EDUCATIONEVIDENCE

EVIDENCEENGAGEMENT

BIOTERRORISM AGENTS

EDUCATIONEVIDENCE

ENGAGEMENTEDUCATION

AND BARRIER PROTECTION

A SELF STUDY GUIDERegistered Nurses

®

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noverviewAnsell Healthcare Products LLC has an ongoing commitment to the development of quality hand barrier products and services for the healthcare industry. This self-study, Clinical Reference Manual: Bioterrorism Agents and Barrier Protection is one in a series of continuing educational services provided by Ansell. This educational module examines the history and evolution of bioterrorism, including an extensive review of the six primary biological agents and their respective clinical presentations, as well as prevention strategies and infection control measures and appropriate barrier protection for each of the agents.

ProgrAm oBjectivesUpon completion of this educational activity, the learner should be able to:

1. Discuss the history of bioterrorism.2. Discuss the disease caused by Bacillus anthracis, Anthrax.3. Discuss the disease caused by Variola virus, Smallpox.4. Discuss the disease caused by Clostridium botulinum, Botulism.5. Discuss the disease caused by Francisella.6. Discuss the diseases referred to as Hemorrhagic Fever Viruses.7. Discuss the disease caused by Yersinia pestis, Plague.8: Describe the characteristics of good barrier protection for the different gloving materials available.

intended AudienceThe information contained in this self-study guidebook is intended for use by healthcare professionals who are responsible for or involved in the following activities related to this topic:

• Educatinghealthcareworkers• Establishinginstitutionalordepartmentalpoliciesandprocedures• Decision-makingresponsibilitiesforhand-barrierproducts• MaintainingregulatorycompliancewithagenciessuchasOSHA,ADAandCDC• Managingemployeehealthandinfectioncontrolservices

instructionsAnsell Healthcare is a provider approved by the california Board of registered nursing, Provider # ceP 15538 for 3 contact hour(s). obtaining full credit for this offering depends on completion of the self-study materials online as directed below.Thiscontinuingeducationactivityisapprovedfor3.75CEcreditsbytheAssociationofSurgicalTechnologists,Inc., for continuing education for the Certified Surgical Technologist and Certified Surgical First Assistant. This recognition does not imply that AST approves or endorses any product or products that are included in the presentation.

Approval refers to recognition of educational activities only and does not imply endorsement of any product or company displayed in any form during the educational activity.

To receive contact hours for this program, please go to the “Program Tests” area and complete the post-test. You will receive your certificate via email.

An 85% PAssing score is reQuired For successFuL comPLetion

Allow 4 to 6 weeks for processing and issuance of a certificate. Any learner who does not successfully Any learner who does not successfully complete the post-test will be notified and given an opportunity to resubmit for certification.

For more information about our educational programs or hand-barrier-related topics, please contact Ansell Healthcare EducationalServicesat1-732-3452162ore-mailusatedu@ansellhealthcare.com.

Planning Committee Members: Lori Jensen, RN PamelaWerner,RN,BSN,CNOR,MBA

The planning committee members declare that they have an affiliation and financial relationship as employees of Ansell Healthcare, which could be perceived as posing a potential conflict of interest with development of this self-study module. This module will include discussion of commercial products referenced in generic terms only.

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contents

What is Bioterrorism? ..............................................................................................1

HistoryandEvolutionofBioterrorism ......................................................................1

Bacillus anthracis, Anthrax ......................................................................................3

Variola virus, Smallpox ............................................................................................5

Clostridium botulinum, Botulism .............................................................................8

Hemorrhagic Fever Viruses ...................................................................................10

Francisella tularensis, Tularemia ...........................................................................13

Yersinia pestis, Plague .........................................................................................15

PersonalProtectiveEquipment ..............................................................................17

Post-Test ...............................................................................................................20

Bibliography ..........................................................................................................21

Notes ...............................................................................................................22–23

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1

wHAt is Bioterrorism?

Bioterrorism is defined as the deliberate

or threatened use of bacteria, viruses, or

toxins to cause disease, death, disruption,

or fear. The most likely large-scale attack of

bioterrorism is expected to be an aerosolized

agent. Any of the Category A diseases have

the potential to be aerosolized: anthrax,

smallpox, botulism, viral hemorrhagic

fevers, tularemia, and plague.

HistorY And evoLution oF Bioterrorism

KeY BioTerrorisT eVenTs • GenevaProtocolsignedtoprohibitresearch

and development of biological weapons.

• UnitedStatesoffensivebiologicalweaponsprogram dismantled.

• BiologicalandToxinWeaponsConvention signed.

Bioterrorism is not a new phenomenon

and has been used as a weapon for

centuries. 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 in Ukraine),

the Tartars catapulted plague-infected

corpses over the walls of the city, which

probably led to the Black Death plague

epidemic that followed. It has been said

that during Pizarro’s conquest of South

America in the 1600s, he ensured his

victory by giving the natives “gifts” of

clothing that had been tainted with the

smallpox virus. In 1763, during the French

and Indian War and under the guise of

friendship, Native Americans 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

weremadeagainsttheGermansfor

attempting to spread cholera in Italy and

plague in Leningrad, and use biological

bombs over Britain. Also, it was alleged

thattheGermansdeployedanthraxagainst

their enemies in both World Wars I and II.

Othersignificanteventsinthehistoryof

bioterrorism include:

1925:TheGenevaProtocolwassigned.This document prohibited research and development of biological weapons, although history has proven that offensive biological programs continued despite the treaty.

1940: Japanese dropped plague, by planes, at Ninpo.

1969: President Nixon dismantled the United States offensive biological weapons program, although research related to defense against biological weapons continues to this day.

1972: The Biological and Toxin Weapons Convention was signed and ratified by 140 nations. This agreement required termination of all offensive weapons research and destruction of existing stockpiles of agents.

Protection against Bioterrorism

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1978:InLondon,anallegedKGBagent assassinated a Bulgarian exile using ricin toxin.

1984: To alter the outcome of a local election, Rajneesh cult members sprayed salmonellaonsaladbarsinOregon,causing more than 700 people to become ill.

1995: A sarin nerve agent attack aimed at subway passengers in Tokyo.

2001: Letters laden with anthrax were mailed to media, news organizations, and politicians.

The threat of biologic weapons (BW) has

increased over the last two decades with a

number of countries working on offensive

weapons (USAMRIID). Biological weapons

have distinct advantages over traditional

weapons. First, they 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.

At a cost of $2000 or more for

conventional weapons, a $1 in biological

weapons could produce similar results.

(AORN2004)Whilenuclearweapons

production requires specific facilities,

anthrax can be germinated in a basement

laboratory. Also, 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. The whereabouts

of these Soviet scientists is an unknown

factor and the whereabouts of their

products is unclear.

Biological agents can be delivered in

several different ways, including orally

in food, and through water or air. Today,

most experts predict the most likely

method of biological attack would be a

large-scale attack using 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 Centers for Disease Control (CDC) and

the US Army Medical Research Institute of

Infectious Diseases (USAMRIID) 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. The CDC identified the Category

A agents as high priority agents that pose

a risk to national security.

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Category A consists of six diseases:

anthrax, smallpox, botulism, viral

hemorrhagic fevers, tularemia, and

plague. This study guide will review

the six Category A diseases, providing

a description, clinical manifestations,

diagnosis, treatment, post-exposure

prophylaxis, and infection control,

including appropriate barrier protection.

Bacillus anthracis, AntHrAx

DeFiniTionAnthrax is caused by Bacillus anthracis,

a gram-positive spore-forming bacterium,

and is found in soil worldwide. Humans

contract the disease from close contact

with animals or animal products infected

withthebacteria.Ofthethreeroutesof

exposure – inhalation, cutaneous, and

gastrointestinal – inhalational anthrax

is the one that is of greatest concern as

a bioweapon. (USAMRIID 2005) Inhaled

spores typically germinate 1-6 days but

there have been reports of illness up to 6

weeks after exposure 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:

Cutaneous Most common natural form. Mortality of 10% to 20% if untreated; less than 1% when treated.

Inhalation Most lethal form, with mortality of 45% to 87% following inhalation of spores. Inhalation anthrax may be complicated by hemorrhagic meningitis in 50% of cases andGIhemorrhagein80%ofcases. Most likely form of the disease to occur in a bioterrorist event.

Gastrointestinal Results from the ingestion of large numbers of vegetative bacilli from poorly cooked infected meat. Due to difficulty in early diagnosis, mortality is high.

ANTHRAX INCUB A TIO N PERIOD

EARLY SIGNS/SYMPTOMS

LATER SIGNS/SYMPTOMS

Inhalational (primary involvement is the mediastinum)

Cutaneous

Gastrointestinal 1-6 days.

1-6 up to 40 days.

1-2 days.

Non-specific febrile syndrome including fever, malaise, headache, fatigue and drenching sweats.

Small papular or vesicular rash that may be pruritic.

Fever, focal abdominal pain, vomiting.

Hematemisis.

Same as above.

Abrupt development of severe respiratory distress with dyspnea, stridor, cyanosis, septicemia, shock and death.

CliniCAl mAniFesTATions oF THe THree Forms oF AnTHrAx

Scanning electron micrograph (SEM) of bacillus anthracis in lung tissue

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DiAGnosisRapid field tests results have

uncertain sensitivity and specificity

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 facility’s

standard routine. Confirmatory tests

must be performed by special reference

laboratory in the Laboratory Response

Network (LRN) (JAMA 2002). 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. 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

provide directions to obtain and send

these cultures.

TreATmenTTreatment consists of hospitalization, intravenous antibiotics, and intensive supportive care. Antibiotic treatment should be administered as soon as the diagnosis issuspected.Earlyinitiationcanreducemortality, which approaches 100% when treatment is delayed.

PosT-exPosUre ProPHYlAxisAntibiotics should be administered to all persons that have been exposed or potentially exposed to the release of anthrax before symptoms have occurred. Patient contacts (family, friends, and healthcare workers) who were not originally exposed to the release do not require prophylaxis.

VACCinATion The Department of Defense (DoD) and the Department of Health and Human Services have purchased a stockpile of vaccine doses. Vaccination is currently required for most military deployed to Iraq, Afghanistan and S. Korea. It is not currently being used on the general public. Researchers continue to develop and test new Anthrax vaccine(s) (USAMRIID 2005).

inFeCTion ConTrolAll precautions are utilized to decrease the spread of recognized and unrecognized infection and to prevent exposure to all bodily fluids.

Standard Precautions – Is recommended for all forms of B. Anthrax1. Handwashing

Wash hands immediately after gloves areremoved, between patient contacts, andwhen otherwise indicated to avoid transferof microorganisms to other patients orenvironments. Hand wash with soap and wateror2%CHGaftersporecontact.(Weber2003)

Anthrax lesion on the skin caused by the bacterium Bacillus anthracis

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2. GlovesWear gloves when touching blood,bodily fluids, secretions, excretions, andcontaminated items; put on clean gloves justbefore touching mucous membranes andnonintact skin.

Change gloves between tasks andprocedures on the same patient aftercontact with material that may contain ahigh concentration of microorganisms.

Remove gloves promptly after use, beforetouching noncontaminated items andenvironmental surfaces, and before goingto another patient. Wash hands immediatelyto avoid transfer of microorganisms to otherpatients or environments.

3. Masks, Eye Protection, Face ShieldsWear a standard surgical mask and eyeprotection or a face shield to protect mucousmembranes of the eyes, nose, and mouthduring procedures and activities that arelikely to generate splashes or sprays.

Transmission Based PrecautionsSeveral sources recommend contact precautions for cutaneous anthrax for persons with draining lesions.

Contact Precautions• Placepatientinaprivateroom.

• Glovesshouldbewornwhenenteringthe room and removed before leaving theroom. Hands should be washed with anantimicrobial agent or soap and water withspore contact.

• Gownsshouldbewornwhenenteringtheroom if it is anticipated that clothing willhave contact with the patient, environmentalsurfaces, or items in the room. The gownshould be removed before leaving thepatient’s room.

• Patienttransportshouldbelimitedtoessential purposes only.

• Noncriticalpatient-careequipmentshouldbededicated whenever possible.

Variola Virus, smALLPoxDeFiniTionSmallpox is the most devastating infectious disease in the history of mankind. This “ancient scourge” threatened 60% of the world population even in 1967 when World Health Organization(WHO)launchedan intensified plan to eradicate smallpox. (AORN2004)Thevariolavirusthatemerged in human populations dates back to the 12th Century BC.

Literature dating from approximately 3700BCinEgyptand1100BCinChinasuggests 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 eighteenth Egyptiandynasty.Researchfromthemummy of Pharaoh Ramses V, who died in 1157 BC, indicates that he most likely diedofsmallpox.FromancientEgypt,traders spread the disease to India, and thentoEuropeduringtheMiddleAges.

Spanish colonists brought smallpox to the United States in the fifteenth and sixteenth centuries. After an extensive andsuccessfuleradicationprogram,WHO declaredEndemicsmallpoxeradicatedin 1980. There was a suspected report of smallpox in NYC in 2002, (cnn.com) 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.

Gloves should be worn as standard procedure when handling contaminated items

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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.

The potential for secret stockpiles to exist outside these facilities continues to be an unknown factor. In the aftermath oftheeventsofSeptemberandOctober2001, there is heightened concern that the variola virus might be used as a bioterrorism agent. (USAMRIID)

Variola Major Is a severe and more common form of smallpox, with a more extensive rash and higher fever. The fatality rate is around 30%. There are four types of variola major smallpox:

1. Ordinary:themostfrequentform,accounting for 90% of all cases.

2. Modified: a mild form occurring in personspreviously vaccinated for smallpox.

3. Malignant/ Flat: Characterized by lesionsthat do not develop to the pustular stage.

4. Hemorrhagic: a very rare and veryfatal form.

Variola Minor This is a much less severe and less common form of smallpox, with death rates of 1% or less.

CliniCAl mAniFesTATionsoF smAllPox

Exposuretothevirusisfollowedbyan

incubation period during which people

do not have any symptoms, may feel fine

and do not shed the virus. 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° Fahrenheit. During this stage the

person may be contagious. Two to three

days later the affected person moves to

the eruptive stage. The smallpox rash is

very characteristic. The 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

throat. At this time, a rash will also appear

on the skin starting on the face hands and

forearms. 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 patient 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 belly button (this is a major

distinguishing characteristic of smallpox).

Transmission electron micrograph (TEM) of the smallpox virus

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Fever will rise again and stay high until scabs form over the bumps. The bumps will become pustules that are 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 3 weeks after the rash first appeared, the scabs fall off and the person is no longer contagious.

TrAnsmissionPerson-to-person transmission of smallpox occurs through aerosol droplets expelled from the oropharynx of infected persons, or by direct contact with an infected person. It is the highest after face-to-face contact with a patient after developing fever and during the first week of the rash. The virus can also be spread through contaminated bedding and clothing, and through direct contact with infected bodily fluids. It is not known to be transmitted by insects or animals.

DiAGnosisSmallpox 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 is 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 polymorphismanalysis,andEnzyme-LinkedImmunoabsorbentAssay(ELISA).Culture for smallpox is available only at the LRN National Labs, at the CDC and USAMRIID and are performed under BLS-4 conditions. Notification of the local and state health departments is necessary.

The eruptive stage of smallpox

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TreATmenTCurrently, there are no known effective antivirals. Provide the patient 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 3 to 5 days. Contacts include all household members, patients, staff, and visitors to the hospital at the same time as the smallpox case.7 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

Patient(s) should be isolated and all precautions used until all scabs separate.

Standard Precautions

1. 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.

2. Gloves Wear gloves when touching blood, bodily fluids, 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.

3. 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.

Transmission Based PrecautionsAirborne Precautions • Placepatientinasingleoccupancy,Airborne

Infection Isolation Room (AIIR) (formally – Negative Pressure Isolation Room)

• For mass exposure contain those exposed in a designated area and utilize barrier precautions.

• Useexternalairexhaustorhighefficiencyparticulate air filters if the air is recirculated.(CDC 2007)

Contact Precautions• Placepatientinaprivateroom.

• Glovesshouldbewornwhenenteringthe room and removed before leaving the room. Hands should be washed with an antimicrobial agent or a waterless handwashing agent immediately after removing gloves.

• Gownsshouldbewornwhenenteringtheroom 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.

• Patienttransportshouldbelimitedtoessential purposes only.

• Noncriticalpatient-careequipmentshouldbe dedicated whenever possible.

clostridium Botulinum, BotuLismDeFiniTionBotulism is a rare but serious paralytic illness caused by a nerve toxin produced by the bacterium Clostridium botulinum,

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the most potent neuro toxin known to humans. There are seven (7) neurotoxins produced by this spore-forming bacillus. Thetoxins,AthroughG,arethemostpotent neurotoxins known. There are three (3) main types of botulism that effecthumans: foodborne, infant and wound.In the US an average of 145 cases a yearare reported:

• Foodborne-15%• Infantbotulism-65%• Wound-20%(CDCposted2009)

It is possible that the aerosolized form of botulism could be used as a biological weapon. The paralytic symptoms would appear after inhalation or the contamination of food or water supplies. (USAMRIID)

The clinical manifestations are similar for each of the botulism routes and are dependent on the route of exposure and dose received.

DiAGnosisThe patient’s clinical history and physical examination can be an indicator of botulism, patient(s) seeking medical services that exhibit progressive symmetrical descending flaccid paralysis strongly suggests botulism. The most sensitive testing for botulism is mouse neutralization (bioassay) of the patient serum.

TreATmenTTreatment consists of mechanical ventilation support if necessary and supportive care. Respiratory failure due to paralysis is the most serious concern and is usually the cause of death. Antitoxin is available, and is particularly effective infoodbornecases.Earlyadministrationof antitoxin can neutralize the circulating toxins in the body. This can prevent patients from worsening, but recovery still takes many weeks.

ProPHYlAxis A toxiod of C. Botulism for types A, B, C, D&EisavailableunderInvestigationalNew Drug (IND) therapy only. The vaccine has several contraindications due to hypersensitivities inherent in its production.

BOTULISM INCUB A TIO N PERIOD

EARLY SIGNS/SYMPTOMS

LATER SIGNS/SYMPTOMS

Botulism (all forms) 12-36 hours, longer if exposed to low doses of toxin

Generally no fever. Symmetric cranial neuropathies, such as drooping eyelids, difficulty swallowing or speaking. Mental status generally alert.

Sensory exam generally normal.

Blurred vision.

Symmetric descending weakness — generalized weakness and progressive to respiratory failure

CliniCAl mAniFesTATions oF BoTUlism

Botulism bacteria, 80x on 35mm film

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inFeCTion ConTrolStandard precautions are adequate for

HCW as B. Toxin is not dermally active

and secondary aerosols are not a hazard

(USADRIIM).

Standard Precautions1. 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.

2. Gloves Wear gloves when touching blood, bodily fluids, 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.

3. 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

DeFiniTionViral hemorrhagic fevers (VHFs) refer

to a group of illnesses that are caused

by several distinct families of viruses.

These viruses occur in different endemic

locations. Their transmission if from

rodent reservoir, dust contaminated

excreta, ticks, body fluid or contaminated

meats of infected animals and mosquito

borne.Eachdiseasecausesafebrile

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.Exceptfordenguevirus,allthe

VHFs are laboratory infectious by aerosol.

The four (4) viral family of viruses considered dangerous due to their potential for weaponization by aerosol are:

Arenaviridae•LassaFever•Argentine,Bolovian,VenezuelanVHF Caused by Tuninvirus, machupo, Guanarito and sabia viruses

Bunyaviridae•Hantavirusgenus•CongoCrimeanVHF(Nairovirusgenus)•Rift Valley Fever virus (Phlebovirus genus)

Filoviridae•Ebola•Marburg

Flaviviridae•Dengue•Yellow

DiAGnosisDefinitive diagnosis requires the resources

found at reference laboratories that have

biocontainment capability.

Patients presenting with an acute febrile

illness and indications of vascular

involvement, especially if a detailed history

includes travel to an endemic area should

have VHF as a presumptive diagnosis.

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Notification of the local health department

is necessary. For decisions regarding

obtaining and processing diagnostic

specimens, contact local, state, and

regional laboratory authorities or the CDC.

TreATmenTPatients receive supportive therapy

because there is no established cure for

VHFs. Ribavirin, an antiviral drug, has been

effective in treating some individuals with

Lassa fever. Treatment with convalescent-

phase plasma has been used with success

for some VHFs.

PosT-exPosUre ProPHYlAxisThere is no post-exposure prophylaxis

currently available for VHFs. There is

a licensed live attenuated yellow fever

vaccine and presently no other VHF agents

available for use in USA. (USAMRIID)

inFeCTion PreVenTionPatients with VHF have large quantities

of infectious viruses in their blood and

bodyfluidsandsecretions.Extremecare

should be taken to avoid sharps injuries.

Strict adherence to all infection control

precautions, in addition to increased barrier

ComPArison oF VHF AGenTs & DiseAses (UsAmriiD)

Virus Disease Endemic Area Mortality Nosocomial

transmissionCharacteristic

features Countermeasures

Flavivirus

Yellow fever virus

Yellow fever Africa, South America

Overall3-12%, 20-50% if severe second phase develops

No

Oftenbiphasic,severe second phase with bleeding, very high bilirubin and transaminases, jaundice, renal failure

17-D live attenuated vaccine very effective in prevention, no post-exposure countermeasure available

KFD virusKyasanur Forest Disease

Southern India 3-5% No

Flu-like syndrome with additionofcough,GIsymptoms, hemorrhage, bradycardia

Formalin - inactivated vaccine available in India

OHFvirusOMSKhemorrhagic fever

Siberia 0.2-3% NoFrequent sequelae of hearing loss, neuropsych complaints, alopecia

TBEvaccines(notavail.in US) may offer some cross-protection

Filoviruses

EbolavirusEbolahemorrhagic fever

Africa, Phillipines (EbolaReston)

50-90% for Sudan/Zaire Common

Severe illness, maculopapular rash, profuse bleeding and DIC

Anecdotal success with immune serum transfusion

Marburg virus

Marburg hemorrhagic fever

Africa 23-70% Yes

Bunyaviruses

CCHFCrimean-Congo hemorrhagic fever

Africa,SEEurope,Central Asia, India

30% Yes Oftenprominentpetechial/ecchymotic rash

Anectotal success with Ribavirin

RVF Rift Valley fever Africa <0.5% No

Hemorrhagic disease rare, classically associated with retinitis and encephalitis. Significant threat to livestock - epidemics of abortion and death of young

Human killed vaccine - DODIND,liveattenuatedvaccine in clinical trials

Hantavirus (Hantaan, Dobrava, Seoul, Puumala)

Hemorrhagic fever with renal syndrome (HFRS)

Europe,Asia, South America (rare)

5% for Asian HFRS No

Prominent renal disease, marked polyuric phase during recovery, usually elevated WBC

Effectivelocallyproducedvaccines in Asia (not avail inU.S.).Experimentalvaccine at USAMRIID. Ribavirin effective in randomized, controlled clinical trial

Arenaviruses

Lassa virus Lassa fever West Africa 1-2% Yes

Frequent inapparent/mild infection, hearing loss in convalescence common

Ribavirin effective in clinical trial with non-randomized controls

JuninArgentine hemorrhagic fever

Argentinean pampas 30% Rare ProminentGIcomplaints,

late neurologic syndromeImmune plasma, Ribavirin effective Candid 1 vaccine

Machupo Bolivian hemorrhagic Bolivia 25-35% Rare Similar to AHF

Protective but not avail. in U.S. Immune plasma effective, Ribavirin probably effective, Candid 1 vaccine protects monkeys

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precautions as suggested by USAMRIID,

should be taken when VHFs are suspected.

Additional measures may include:

• AIIRwith6-12airexchanges

• Allenteringroomshouldwear:

– Double gloves

– Impermeable gowns

– Leg and shoe coverings

– Eyeprotection

– N-95(HEPA)maskorpositivepressure

air-purifying respirators (PAPR’s)

• Accessrestrictedtonecessary

caregivers

Person-to-person spread of VHF is via

direct contact with body fluids, cadavers,

and symptomatic patients. Inadequate use

of infection precaution methods also can

be the cause of spread. All precautions

should be employed

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.

TRANSMISSION BASED PRECAUTIONS

Airborne Precautions • PlacethepatientinaprivateroomwithAIIR.

• Useexternalairexhaustorhigh-efficiencyparticulate air filters if the air is recirculated.

• Keepthedoortotheroomclosed.

• N-95respirator.

Contact Precautions

• Placepatientinaprivateroom.

• Glovesshouldbewornwhenenteringthe room and removed before leaving

the room. Hands should be washed with an antimicrobial agent or a waterless handwashing agent immediately after removing gloves.

• Gownsshouldbewornwhenenteringtheroom if it is anticipated that clothing willhave contact with the patient, environmentalsurfaces, or items in the room. The gownshould be removed before leaving thepatient’s room.

• Patienttransportshouldbelimitedtoessential purposes only.

• Noncriticalpatient-careequipmentshouldbe dedicated whenever possible.

Droplet Precautions

• Placethepatientinaprivateroomorinaroom with other patients who have the sameinfection.

• Whenaprivateroomandlikeinfectionpatients are unavailable, spatial separationof a least three feet should be maintained.

• Healthcareworkersshouldwearastandardsurgical mask when working within threefeet of the patient.

Standard Precautions

1. HandwashingWash hands immediately after gloves areremoved, between patient contacts, andwhen otherwise indicated to avoid transferof microorganisms to other patients orenvironments.

2. GlovesWear gloves when touching blood, bodily fluids,secretions, excretions, and contaminateditems; put on clean gloves just beforetouching mucous membranes and nonintactskin. Change gloves between tasks andprocedures on the same patient after contactwith material that may contain a highconcentration of microorganisms. Removegloves promptly after use, before touchingnoncontaminated items and environmentalsurfaces, and before going to anotherpatient, and wash hands immediately toavoid transfer of microorganisms to otherpatients or environments.

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3. Masks, Eye Protection, Face ShieldsWear a standard surgical mask and eyeprotection or a face shield to protect mucousmembranes of the eyes, nose, and mouthduring procedures and activities that arelikely to generate splashes or sprays. Placeall persons who have had close or high-riskcontact with a patient suspected of havingVHF during the 21 days following onset ofsymptoms under medical surveillance. Ifmultiple patients with suspected VHF areadmitted to one healthcare facility, groupthem in the same part of the hospital tominimize exposure to other patients andhealthcare workers.

Francisella tularensis, tuLAremiA

DeFiniTionTularemia is an acute onset infectious disease caused by Francisella tularensis.

There are several forms of the disease; Typhoidal tularemia with pneumonia, and rarely ulceroglandular or oculoglandular forms of the disease, as well as others. The natural occurring form of the disease may present in infected animals and is transmitted by bites of infected ticks, deerflies or mosquitos. Inhaling or ingesting, as may be delivered by dry aerosol or sprayed over food and water sources as a potential BW may cause the disease. The potential use of this Category A agent is of grave concern because it

can be extremely virulent at low doses. Inhalation of, as low as 10 colony-forming units can cause disease.

Tularemia occurs throughout much of NorthAmerica,Europe,andAsia.

It is resistant for months in cold temperatures below freezing.

CliniCAl mAniFesTATions oF TUlAremiATularemia is mostly a disease of rural exposure due to its animal hosts. Persons that hunt and farm are more likely to be exposed to naturally occurring disease. Most cases occur June to September. Winter cases occur among hunters and trappers when they handle infected animal hides and carcasses.

Cases occurring in urban areas or in

those with no risk factors should alert

TULAREMIA INCUB A TIO N 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, or hemoptysis.

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.

CliniCAl mAniFesTATions oF TUlAremiA

Tularemia is commonly transmitted through tick bites

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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.

DiAGnosisThere is no rapid diagnostic testing

available for tularemia. F. tularensis

may be diagnosed through recovery

of organisms in culture from blood, ulcers,

conjunctival exudates, sputum, gastric

washings and throat swabs. It requires

the use the use of special diagnostic and

safety procedures. Results can be read

out in several hours if the designated

reference laboratory in the National

PH Laboratory Network is notified and

receives the appropriate collected

specimens. Notify local health department.

TreATmenTThe disease can be fatal if not treated

with the right antibiotics. Administration of

parenteral antibiotics.

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 an investigational live

attenuated vaccine. Research to find and

evaluate new and better vaccine is on going.

inFeCTion ConTrolPerson-to-person transmission of tularemia has not been documented; therefore, standard precautions would be appropriate for patients with tularemia.

Standard Precautions

1. HandwashingWash hands immediately after gloves areremoved, between patient contacts, andwhen otherwise indicated to avoid transferof microorganisms to other patients orenvironments.

2. GlovesWear gloves when touching blood,bodily fluids, secretions, excretions, andcontaminated items; put on clean gloves justbefore touching mucous membranes andnonintact skin. Change gloves between tasksand procedures on the same patient aftercontact with material that may contain a highconcentration of microorganisms. Removegloves promptly after use, before touchingnoncontaminated items and environmentalsurfaces, and before going to anotherpatient, and wash hands immediately toavoid transfer of microorganisms to otherpatients or environments.

3. Masks, Eye Protection, Face ShieldsWear a standard surgical mask and eye

Wearing gloves is an effective precaution against infection

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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

Yersinia pestis, PLAgue

DeFiniTionPlague is a disease caused by Yersinia 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 tissues or by inhaling infected droplets.

There are three (3) forms of plague that may affect humans:

• Bubonic• Septicemic• Primary pneumonic (USAMRIID 2005)

Y. Pestis is contagious in the pneumonicform of the disease which makes it anideal form for use as a biological weapon.The mortality for untreated pneumonicplague approaches 100%. The organismincubates for up to six (6) days and is dosedependent.Onsetofprimarypneumonicplague is acute and fulminent. See chartbelow for specifics. Pneumonic plaguecan be readily spread person-to-person.Most of the secondary cases are to homecaregivers (80%), medical professionals(14%), and persons in close contact up tosix (6) feet.

CliniCAl mAniFesTATions oF PlAGUePneumonic plague will infect the lungs as a result of inhalation of the organisms (primary pneumonic) or spread there due to septicemic (secondary pneumonic) plague.

DiAGnosisFrom an epidemiological perspective the arrival of an increasing number of patients with rapidly progressing pneumonia accompanied by bloody sputum should create a high degree of suspicion. This would be the manifestation of the intentional release of pneumonic plague. A delay in diagnosis and treatment is associated with high fatality rates. There are no readily available rapid tests to detect plague. Definitive diagnosis is made by culture from clinical specimen.

PLAGUE INCUB A TIO N PERIOD

EARLY SIGNS/SYMPTOMS

LATER SIGNS/SYMPTOMS

Pneumonic plague

Bubonic

1-6 days, dose dependent.

2-8 days.

High fever, chills, HA, malaise, myalgias.

Acute and fulminant onset of non-specific symptoms.

Increasing dyspnea, stridor, cyanosis, rapidly progressive respiratory failure, circulatory collapse.

Characteristic Bubo.

CliniCAl mAniFesTATions oF PlAGUe

Yersinia pestis bubonic plague x250

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Report the possibility of plague to the local healthdepartment.Othertestsneedtobe coordinated through the local health department.

TreATmenTAlthough early treatment is important, plague is not believed to be as contagious as once thought. Persons transmit the plague infection most at the end stage of the disease. Parenteral antibiotics,

given early, in the first 20-24 hours, clears the sputum of the plague bacillus. (CDC)

PosT-exPosUre ProPHYlAxisThose individuals with face-to-face contact (within 6 ft) to person or persons with pneumonic plague or exposed to the aerosol of a potential BW attack should receive antibiotic prophylaxis for 7 days. No vaccine is currently available for plague.

Research is ongoing 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 ConTrolDroplet precautions, a transmission based technique, in addition to Standard Precautions should be implemented until affected patients have been on the appropriate antibiotic of 48 hours.

A biohazard clean suit is an example of personal protective equipment

Select a strong, comfortable medical glove related to the procedure or task at hand

17

Droplet Precautions

•Placethepatientinaprivateroomorin a room with other patients who have the same infection. Special air handling capabilities is not required.

•Whenaprivateroomandlikeinfectionpatients are unavailable, spatial separation of a least three feet should be maintained.

•Healthcareworkersshouldwearastandard surgical mask when working within three feet of the patient. A mask is to be donned prior to entering the patient room.

Standard Precautions

1. 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.

2. Gloves Wear gloves when touching blood, bodily fluids, 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.

3. 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 could cause aerosolization. If it is absolutely necessary to perform these procedures, wear an N-95 mask and perform the procedure in a negative pressure room.

PersonAL Protective eQuiPment (PPe)

DeFiniTionInformeduseofPPEisacriticalcomponent of a hospital’s infection prevention and bioterrorism response program. Where there is likelihood of contact with potentially infectious material, appropriatePPEincludesgloves,gowns,laboratory coats, face shields, masks, eye protection, and ventilation devices.

PPEreferstoavarietyofbarriersand/orrespirators to protect mucus membranes, airways, skin , and clothing from contact with infectious agents.

meDiCAl GloVes When selecting a medical glove, an important 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, bodily fluids, and other potentially infectious material require a glove that provides appropriate barrier protection.

lATex meDiCAl GloVesNatural rubber latex (NRL), commonly referred to as “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, powder-free gloves, many clinicians are confidently continuing to wear gloves made of latex. Latex gloves

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are recommended as the first choice for barrier protection in the healthcare environment, except for wearers who are allergic to latex proteins. In the event of bioterrorist activity, clinical personnel can have confidence in the barrier properties of the latex glove to protect them. Double-gloving in a bioterrorist event is also recommended. Latex is available in both surgical and examination gloves.

lATex-Free meDiCAl GloVesFor healthcare workers allergic to latex, the preferred recommendation as an alternative for medical examination gloves would be a latex-free material of nitrile or neoprene, and a latex-free material of neoprene or polyisoprene for surgical gloves. In independent testing for barrier properties, studies showed that nitrile, neoprene, and latex gloves are comparable in barrier properties during in-use performance testing.

Nitrile Nitrile is a petroleum-based, cross-linked film. It is extremely strong with puncture resistance superior to all glove films. Nitrile’s elasticity is very good and the gloves tend to conform to the shape of the wearer’s hands, providing good comfort and fit. There are no latex proteins in nitrile; therefore, there is no chance of latex allergy with use. Nitrile exhibits excellent chemical resistance and is recommended as a preferred alternative to latex for a bioterrorist event. Nitrile is available in examination gloves.

Neoprene (Polychloroprene) Neoprene is a petroleum-based cross-linked film that provides a similar fit, feel, and barrier protection to latex. Neoprene contains no latex proteins, and is available without chemical accelerators, making it a great choice for those with Type IV chemical allergy. It is a strong material, with good resistance to many chemicals, and provides great comfort. Neoprene’s elasticity is close to that of latex with very high memory. The film is able to retain its

original shape and is somewhat puncture resistant. Neoprene is available in both surgical and examination gloves.

Polyisoprene Polyisoprene is a petroleum-based, cross-linked film. Polyisoprene provides high strength, elasticity, and comfort. It contains no latex proteins, but contains some curing agents that can cause allergic reactions. Polyisoprene is durable and is somewhat puncture resistant. Polyisoprene provides good barrier protection but is more permeable than latex, and is recommended as a preferred alternative to latex in a bioterrorist event if nitrile or neoprene are not available. Polyisoprene is available in surgical gloves.

Polyvinyl Chloride (PVC) Many hospitals provide a latex-free material called Polyvinyl chloride (PVC), commonly known as “vinyl”, as a choice for exam gloves. PVC is a petroleum-based film, but it is not molecularly cross-linked. Because it lacks cross-linking, 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. Repeated studies have demonstrated that vinyl gloves have higher failure rates when tested in simulated and actual conditions. (CDC 2007) Vinyl is the weakest of the glove films, with poor elasticity, memory and fit. In 2007 the CDCreleasedtheGuidelineforIsolationPrecautions: Preventing Transmission of Infectious Agents in Healthcare Settings. This document also emphasized the poor barrier properties of vinyl gloves. It reads, “While there is little difference in the barrier properties of unused intact gloves, studies have shown repeatedly that vinyl gloves have higher failure rates than latex or nitrile gloves when tested under simulated and actual clinical conditions.” For this reason either latex or nitrile gloves are preferable for clinical procedures that

19

require manual dexterity and/or will involve more than brief patient contact. Because of these poor physical properties, vinyl would not be an acceptable choice to use when handling the diseases caused by biological agents. Polyvinyl chloride is only available in examination gloves.

seleCTinG A GloVe THAT is riGHT For YoU Gloveselectionisseriousbusiness.Thetwoprimary 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, to ensure that your gloves will be of consistent quality and regularly available.

ConClUsion

“Biological weapons are widely available,” statesformerFLGovernorandUSSenatorBobGraham,and“Thenumberofpeoplewhocan manipulate pathogens has increased.”

The healthcare community is on the forefront of access, preparedness and recognition. We need to keep our skills and knowledge current to be able to service our communities.

LocalLawEnforcementAuthorities* LocalorCountyHealthDepartment* StateHealthDepartment* CDCEmergencyResponseHotline: 770-488-7100CDC Bioterrorism Preparedness & Response Program: 404-639-0385CDCEmergencyPreparednessResources: http:www.bt.cdc.govStrategic National Stockpile: Access through State Health DeptFBI (general point of contact): 202-324-3000FBI (suspicious package info): http://www.fbi.gov/pressrel/pressrel01/mail3.pdfUSAMRIIDGeneralInformation: http://www.usamriid.army.mil USAMRICD Training Materials: http://ccc.apgea.army.milU.S. Army Medical NBC Defense Information: http://www.nbc-med.org Johns Hopkins Center for Civilian Biodefense: http://www.hopkins-biodefense.org Infectious Diseases Society of America: www.idsociety.org/bt/toc.htm

Table3.PointsofContactandTrainingResources.*Clinicians&ResponsePlannersareencouragedtopostthis list in a an accessible location. Specific local and state points of contact should be included.

ePiDemioloGiC ClUes oF A BW or TerrorisT ATTACK

The presence of a large epidemic with a•similar disease or syndrome, especially ina discrete population

Many cases of unexplained diseases or•deaths

More severe disease than is usually•expected for a specific pathogen or failureto respond to therapy

Unusual routes of exposure for a pathogen,•such as the inhalational route for diseasesthat normally occur through otherexposures

A disease that is unusual for a given•geographic area or transmission season

Disease normally transmitted by a vector•that is not present in the local area

Multiple simultaneous or serial epidemics•of different diseases in the samepopulation

A single case of disease be an uncommon•agent (smallpox, some viral hemorrhagicfevers, inhalational anthrax, pneumonicplague)

A disease that is unusual for an age group•

Unusual strains or variants of organisms or•antimicroboal resistance patterns differentfrom those known to be circulating

A similar or exact genetic type among•agents isolated from distinct sources atdifferent times or locations

Higher attack rates among those exposed•in certain areas, such as inside a buildingif released indoors, or lower rates in thoseinside a sealed building if released outside

Disease outbreaks of the same illness•occurring in noncontiguous areas

A disease outbreak with zoonotic impact•

Intelligence of a potential attack, claims•by a terrorist or aggressor of a release,and discovery of munitions, tampering,or other potential vehicle of spread (spraydevice, contaminated letter)(USAMRIID 2005)

23

BiBLiogrAPHY

Davis D, Bor B. Biological Contamination and Bioterrorism Preparedness: Key Considerations for Infection Control Practitioners. inf Control Today. July 2002: 40-44.

SinclairR,BooneS,GreenbergD,KeimP,GerbaG. PersistenceofCategoryASelectAgentsintheEnvironment.App environ micro. 2008: pg 555-563.

Pattillo M. Bioterrorism. Advance for nurses. Oct2005:17-22.

Cosgrove S, Perl T, Song X, Sisson S. Ability of Physicians to Diagnose and Manage Illness Due to Category A Bioterrorism Agents. Arch int med. 2005;165: 2002-2006

Beasley A, Kenenally S, Mickel N, Korowicki K, McCann S, Arundell J, Simmons W, Williams H. Treating Patients withSmallposintheOperatignRoom.Aorn Journal. 2004;80: 681-689.

Chronological History of Bioterrorism- History of Bioterrorism. Biological Terrorism Response Manual. http://www.bio-terry.com/HistoryBioTerr.html. accessed 25 May 2010.

Phillips M. Bioterrorism: A Brief History. DCMS online. 2005: 32-35

www.dcmsonline accessed 25 May 2005.

Percentage of Hospitals with Staff Members Trained to Respond to Selected Terrorism-Related Diseases of Exposures.MMRW2007;56:401.

US Army Medical Research Institute of Infectious Diseases (USAMRIID). Medial Management of Biological CasualtiesHandbook.SixthEdition.Apr2005

Reidel S. Biological warefare and Bioterrism: a historical review. BUmC Proceedings. 2004;17:400-4006.

Weiss M, Weiss P, Weiss J. Antrax Vaccine and Public Health Policy. Am J Public Health. Nov 2007; 97: 1945-1951.

Inglesby T, et al. Anthrax as a Biological Weapon, 2002 Updated Recommendations for Management. JAmA. 2002; 287: 2236-2252.

MMRW. Human Plague-Four States, 2006, MMWR 2006; 55: 940-943.

McLendon M, Apicella M, Allen L. Francisella tularensis: Taxonomy,Genetics,andImmunopathogenesisofaPotential Agent of Bioterrorism, Annu Rev Microbiol. 2006;60:167-185.

Dennis d, etal. Tularemia as a Biological Weapon, Medical and Public Management. JAMA 2001;285: 2763-2773.

WHO-http://www.who.int/mediacentre/factsheets/smallpox/en/ Smallpox. accessed 13 June 2010.

Chickenpox and Smallpox, How to Recognize the Difference http://www.idph.state.il.us/Bioterrorism/smallpoxchickenpox15.htm accessed 13 June 2010

Travelers’ Health Yellow Book, http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-5/viral-hemorrhagic-fevers.aspx. Accessed 14 June 2010

CDC.GuidelinesforIsolationOrecautions:PreventingTransmission of Infectious Agents in the HealthcareSetting 2007. http://www.cdc.gov/hicpac/pdf/isolation/Isolation2007.pdf

CDC Summary of Annual US Botulism Cases. http://botulismtoolkit.com/?p=736

Weber DJ. Journal of the American Medical Association 2003;289:1274

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