The document discusses the history, epidemiology, clinical presentation, diagnosis, and treatment of plague. Some key points: - Plague caused 20 million deaths in Europe during the 14th century Black Death pandemic. It has also been studied as a biological weapon. - Caused by the bacterium Yersinia pestis, plague typically occurs in 10-15 cases per year in the southwest US through flea bites. Pneumonic plague can spread from person to person. - Clinical forms include bubonic, septicemic, and pneumonic plague. Pneumonic plague has the highest mortality if not treated quickly with antibiotics.

1. Plague
History & Significance
14th Century: “Black Death” responsible for
>20 million deaths in Europe
Used as a BW agent by Japan in WW II
Studied by Soviet and, to a smaller extent,
U.S. BW programs
1995: Larry Wayne Harris arrested for illicit
procurement of culture via mail

2. Plague
Epidemiology
 Caused by Yersinia pestis
 About 10-15 cases/year U.S.
Mainly SW states
 Human plague occurs from bite of an infected flea
(bubonic)
 Only pneumonic form of plague is spread person-
to-person
Last case of person-to-person transmission in U.S. occurred in 1924

3. Yersinia Pestis
 Gram negative,
non-motile, non-
spore-forming
bacillus
 Resistant to
freezing
temperature and
drying, killed by
heat and sunlight
Source: Centers for Disease Control and
Prevention, Division of Vector-Borne
Infectious Diseases, Fort Collins, CO

4. Plague
Case Definition
 Characterized by fever, chills, headache,
malaise, prostration, & leukocytosis that
manifests in one or more of the following
clinical forms:
◦ Regional lymphadenitis (bubonic)
◦ Septicemia w/o evident bubo (septicemic)
◦ Plague pneumonia
◦ Pharyngitis & cervical lymphadenitis (pharyngeal)
MMWR 1997;46(RR-10)

5. Plague
Case Definition, cont.
Laboratory criteria for diagnosis:
Presumptive
Elevated serum antibody titers to Y. pestis F1 antigen (w/o
documented 4-fold change) in a patient with no history of plague
vaccination OR
Detection of F1 antigen in a clinical specimen by fluorescent
assay
Confirmatory
Isolation of Y. pestis from a clinical specimen OR
4-fold or greater change in serum antibody titer to Y. pestis F1
antigen
MMWR 1997;46(RR-10)

6. Plague: Case Classification
Suspected: Clinically compatible case w/o
presumptive or confirmatory lab results
Probable: Clinically compatible case with
presumptive lab results
Confirmed: Clinically compatible case with
confirmatory lab results
MMWR 1997;46(RR-10)

7. Plague
Clinical Forms
 Bubonic plague
Most common naturally-occurring form
Mortality 60% untreated, <5% treated
 Primary or secondary septicemic
plague
 Pneumonic plague
Most likely BT presentation
From aerosol or septicemic spread to lungs
Survival unlikely if treatment not initiated
w/in 24 hours of the onset of symptoms

8. Pneumonic Plague
Clinical Presentation
 Incubation: 1-6 days (usually 2-4 days)
 Acute onset of fever with cough, dyspnea, and
chest pain
 Hemoptysis characteristic; watery or purulent
sputum also possible
 Prominent GI symptoms may be present, including
nausea, vomiting, diarrhea, and abdominal pain

9. Pneumonic Plague
Clinical Presentation
Other symptoms include headache, chills,
malaise, myalgias
Rarely, cervical bubo present
Rapid progression to respiratory failure &
shock

10. Bubonic Plague
 Incubation: 2-8 days
 Sudden onset nonspecific symptoms: fever, chills,
malaise, muscle aches, headache
 Regional lymphadenitis (buboes)
Swollen, very painful lymph nodes
Typically inguinal, femoral, axillary, or cervical
Erythema overlying skin
May have surrounding edema
Concurrent with or shortly after onset of other symptoms

11. Septicemic & Bubonic Plague
Source: CDC NVBID

12. Plague
Infection Control
Person-to-person transmission via
respiratory droplets
Standard respiratory droplet precautions
Treatment = 10 days antibiotics
 Case isolation for at least the first 48 hrs of
antibiotic treatment
Bubonic plague - standard precautions

13. Plague
Infection Control
Antibiotic prophylaxis for close contacts
Duration: 7 days or duration of risk of
exposure + 7 days
Close contacts refusing prophylaxis:
Observe 7 days after last exposure and treat
if fever or cough develop
Bubonic contacts:
Observe 7d and treat if symptoms develop

14. Bacillus Species
 The genus Bacillus includes large aerobic,
spore-forming, Gram-positive rods occurring in chains.
 Most members of this genus are saprophytic organisms
prevalent in soil, water, air and on vegetation,
such as Bacillus subtilis & B. cereus .
 Some are insect pathogens, such as B. thuringiensis . This
organism is also capable of causing disease in humans.
 B. cereus can grow in foods and cause food poisoning by
producing either an enterotoxin (diarrhea) or an emetic toxin
(vomiting).

15. Morphology and identification
A. Typical Organisms
The typical cells, measuring 1 ×
3–4 μm, have square ends and
are arranged in long chains;
spores are located in the center
of the bacterial cell.

16.  Colonies of B. anthracis are flat or slightly convex
with irregular edge and have a ground-glass
appearance in transmitted light.
B. Culture
 Hemolysis is uncommon with
B anthracis but common with B cereus.
B. anthracis B. cereus
…..Morphology and identification
 Gelatin is liquefied by B. cereus.
B. anthracis growth in gelatin stabs
resembles an inverted fir tree.
Bacillus cereus colonies are large flat and dry.

17. Diagnostic Laboratory Tests
Specimens to be examined are fluid or pus from a local lesion, blood,
pleural fluid, and cerebrospinal fluid in inhalational anthrax
associated with sepsis and stool or other
intestinal contents in the case of gastrointestinal anthrax.
• Stained smears
Gram stain show chains of large gram-positive rods
 Culture
 When grown on blood agar plates, the
organisms produce Non-hemolytic gray to white,
tenacious colonies with a rough texture and a
ground-glass appearance. Comma-shaped
outgrowths (Medusa head, “curled hair”) may project
from the colony.
 In semisolid medium, anthrax bacilli are always non-
motile.

18. - Definitive identification requires lysis by a specific anthrax -
bacteriophage,
- Detection of the capsule by fluorescent antibody,
- identification of toxin genes by polymerase chain reaction
(PCR),
- Enzyme-linked immunoassay (ELISA)
Clinical laboratories that recover large gram-positive rods
from blood, cerebrospinal fluid, or suspicious skin lesions,
which phenotypically match the description of B anthracis
as mentioned, should immediately contact their public
health laboratory and send the organism for confirmation.
…..Diagnostic Laboratory Tests