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Bioterrorism Agents

and Barrier Protection

What is

bioterrorism?

Bioterrorism is defined as the deliberate or threatened

use of bacteria, viruses or toxins to cause disease,

death, disruption or fear.

History and Evolution of

Bioterrorism

Key events of bioterrorism use:

- Geneva Protocol signed to prohibit research and

development of biological weapons.

- U.S. offensive biological weapons program

dismantled.

- Biological and Toxin Weapons Convention signed.

The most likely large-scale attack of bioterrorism

is expected to be an aerosolized agent. Category A

diseases: anthrax, smallpox, botulinum, viral hemorrhagic

fever, tularemia, and plague.

Bioterrorism is not a new phenomenon. Bioterrorism

has been used as a weapon for many years.

In 700 BC, the Assyrians poisoned the water wells of

their enemies with the poison rye ergot.

In the 1300s, during the siege of Kaffa, now the

Ukraine, the Tartars catapulted plague-infected

corpses over the walls of the city, which probably led

to the Black Death plague epidemic that followed.

In the 1600s, it has been said that during Pizarro’s

conquest of South America, he ensured his victory

by giving the natives “gifts” of clothing that had been

tainted with the variola virus.

In 1763, during the French Indian War, under the

guise of friendship, Native American Indians were

given gifts of blankets that had been previously used

by patients that died of the smallpox virus.

In 1797, Napoleon attempted to force the surrender of

Mantua by infecting the citizens with swamp fever.

During the Civil War, Confederate troops left

carcasses of dead animals, usually horses, in the

Union soldiers’ source of drinking water.

During World War II, allegations were made against

the Germans for attempting to spread cholera in Italy,

plague in St. Petersburg, and biological bombs over

Britain. Also, it was said they used Anthrax on US

soldiers’ horses and mules.

In 1925, the Geneva Protocol was signed. This

document prohibited research and development of

biological weapons, although history has proven that

offensive biological programs continued despite the

treaty.

In 1940, the Chinese dropped ceramic containers

containing plague-infected fleas on Manchuria.

In 1969, President Nixon dismantled the U.S.

offensive biological weapons program, although

research related to defense against biological weapons

continues to this day.

In 1972, the Biological and Toxin Weapons

Convention was signed and ratified by 140 nations.

The agreement required termination of all offensive

weapons research and destruction of existing

stockpiles of agents.

In 1978, in London, an alleged spy assassinated Secret

Service agents, using ricin toxin.


In 1984, to alter the outcome of a local election,

Rejneeshee Cult members sprayed salmonella on

salad bars in Oregon, sickening more than 700

people.

In 1995, the Aun Shinrikyo cult used Sarin gas to

attack Tokuyo subway passengers.

More recently, in 2001, letters laden with anthrax

were mailed to media, news organizations and

politicians.

Biological weapons have distinct advantages over

traditional weapons. First, you can attack a very large

area in a very short period of time using aerosolized

biological agents.

The detection of the biological release would most

likely be delayed since these agents are odorless,

colorless and tasteless. Unless the terrorists call and

announce the agent they released, the public will not

be aware until victims become ill, which is usually

days or weeks later.

Using biological agents as weapons also has the

advantage of a delayed recognition in the medical

community. The diseases produced by biological

agents all present with very similar symptoms in the

beginning, usually non-specific flu-like symptoms

that make early diagnosis difficult. Further, many

physicians have not seen these diseases in their

medical practice and have only read about them in

medical textbooks.

Another reason that the threat of using biological

agents as weapons has increased is that biological

weapons are very inexpensive to create. Experts once

estimated that fifteen hundred dollars in traditional

nuclear weapon killing power is equal to about a

penny’s worth of anthrax. 5 While nuclear weapons

production requires specific facilities, anthrax can be

germinated in a basement lab.

An additional reason that the threat of using

biological agents as weapons has increased, is that the

knowledge to produce and disseminate these agents is

easily accessible through current technology, such as

the Internet.

Furthermore, at the end of the Cold War, many

Russian scientists working in offensive biological

programs lost their jobs. It has been reported that

some of these Soviet scientists went to work for

terrorist organizations and rogue nations, taking their

knowledge, equipment and even samples, including

smallpox, with them.

Biological agents can be delivered in several different

ways, including orally in food, water or air. Today,

most experts predict the most likely method of

biological attack would be a large-scale attack of an

aerosolized agent that may or may not be contagious.

Which biological agents would pose the greatest

threat when used as a weapon? Potentially, thousands

of agents could be used in a bioterrorism attack.

However, the CDC, and USMARIID narrowed the

list based on a number of criteria, including how

easy it is to obtain and produce the agent, the agent’s

stability in the environment, and whether the agent is

contagious and/or lethal. Next, the CDC grouped the

agents into three categories based on the likelihood

of their use as a biological weapon. The categories

are A, B and C, with Category A being the most likely

agents to be used. Category A consists of 6 diseases:

anthrax, smallpox, botulism, viral hemorrhagic fever,

tularemia and plague.

This study guide will go over the 6 Category A

diseases, description, clinical manifestation,

diagnosis, treatment, post-exposure prophylaxis

and infection control including appropriate barrier

protection.


Anthrax

Anthrax is caused by the Bacillus anthracis, a grampositive

spore-forming bacterium. This bacterium

is found in soil worldwide. Humans contract the

disease from close contact with animals or animal

products infected with the bacteria. Of the three

routes of exposure – inhalation, cutaneous, and

gastrointestinal, inhalational anthrax is the one that is

of greatest concern as a bioweapon. 6 Inhaled spores

can germinate for up to 60 days in the mediastinal

lymph nodes, therefore, the time period between

exposure and onset of symptoms may be as long as

several weeks.

There are three forms of anthrax:

Skin (cutaneous)

Most common natural form. Mortality 10% to 20%

if untreated, less than 1% when treated.

Lungs (inhalation)

Most lethal form, with mortality of 45% to 87%

following inhalation of spores. Most likely form of

the disease to occur in a bioterrorism event

Digestive (gastrointestinal)

Rare, but highly fatal form that occurs after ingestion

of spores. There is a potential use in a bioterrorism

event, which might be seen in an aerosol release. 7

Clinical manifestation of the three forms of Anthrax 17

Anthrax Incubation Period Early Signs/ Symptoms Later Signs/ Symptoms

Inhalational

(primary involvement is

the mediastinum)

Cutaneous 1-7 days, possibly up to

12 days.

Gastrointestinal 1-7 days, typically 2-5

days.

Diagnosis

2-60 days. Flu-like symptoms including

fever, malaise, headache,

cough, fatigue and anorexia,

prominent absence of

rhinitis.

There are no specific laboratory tests for inhalation

anthrax, but a widened mediastinum with or without

infiltrates on chest x-ray is highly suggestive in a

young or otherwise healthy person with the typical

presentation. Bloody pleural effusions are also

common. Basic diagnostic testing should include

gram stain and culture of blood, which can be obtained

following your facilities standard routine. If the culture

grows gram + bacilli, it must be sent to the state

laboratory to be analyzed further. 1 The state laboratory

needs to be notified ahead of time that anthrax is a

possibility. The local health department will investigate

and give directions on how to obtain and send the

cultures.

There are no available rapid specific tests for early

anthrax disease.

B. anthracis can be cultured from the lesion for

laboratory confirmation in the cutaneous form. The

local health department will need to be notified and

give directions to obtain and send the cultures. 4

Fever and malaise, small

papular or vesicular rash

that may be pruritic.

Fever, abdominal pain,

vomiting and bloody diarrhea

and headache.

Treatment

Fever, chest pain, severe

respiratory distress, diaphoresis,

shock and death.

Painless ulceration with overlying

eschar, localized edema, often on

the head, forearms and hands.

Shock and death.

Treatment consists of hospitalization, IV antibiotics

and intensive supportive care. Antibiotic treatment

should be administered as soon as the diagnosis is

suspected because early initiation can reduce the

mortality, which approaches 100%, when treatment is

delayed.

Post-Exposure Prophylaxis

Antibiotics should be administered to all persons that

have been exposed or potentially exposed to the release

of anthrax before symptoms have occurred. Patient

contact, (family, friends and healthcare workers)

who were not originally exposed to the release do not

7, 9

require prophylaxis.

Vaccination

A licensed cell-free, effective and safe vaccine exists,

but is currently not available to the general public.


Infection Control

Regardless of the form of the anthrax disease, Standard

Precautions are recommended.

Standard Precautions include the following:

Handwashing

Wash hands immediately after gloves are removed,

between patient contacts, and when otherwise

indicated to avoid transfer of microorganisms to other

patients or environments.

Gloves

Wear gloves when touching blood, body fluid,

secretions, excretions, and contaminated items; put on

clean gloves just before touching mucous membranes

and nonintact skin.

Change gloves between tasks and procedures on the

same patient after contact with material that may

contain a high concentration of microorganisms.

Remove gloves promptly after use, before touching

noncontaminated items and environmental surfaces,

and before going to another patient. Wash hands

immediately to avoid transfer of microorganisms to

other patients or environments.

Smallpox

Smallpox is the most devastating infectious disease in

the history of mankind. It has killed over 500 million

people worldwide.

The Variola virus that emerged in human populations

thousands of years ago causes smallpox. 8 Literature

dating from approximately 3700 BC in Egypt and

1100 BC in China suggests that the original sources

of smallpox were in Asia and Africa. There is evidence

that a major smallpox epidemic occurred at the end of

the 18th Egyptian dynasty. Research from the mummy

of Pharaoh Ramses V, who died in 1157 BC, indicate

that he most likely died of smallpox. From ancient

Egypt, traders spread the disease to India, and then to

Europe during the Middle Ages.

Smallpox was then brought to the US by the Spanish

colonists in the fifteenth and sixteenth centuries. After

an extensive and successful eradication program, the

World Health Assembly certified the global eradication

of smallpox in 1980. There has not been a reported

case of smallpox in over twenty years. Successful

efforts to prevent the spread of smallpox through

vaccination changed the course of history of Western

medicine. Most people think that since smallpox was

eradicated, it is no longer a threat. However, when

smallpox was eradicated two samples were maintained

for research purposes. These samples were kept at the

CDC and in a research facility in Russia.

Masks, eye protection, face shields

Wear a standard surgical mask and eye protection or a

face shield to protect mucous membranes of the eyes,

nose, and mouth during procedures and activities that

are likely to generate splashes or sprays.

Several sources recommend Contact Precautions for

cutaneous anthrax for persons with draining lesions.

Contact Precautions include the following:

• Place patient in a private room.

• Gloves should be worn when entering the room

and removed before leaving the room. Hands should

be washed with an antimicrobial agent or a waterless

handwashing agent immediately after removing

gloves.

• Gowns should be worn when entering the room if

it is anticipated that clothing will have contact with

the patient, environmental surfaces, or items in the

room. The gown should be removed before leaving

the patient’s room.

• Patient transport should be limited to essential

purposes only.

• Noncritical patient-care equipment should be

dedicated whenever possible.

After the end of the Cold War, unemployed Soviet

scientists went to work for terrorist organizations and

rogue nations, taking their knowledge, equipment

and samples including smallpox, with them. 16 In the

after-math of the events of September and October

2001, there is heightened concern that the variloa virus

might be used as a bioterrorism agent. 7

There are two forms of smallpox:

Variola Major

A severe and more common form of smallpox, with a

more extensive rash and higher fever.

There are four types of variola major smallpox:

1. Ordinary - the most frequent accounting for 90% of

all cases.

2. Modified - a mild form occurring in persons

previously vaccinated for smallpox.

3. Flat - a very rare and fatal form.

4. Hemorrhagic -a very rare and very fatal form.

Variola Minor

The much less severe and less common form of

smallpox with death rates of 1% or less.


Clinical Manifestation of

Smallpox

Exposure to the virus is followed by an incubation

period during which people do not have any symptoms

and may feel fine. The incubation period averages

about 12 to 14 days with a range from 7 to 17 days.

During this time people are not contagious and cannot

spread the virus to others. Typically, a two stage illness

will follow. First is the Prodrome stage, lasting from

2 to 4 days. During this stage the person will present

with “flu-like” symptoms including fever, malaise,

head and body aches, and sometimes vomiting. The

fever is usually high, in the range of 101 to 104 degrees

Fahrenheit. During this stage the person is sometimes

contagious. They then move to the next stage of the

disease, the Eruptive stage. A rash emerges first as

small red spots on the tongue and in the mouth.

These spots develop into sores that break open and

spread large amounts of the virus into the mouth and

4, 7 throat.

This is the most contagious time. At this time, a rash

will also appear on the skin, starting on the face and

spreading to the arms and legs and then to the hands

and feet. The rash will usually spread to all parts of

the body within 24 hours. The fever usually breaks

as the skin rash appears and the person may feel

better. Around the third day of the skin rash, the rash

becomes raised bumps. By the fourth day, the bumps

fill with thick, opaque fluid and have a depression

in the center that looks like a bellybutton. (This is

a major distinguishing characteristic of smallpox).

Fever will rise again and stay high until scabs form

over the bumps. The bumps will become pustules,

raised, round and firm to the touch. The pustules then

begin to form a crust and then scab over. The pustules

and scab portion takes approximately 5 days, and the

person remains very contagious during this time. At

this time the scabs begin to fall off, leaving pitted scars.

This takes another 6 to 7 days, and the person remains

contagious. About three weeks after the rash first

appeared the scabs fall off and the person is no longer

contagious.

Transmission

Humans are the only natural reservoirs of Variola

virus. Person-to-person transmission of smallpox

occurs by aerosol droplets expelled from the

oropharynx of infected persons, or by direct contact

with an infected person. The virus can also be spread

through contaminated bedding and clothing. Smallpox

can also be spread through direct contact with infected

bodily fluids. It is not known to be transmitted by

insects or animals.

Diagnosis

Smallpox is most frequently misdiagnosed as varicella,

or chickenpox, which is caused by the herpes virus.

The most effective criteria for distinguishing the

two infections is an examination of the following

characteristics of the lesions:

Time and pattern of appearance

The most obvious distinction between smallpox

and chickenpox is the manner in which the skin

lesions appear. In chickenpox, the lesions occur in

successive “crops.” It is possible to determine several

different stages of lesion maturation and development

at the same time. In smallpox, the lesions appear

simultaneously. All lesions have the same maturation.

Density and location

Chickenpox lesions tend to be denser over the trunk,

while smallpox lesions are denser on the face and

extremities. Smallpox are almost always seen on the

palms and soles of the feet, which is unusual for

chickenpox.

Smallpox can be confirmed in the laboratory by

electron microscopic examination of vesicular

or pustule liquid or scabs. Definitive laboratory

identification and characterization involves growth

of the virus in the cell culture, and characterization

of strains by use of biologic assays, including

polymerase chain reaction, restriction fragment-length

polymorphism analysis and ELISA. Confirmation

using these methods can be accomplished in a few

hours. Notification of the local and state health

department is necessary.

Treatment

Currently there are no known effective antivirals.

Give the person supportive care and antibiotics for

secondary infections.

The discovery of a single suspected case of smallpox

must be treated as an international health emergency

and immediately brought to the attention of national

officials through local and state health authorities.

Post Exposure

Prophylaxis

All contacts must be vaccinated within three to five

days. Contacts include all household members,

patients, staff and visitors to the hospital at the same

time as the smallpox case. 9

Monitor all patient contacts for 17 days, and if one

of the contacts starts showing signs of a fever, they

should be isolated as soon as possible. Patients

become infectious the day before the rash, so conduct

a thorough history of all contacts the day before they

broke out, and monitor all of those contacts.


Infection Control

Standard Precautions include the following:

Handwashing

Wash hands immediately after gloves are removed,

between patient contacts, and when otherwise

indicated to avoid transfer of microorganisms to other

patients or environments.

Gloves

Wear gloves when touching blood, body fluid,

secretions, excretions, and contaminated items. Put on

clean gloves just before touching mucous membranes

and nonintact skin.

Change gloves between tasks and procedures on the

same patient after contact with material that may

contain a high concentration of microorganisms.

Remove gloves promptly after use, before touching

noncontaminated items and environmental surfaces,

and before going to another patient, and wash hands

immediately to avoid transfer of microorganisms to

other patients or environments.

Botulism

Botulism is a rare but serious paralytic illness,

caused by a nerve toxin, produced by the bacterium

Clostridium botulinum toxin, the most potent toxin

known to humans. Of the seven antigenic types of C

botulinum (A-G), human botulism is caused mainly by

types A, B, and E.

The most common type of human botulism is

acquired through the ingestion of toxin-contaminated

food in which C botulinum spores have germinated

(gastrointestinal). Other routes of transmission include

the inhalation of aerosolized toxin and the germinating

in vivo in either a contaminated wound (wound

botulism), or the gastrointestinal tract of infants (infant

botulism). 10

Masks, eye protection, face shields

Wear a standard surgical mask and eye protection or a

face shield to protect mucous membranes of the eyes,

nose, and mouth during procedures and activities that

are likely to generate splashes or sprays.

Airborne Precautions include the following:

• Place the patient in a private room with

negative air-pressure ventilation.

• Use external air exhaust or high-efficiency particulate

air filters if the air is recirculated. 3,12

• Keep the door to the room closed.

Contact Precautions include the following:

• Place the patient in a private room if available.

• Wear gloves when entering the room, change gloves

after having contact with infectious material, remove

gloves before leaving the room and wash hands

using an antimicrobial agent.

• Wear a gown when entering the room if clothing will

have patient contact.

• Transport the patient for essential purposes only.

• Dedicate the use of noncritical, patient care

equipment.

In the United States an average of 110 cases of

botulism are reported annually. Of these, 25% are

foodborne, 72% infant, and 3% wound botulism. It

is speculated that inhalation botulism would be the

primary form of the disease if the botulism toxin were

weaponized. 8 The clinical manifestations are similar

for each of the botulism routes and are dependent on

the level of toxin exposure.

Diagnosis

Patient’s history and physical examination can be an

indicator of botulism, although usually not conclusive.

Brain scan, spinal fluid examination, nerve conduction

tests and a tensilon test. The most direct way to confirm

botulism is to isolate botulism bacteria in stool or serum.

Notification of the local health department is necessary.


Clinical manifestations of Botulism 17

Botulism Incubation Period Early Signs/ Symptoms Later Signs/ Symptoms

Botulism (all forms) 2-8 hours (if inhaled as an

aerosol) typically 12-72 hours

for foodborne ingestion.

Treatment

Incubation period for

inhalational form not

established.

Treatment consists of mechanical ventilation support

if necessary and supportive care. If diagnosed early,

foodborne and wound botulism can be treated with an

antitoxin which blocks the action of toxin circulating in

the blood. This can prevent patients from worsening,

but recovery still takes many weeks. Mortality rate is

approximately 8% to 10%.

Generally no fever.

Symmetric cranial

neuropathies, such as

drooping eyelids, difficulty

swallowing or speaking.

Mental status generally alert.

Sensory exam generally

normal.

Blurred vision.

Infection Control

Symmetric descending

weakness – first paralysis

of the arms, followed by

respiratory muscles and legs.

Respiratory failure.

Standard Precautions are adequate since person-toperson

transmission does not occur. 11

Standard Precautions include the following:

Handwashing

Wash hands immediately after gloves are removed,

between patient contacts, and when otherwise

indicated to avoid transfer of microorganisms to other

patients or environments.

Gloves

Wear gloves when touching blood, body fluid,

secretions, excretions, and contaminated items; put on

clean gloves just before touching mucous membranes

and nonintact skin.

Change gloves between tasks and procedures on the

same patient after contact with material that may

contain a high concentration of microorganisms.

Remove gloves promptly after use, before touching

noncontaminated items and environmental surfaces,

and before going to another patient, and wash hands

immediately to avoid transfer of microorganisms to

other patients or environments.

Masks, eye protection, face

shields

Wear a standard surgical mask and eye protection or a

face shield to protect mucous membranes of the eyes,

nose, and mouth during procedures and activities that

are likely to generate splashes or sprays.


Hemorrhagic

fever viruses

Viral hemorrhagic fevers (VHFs) refer to a group of

illnesses that are caused by several distinct families

of viruses. Each disease causes a febrile syndrome

characterized by hemorrhagic complications, but

mortality rates, incubation periods and susceptibility to

antiviral therapy vary depending on the etiologic agent.

While some types of hemorrhagic fever can cause

relatively mild illnesses, many of these viruses cause

severe, life-threatening disease. These organisms pose

a biological threat due to their potential to cause severe

morbidity and because transmission can occur from

13, 14

person to person.

The viruses that are considered the most dangerous

if weaponized include the filoviruses (Ebola and

Marburg), New World aarenaviruses (Lassa fever,

Junin, Machupo, Guanarito, Sabia), flaviviruses (Omsk

hemorrhagic fever, Kyasanur Forest disease), and

bunyaviruses (Rift Valley fever).

Diagnosis

Patient presenting with a fever greater than 101

degrees Fahrenheit with at least two accompanying

symptoms would be suspect. Notification of the

local health department is necessary. For decisions

regarding obtaining and processing diagnostic

specimens, contact local, state, and regional laboratory

authorities or CDC.

Treatment

Patients receive supportive therapy because there is

no established cure for VHF’s. Ribavirin, an anti-viral

drug, has been effective in treating some individuals

with Lassa fever. Treatment with convalescent-phase

plasma has been used with success in some patients.

Post Exposure

Prophylaxis

There is no post exposure prophylaxis currently

available for VHF. 13

There is currently no vaccine for VHF.

Infection Control

Appropriate isolation precautions for patients with

suspected or confirmed VHF include a combination of

Airborne, Contact, Droplet and Standard Precautions.

Although airborne transmission of these agents

appears to be rare, airborne transmission theoretically

may occur; therefore, airborne precautions should be

instituted for all patients with suspected VHF.

Airborne Precautions include the following:

• Place the patient in a private room with negative

air-pressure ventilation.

• Use external air exhaust or high-efficiency

particulate air filters if the air is recirculated.

• Keep the door to the room closed.

Contact Precautions include the following:

• Place the patient in a private room if available.

• Wear gloves when entering the room, change gloves

after having contact with infectious material, remove

gloves before leaving the room and wash hands

using an antimicrobial agent.

Provide the following Personal Protective Equipment

(PPE) for healthcare providers:

• N-95 respirator or (PAPR)

• Double gloves

• Impermeable gowns

• Face shields

• Goggles

• Leg and shoe coverings

Droplet Precautions include the following:

• Place the patient in a private room or in a room with

other patients who have the same infection.

• When a private room and like infection patients are

unavailable, spatial separation of a least three feet

should be maintained.

Healthcare workers should wear a standard surgical

mask when working within three feet of the patient.


Clinical manifestations of VHF 17

VHF Incubation Early Signs/ Symptoms Later Signs/ Symptoms

Ebola virus 2-21 days. Fever, severe fatigue headache,

myalgias, abdominal pain,

diarrhea, may include chest

pain, cough, pharyngitis,

lymphadenopathy photophobia,

conjunctival infection.

Marburg virus 2-14 days. Fever, exhaustion, headache,

vomiting, conjuncitvitis,

enanthem on soft palate,

myalgias backache, clouded

consciousness.

Lassa fever 5-16 days. Gradual development of fever,

weakness, malaise.

Rift Valley fever 2-6 days. Fever headache, photophobia,

and retro-orbital pain.

Kyasanur Forest

disease

Omsk hemorrhagic

fever

New World

aarenaviruses,

(Machupo, Junin,

Guanarito, Sabia)

Standard Precautions include the following:

2-9 days. Sudden onset of fever, myalgias,

headache.

2-9 days. Fever, headache, vomiting,

enanthem on palate, hyperemia

of skin on upper body & mucous

membranes.

7-16 days. Gradual onset of fever, sore

throat, myalgias, low back pain,

abdominal pain.

Handwashing

Wash hands immediately after gloves are removed,

between patient contacts, and when otherwise

indicated to avoid transfer of microorganisms to other

patients or environments.

Gloves

Wear gloves when touching blood, body fluid,

secretions, excretions, and contaminated items; put on

clean gloves just before touching mucous membranes

and nonintact skin.

Change gloves between tasks and procedures on the

same patient after contact with material that may

contain a high concentration of microorganisms.

Remove gloves promptly after use, before touching

noncontaminated items and environmental surfaces,

and before going to another patient, and wash hands

immediately to avoid transfer of microorganisms to

other patients or environments.

Maculopapular rash predominantly on trunk,

appearing about 5 days after onset of illness,

jaundice, and pancreatitis often occur. As

disease progresses, bleeding may develop,

such as mucous membrane hemorrhages,

hematemesis, bloody diarrhea, petechiae,

ecchymoses.

Maculopapular rash appearing on 5 th to 7 th

day on trunk, face, neck, and proximal regions

of extremities, nonpruritic. Jaundice and

pancreatitis. As disease progresses bleeding

develops.

Arthralgias, back pain, nonproductive cough

by 3 rd day, then severe exudative pharyngitis,

maculopapular rash may be seen on fair

skinned patients, severe exhaustion by 8 th day.

As disease progresses bleeding develops.

Hepatitis, bleeding, encephalitis, retinitis.

Vomiting and diarrhea. Enanthem with papulovesicular

lesions on soft palate. Conjunctival

congestion, subconjunctival hemorrhage,

mild iritis, retinal and vitreous hemorrhage.

cervical and axilary lymphadenopathy, bleeding

from nose, gums, GI tract.

Sever fever, generalized lymphadenopathy,

splenomegaly and pneumonia.

Vascular, neurologic manifestations may occur

5-7 days after illness onset, bleeding.

Masks, eye protection, face

shields

Wear a standard surgical mask and eye protection or a

face shield to protect mucous membranes of the eyes,

nose, and mouth during procedures and activities that

are likely to generate splashes or sprays.

Place all persons who have had close or high-risk

contact with a patient suspected of having VHF

during the 21 days following onset of symptoms under

medical surveillance.

If multiple patients with suspected VHF are admitted

to one healthcare facility, group them in the same part

of the hospital to minimize exposure to other patients

and healthcare workers


Tularemia

Tularemia, is an acute infectious disease caused

by Francisella tularensis. The organism is naturally

occurring in a wide range of animal hosts, such as

moles, mice, water rats, squirrels, rabbits and hares,

and can be recovered from contaminated water, soil

and vegetation. It requires inoculation, as inhalation of

as few as ten organisms can cause disease.

Tularemia occurs throughout much of North America,

Europe and Asia. It is transmitted to humans

primarily through tick bites or handling infected

animals. Tularemia peaks with cases in rural areas in

moderate climates such as in the Midwestern United

States in summer, and again in winter during hunting

seasons.

Clinical manifestations of Tularemia 17

Diagnosis

There is no rapid diagnostic testing for tularemia

available. Physicians who suspect tularemia should

collect specimens of respiratory secretions and

blood. F. tularensis may be identified through direct

examination of secretions, exudates or biopsy

specimens using Gram stain, direct fluorescent

antibody, or immunohistochemical stains. Growth

of F tularensis in culture is the definitive means of

confirming the diagnosis. It can be grown from

pharyngeal washings, sputum, and even gastric

aspirates. Notify local health department.

F tularensis could be used as a biological weapon in a

number of ways, but the greatest concern would be

focused on an aerosolized release that would cause

pneumonic tularemia. Cases occurring in urban areas

or in those with no risk factors should alert healthcare

personnel to the possibility of a biological attack.

Treatment of tularemia is critical to avoid progression

to respiratory failure; meningitis; kidney, spleen, or

liver involvement; sepsis; shock and death.

Tularemia Incubation Period Early Signs/Symptoms Later Signs/Symptoms

Pneumonic tularemia 3-5 days, can range from

1-14 days.

Abrupt onset fever,

headache, chills, rigors,

body aches, sore throat, dry

cough, dyspnea, tachypnea,

pleuritic pain, hemoptysis,

nausea, vomiting diarrhea.

Treatment

Illness may be rapidly

progressive and severe

or may be indolent with

progressive weakness and

weight loss over several

weeks to months. The

progression of pneumonia

tends to be slower than that

of pneumonic plague.

If untreated, can progress

to respiratory failure,

meningitis, sepsis, shock and

death.

Supportive care for the patient. Administration of

parental antibiotics. Mechanical ventilation support

may be necessary.

Post-Exposure Prophylaxis

Post-exposure prophylaxis with antibiotics should

be initiated following confirmed or suspected

bioterrorism exposure, and for post-exposure

management of healthcare workers and others who

had unprotected face-to-face contact with symptomatic

patients.

There is a live attenuated vaccine commercially

available for researchers with minimal adverse effects.

There is no proven efficacy verses pneumonic

tularemia.


Infection Control

Person-to-person transmission of tularemia has not

been documented, therefore, Standard Precautions are

considered adequate for patients with tularemia. 3

Standard Precautions include the following:

Handwashing

Wash hands immediately after gloves are removed,

between patient contacts, and when otherwise

indicated to avoid transfer of microorganisms to other

patients or environments.

Gloves

Wear gloves when touching blood, body fluid,

secretions, excretions, and contaminated items. Put on

clean gloves just before touching mucous membranes

and nonintact skin.

Change gloves between tasks and procedures on the

same patient after contact with material that may

contain a high concentration of microorganisms.

Remove gloves promptly after use, before touching

noncontaminated items and environmental surfaces,

and before going to another patient. Wash hands

immediately to avoid transfer of microorganisms to

other patients or environments.

Masks, eye protection, face

shields

Wear a standard surgical mask and eye protection or a

face shield to protect mucous membranes of the eyes,

nose, and mouth during procedures and activities that

are likely to generate splashes or spray.

Plague

Plague is a disease caused by Yersinis pestis, a

bacterium found in rodents and their fleas in many

areas around the world. Under natural conditions,

plague is transmitted to humans via rodent fleas

infected with the bacterium, although humans can also

contract it by direct contact with infected animal body

and tissues or by inhaling infected droplets.

Of the three types of plague—bubonic, septic, and

pneumonic—primary pneumonic plague is the most

feared as a possible weaponized agent. 2,7 Yersinia

pestis used in an aerosol attack could cause cases of

the pneumonic form of plague. One to six days after

becoming infected with the bacteria, people would

begin to develop the plague. 7 At this time, the bacteria

can spread to others who have had close contact with

them. Because of the delay between being exposed to

the bacteria and becoming sick, people could travel

over a large area before becoming contagious and

possibly infecting others. This would make controlling

the disease very difficult.

A bioweapon carrying Y pestis is possible because

the bacterium occurs in nature and could be isolated

and grown in quantity in a laboratory. The mortality

rate is almost 60% for treated patients, and 100% for

untreated patients.


Clinical manifestations of Plague 17

Plague Incubation Period Early Signs/Symptoms Later Signs/Symptoms

Pneumonic Plague 1-4 days. Acute onset of fever, cough,

chest pain, dyspnea, hemoptysis,

tachypnea, cyanosis, nausea,

vomiting diarrhea.

Diagnosis

There are no readily available rapid tests available to

detect plague. Physicians should obtain samples of

blood, sputum, CSF and bubo fluid (if these exist).

Definitive diagnosis made by culture. Report possibility

of plague to the local health department. Cultures can

be performed by hospital laboratory. Other tests need

to be coordinated through the local health department.

Plague is difficult to diagnose because it presents like

regular pneumonia. One differentiating symptom

is hemoptysis. If the patient is coughing up blood,

consider plague. 2

Treatment

Early treatment is extremely important, as mortality

rates rise considerably if treatment is not initiated

within 24 hours of symptom onset. Parental antibiotics

will be given for at least 14 days. 7

Post-Exposure Prophylaxis

Oral antibiotic treatment for seven days should be

provided to anyone exposed to the initial release, and to

anyone who comes within two meters of a pneumonic

plague patient.

There is no available vaccine in the U.S. since 1999.

Research continues to develop new and improved

plague vaccines, particularly in light of the current

bioterrorist threat and concerns about intentional

dissemination of aerosolized plague organisms.

Infection Control

Droplet Precautions plus eye protection, in addition

to Standard Precautions should be implemented.

Patients are considered infectious for 48 to 72 hours

after initiation of appropriate antibiotic therapy with

evidence of clinical improvement. 2,4

Droplet Precautions include the following:

• Place the patient in a private room or in a room with

other patients who have the same infection.

• When a private room and like infection patients are

unavailable, spatial separation of a least three feet

should be maintained.

Healthcare workers should wear a standard surgical

mask when working within three feet of the patient.

Increasing dyspnea, stridor, cyanosis,

rapidly progressive respiratory failure

and sepsis within 2-4 days of

illness onset.

Standard Precautions include the following:

Handwashing

Wash hands immediately after gloves are removed,

between patient contacts, and when otherwise

indicated to avoid transfer of microorganisms to other

patients or environments.

Gloves

Wear gloves when touching blood, body fluid,

secretions, excretions, and contaminated items. Put on

clean gloves just before touching mucous membranes

and nonintact skin.

Change gloves between tasks and procedures on the

same patient after contact with material that may

contain a high concentration of microorganisms.

Remove gloves promptly after use, before touching

noncontaminated items and environmental surfaces,

and before going to another patient. Wash hands

immediately to avoid transfer of microorganisms to

other patients or environments.

Masks, eye protection, face

shields

Wear a standard surgical mask and eye protection or a

face shield to protect mucous membranes of the eyes,

nose, and mouth during procedures and activities that

are likely to generate splashes or sprays.

In all forms of plague, avoid surgery, autopsy, or any

other procedure that would cause aerosolization. If it is

absolutely necessary to perform these procedures, wear

an N95 mask and perform the procedure in a negative

pressure room. 9


Personal

Protective

Equipment

Personal Protective

Equipment (PPE)

Informed use of Personal Protective Equipment (PPE)

is a very critical component of a hospital’s infection

control and bioterrorism response program. Where

there is likeliood of contact with potentially infectious

material, appropriate PPE includes gloves, gowns,

laboratory coats, face shields, masks, eye protection

and ventilation devices.

Medical Gloves

When choosing a glove, the first consideration should

be the barrier requirement related to the procedure

or task at hand. Be aware of the level of exposure risk

that the patient-care activities will require. Procedures

that involve exposure to blood, body fluids and other

potentially infectious material require a glove material

that provides appropriate barrier protection.

Latex

Latex remains the gold standard for hand barrier

protection due to its strength, proven barrier

protection, elasticity, fit, feel, comfort and relatively

low cost. With the availability of low-protein, powderfree

gloves, many clinicians are confidently continuing

to wear gloves made of natural rubber latex. Latex

gloves are recommended as the first choice for barrier

protection in the healthcare environment, except for

wearers who are allergic to latex proteins.

Latex-Free Medical

Gloves

For healthcare workers that are allergic to natural

rubber latex, the other recommended alternative for

medical exam gloves would be a latex-free material

of nitrile or neoprene. In independent testing for

barrier properties, the studies showed that nitrile and

latex examination gloves are comparable in barrier

properties during in-use performance. 16

Nitrile

Nitrile’s puncture resistance is far superior to that

of latex, and it exhibits excellent resistance to most

chemicals. Nitrile’s elasticity is very good, and the

gloves tend to conform to the shape of the wearer’s

hand, providing good comfort and fit. There are no

natural rubber latex proteins in nitrile, so there is no

chance of latex allergy with use. Please see discussion

of neoprene under surgical glove choices.

Polyvinyl chloride

Many hospitals provide a latex-free material called

Polyvinyl choloride (PVC), commonly known

as “vinyl,” as a choice for exam gloves. PVC is a

petroleum-based film, but it is not molecularly crosslinked.

Because it lacks crosslinking, the individual

molecules of vinyl tend to separate when the film

is stretched or flexed. This causes small holes and

breaches to form during glove donning and normal

use. Studies have shown that 63% of vinyl exam

gloves permitted leakage of a test virus after normal

use, compared with 7% of latex exam gloves. 16 Vinyl

is the weakest of the glove films, with poor elasticity,

memory and fit. Because of these poor physical

properties, vinyl would not be an acceptable choice

of glove to use when handling the diseases caused by

biological agents.

Neoprene

For healthcare workers needing a surgical glove, a

neoprene glove or copolymer glove would provide

an excellent barrier. Neoprene is petroleum based

crosslinked film that provides barrier protection

similar to latex. It is a strong glove, with good

resistance to many chemicals, and very comfortable

to wear. It contains no natural rubber latex proteins,

and some contain no chemical accelerators, alleviating

any type of allergic reactions. A neoprene glove is

recommended as an alternative to natural rubber latex,

especially because of its barrier protection. Both exam

and surgical gloves are available in neoprene.

Copolymer

A copolymer glove is a petroleum-based, crosslinked

film, providing high strength, elasticity, comfort

and barrier protection. It contains no natural rubber

latex proteins or chemical accelerators, alleviating

any type of allergic reaction. Copolymer gloves are

recommended as an alternative to natural rubber latex,

because of their similarity to latex with respect to fit,

feel, comfort and barrier protection.

When selecting a medical glove, the two primary

considerations should be barrier protection and

allergen content. If a glove does not provide an

intact barrier, it is not doing its job. To maximize

barrier effectiveness, you may wish to choose a glove

manufacturer that is reliable and experienced, so that

your gloves will be of consistent quality and regularly

available.


Footnotes

1. Center for Disease Control and Prevention. Bioterrorism

alleging use of anthrax and interim guidelines for

management---United States, 1998. MMWR, 1999; 48:69-74.

2. DOD DFFUaE. NBC Domestic preparedness response

workbook. 1998.

3. Centers for Disease Control and Prevention, the Hospital

Infection Control Practices Advisory Committee (HICPAC).

Recommendations for isolation prcautions in hospitals.

Am J Infect Control 1996;24:24-52.

4. American public health association. Control of communicable

diseases in man. Washington DC:American public health

association; 1995.

5. Holloway HC, Norwood AE, Fullerton CS, Engel CC Jr, Ursano RJ.

The threat of biological weapons. Prophylaxis and mitigation of

psychological and social consequences. JAMA 1997; 278:425-7.

6. Pile JC, Malone JD, Eitzen EM, Friedlander AM. Anthrax as

a potential biological warfare agent. Arch Intern Med 1998;

158:429-34.

7. Franz D, Jahrling PB, Friedlander AM, McClain DJ, Hoover DL,

Bryne WR, et al. Clinical recognition and management of patients

exposed to biological warfare agents. JAMA 1997;278:399-411.

8. U.S. Army medicaal research institute of infectious diseases.

Medical management of biological casualties. Fort Detrick:

USAMRIID; 1998.

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Center for Disease Control and Prevention. Bioterrorism alleging

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Centers for Disease Control and Prevention, the Hospital

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Centers for Disease Control and Prevention. Summary of notifiable

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psychological and social consequences. JAMA 1997; 278:425-7.

Infection Control for Viral Hemorrhagic Fevers in the African

Healthcare Setting. CDC and WHO 1998:1-198.

Inglesby T. V., Henderson D. A., Barlett J. G., Ascher M. S., Eitzen

E., Friedlander A. M., Hauer J., McDade J., Osterholm M.T., O’Toole

T., Parker G., Perl TM, Russell R.K., and Tonat K. Smallpox as a

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