DPT 8.0

The Biologic Incident

Management of Biological Casualties

DPT 8.0

Hospital Management of Biological Casualties

DPT 8.0

Biological Warfare AgentsTerminal Objective

• Be able to describe the various types of biological warfare agents and recognize the signs and symptoms of exposure.

• Be able to describe how to properly manage and treat infectious victims

• Know which agents are a risk for secondary transmission and how to protect against this spread using personal protective equipment (PPE) and isolation measures.

DPT 8.0

Biological Warfare (BW) Agents - History

• Oldest of the NBC triad of agents

• Used for > 2,000 years

– Sieges of middle ages

– Smallpox blankets given to Native Americans

– Germany in World War I

– Japan in World War II

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Aerosol / Infectivity Relationship

18-20

15-18

7-12

4-6(bronchioles)

1-5 (alveoli)

Infection SeverityParticle Size

(Micron, Mass Median Diameter)

The ideal aerosol contains a homogeneous population

of 2 or 3 micron particulates that contain one or more

viable organisms

Maximum human respiratory infection is

a particle that falls within the 1 to 5 micron

size

Less Severe

More Severe

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BW - Epidemiologic Clues

• Large epidemic with high illness and death rate

• HIV(+) individuals may have first susceptibility

• Respiratory symptoms predominate

• Infection non-endemic for region

• Multiple, simultaneous outbreaks

• Multi-drug-resistant pathogens

• Sick or dead animals

• Delivery vehicle or intelligence information

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BW - Epidemiological Information

• Travel history

• Infectious contacts

• Employment history

• Activities over the preceding 3 to 5 days

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Biological Agents - Types and Characteristics

• Bacteria

• Viruses

• Toxins

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Bacteria as Biological Agents

• Bacteria– Single celled microorganism

– Invade tissue; cause inflammatory reaction or produce toxins

– May form spores

• Anthrax

• Plague

• Tularemia

• Q Fever

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Anthrax - Microbiology

• Bacillus anthracis - gram +, spore-forming bacillus

• Endemic infection in animals

• Humans develop infection naturally from handling contaminated fluids or hides (“Woolsorters Disease”)

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Anthrax - Pathogenesis

• Inoculation, ingestion, or inhalation of spores which may travel to the regional lymph nodes

• Vegetative bacteria produce edema factor and lethal factor (toxins)

• Inhalation route has highest mortality and is most likely route to be used by terrorists

• Inhaled anthrax causes a mediastinitis rather than a pneumonia

• Untreated skin infection - 21% mortality if septicemia develops (treated 1%)

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Cutaneous Anthrax

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Gastrointestinal Anthrax

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Inhalational Anthrax

• 2 to 6-day incubation period followed by fever, myalgias, cough, and fatigue

• Initial improvement followed by abrupt onset of respiratory distress, shock, and death in 24 to 36 hours

• Physical findings are nonspecific, pneumonia is rare

• Chest x-ray - may show widened mediastinum with or without a bloody pleural effusion

• 50 % of cases have associated hemorrhagic meningitis

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Prevention of Secondary Anthrax Transmission

• No documented cases of person-to-person transmission of inhalational anthrax has ever occurred

• Cutaneous transmissions are possible

• Universal precautions required

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Anthrax - Soviet Incident

An accident at a Soviet military compound in Sverdlovsk (microbiology facility) in 1979 resulted in an estimated 66 deaths downwind.

Biological Warfare research,

production and storage facility

Biological Warfare research,

production and storage facility

Path of airborne Anthrax

Path of airborne Anthrax

MOSCOW

Sverdlovsk

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Inhalational Anthrax - Sverdlovsk

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Inhalational Anthrax Post Mortem - Sverdlovsk

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BW Anthrax - Diagnosis

• Clinical picture of sudden onset of respiratory distress with mediastinal widening on x-ray

• A small number of patients may present with GI or cutaneous anthrax

• Gram stain of blood and blood cultures - but these may be late findings in the course of the illness

• ELISA and immunohistology testing may confirm diagnosis but samples must go to reference laboratory

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Anthrax - Treatment

Acute Treatment

• Usually futile in severe mediastinitis patients who inhaled or ingested spores

• Ciprofloxacin - 400 mg IV q 8 to 12 hr

• Doxycycline - 100 mg IV q 12 hr X 4 wks

• Vaccination begins at the start of drug therapy

Post-exposure

• Oral prophylaxis

– Ciprofloxacin (500 mg po q 12 h) X 4 wks until 3 doses of vaccine

– Doxycycline (100 mg po q 12 h) X 4 wks until 3 doses of vaccine

• FDA licensed vaccine

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Anthrax - Pediatric Treatment

Prophylaxis

• Penicillin

• Doxycycline

IV Therapy

• Penicillin

• Doxycycline

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Anthrax Disease Complex Summary

GI

Papule vesicleedema + eschar

ResolveToxic shock

andDeath

HemorrhagicMeningitis

Cutaneous

Inhalational

Tracheobronchial Lymphadenitis

Mediastinitis, cyanosis,stridor, pulmonary

edema

1 - 6 days

ABRUPT ONSET

50%

20%

24 - 36 hours

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Plague - Microbiology

• Yersinia pestis - gram(-), non-motile, non-spore forming bacillus

• Fleas living on infected rodents spread infection to humans

• Recovery offers temporary immunity

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Plague - Pathogenesis

• Produces disease by being consumed by macrophages and transported to regional lymph nodes, causing regional adenitis

• Bacteremia - spread to other organs (lungs, spleen, liver, and brain)

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Plague Transmission

PNEUMONIC

BUBONIC

and

SEPTICEMIC

SECONDARY PNEUMONIC and

OROPHARYNGEAL

Fleas (active or dormant)

Rodent

Aerosol

Surface contact

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Pneumonic PlaguePrevention of Secondary Infection

• Secondary transmission is possible and likely

• Standard, contact, and aerosol precautions for at least 48 hrs until sputum cultures are negative or pneumonic plague is excluded

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Plague Endemic Counties

Counties with Plague-Positive Samples

1970 - 1994

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Inhalational (Pneumonic) Plague Signs and Symptoms

• 2 to 3 day incubation period followed by high fever, myalgias, chills, HA, and cough with bloody sputum

• In contrast to anthrax, pneumonia and sepsis develop acutely and may be fulminant with patients developing dyspnea, stridor, cyanosis, and circulatory collapse

• Patchy infiltrates or consolidation seen on chest x-ray

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Bubonic PlagueSigns and Symptoms

• Erythema, fever, rigors

• Bubo formation in regional lymph nodes

• Bubo aspiration and gram stain is diagnostic– Differentiate from• Tularemia• Cat-scratch fever

• Staph-strep lymphadenitis

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Acral Gangrene

Acral gangrene may be a late complication of pneumonic or septicemic plague, and may occur in the finger, toes, earlobes, nose, and penis.

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Plague - Acral Gangrene

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Plague - Diagnosis

• Gram stain and culture of lymph node aspirates, sputum, or CSF samples

• Bipolar staining “Safety Pin” may be present

• Immunoassays are also available

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Plague - Treatment

• Care is otherwise supportive• Vaccine effective only for bubonic plague • Prophylaxis - tetracycline or doxycycline• Antibiotics must be started within 24 hours of symptoms to

impact survival• Streptomycin (30 mg/kg/day IM divided BID for 10 days)• Doxycycline (100 mg IV BID for 10 days)• Chloramphenicol for plague meningitis

Respiratory isolation mandatory for at least the first 48 hours of treatment

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Plague - Pediatric Treatment

Prophylaxis

• Doxycycline

• Trimethoprim/Sulfamethoxazole

IV Therapy

• Streptomycin (over 1 year of age)

• Gentamicin

• Chloramphenicol

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Plague Disease Complex

Inhalational

SystemicToxicity

Respiratory failure & circulatory collapse

Liverenzymes

6% latemeningitis

Fulminant Pneumonia

Fever, URI syndrome

Sudden onset

Leukemoidreaction

Gram - verods in sputum

Fever/rigors Erythema

Tender bubo1 - 10 cm

APTTecchymosis

DIC

Stridor, cyanosis,productive cough,bilateral infiltrates

Pharyngitis2 -3 days 2 - 10 days

24 hrs

9%

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Viruses as Biological Agents

• Smallpox

• Viral Hemorrhagic

Fevers (VHF)

• Venezuelan Equine

Encephalitis (VEE)

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Viruses - General Characteristics

• RNA or DNA within a protein coat

• Require a host to function and survive

• Many viruses attack a specific type of cell causing disease or cancer

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Viruses - General Characteristics

• May cause disease through direct cytopathic effect, immune complex deposition and other effects

• May result in end-organ system failure, vascular damage

• Few antiviral medications available

• Vaccination is the most effective means of preventing infection

DPT 8.0

Smallpox - Microbiology

• Variola (Var-ï-óla) virus, an Orthopox virus, both minor and major forms of smallpox exist

• Structure is a large DNA virus

• Declared eradicated in 1980 and the U.S. stopped its civilian vaccination in 1981, U.S. military stopped in 1985

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Smallpox - Pathogenesis

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Smallpox - Case Study

• In 1963, en route by air from Australia to Sweden, a seaman stops in Djakarta, Singapore, Rangoon, Calcutta, Karachi, Teheran, Damascus, and Zurich

• Fifteen days later he develops a fever and rash

• Diagnosed with smallpox; 19 cases identified

• More than 300,000 vaccinated worldwide

DPT 8.0

Smallpox - Diagnosis & Treatment

DIAGNOSIS

• Clinical presentation

• Demonstrate virus from vesicular sampling via electron microscopy

• Confirmation by tissue culture

TREATMENT

• Supportive

• Vaccine still available from CDC

• Immune globulin may also be available from CDC

DPT 8.0

Smallpox - Prevention of Secondary Infection

• Contagious

• All contacts are quarantined for at least 17 days

• Infectious until all scabs are healed over

DPT 8.0

Monkeypox Virus

DPT 8.0

Smallpox / Monkeypox - Clinical Course Summary

Inhalational

Replication in regional node of airways12 day incubation

ViremiaAcute malaise, fever,rigors, headache

Exanthema onface, arms, hands

Macules papules pustular vesicles

Scabs separate+ pt non-infective

Flat Smallpox

HemorrhagicSmallpoxrapid death beforetypical lesions

8 - 10 days

2 - 3 days

variants

+ mental status changes

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Viral Hemorrhagic Fevers (VHF) - Microbiology

• RNA viruses causing high fevers and generalized vascular damage

• Human infections by insect bites or by contact with blood and body fluids

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VHF Pathogenesis

• Fever, myalgias, prostration

• Cases evolve into shock and generalized mucous membrane hemorrhage

• Conjunctival injection, petechial hemorrhage, and hypotension

• Abnormal renal and LFT - poor prognosis

• Mortality varies; 50 - 80% Ebola Zaire

• Disease severity and survival depends on various host factors; target organ is the vascular bed.

DPT 8.0

VHF Treatment

• Hemodynamic resuscitation and monitoring– Invasive Swan Gantz catheter as feasible

• Careful fluid management– use of colloid

• Vasopressors and cardiotonic drugs

• Cautious sedation and analgesia

• No anti-platelet drugs or IM injections

• Coagulation studies and replacement of clotting factors / platelet transfusions

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Prevention of Secondary VHF Transmission

• No vaccine is available at this time

• Single room w/ adjoining anteroom as only entrance

– handwashing facility with decontamination solution

• Negative air pressure if possible

• Strict barrier precautions

– gloves, gown, mask. shoe covers, protective eyeware/faceshield

– consider HEPA respirator for prominent hemorrhage, vomiting, diarrhea, cough

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Prevention of Secondary VHF Transmission

• Chemical toilet

• All body fluids disinfected

• Disposable equipment/sharps into rigid containers and autoclaved/incinerated

• Double-bag refuse-outside bag disinfected

• Electronic/mechanical equipment can be paraformaldehyde disinfected

DPT 8.0

Prevention of Secondary VHF Transmission

• Wash / irrigate wound site immediately

• Mucous membranes (eye, mouth, nose)

– Continuous irrigation with rapidly flowing water or sterile saline for >15 minutes

• Skin

– Scrub for >15 minutes while copiously soaking the wound with detergent solution

– Germicidal solution

(Dilute 1 part laundry bleach with 9 parts tap water)

DPT 8.0

The VHF RNA Viruses

Acute onsetfebrile illness

High fever, myalgia,GI disturbances

Severe systemic illnesscoagulation abnormalities

Rapid progression into shock and death

Renalfailure

Pulmonary Syndrome

Majororgan

necrosis

Four Corners Agent

Ebola

Marburg

Hantaan

Oropharangeal lesions

Severe bleedingecchymosis

Jaundice Syndrome

Lassa

Machupo

Congo fever

Yellow feverDengue (2x)Rift Valley

7 days

DPT 8.0

• April 5, 1995 - Zaire laboratory worker - fever and bloody diarrhea

• May 17 - 93 cases - 92% fatality - most cases were in health care providers

• June 25 - 296 cases

Ebola Case Study

When institutional barrier precautions were implemented by WHO/CDC - the infection rate

among health care workers dramatically decreased.

DPT 8.0

Toxins as Biological Agents

• Botulinum

• Ricin

• Staphylococcal Enterotoxin B (SEB)

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Toxins General Characteristics

• Naturally produced poisons

• More toxic per weight than manmade chemical agents

• Non-volatile

• Minimal absorption in intact skin

• Not prone to person-to-person transmission

DPT 8.0

Botulinum Toxin - Characteristics

• Neurotoxin produced by Clostridium botulinum - Botulism

• Most lethal compound per weight (15,000 times more toxic than the nerve agent VX)

• Different toxicity if inhaled or ingested

HcHc

HNHN

light chainlight chainneutralizing epitopesneutralizing epitopes

Bot A ToxinBot A Toxin

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Botulism - Pathogenesis

• Blocks the release of ACh at 3 places in the presynaptic terminal of the neuromuscular junction and autonomic nervous system

• Bulbar palsies and skeletal muscle weakness MUSCLE

NERVE

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Botulism - Signs & Symptoms

• Descending paralysis

• Bulbar palsies – blurred vision– mydriasis– diplopia– ptosis– photophobia– dysphagia– dysarthria

“Floppy” babyflaccid paralysis

DPT 8.0

Botulism - Diagnosis and Treatment

• Clinical diagnosis - bulbar palsy with descending paralysis

• Mouse neutralization assay can confirm diagnosis

• Treatment is supportive

– Long-term mechanical ventilation

• Antitoxins are available; must be administered early

• CDC vaccine protective for A and B toxins

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Ricin - Characteristics

• Toxic by multiple routes of exposure

• Can be dispersed as an aerosol

• Effective orally, by injection, or inhalation

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Ricin - Pathogenesis

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Ricin - Signs & Symptoms

• Fever, chest tightness, cough, SOB, nausea, and joint pain 4 to 8 hours after inhalation

• Airway necrosis and edema leads to death in 36 to 72 hours

• Ingestion causes N,V, severe diarrhea, GI hemorrhage, and necrosis of the liver, spleen, and kidneys - shock and death within 3 days

• Injection causes marked necrosis of muscles and lymph nodes with multiple organ failure leading to death

DPT 8.0

Ricin - Diagnosis & Treatment

DIAGNOSIS

• Difficult

• Routine labs are nonspecific

• ELISA of blood

• Immunohistochemical tests may confirm

TREATMENT

• Supportive - oxygenation and hydration

• No antitoxin or vaccine available

DPT 8.0

Teaching Points

• BW EXPOSURE: WET OR DRY AGENT AEROSOLS• BACTERIAL AGENTS

– LETHAL: Anthrax, Tularemia, Plague– NON-LETHAL: Q Fever

• VIRAL AGENTS

– LETHAL: Smallpox / Monkeypox, Viral Hemorrhagic Fevers

– NON-LETHAL: Venezuelan Equine Encephalitis

• TOXINS– LETHAL: Ricin, Botulinum Toxin A– NON-LETHAL: Staphyloccal Enterotoxin B

• SECONDARY INFECTION IS POSSIBLE WITH– Plague, Smallpox/Monkeypox, and VHF

DPT 8.0

Biological Agents

Case Study

Emergency departments always seem busier during a full moon despite evidence to the contrary. Tonight was no exception. Over a 6-hour period, it seemed that almost half of the patients presented with similar complaints of high fever, cough, shortness of breath, and generalized ill feeling. Five young, previously healthy individuals required intubation and mechanical ventilation for severe respiratory distress. Strangely, most of the patients knew each other from work and none of their family members were suffering similar symptoms. At 11 p.m., the only other community hospital in the area went on diversion because all of their intensive care unit (ICU) beds were full and their need for mechanical ventilators was at a critical level. The public health officer on call was not aware of any recent infectious outbreak.

DPT 8.0

Biological Agents

• What might the causative agent be?

• How could you identify common factors which might relate

the patients to each other?

• How long ago might the attack have occurred?

• If you are suspicious that patient illnesses could be the

result of a biological attack, whom should you notify?

• What precautions should you and other healthcare

providers take?