Terrorism
and Disaster

WHAT
CLINICIANS
NEED TO
KNOW

Viral Hemorrhagic
FeversSponsored for CME Credit by
Rush University Medical Center
Release Date: April 1, 2005
Expiration Date: March 31, 2007

errorism
Tand isaster
D
SERIESEDITORS
Rush University
Medical Center
Chicago, Illinois
Stephanie R. Black, MD*
Assistant Professor of Medicine
Section of Infectious Diseases
Department of Internal Medicine
Daniel Levin, MD*
Assistant Professor
General Psychiatry Residency Director
Department of Psychiatry
Gillian S. Gibbs, MPH*
Project Coordinator
Center of Excellence for Bioterrorism
Preparedness
Linnea S. Hauge, PhD*
Educational Specialist
Department of General Surgery

AUTHORS
Rush University
Medical Center
Chicago, Illinois

WHAT
CLINICIANS
NEED TO
KNOW

Uniformed Services University
Health Sciences
Bethesda, Maryland
David M. Benedek, MD, LTC, MC, USA
Associate Professor of Psychiatry
Steven J. Durning, MD, Maj, USAF, MC*
Associate Professor of Medicine
Thomas A. Grieger, MD, CAPT, MC, USN*
Associate Professor of Psychiatry
Associate Professor of Military &Emergency Medicine
Assistant Chair of Psychiatry for Graduate& Continuing Education
Molly J. Hall, MD, Col, USAF, MC, FS*
Assistant Chair & Associate Professor
Department of Psychiatry
Derrick Hamaoka, MD, Capt, USAF, MC, FS*
Director, Third Year Clerkship
Instructor of Psychiatry
Paul A. Hemmer, MD, MPH, Lt Col, USAF, MC*
Associate Professor of Medicine
Benjamin W. Jordan, MD, CDR, MC, USNR, FS*
Assistant Professor of Psychiatry

Stephanie R. Black, MD*
Assistant Professor of Medicine
Section of Infectious Diseases
Department of Internal Medicine

James M. Madsen, MD, MPH, COL, MC-FS, USA*
Associate Professor of Preventive Medicine
and Biometrics
Scientific Advisor, Chemical Casualty Care
Division, US Army Medical Research Instituteof Clinical Defense (USAMRICD), APG-EA

Daniel Levin, MD*
Assistant Professor
General Psychiatry Residency Director
Department of Psychiatry

Deborah Omori, MD, MPH, FACP, COL, MC, USA*
Associate Professor of Medicine
Michael J. Roy, MD, MPH, FACP, LTC, MC*
Associate Professor of Medicine
Director, Division of Internal Medicine
Jamie Waselenko, MD, FACP**
Assistant Professor of Medicine
Assistant Chief, Hematology/Oncology
Walter Reed Army Medical Center
Washington, DC

Guest Faculty
Ronald E. Goans, PhD, MD, MPH*
Clinical Associate Professor
Tulane University School of Public Health &Tropical Medicine
New Orleans, LA
Sunita Hanjura, MD*
Rockville Internal Medicine GroupRockville, MD
Niranjan Kanesa-Thasan, MD, MTMH*
Director, Medical Affairs & Pharmacovigilance
AcambisCambridge, MA
Jennifer C. Thompson, MD, MPH, FACP*
Chief, Department of Clinical Investigation
William Beaumont Army Medical Center
El Paso, TX

Faculty Disclosure Policy
It is the policy of the Rush University Medical
Center Office of Continuing Medical
Education to ensure that its CME activities
are independent, free of commercial bias
and beyond the control of persons or organizations with an economic interest in influencing the content of CME. Everyone who
is in a position to control the content of an
educational activity must disclose all relevant
financial relationships with any commercial
interest (including but not limited to pharmaceutical companies, biomedical device manufacturers, or other corporations whose products or services are related to the subject
matter of the presentation topic) within thepreceding 12 months If there are relationships that create a conflict of interest, thesemust be resolved by the CME Course
Director in consultation with the Office ofContinuing Medical Education prior to theparticipation of the faculty member in thedevelopment or presentation of course
content.
* Faculty member has nothing to disclose.
**Faculty disclosure: CBCE Speaker’s Corefor SuperGen.

Viral Hemorrhagic
FeversCASE AUTHORS:

Steven J. Durning, MD, Maj, USAF, MC
Michael J. Roy, MD, MPH, FACP, LTC, MC

ACCREDITATION & DESIGNATION STATEMENT
Rush University Medical Center is accredited by the Accreditation Council for Continuing
Medical Education (ACCME) to provide continuing medical education for physicians.
Rush University Medical Center designates this educational activity for a maximum of 1
credit of category 1 credit toward the AMA Physician’s Recognition Award. Each physician
should claim only those credits that he/she actually spent in the activity.
This CME activity was planned and produced in accordance with the ACCME Essentials.
CME credits are available free of charge through March 2007.

DISCLAIMER
This project was funded by the Metropolitan Chicago Healthcare Council (MCHC)
through a grant from the Health Resources and Services Administration (HRSA).
The opinions or assertions contained herein are the private views of the authors and are not
to be construed as official or as representing the opinion of Rush University Medical Center,
the Department of the Army, Department of the Navy, Department of the Air Force,
Department of Defense, MCHC or HRSA.
FDA Approved Drug and Devices Assurance Statement
In accordance with requirements of the FDA, the audience is advised that information presented in this continuing medical education activity may contain references to unlabeled orunapproved uses of drugs or devices. Please refer to the FDA approved package insert foreach drug/device for full prescribing/utilization information.

INSTRUCTIONS
The questions that appear throughout this case are intended as a self-assessment tool. For
each question, select or provide the answer that you think is most appropriate and compare
your answers to the key at the back of this booklet. The correct answer and a discussion of
the answer choices are included in the answer key.
Note: These self-assessment questions are not intended for CME credit. To apply for CME
credit, you must complete the CME Test at the back of this booklet and submit it according
to the directions provided.
In addition, a sign is provided in the back of this booklet for posting in your office or clinic.
Complete the sign by adding your local health department’s phone number.
Design and layout © 2005 Rush University Medical Center. The text contained herein falls under the U.S.
Copyright Act of 1976 as a “U.S. Government Work” and is therefore considered Public Domain Information,
however Rush University Medical Center reserves the right to copyright the design and layout of that information.

1

Viral Hemorrhagic
FeversCASE AUTHORS:

Steven J. Durning, MD, Maj, USAF, MC
Michael J. Roy, MD, MPH, FACP, LTC, MCINTENDED AUDIENCEInternal medicine, family medicine, and emergency medicine physicians, and otherclinicians who will provide evaluation and care in the aftermath of a terrorist attack
or other public health disasterE D U C AT I O N A L O B J E C T I V E S
Upon completion of this case, participants will be able to:• Describe the natural and intentional sources of transmission and spread of viralhemorrhagic fevers (VHF), including use as a biologic weapon.
• Discuss the initial presentation and clinical manifestations of VHF, including
methods for confirming this diagnosis.
• Outline important strategies for infection control for healthcare workers caring
for patients with cases of suspected VHF.
• Describe processes for communication with public health authorities and media
about VHF.
• Describe the current recommended therapy for patients with VHF.

CASE HISTORY
A 32-year-old newspaper reporter with no significant past medical history presents
to your office complaining of a 2-day history of fevers, diffuse myalgias, and severe
pharyngitis. He also complains of vomiting and bloody diarrhea that began this morning. On physical examination, his vitals are T=102.8˚F, BP=100/80, HR=80, RR=15.
He has marked edema of the posterior pharynx, as well as a nonpruritic maculopapular eruption over his chest and back. He has not had recent travel overseas, exposure
to pets, or recent outdoor recreational activities. He received an influenza vaccination
earlier this year. He states that two of his coworkers have been absent from workand had been referred by the Tribune’s health insurance provider to your office for
evaluation.
Two of your practice partners confirm that recently they each have seen a worker
from the Tribune who presented with fevers, diffuse myalgias, and pharyngitis. One
patient was a 40-year-old editor with a history of diabetes. Her most prominent findings on presentation were conjunctivitis, facial flushing, and new onset of nondependent edema. Initially, she was sent home with close follow-up. The other2

patient was a 24-year-old photographer whose examination was remarkable for
hypotension, relative bradycardia, somnolence, oropharyngeal bleeding, and petechiaeover his chest and abdomen. He was transferred to a nearby hospital immediately.
Like your patient, neither of these 2 people reported other sick contacts, overseas
travel, exposure to unusual pets, or recent outdoor recreational activities. They also allreported receiving their annual influenza vaccination.

QUESTION 1
You are called to the emergency room to evaluate a patient with suspected Ebola
virus infection. The presence of which of the following should raise concern
regarding a potential bioterrorism-related outbreak?
a. No history of travel to Africa
b. News of an outbreak of pharyngitis among local children on a school tripc. Temporal cluster of patients presenting with fever and increased vascularpermeability on examinationd. Abrupt onset of fever and signs of increased vascular permeability on exame. a and c only
Reminder: You can find the Answer Key & Discussion on page 9.
COMMENT: This case vividly illustrates the varying typical presentations of Ebola or Marburg
hemorrhagic fever syndrome, two of the several etiologies of VHF. The VHF agents are a diverse groupof RNA viruses that present with common clinical characteristics known as the VHF syndrome. The
Ebola and Marburg viruses are specific etiologies of VHF in humans (see Table 1).
VHF syndrome can manifest as an acute febrile illness similar to influenza (characterized by prominent
nonspecific findings such as malaise, myalgias, and prostration), but patients with VHF are also at risk
for virus-induced endothelial damage that increases vascular permeability. Early signs of this process
may include conjunctival injection, flushing, and petechiae or ecchymoses; later signs of vascular permeability include hypotension, shock, or disseminated intravascular coagulation (DIC). VHF should besuspected in any patient presenting with a febrile illness accompanied by evidence of vascular involvement (ie, flushing, nondependent edema, hypotension, petechiae, and/or hemorrhagic diathesis), who
has traveled to an area where a hemorrhagic fever virus is known to circulate (see Table 1) and/or
where evidence suggests a possible bioterrorism-related outbreak. In this case, the near simultaneouspresentation of 3 individuals who work in close proximity and lack other likely etiologies for their
symptoms should immediately raise the possibility of a bioterrorism-induced outbreak. This concern
should be further heightened given their work in the media environment, which was targeted in theanthrax attacks in the fall of 2001.
The Filovirus hemorrhagic fevers, Marburg and Ebola, share similar pathologic and clinical features andhave specific findings that facilitate their differentiation from other forms of VHF. Ebola virus, named
after a small river in northwest Zaire, is morphologically similar to, but antigenically distinct from,
Marburg virus, which is named after the city in Germany where it was first identified. These two viruses cause necrosis of parenchymal cells in the liver, spleen, lung, kidney, skin, testes and other organs.
Highly suggestive findings of Filovirus hemorrhagic fever include severe posterior pharyngeal edemathat can cause dysphagia or dyspnea, and an evanescent nonpruritic maculopapular rash that is followed by desquamation of the affected skin.2 Previous case reports and experiments in primates haveshown that neutrophilia, lymphopenia, and abnormalities of platelet number (thrombocytopenia) andfunction often occur early in the illness.5,6 Evidence suggests that lymphopenia is due to early virusinduced apoptosis, while thrombocytopenia is often a manifestation of DIC that can occur with Ebola

3and Marburg hemorrhagic fever. Anemia may also be seen in the setting of DIC, however, the hemoglobin is usually normal on presentation; hemoglobin may alternatively be increased in the presence ofconcurrent dehydration. Elevated liver transaminase levels, with AST greater than ALT, are common.5
Proteinuria has also been reported with these agents and typically occurs early in the course of disease.
Several subtypes of Ebola virus have been identified, and all but one have originated in Africa andbeen highly pathogenic to humans (case lethality rates up to 88%). Devastating outbreaks of Ebola
were documented in central Africa in 1976. A U.S. Army SWAT team was called in to quell a 1989 outbreak in a laboratory in Reston, Virginia that was traced to monkeys imported from the Philippines forresearch purposes — an event that was described so compellingly by Richard Preston in his book, The
Hot Zone.7 There have been numerous cases of Ebola in Gabon and the Republic of Congo in recent
years, attributed to handling infected gorilla, chimpanzee, or duiker carcasses.8 The initial Marburg
virus outbreak was traced to monkeys imported from Uganda. Marburg hemorrhagic fever has subsequently been reported in South Africa and Kenya. The natural reservoirs of Ebola and Marburg viruseshave not been determined.8
The differential diagnosis of VHF is quite extensive and includes other infections associated with fever,rash, and hemorrhage such as falciparum malaria, acute African trypanosomiasis, typhoid fever, leptospirosis, pneumonic plague, and bacterial septicemia.

You obtain the following lab results for your patient:Complete blood count: WBC=2,000/mm3, hemoglobin=15.1gm/dL,
platelets=100,000/mm3.
Serum chemistries: Sodium=141mEq/L, potassium=4.0mEq/L, chloride=100mEq/L,
bicarbonate=20mEq/L, BUN=22mg/dL, creatinine=1.1mg/dL.
Liver panel: AST=80U/L, ALT=60U/L, albumin=4.1mg/dL, total bilirubin=1.5mg/dL
Alkaline phosphatase=100U/L.
Urinalysis: 1+ protein with 0 RBCs, 0 WBCs, and no sediment findings.
Similar laboratory findings were present in his two coworkers, and the one who wassent to the hospital also had schistocytes on his peripheral blood smear, indicative of
DIC.

QUESTION 2Given these laboratory findings, what is the most appropriate next step?
a. Send the patient home and advise him to drink plenty of fluids.
b. Contact local public health officers due to concern for a potential
bioterrorism-induced outbreak, and admit to hospital.
c. Arrange for immediate air transport to a nearest tertiary care hospitaland contact local public health officers.
d. Administer an empiric course of doxycycline.

4

Table 1. Recognized Causes of VHF in Humans*
Virus Genera

DiseaseNatural Distribution

Vector/Exposure

Incubation Period (days)

Arenavirus

Lassa fever
Argentine HF†
Bolivian HF
Brazilian HF
Venezuelen HF

AfricaSouth America
South America
South America
South America

Rodent‡RodentRodentRodentRodent

5-16
7-14
9-15
7-14
7-14

Phlebovirus

Rift Valley fever

AfricaMosquito§

2-5

Nairovirus

Crimean-Congo HF

Europe, Asia, Africa

Tick

3-12

Hantavirus
syndrome

Hantavirus Renal

Rodent9-35

Hantavirus Pulmonary
Syndrome

Asia, Europe, likely
worldwide
North & SouthAmerica

Rodent3-28

Filovirus

Marburg
Ebola

AfricaAfricaUnknown¶
Unknown¶
Exposure to Carcasses#

3-16
2-21

Flavivirus

Yellow fever
Dengue HF

Africa, South America
Asia, Americas,
AfricaIndia
States of theformer Soviet Union

Mosquito
Mosquito

3-6
Unknown

Tick
Tick**

3-8
3-8

Kyasanur Forest disease
Omsk HF* Data from Jahrling 1, Isaacson2, Rigquelme3, and Peters4.
† HF = Hemorrhagic Fever‡ Nosocomial transmission is a less likely source of human infection than the listed vector.
§ Domestic animal slaughter is a less likely source of human infection than the listed vector.
 Domestic animal slaughter and nosocomial transmission are less likely sources of human infection than the listed vector.
¶ Nosocomial transmission is uncommon.
# Gorilla, chimpanzee, or duiker carcasses**Muskrat contaminated water is a less likely source of human infection than the listed vector.

The local health department instructs you to place the patient in isolation while waiting for a mobile laboratory that will be sent from the Centers for Disease Control andPrevention (CDC) to assist with handling of blood and body fluid specimens from thepatient.

QUESTION 3
Which of the following is not an accepted means to confirm the diagnosis of
Ebola or Marburg virus?
a. Demonstrating IgM or a 4-fold rise in IgG antibodies titers for the virus
b. Electron microscopyc. Viral isolation
d. Reverse transcriptase polymerase chain reaction (RT-PCR) assay
e. Toxin isolation

5

COMMENT: Biosafety Level 4 (BSL-4) is required for laboratory work with dangerous and exotic
agents of VHF, such as Ebola, Marburg, Rift Valley Fever, and hantavirus, because these viruses pose ahigh individual risk of aerosol-transmitted laboratory infections and life-threatening disease. Laboratory
personnel should be verbally notified that VHF is a diagnostic consideration, and specimens should
remain in the custody of a designated individual until testing is completed. Laboratory staff that work
under this Biosafety Level have specific and thorough training in handling extremely hazardous infectious agents; they also understand the primary and secondary containment functions of the standard
and special practices, the containment equipment, and the laboratory design characteristics. BSL-4 laboratories are typically located within a dedicated, specially structured building, or in the instance of alaboratory building that is used for other investigations, within a controlled area which is completely
isolated from all other areas of the building. Entry into a BSL-4 area is through an airlock fitted with
airtight doors. Personnel who enter a BSL-4 area wear a one-piece positive pressure suit that is ventilated by a life-support system protected by HEPA filtration. A chemical shower is provided to decontaminate the surface of the suit before the worker leaves the area.
All suspected cases of infection with VHF should be reported immediately to local and state healthdepartments and to the CDC. The CDC can be contacted 24 hours a day by calling the emergency
response hotline at 770-488-7100. Specimens for virus-specific diagnostic testing should be sent to
the CDC as rapidly as possible, following CDC instructions. Given the potential for spread with contact
with blood, laboratory testing should be kept to the minimum required for the immediate care of thepatient until a mobile CDC laboratory arrives. Further, all specimens submitted to the laboratory should
be labeled as biohazardous material.

QUESTION 4Given your high clinical suspicion of Filovirus hemorrhagic fever, you place thepatient in isolation as instructed by the local public health official and the CDC.
Which of the following isolation precautions should be instituted?
a. Place the patient in a private room; universal precautions for hospital
personnelb. Place the patient in a private room with negative pressure; barrier precautions
for hospital personnelc. Place the patient in a private room with negative pressure; Biosafety Level 4
for hospital personnel
d. Transfer the patient to the CDC mobile unit as soon as possible; Biosafety
Level 4 for all contacts

COMMENT: As the Filovirus hemorrhagic fevers are lipid containing RNA viruses, they are readily
inactivated by disinfectant solutions to include 0.5% sodium hypochlorite, glutaraldehyde, and phenolicdisinfectants. Likewise, soaps and detergents also induce viral inactivation and thus should be used liberally. Further, patients with Filovirus hemorrhagic fever should use a chemical toilet, by autoclaving or
treating with several ounces of bleach for more than 5 minutes,5 before flushing or disposing in a drain
connected to a sanitary sewer.
Disinfectant solution should also be copiously applied to the outer surface of airtight bags for all materials used by the patient (such as disposable linen and pajamas), disposable items worn by caretakers,
and the outside and inside of containers in the patient’s room, such as disposable sharps containers. If
available, an anteroom for putting on and removing protective clothing is useful.5

6

If an individual is exposed to potentially infected material (eg, through an injection or a cut on thehand) the individual should immediately wash the affected area of the skin, apply a disinfectant solution, and notify the VHF patient’s physician. These individuals should be considered high-risk contacts
and placed on surveillance.

INFECTION CONTROLPRECAUTIONSWITH SYMPTOMATIC
VHF PATIENTS

Spills of potentially contaminated fluids should be liberally covered with disinfectant and left to soak
for a minimum of 30 minutes.5 The contaminated area should then be wiped up with an absorbent
material that is likewise soaked in disinfectant.

• Patient placed in private negative
pressure room (with an anteroom,
if available)• Caretakers of patient use barrier
precautions: gloves, gowns, N-95
masks, eye protection, leg covers,
shoe covers

QUESTION 5Your patient expresses concern for his family. He has a 10-year-old son and hiswife is 20 weeks pregnant. He reports that they are both feeling well, with nosymptoms of illness. What should you do regarding his family’s care?
a. Isolate both his wife and 10-year-old son
b. Isolate his wifec. Conduct daily medical surveillance of family members without isolating themd. Admit his wife and son to the hospital

COMMENT: The levels of contact risk are summarized in Table 2, and details on the definitions ofcontact risk are as follows:
1. Casual contacts
Persons who have remote contact with the suspected case of VHF. Individuals in this category include
people who sat next to the suspected case of VHF on the bus or metro, stayed in the same hotel as thesuspected case, or shopped in the same mall as the suspected case. Since the agents of VHF are notspread by such casual contact, no special surveillance is indicated.
2. Close contacts
Persons who have more than casual contact with the patient. Close contacts include persons livingwith the patient, those caring for the patient (eg, nurses, physicians), and/or those who have shookhands with or hugged the patient. State and local health departments should identify close contacts assoon as VHF is considered to be a likely diagnosis.
Once the diagnosis of VHF is confirmed, close contacts should be placed under surveillance. This requires
close contacts to record their temperature twice daily and report any temperature over 101˚F or any
symptom of illness. Surveillance should be continued for 3 weeks after the person’s last contact with
the index case. If a fever ≥101˚F and/or symptoms of illness develop, the patient should be immediately
placed in isolation and treated as a VHF patient.5
3. High-risk contacts
High-risk contacts are individuals who have had mucous membrane contact with the patient, such as
kissing or sexual intercourse, or have had a needlestick or other penetrating injury involving contact
with the patient’s blood and/or other body fluids. These patients should be placed under surveillance assoon as VHF is considered a likely diagnosis in the index case. Again, if a high-risk contact develops
fever ≥101˚F and/or other symptoms of illness, the patient should be immediately placed in isolationand treated as a VHF patient.5

7• Disinfectant solution applied toouter surface of airtight bags for
all materials used by the patient,disposable items worn by caretakers, and the outside and inside ofcontainers in the patient’s room
• Mark all patient blood and/or
other body fluid specimens asbiohazards• Face shields or masks with eye
protection should be worn toprevent contact with blood, body
fluids, or respiratory secretions
that may be rendered airborneby coughing or sneezing

MANAGING
PUBLIC FEAR
It is important to clearly convey risk
categories to the lay press once anoutbreak is identified due to theheightened concern and possible
fear that can be connected with theidentification of VHF. It is also important to discuss these categories to
educate the public regarding risk andto prevent rumors. The media canalso be used to provide emergency
information about personal protection or evacuation. Ongoing communication with the media is necessary. Establishing and maintaining
good relations with the media andidentifying internal media liaisonsshould be part of hospital and publichealth center disaster preparedness
plans.

Table 2. Risk Categories for Contacts of Patients With VHF*
Risk Category

Description

Surveillance†

Casual contacts

Remote contact with index case,eg, stayed in same hotel

VHF not spread by casual contact,no special surveillance required

Close contacts

More than casual contact, eg, livingwith contact caretaker, shook handswith contact

Place under surveillance once index
case is confirmed

High-risk contacts

Mucous membrane contact, eg, kissing,or penetrating injury involving contract
with index case’s blood (needlestick)

Place under surveillance as soon as
consider diagnosis of VHF in index case

*CDC Update: Management of patients with suspected viral hemorrhagic fever—United States5†Surveillance should be continued for 3 weeks after the person’s last contact with the index case. If a fever >101˚F and/or symptoms of illness develop, the patient should be immediately placed in isolation and treated as a
VHF patient.

QUESTION 6
The CDC mobile laboratory calls you because they have confirmed a diagnosisof Ebola virus. Which of the following statements best describes the current
therapy for Ebola virus?
a. Supportive care onlyb. Supportive care + ribavirinc. Supportive care + immunoglobulin
d. Supportive care + vaccine

COMMENT: Treatment of Ebola virus is supportive, as there is currently no definitive treatment for
Ebola virus. Aspirin and other antiplatelet agents or anti-clotting factor drugs should be avoided, as
they may potentiate hemorrhage. Secondary bacterial infections are relatively common and should be
aggressively sought and treated. Intravenous lines, catheters, and other invasive techniques should be
avoided unless clearly indicated given the concern of diffuse hemorrhage. The diffuse nature of vascular
involvement often leads to multi-system organ failure.
The management of bleeding in VHF patients is controversial. Uncontrolled observations support
administration of fresh frozen plasma, clotting factor concentrates, and platelets. Corticosteroids may
be helpful, but remain an untested modality for treating shock due to Ebola virus.1 Patients withhypotension and shock, due to advanced capillary leak syndrome, often respond poorly to fluid resuscitation and develop pulmonary edema. Judicious use of saline solution and consideration of dopamine
may be helpful for persistent hypotension. Alpha-adrenergic agents have not been shown to be helpful
except in rare cases when emergent intervention to treat refractory hypotension is needed.
Ribavirin is ineffective against the Filoviruses. Immunoglobulin therapy for experimental animals infected with Ebola virus has been disappointing. In a small, uncontrolled trial, transfusion of blood frompatients convalescing from Ebola virus infection resulted in a markedly lower case fatality rate (13%)
among 8 transfused patients in comparison with the overall case fatality rate of 80% during a 1995
epidemic; however these patients were transfused late in the course of their illness, when they may
well have survived without the transfusion.

8

There are no current vaccines available against Ebola virus, however two recent vaccine candidates
raise great hope. The first is a DNA-based vaccine, and the second is a harmless Ebola virus-like particle(VLP); they have been shown to evoke good humoral and cellular response, and are now in Phase 3
human studies.9,10
Yellow fever virus is the only VHF for which vaccine is available. Yellow fever is endemic in Africa andSouth America and vaccination should be considered before traveling to these regions. A vaccine has
been licensed in the Republic of Korea for Korean Hemorrhagic Fever, and investigational vaccines arebeing studied for other VHF.

CASE CONCLUSION
The 3 patients described in this case scenario survived with aggressive supportive care.
They had no physical long-term sequelae due to their illness.

ANSWER KEY & DISCUSSIONQUESTION 1
You are called to the emergency room to evaluate a patient with suspected Ebola
virus infection. The presence of which of the following should raise concern
regarding a potential bioterrorism-related outbreak?
a. No history of travel to Africa
b. News of an outbreak of pharyngitis among local children on a school tripc. Cluster of patients presenting with fever and increased vascular permeability
on examinationd. Abrupt onset of fever and signs of increased vascular permeability on exame. a and c only
ANSWER: The correct answer is e. Given the fact that this patient has not traveled to a region
where the Ebola virus is endemic, and that there is a cluster of people presenting with similar symptoms, the possibility of a bioterrorism attack should be considered and the local health department
should be notified immediately according to your emergency preparedness and disaster plan.

QUESTION 2Given these laboratory findings, what is the most appropriate next step?
a. Send the patient home and advise him to drink plenty of fluids
b. Contact local public health officers due to concern for a potential
bioterrorism-induced outbreak, and admit to hospitalc. Arrange for immediate air transport to a nearest tertiary care hospitaland contact local public health officers
d. Administer an empiric course of doxycycline
ANSWER: The correct answer is b. As previously discussed, this patient’s presentation is consistent
with VHF syndrome. You also have reasonable evidence that 2 close contacts may have the same illness. Given that this patient and his coworkers have neither a history of travel to an area endemic for
VHF or exposure to exotic animals, you should be very concerned that this may represent the deliberatedissemination of VHF. Given the prominent rash and pharyngeal findings on physical examination, you
should be particularly concerned about an Ebola or Marburg virus or Lassa fever outbreak. Therefore,
you should contact local public health officials immediately.

9

VHF agents are characteristically stable viruses that are highly infectious fine-particle aerosols. Sending
the patient home may lead to further spread of VHF to close contacts. Unnecessary transport should
be avoided in patients where the diagnosis of VHF is suspected. In particular, air transport should be
avoided since changes in ambient pressure with flight can further damage fragile capillary beds, resulting in pulmonary hemorrhage. Doxycycline is not effective therapy for VHF and may exacerbate thealterations in liver function tests.

QUESTION 3
Which of the following is not an accepted means to confirm the diagnosis of Ebola
or Marburg virus?
a. Demonstrating IgM or a 4-fold rise in IgG antibodies titers for the virus
b. Electron microscopyc. Viral isolation
d. Reverse transcriptase polymerase chain reaction (RT-PCR) assay
e. Toxin isolation
ANSWER: The correct answer is e. Scientists have not developed an assay to detect toxin proteinsin Ebola or Marburg virus infections to date. Choices a-d are all acceptable means for making a diagnosis of Marburg or Ebola virus, and each of these tests will discriminate between the two Filovirus
hemorrhagic fevers. Appropriate precautions should be observed in collection, handling, shipping, andprocessing of blood and/or other body fluid diagnostic samples. Due to the potential risks associatedwith handling these infectious materials, laboratory testing should be the minimum necessary for diagnostic evaluation and patient care. Clinical laboratory specimens should be placed in plastic bags thatare sealed, and then transported in clearly labeled (as biohazardous material) durable, leakproof containers directly to the specimen handling area of the laboratory. Care should be taken not to contaminate the external surfaces of the container.5 Viral isolation should not be attempted without maximum
Biosafety Level (BSL-4) containment. RT-PCR identification of VHF agents may grow in use due to theneed of maximum biosafety with viral isolation, time lag with IgM assay (need acute and convalescentsera) and equipment, as well as technical expertise needed with electron microscopy.

QUESTION 4Given your high clinical suspicion of Filovirus hemorrhagic fever, you place thepatient in isolation as instructed by the local public health official and the CDC.
Which of the following isolation precautions should be instituted?
a. Place the patient in a private room; universal precautions for hospital personnel.
b. Place the patient in a private room with negative pressure; barrier precautions for hospital personnel.
c. Place the patient in a private room with negative pressure; Biosafety Level 4
for hospital personnel.
d. Transfer the patient to the CDC mobile unit as soon as possible; Biosafety
Level 4 for all contacts.
ANSWER: The correct answer is b. The patient was vomiting. Patients with symptoms such as
prominent cough, vomiting, diarrhea, as well as hemorrhage, should be placed in a negative-pressureroom, given the potential for aerosolization of the virus and possibility of infecting other individuals.
This being said, the available evidence indicates that the majority of reported nosocomial VHF cases,
including Filovirus hemorrhagic fever, have been acquired by inoculation with virus-contaminatedinstruments or by direct contact with blood or body fluids from infected patients.

10In addition to isolation in a negative pressure room, the caretakers of symptomatic patients should use
barrier precautions to prevent skin or mucous membrane exposure to blood, other body fluids, or secretions. All persons entering a VHF patient’s room should wear gloves and gowns to prevent contact withsurfaces that may be contaminated. Further, face shields or masks with eye protection should be wornto prevent contact with blood, body fluids, or respiratory secretions that may be rendered airborne bycoughing or sneezing. Leg and shoe covers should also be worn to minimize the risk of transmission
outside of the room.
Patients with suspected VHF who do not have a prominent cough, vomiting, diarrhea, or hemorrhage
can be placed in a private room with institution of universal precautions.5 Individuals attempting virus
isolation or cultivation must institute Biosafety Level 4 (BSL-4) precautions. Specimens in clinical laboratories should be handled in a class II biological safety cabinet following BSL-3 practices. Routine
procedures can be used for automated analyzers and should be disinfected per manufacturer's recommendations. Serum used in laboratory tests should be pre-treated, though 100% inactivation of virus
should not be assumed.5

QUESTION 5Your patient expresses concern for his family. He has a 10-year-old son and hiswife is 20 weeks pregnant. He reports that they are both feeling well with nosymptoms of illness. What should you do regarding his family’s care?
a. Isolate both his wife and 10-year-old son
b. Isolate his wifec. Conduct daily medical surveillance of family members without isolating themd. Admit his wife and son to the hospital
ANSWER: The correct answer is c. A contact is an individual who has been exposed to an
infected person or to an infected person’s secretions, excretions, or tissue within 3 weeks (conservative
incubation period) of the patient’s onset of illness. Contacts can be divided into 3 levels of risk: casual
contacts, close contacts, and high-risk contacts. The patient’s wife and son are high-risk contacts. The
patient’s wife and son should be placed under surveillance, given the clinical suspicion of VHF.

QUESTION 6
The CDC mobile laboratory calls you because they have confirmed a diagnosisof Ebola virus. Which of the following statements best describes the current
therapy for Ebola virus?
a. Supportive care onlyb. Supportive care + ribavirinc. Supportive care + immunoglobulin
d. Supportive care + vaccine
ANSWER: The correct answer is a. The only current treatment of Ebola is supportive care. Aspirin
and other antiplatelet agents or anti-clotting factor drugs should be avoided, as they may potentiate
hemorrhage. Secondary bacterial infections are relatively common and should be aggressively sought
and treated. Intravenous lines, catheters, and other invasive techniques should be avoided unlessclearly indicated given the concern of diffuse hemorrhage. The diffuse nature of vascular involvement
often leads to multi-system organ failure.
Ribavirin is ineffective against the Filoviruses. Immunoglobulin therapy for experimental animals
infected with Ebola virus has been disappointing. There are no current vaccines for Ebola virus.

11

REFERENCES
1. Jahrling PB. Viral Hemorrhagic Fevers. In: Sidell FR, Takafuji ET, Franz DR, eds.
Textbook of Military Medicine: Medical Aspects of Chemical and Biologic Warfare.
Washington, DC: Borden Institute; 1997:592-601.
2. Isaacson M. Viral Hemorrhagic Fever hazards for travelers in Africa. CID.
2001;33:1701-1712.
3. Riquelme R, Riquelme M, Torres A, et al. Hantavirus Pulmonary Syndrome,
Southern Chile. EID. 2003:1438-1443.
4. Peters CJ. California Encephalitis, Hantavirus Pulmonary Syndrome, andBunyavirid Hemorrhagic Fevers. In Mandell GL, Bennett JE, Dolin R, eds.
Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases.
Edinburgh, UK: Churchill Livingstone; 2000:1850-1855.
5. CDC Update: Management of patients with suspected viral hemorrhagic fever—United States. MMWR. 1995;44:475-479.
6. Fisher-Hoch SP, Platt GS, Neild GH, et al. Pathophysiology of shock and hemorrhage in a fulminating viral infection (Ebola). J Infect Dis. 1985;152:887-894.
7. Preston R. The Hot Zone: A Terrifying True Story. New York, NY: Random House;
1995.
8. Leroy EM, Rouquet P, Formenty P, et al. Multiple Ebola Virus transmission
events and rapid decline of central African wildlife. Science. 2003;303:387-397.
9. Balter M. On the trail of Ebola and Marburg Viruses. Science. 2003;290:923-925.
10. Vastag B. Ebola vaccines tested in humans, monkeys. JAMA. 2004;291:549-550.

SUGGESTED READING
1. CDC Update: Outbreak of Ebola Hemorrhagic Fever—Uganda, August 2000January 2001. MMWR. 2001;50:73-76.
2. CDC Update: Filovirus infection associated with contact with nonhumanprimates or their tissues. MMWR. 1990;39:404-405.
3. Geisbert TW, Marty A, Jahrling B. Viral Hemorrhagic Fevers. In: Roy MJ, ed.
Physician’s Guide to Terrorist Attack. Totowa, NJ: Humana Press; 2003:221-242.
4. Dieter Klenk H, Feldman H. Symposium on Marburg and Ebola Viruses. Virus
Res. 2001;80:117-123.
5. Thacker PD. An Ebola epidemic simmers in Africa. JAMA. 2003;290:317-319.

12

EVALUATION FORMTERRORISM AND DISASTER: WHAT CLINICIANS NEED TO KNOW
Viral Hemorrhagic Fevers (VHF)
Participant Information
Name/Degree

Practice setting: ❏ Hospital/In-patient ❏ Outpatient/Clinic ❏ Other

Address

Email

City

Clinical Specialty

State

Zip

Telephone

Signature
Date

Instructions for Physicians Receiving Credit
The questions that follow may be used to obtain continuing medical education credit. To obtain 1 hour of Category 1 credit towards
the AMA Physician’s Recognition Award, read this case study, which will take one hour of your time, circle the correct answer to each of
the CME questions, complete the evaluation form, and return both the CME question page and the evaluation form via mail or fax to:
Rush University Medical Center
Office of Continuing Medical Education
600 South Paulina Street, Suite 433 AAF
Chicago, Illinois 60612
Fax: (312) 942-2000

Case Study Evaluation
Please rate this case study according to the following scale: 1=Very Poor 2=Poor 3=Fair 4=Good 5=Very Good 6=Excellent
1. Accredited CME activities must be “free of commercial bias for or against any product.” In this regard,
how would you rate this activity? If you perceived any bias, please provide specific comments below.

1 2 3 4 5 6oooooo__________________________________________________________________________

oooooo2. How well did the case study satisfy your purpose for reading it?

oooooo

3. To what extent were the stated objectives of the case study achieved?

oooooo4. In general, was the case study well organized and presented?
5. To what extent has this CME activity improved your preparedness to recognize and care for victims of aterrorism attack or other public health disaster?
6. What was your overall rating of this case study?

oooooooooooo7. I would recommend this case study to a colleague.

o Yes

8. Based upon your review of this case, what specific action(s) could you take to enhance disaster
preparedness in your workplace?

Please estimate the probability
that you will act on this item
(0-100% where 100% = certainty)o No

A. ________________________________________________________________________

A. ___________

B. ________________________________________________________________________

B. ___________

C. ________________________________________________________________________

C. ___________o Please check this box if you prefer not to be contacted for follow-up about the impact of this activity on your clinical practice.

13

QUESTIONS FOR CONTINUINGMEDICAL EDUCATION
1. A technician sustains a needlestick injury from a syringe containing theblood of a patient with suspected Ebola virus hemorrhagic fever. Given thisinformation, what is the most appropriate next step?
a. Place the laboratory technician into isolationb. Place the laboratory technician under surveillancec. Admit the laboratory technician to a private room with negative pressured. Administer ribavirin therapy and place the patient into isolation
2. Which of the following is not an etiologic agent of VHF?
a. Ebola virus
b. Hantavirus
c. Dengued. Omsk viruse. SARS
3. A patient is admitted to your service with VHF syndrome. Which of thefollowing statements best describes the current therapy for VHF?
a. Supportive care onlyb. Supportive care + immunoglobulinc. Supportive care + vaccine
d. Supportive care + corticosteroidse. Supportive care + platelet transfusion
4. You admit a patient with suspected Marburg virus hemorrhagic fever.
Which of the following statements best describes the role of communication
with the press?
a. Educate public on risk of disease transmissionb. Prevent rumors
c. Provide information on evacuationd. All of the above
e. a and c only
5. An approved vaccine is available for which of the following causes of VHF?
a. Dengueb. Ebolac. Yellow feverd. Hantaviruse. Lassa fever

14

NOTES

15

NOTES16

errorism
Tand isaster
D
Rush University Medical Center
faculty, in collaboration with facultyfrom the Uniformed Services
University of the Health Sciences(USUHS) authored a case series
to provide continuing medical
education (CME) for terrorism
preparedness and other publichealth emergencies.
A series of 14 case studies was developed to provide innovative learning
opportunities for health professionals
to problem-solve issues related toterrorism or other public healthemergencies. Due to the complicated and volatile nature of a terrorist
event, the case studies were designed
to expand outside the clinicianpatient interaction and involve:• deploying outside resources• notifying appropriate officials• coordinating a response team• dealing with media andconcerned public• initiating emergency/disaster plans
Each case provides the CME user
with decision-making challenges
within his or her discipline, alongwith scenarios that address broader
interdisciplinary issues. This interdisciplinary approach is particularly
important in disaster preparedness,when health professionals will likely
be called on to work outside their
day-to-day experiences.

WHAT
CLINICIANS
NEED TO
KNOW

Authored by experts in the field,
each self-paced case includes athorough case history, questions totest your knowledge, a resource listof additional readings and relevant
websites. One-hour CME andCEU credit is available for eachcase, following the successful completion of the CME questions
included with each case. The CME
and CEU credit is available free ofcharge through March 2007.
The cases in the series include:
MEDICINE
The medicine cases address recognitionof the agent, diagnosis, treatment, andmedical case management.
• Pneumonic Plague• Radiation Attack• Sarin• Smallpox• Staphylococcal Enterotoxin B• Viral Hemorrhagic Fevers
PSYCHIATRY
The psychiatry cases address issuesof disaster psychiatry.
• Emergency Mental Health
After a Suicide Bombing• Psychiatric Sequelae in a
Survivor of 9/11
• Psychosocial Managementof a Radiation Attack

INTERDISCIPLINARY
The interdisciplinary cases address
basic medical management,general
disaster planning, communicatingwith the media and concerned
public, and psychosocial casemanagement.
• Inhalational Anthrax• Pulmonary Toxicants• SARS• Smallpox• Viral Encephalitis
For more information or to order
your free copy of any of the casesin this series, please contact:
Office of Continuing
Medical Education
Rush University Medical Center
Suite 433 AAF
Chicago, Illinois 60612
Telephone: (312) 942-7119
Facsimile: (312) 942-2000
E-mail: cme_info@rush.edu