur in minutes, hours, or days.
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T-2 Mycotoxins: Signs, Symptoms, and Treatment

Inhalation
Signs & Symptoms

• Upper respiratory exposure may result in the following:

- Nasal itching - Pain - Sneezing
- Epistaxis - Rhinorrhea

• Pulmonary/tracheobronchial toxicity produces:

- Dyspnea - Wheezing - Cough

Treatment

• Respiratory support may be necessary

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T-2 Mycotoxins: Signs, Symptoms, and Treatment

Ingestion
Signs & Symptoms

• Mouth and throat exposure causes pain and blood-tinged saliva

and sputum.
• Following occur with Gastrointestinal (GI) toxicity:
- Anorexia
- Nausea
- Vomiting
- Watery or bloody diarrhea with crampy abdominal pain

Treatment

• Standard therapy for poison ingestion, including the use of

superactivated charcoal, should be administered.
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T-2 Mycotoxins: Signs, Symptoms, and Treatment

Ocular Signs and Symptoms

• Ocular exposure can cause the following symptoms within
minutes:
- Eye pain - Tearing - Redness
- Blurred vision - Foreign body sensation

Ocular Treatment
● Treatment for T-2 ocular involvement is flushing eyes with
copious amounts of water and timeliness is essential

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T-2 Mycotoxins: Signs, Symptoms, and Treatment

Dermal
Signs & Symptoms

• Early symptoms of skin exposure begin within minutes to hours:

- Burning skin pain - Redness
- Tenderness - Blistering

• Progresses to skin necrosis with leathery blackening and sloughing

of large areas of skin.

Treatment

• Timely decontamination is essential

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T-2 Mycotoxins: Laboratory Diagnosis

• Mycotoxins and metabolites are eliminated in the urine and feces;

50 to 75% is eliminated within 24 hours

• Metabolites can be detected as late as 28 days

after exposure

• Pathologic specimens include blood, urine, lung,

liver, and stomach contents

• A Gas Chromatography-Mass Spectrometry

(GCMS) technique can test environmental and
clinical samples

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 Biological Agents

Questions?

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