Terrorism
and Disaster

WHAT
CLINICIANS
NEED TO
KNOW

Pneumonic Plague

Sponsored 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.

Pneumonic Plague
CASE AUTHOR: Jennifer C. Thompson MD, MPH, FACP

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

Pneumonic Plague
CASE AUTHOR: Jennifer C. Thompson MD, MPH, FACPINTENDED 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 epidemiologic characteristics of plague that distinguish bioterrorist
events from natural endemic outbreaks of disease.
• Describe the clinical features of pneumonic, septicemic, and bubonic plague.
• List the differential diagnoses of pneumonic plague and identify specimens andlab tests needed to confirm the diagnosis.
• Discuss the ramifications of a plague outbreak including healthcare workers’ fear
and absenteeism and depletion of healthcare teams.
• Describe infection control precautions and recommendations for notifying
infection control and the local health department.
• Summarize basic treatment regimens, post-exposure prophylaxis, andmanagement relevant to adult, pediatric, and pregnant patients with plague.

CASE HISTORY
A 29-year-old man from New Mexico was attending a professional conference inWashington, DC when he began experiencing abdominal pain, diarrhea, nausea,
vomiting, and cough. He developed fever and chills and presented to a local primarycare clinic. On evaluation he was febrile to 104˚F and orthostatic. The lung examination was normal. The abdomen was soft and non-tender with slightly hyperactive
bowel sounds. There was no lymphadenopathy. He was administered intravenous
fluids and an anti-emetic for presumed gastroenteritis.
COMMENT: The presence of cough may be a subtle clue that this was not a typical case of gastroenteritis. However, it is easy to see how this symptom might have been missed or discounted in abusy acute care clinic. The challenge of diagnosing many agents of bioterrorism is that the initial signs
and symptoms are often indistinguishable from common illnesses that are seen in day-to-day medical
practice. Table 1 describes the 3 primary manifestations of plague and their associated differential
diagnoses.

2

Table 1. Clinical Features of Plague
Bubonic

Pneumonic

Septicemic

Exposure

Innoculation of bacteria from
infected flea; exposure of abradedskin to contaminated tissue

Hematogenous spread to lungs during
Same as bubonic or pneumonic
bacteremia associated with bubonic orplaguesepticemic plague; alternatively, primarypneumonic plague occurs after inhalationof bacteria during contact with person
or animal with plague pneumonia

Incubation
Pathophysiology

3-6 days
After inoculation, Y. pestis migrates
to regional lymph nodes where
aggressive intracellular multiplication
occurs, resulting in enlargement,
inflammation and associatedhemorrhage with necrosis

1-5 days
Inhalation of aerosolized organisms
into the lungs results in foci of infection

3-6 days
Rapid progression results in releaseof organisms causing overwhelming
bacteremia prior to the developmentof lymphadenopathy; or enlarged
lymph nodes may be internal(e.g. abdominal, mediastinal) anddifficult to appreciate

Primary
manifestations

Fever, malaise, focal lymphadenopathy(1 – 10 cm), often in femoral or inguinal
areas that becomes extremely tender

Cough and hemoptysis, chest pain.
Chest radiographs may demonstrate
infiltrates, cavities or consolidation

Systemic toxicity with Y. pestis
bacteremia

Othermanifestations

May progress to sepsis syndrome
with disseminated intravascular
coagulation (DIC)

Gastrointestinal symptoms e.g. nausea,
vomiting, diarrhea, abdominal pain
may occur

DIC and acral necrosis may occur

Differential
diagnosis

Staphylococcal, streptococcal or
pasturella infections
Tularemia (Francisella tularensis)
Cat scratch disease (Bartonella henselae)
Chancroid (Haemophilus ducreyi)
Lymphogranuloma venereum (Chlamydia
trachomatis)
Mononucleosis, CMV, Toxoplasmosis

Typical and atypical agents ofcommunity acquired pneumonia

Sepsis due to gram negative or gram
positive agents, especiallymeningococcemia,
pneumococcal sepsis

By the following morning the patient’s condition had deteriorated, and he reported to a local emergency room complaining of weakness, cough, and chest pain in
addition to gastrointestinal symptoms. He described a single episode a few hours earlier in which he had expectorated a small quantity of blood. He appeared extremely ill
and was intermittently incoherent. His temperature was 104.4˚F, and his blood pressure was 78/50 mm Hg. A chest radiograph revealed bilateral pulmonary infiltrates.
The patient was admitted to the intensive care unit. Aggressive resuscitation was initiated with intravenous fluids in conjunction with empiric antibiotic therapy withpiperacillin-tazobactam, azithromycin and vancomycin. He developed an increasing
oxygen requirement that required endotracheal intubation and the implementation of
mechanical ventilation. Gram stain of an endotracheal tube aspirate specimen showednumerous small gram-negative coccobacilli.

3

COMMENT: Yersinia pestis (Y. pestis) can readily be isolated from deep sputum specimens, tracheal aspirates, or bronchial washings of patients with pneumonic plague. In addition, patients may bebacteremic allowing for isolation of the organism from the blood. If the patient has CNS signs andsymptoms, a lumbar puncture gram stain and culture may reveal the pathogen. The organism has acharacteristic safety pin appearance (Figure 1) and will grow on most microbiology culture media,
including MacConkey agar plates that are part of the routine laboratory workup of gram negative rods.

FIGURE 1. Wayson stain of
peripheral blood in bacteremic
Y. pestis infection demonstrating thecharacteristic bipolar (“safety pin”)
staining. Figure from Centers for
Disease Control and Prevention.

Over the next 36-48 hours, the patient remained febrile. The microbiology lab
reported that their automated identification system was unable to identify the gramnegative rods that had been isolated from the tracheal aspirate. Manual biochemical
assays were set up in order to make a definitive diagnosis.
The following day, the microbiology lab reported their suspicion that theisolated organism might be Y. pestis. The infectious disease attending physician
was immediately notified.

QUESTION 1
What precautions are required while caring for a patient with suspectedpneumonic plague?
a.
b.
c.
d.

Standard precautions
Contact precautions
Droplet precautions
Airborne precautions

Reminder: You can find the Answer Key & Discussion on page 8.
The proper precautions were implemented. Table 2 reviews the differences
between droplet and airborne transmission. The hospital lab notified the local
health department of their concern for Y. pestis, and the isolated organism wastransported to their laboratory for definitive identification.
In the meantime, with a presumptive diagnosis of pneumonic plague, gentamicin, doxycycline, and ciprofloxacin were added to the patient’s antibiotic regimen;azithromycin was discontinued.
COMMENT: Streptomycin has traditionally been the treatment of choice for plague, since thedrug has a strong, clinically tested record. However, the drug is not in frequent use today, and it is notwidely obtainable, particularly on short notice. Gentamicin is much more readily available and considered to be an alternative agent. In situations where gentamicin and streptomycin are either unavailable
or contraindicated, doxycycline, or chloramphenicol can be used. The fluoroquinolones have also
demonstrated efficacy against the plague bacillus. Most of the available clinical data involve
ciprofloxacin, and for this reason most authorities still recommend this drug as the first choice among
fluoroquinolones. However, in vitro data suggest that levofloxacin would also be effective. Table 3 lists
the doses of drugs that are used in the treatment of plague. Of note, several of these agents are relatively contraindicated in pregnant or lactating women or young children. However, in the event of aproven case of plague, the risks associated with these agents are outweighed by the benefits oftherapy. It is generally recommended that patients receive at least 10 days of therapy, even though
they may show clinical improvement and become afebrile within 4 – 5 days. In cases where the patientis critically ill, many clinicians will use a combination of agents (as in this case) in the hope of improving efficacy. Failure of therapy due to antimicrobial resistance in Y. pestis has not been a problem todate, but naturally occurring strains with multi-drug resistance have been isolated,2 and the potential
for genetic manipulation of the organism for use in a bioterrorist attack is unknown.
4

Table 2. Droplet Vs. Airborne Transmission
Droplet Characteristics
Size

Droplet Transmission
Large

Airborne Transmission
Very small (5 microns or smaller)

Suspension in air

Do not remain suspended in air

Can remain suspended in the air, ie, airborne,
for long periods of time

Dispersal

Travel short distances, 3 feet or less

Travel widely via air currents, ie, greater than 3 feet

Ability to infect others

Requires close contact (within 3 feet or less)between a patient and the susceptible individual

Does not require contact (within 3 feet or less); can beinhaled easily by a susceptible person

Table 3. Recommended Regimens for the Treatment of Plague*
Recommended Regimens
AdultsStreptomycin 30 mg/kg IM in 2 divided doses for a maximum of 2 gm/day
Gentamicin 5 mg/kg/day IV or IM
Gentamicin 2 mg/kg loading dose followed by 1.7 mg/kg IV or IM three times/day
Doxycycline 100 mg IV two times/day
Doxycycline 200 mg IV once/day
Ciprofloxacin 400 mg IV two times/day
Chloramphenicol 25 mg/kg IV four times/dayChildren

Gentamicin 2.5 mg/kg IV or IM three times/day
If ≥ 45 kg, Doxycycline 100 mg IV two times/day
If < 45 kg, Doxycycline 2.2 mg/kg IV two times/day
Ciprofloxacin 15 mg/kg IV two times/day
Chloramphenicol 25 mg/kg IV four times/day* Adapted from Inglesby et al.1

A respiratory therapist caring for the patient commented that she had developed a cough and asked if she might have acquired pneumonic plague. Two nurses
who had cared for the patient at the time of initial presentation reported flu-like
symptoms and were worried that they too might have acquired plague. Anothernurse, who was 4 months pregnant, refused to care for the patient because of fearthat the droplet precautions that had been instituted would not provide adequate
protection for her and her unborn baby.
COMMENT: It is critical to notify your infection control department and your local health department as soon as a case of plague is suspected or confirmed. Infection control practitioners and thehospital epidemiologist will determine the continued risk to people in the facility, as well as follow-up
on any healthcare workers exposed to the source patient since admission.Table 4 reviews the recommended prophylactic regimens for people exposed to a patient with pneumonic plague.
Health department officials can often facilitate the transportation of specimens or isolates to a reference laboratory where a definitive identification can be made, and they will initiate the detailed andsystematic investigation that is required in order to identify exposed individuals, and ascertain whether
a bioterrorist event has occurred. Health department personnel are also trained in risk communication,a skill that can prove invaluable in the face of widespread panic and fear.

5ABSENTEEISM4
In the United States, healthcare professionals have little experience indiagnosing and managing causalities
caused by chemical, radiological, or
biological agents. As a result, in theimmediate aftermath of a bioterrorism event involving one of theseagents, healthcare professionals may
experience fear, shock, anger, helplessness, and may have concerns
about the health and safety of theirfamilies and friends. Potentially,
these feelings can contribute toabsenteeism among the healthcare
staff. For example, in 1994, during
an outbreak of pneumonic plague inSurat, India, 80% of the private
physicians fled the city.
Familiarity with chemical and biological agents, as well as training anddrilling on your emergency plan may
enhance performance by healthcare
staff and help to minimize or prevent
absenteeism.

Table 4. Prophylactic Regimens for People Exposed to a
Patient With Pneumonic Plague*
AdultsChildren

Recommended
Recommended
Alternative
Recommended
Recommended
Recommended
Alternative

Post-exposure Prophylaxis
Doxycycline 100 mg orally twice per day
Ciprofloxacin 500 mg orally twice per day
Chloramphenicol 25 mg/kg IV or orally four times per day
If ≥ 45 kg, Doxycycline 100 mg orally twice per day
If < 45 kg, Doxycycline 2.2 mg/kg orally twice per day to a maximum of 200 mg/day
Ciprofloxacin 20 mg/kg orally twice per day
Chloramphenicol 25 mg/kg IV or orally four times per day* Adapted from Inglesby et al.1

QUESTION 2
An appropriate post-exposure intervention for people who have been in contact
with a patient with pneumonic plague includes which of the following?
a. Administration of the plague vaccine within 72 hours of exposureb. Administration of anti-plague immunoglobulin within 72 hours of exposurec. Administration of prophylactic antibiotics for 7 days

Two health department officials came to the hospital to assist with identification of contacts and to conduct an investigation into the source of the case. They
reported that no other cases were confirmed or suspected in the local area.

QUESTION 3
Which of the following scenarios is most suspicious for a bioterrorist event?
a. A 22-year-old college student and his girlfriend acquire bubonic plague while
camping in Colorado.
b. A 60-year-old businessman acquires pneumonic plague while attending a
conference in New York City.
c. A 49-year-old professor acquires septicemic plague while hunting prairie dogs
in New Mexico.
d. A 37-year-old housewife acquires pneumonic plague after her sick cat dies in
Arizona.

COMMENT: The existence of even a single case of pneumonic plague in a non-endemic area
should raise suspicion of an act of bioterrorism and requires further investigation. Table 5 comparescharacteristics of naturally occurring plague infections with the possible features of a bioterrorism
event.

6

Table 5. Clinical and Epidemiologic Characteristics of Plague
Naturally Occurring Infection

Bioterrorism Event

Clinicalmanifestations• Typically bubonic plague with occasional septicemic cases• Pneumonic plague is a relatively rare event that has been
associated with infected cats

• Aerosolization of the plague bacillus
would be expected to result in cases ofpneumonic plague

Numbers of cases• Isolated cases with common risk factors• Large clusters of cases with a common
mechanism of exposure

Geography• Plague is enzootic in the southwestern United States. However,in an era of rapid and global travel, cases may potentiallypresent anywhere, and a careful travel history is required to
identify travel through or from an endemic area.

• Non-enzootic areas• Large metropolitan cities or locations of social,
cultural, or political importanceSeasonality• Most cases occur between April and October• Cases involving direct animal contact have occurredin the colder months (hunting season)• NoneRisk factors• Working, camping, hunting outdoors, and in contact
with fleas and/or host animals• Veterinarians and their staff who may be in contact withsmall animals in an enzootic area
• Contact with domestic cats in an enzootic area
• Communities with very poor hygiene/sanitation whererodents and fleas come in contact with humans• During rodent “die-offs” when infected fleas seek alternative hosts• Non-specific

One of the ICU nurses obtained the name and telephone number of thepatient’s housemate in New Mexico, and the health department officials called her
as part of their investigation. She reported that the day before he left for his trip thepatient had removed a stray cat from the crawlspace of their house. The cat hadoral abscesses and lesions that, in retrospect, were consistent with feline plague. The
animal died in the local animal shelter and was cremated without any diagnostic
studies. While this information transpired, the local health department laboratory
confirmed that the tracheal isolate was indeed Y. pestis. Once the isolate was identified and confirmed and susceptibility results were available, the infectious disease
specialist narrowed the patient’s antibiotic coverage.
COMMENT: As more information becomes available, it is evident that this case was unlikely torepresent a bioterrorist event. Although the patient presented in Washington, DC, a likely target for aterrorist event, he lived in and traveled from New Mexico, where plague is enzootic. Additionally, he
had a clear risk factor for pneumonic plague since he had made close contact with a sick cat thatprobably had feline plague. It was also reassuring that no other cases of plague were identified in the
Washington, DC area; a terrorism event would likely result in a number of cases, rather than a single
index case.

7

QUESTION 4
Other than isolating Y. pestis from a clinical specimen, what test is available to
make the diagnosis of plague?
a. When plague antigen is administered intra-dermally, people who have been
infected with plague have a positive skin test that is analogous to the positive
skin test in patients who have been exposed to tuberculosis.
b. People who have been infected with plague produce an antibody to theplague bacteria that can be detected in the serum.
c. People who have been infected with plague excrete a plague antigen that canbe detected in the urine.

The patient made steady improvement and was successfully extubated on the
7th hospital day. He ultimately made a complete recovery and returned to work
approximately 6 weeks after his initial presentation. Although over 30 people gavea history of close contact with him and received prophylactic antibiotics, no additional cases of plague were identified.

ANSWER KEY & DISCUSSIONQUESTION 1
What precautions are required while caring for a patient with suspectedpneumonic plague?
a.
b.
c.
d.

Standard precautions
Contact precautions
Droplet precautions
Airborne precautions

ANSWER: The correct answer is c. Pneumonic plague may be transmitted from person-to-person
via respiratory droplets if an infected individual is coughing. For this reason, it is recommended thatdroplet precautions and isolation be implemented for all patients with known or suspected plague until
pneumonic plague has been ruled out, or until the patient has received at least 72 hours of effective
therapy and made clinical improvement. Droplet precautions require the use of a surgical mask within
3 feet of an infected patient. Eye protection, in the form of goggles or face shields, is also recommended to protect the conjunctival mucosa. Standard precautions (formerly called universal precautions) are
the precautions that are implemented in the care of all patients, and alone would not provide sufficient
protection against transmission via the droplet route. Contact precautions involve the use of gowns
and gloves and are used in infections such as methicillin-resistant Staphylococcus aureus, which is transmitted via fomites to the hands of health care providers. Airborne precautions require the use of an
N95 respirator and a negative pressure environment. This is the form of protection that is required for
infections such as pulmonary tuberculosis that result in the production of very small (1 – 10 µm) infectious nuclei that remain suspended in the air and can be inhaled into the pulmonary alveoli. There is noevidence of the formation of infectious particles of this size in pneumonic plague.1

8

QUESTION 2
An appropriate post-exposure intervention for people who have been in contact
with a patient with pneumonic plague includes which of the following?
a. Administration of the plague vaccine within 72 hours of exposureb. Administration of anti-plague immunoglobulin within 72 hours of exposurec. Administration of prophylactic antibiotics for 7 days
ANSWER: The correct answer is c. Once a case of pneumonic plague has been diagnosed, it isnecessary to identify individuals that have had close contact with the patient (defined as coming within
2 meters of the index case) prior to the completion of 72 hours of effective therapy. These individuals
should receive post-exposure antibiotic prophylaxis for 7 days.1 Table 4 gives the recommended prophylactic regimens for adults and children. Here again, it is necessary to balance the possible toxicities ofthese agents against the benefits of prophylaxis for special populations such as very young children
and pregnant or lactating women. Close contacts that are receiving post-exposure prophylaxis antibiotics should be monitored for fever, development of cough, or other signs of illness. Should such signs
develop, the patient should receive immediate medical attention with treatment for pneumonic plague
on a presumptive basis until or unless this diagnosis can be definitively excluded. There is no plague
vaccine currently available. Anti-plague immunoglobulin is not a commercially available product, andthere are no data to support its role in post-exposure prophylaxis.

QUESTION 3
Which of the following scenarios is most suspicious for a bioterrorist event?
a. A 22-year-old college student and his girlfriend acquire bubonic plague while
camping in Colorado.
b. A 60-year-old businessman acquires pneumonic plague while attending a
conference in New York City.
c. A 49-year-old professor acquires septicemic plague while hunting prairie dogs
in New Mexico.
d. A 37-year-old housewife acquires pneumonic plague after her sick cat dies in
Arizona.
ANSWER: The correct answer is b. The existence of even a single case of pneumonic plague in a
non-endemic area should raise suspicion of an act of bioterrorism and requires further investigation.
Table 5 reviews some of the characteristics of naturally occurring plague infections for comparison withthe possible features of a bioterrorism event.

9

QUESTION 4
Other than isolating Y. pestis from a clinical specimen, what test is available to
make the diagnosis of plague?
a. When plague antigen is administered intra-dermally, people who have been
infected with plague have a positive skin test that is analogous to the positive
skin test in patients who have been exposed to tuberculosis.
b. People who have been infected with plague produce an antibody to theplague bacteria that can be detected in the serum.
c. People who have been infected with plague excrete a plague antigen that canbe detected in the urine.
ANSWER: The correct answer is b. Serologic testing can be used to confirm the diagnosis ofplague retrospectively. The test available through the Centers for Disease Control and Prevention (CDC)
detects the presence of anti-F1 antibody (antibody to the antigen of the bacterial envelope). The test is
performed using paired serum with acute and convalescent or convalescent and post-convalescentspecimens. A 4-fold or greater change in titer, or a single titer of 1:16 or greater is presumptive evidence of plague infection.3 There is no skin test for plague. There is also no diagnostic plague antigen
that can be detected in the urine of infected patients.

REFERENCES
1. Inglesby TV, Dennis DT, Henderson, DA, et al. Plague as a biological weapon:
medical and public health management. JAMA. 2000;283:2281–2290.
2. Galimand M, Guiyoule A, Gerbaud G, et al. Multidrug resistance in Yersinia
pestis mediated by a transferable plasmid. N Eng J Med. 1997;337:677–680.
3. Perry RD, Fetherston JD. Yersinia pestis: etiologic agent of plague. Clin Microbiol
Rev. 1997;10:35–66.
4. Ursano RJ, Norwood AE, Fullerton CS, Holloway HC, Hall M. Terrorism with
Weapons of Mass Destruction: Chemical, Biological, Nuclear, Radiological, andExplosive Agents. In: Ursano RJ, Norwood AE, eds. Trauma and Disaster
Responses and Management. Washington DC: American Psychiatric Association;
2003:145.

SUGGESTED READING
1. Gage KL, Dennis DT, Orloski KA, et al. Cases of cat-associated human plague inthe western U.S., 1977–1998. Clin Infect Dis. 2000;30:892–900.
2. Inglesby TV, Dennis DT, Henderson, DA, et al. Plague as a biological weapon:
medical and public health management. JAMA. 2000;283:2281 – 2290.
3. McGovern TW, Friedlander AM. Plague. In: Sidell FR, Takafuji ET, Franz DR,
eds. Medical Aspects of Chemical and Biological Warfare. Washington DC: Borden
Institute; 1997;479–502.
4. CDC Plague Home Page. Centers for Disease Control and Prevention. Available
at: http://www.cdc.gov/ncidod/dvbid/plague/index.htm. Accessed December 17,
2004.
5. Infectious Diseases Society of America. Yersinia pestis. Available at:
http://www.idsociety.org/Template.cfm?Section=Bioterrorism. Accessed
December 17, 2004.

10

EVALUATION FORMTERRORISM AND DISASTER: WHAT CLINICIANS NEED TO KNOW
Pneumonic Plague
Participant Information
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Practice setting: ❏ Hospital/In-patient ❏ Outpatient/Clinic ❏ Other

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Signature
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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.
11

QUESTIONS FOR CONTINUINGMEDICAL EDUCATION
1. Which clinical manifestation would be most likely after a bioterrorism
incident involving aerosolization of plague?
a. Bubonic plagueb. Septicemic plaguec. Pneumonic plagued. Plague meningitis
2. Which of the following findings on gram stain is most consistent with
Y. pestis, the etiologic agent of plague?
a. Gram-positive branching filamentsb. Gram-negative coccobacilli
c. Gram-positive rods
d. Gram-negative diplococci
3. Which of the following regimens provides the best combination therapy for an
adult patient with plague?
a. Amikacin, dicloxacillin, ciprofloxacinb. Streptomycin, dicloxacillin, ciprofloxacinc. Gentamicin, doxycycline, ciprofloxacind. Streptomycin, chloramphenicol, trimethoprim-sulfamethoxazole
4. How long do patients with pneumonic plague require isolation and droplet
precautions?
a. For the duration of clinical illness
b. Until the chest x-ray abnormality has resolvedc. For at least 72 hours after the patient is no longer febrile and thecough has resolved
d. Until the patient has received at least 72 hours of effective therapy
and has made clinical improvement
5. What is the best way to clinically manage people who have been in close
contact with a patient with pneumonic plague?
a. Prophylactic antibiotics for 7 days. If there is fever, cough or other signs of
illness during this period, the patient needs to begin treatment for plague
until or unless plague can be ruled out as the cause of the symptoms.
b. Close monitoring for 7 days. If there is fever, cough or other signs of illness
during this period, the patient needs to begin treatment for plague until orunless plague can be ruled out as the cause of the symptoms.
c. Presumptive treatment for plague with droplet precautions until at least
72 hours of therapy have been administered.

12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.

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

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

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