National Wildlife Health Center

Plague

Circular 1372

U.S. Department of the Interior

U.S. Geological Survey
Cover Photos.

1. Plague warning sign (National Wildlife Health Center, NWHC).

2. Prairie dog on alert (U.S. Geological Survey, USGS).

3. Plague infected male Xenopsylla cheopis (Centers for Disease Control and Prevention, CDC/Dr. Pratt).

4. Cat carrying a mouse (Lxowle, Wikimedia Commons, ).

5. Black-footed ferret (Ryan Hagerty, U.S. Fish and Wildlife Service, USFWS, Digital Library). 

6. Rats (Chris Barber, Wikimedia Commons, ).

7. Wright’s stain of Yersinia pestis in a blood smear (Centers for Disease Control and Prevention, CDC).

1 2

3

5 4

6 7 cc c

cc c
Plague

By Rachel C. Abbott and Tonie E. Rocke

National Wildlife Health Center

Circular 1372

U.S. Department of the Interior

U.S. Geological Survey
ii

U.S. Department of the Interior

KEN SALAZAR, Secretary

U.S. Geological Survey

Marcia K. McNutt, Director

U.S. Geological Survey, Reston, Virginia: 2012

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Suggested citation:

Abbott, R.C., and Rocke, T.E., 2012, Plague: U.S. Geological Survey Circular 1372, 79 p.

Library of Congress Cataloging-in-Publication Data

Abbott, Rachel C.

Plague / by Rachel C. Abbott and Tonie E. Rocke ; prepared by the USGS 

National Wildlife Health Center.

 p. ; cm. -- (Circular ; 1372)

Includes bibliographical references.

ISBN 978-1-4113-3376-5

I. Rocke, Tonie E. II. National Wildlife Health Center (U.S.) III. Title.

IV. Series: U.S. Geological Survey circular ; 1372.

[ DNLM: 1. Plague--transmission. 2. Disease Vectors. 3. Yersinia pestis. 

WC 350 ]

614.5’732--dc23

 2012013873
iii

U.S. Department of the Interior

U.S. Geological Survey

Circular 1329

Prepared by the USGS National Wildlife Health Center

Bat Rabies and 

Other Lyssavirus Infections

Prepared by the USGS National Wildlife Health Center 

in cooperation with the U.S. Fish and Wildlife Service

Tularemia

U.S. Department of the Interior

U.S. Geological Survey

Circular 1297

Field Manual of

Wildlife Diseases

General Field Procedures and Diseases of Birds

U.S. Department of the Interior

U.S. Geological Survey

Prepared by the USGS National Wildlife Health Center 

in cooperation with the U.S. Fish and Wildlife Service

Disease Emergence and Resurgence: 

The Wildlife-Human Connection

U.S. Department of the Interior

U.S. Geological Survey

Circular 1285

Prepared by the USGS National Wildlife Health Center

Bat Rabies and

Other Lyssavirus Infections

U.S. Department of the Interior

U.S. Geological Survey Circular 1329

Prepared by the USGS National Wildlife Health Center 

in cooperation with the U.S. Fish and Wildlife Service

Circular 1297

U.S. Department of the Interior

U.S. Geological Survey

Tularemia

Disease Emergence and Resurgence:

The Wildlife-Human Connection

Prepared by the USGS National Wildlife Health Center

in cooperation with the U.S. Fish and Wildlife Service

Circular 1285

U.S. Department of the Interior

U.S. Geological Survey

Related USGS Publications

Bat Rabies and

Other Lyssavirus Infections,

by Denny G. Constantine, USGS Circular 1329

(also available on CD-ROM)

Tularemia, by Milton Friend, 

USGS Circular 1297

(also available on CD-ROM)

Disease Emergence and Resurgence—

The Wildlife-Human Connection,

by Milton Friend, USGS Circular 1285

(also available on CD-ROM)

Field Manual of Wildlife Diseases—

General Field Procedures and Diseases of Birds

edited by Milton Friend and J. Christian Franson, 

USGS Information and Technology Report 1999–001

v

Foreword

Plague has been described as “... one of the major calamities of history, not excluding wars, 

earthquakes, floods, barbarian invasions, the Crusades, and the last war [World War I]” (Zinsser, 

1934). Despite this stark statement, there are many who consider plague to be a disease of the 

past. Still others, including many that reside in, or frequent, plague endemic areas have minimal 

concerns about plague. Contrasts in the number of human fatalities associated with modern 

plague outbreaks and those of the historic plague pandemics and advances in modern medicine 

for treatment of this disease are likely factors that influence current perspectives. Nevertheless, 

plague remains a serious global threat for modern society because of (1) its current stature as a 

naturally emerging infectious disease and (2) the potential for plague to be exploited for nefarious purposes. The latter situation was first attempted during the siege of Caffa in 1345 when 

plague-infected human corpses were catapulted into the city (see Box 1, this publication). Today, 

the catapult used may be a long-range ballistic missile or some other “advance” of modern 

technology. Further, plague poses a significant challenge for the long-term sustainability of some 

North American fauna, most notably the black-footed ferret.

Plague’s “durability” over the ages as an infectious disease of major consequence for society 

stands in testimony to the ability of Yersinia pestis to convert changes within its established, 

time-specific, host-agent-environment relations into opportunities that favor agent perpetuation 

through disease persistence and geographic expansion. Clearly, the ecology of plague is highly 

complex, a factor that contributes to various aspects of its ecology not yet being fully understood. The authors of this publication have admirably addressed this complexity within the context of an extraordinarily rich, well-illustrated, easily read and highly insightful synopsis for one 

of the classic and intriguing diseases of humanity. There is much to be contemplated here, taken 

into consideration, and acted upon, especially as the further urbanization of society continues to 

enhance opportunities for sylvatic plague. This situation involves both the movement of animals 

into “metropolis” and the extension of “metropolis” into free-ranging animal habitats.

Advances in our knowledge of plague also provide insights for infectious diseases in general. 

These insights are important, as noted by Zinsser in his classic treatise on typhus fever:

“Infectious disease is one of the great tragedies of living things—the struggle for 

existence between different forms of life. ... Incessantly, the pitiless war goes on, 

without quarter or armistice—a nationalism of species against species.” 

(Zinsser, 1934, p. 7)

Plague exemplifies the many facets of this battleground.

Milton Friend

September 11, 2011

1

Zinsser, H., 1934, Rats, lice, and history: Boston, Massachusetts, Little, Brown and Company, 301 p.

vii

Contents

Foreword .........................................................................................................................................................v

Overview..........................................................................................................................................................1

Background.....................................................................................................................................................1

Causative Agent.............................................................................................................................................1

Geographic Distribution..............................................................................................................................10

Patterns and Trends ....................................................................................................................................16

Species Susceptibility.................................................................................................................................18

Human Infections................................................................................................................................18

Wild and Laboratory Animal Infections ..........................................................................................18

Rodents........................................................................................................................................18

Shrews.........................................................................................................................................18

Lagomorphs ................................................................................................................................19

Ferrets and Polecats .................................................................................................................19

Carnivores...................................................................................................................................19

Ungulates ....................................................................................................................................25

Nonhuman Primates..................................................................................................................27

Birds.............................................................................................................................................27

Domestic Animal Infections..............................................................................................................27

Cats...............................................................................................................................................27

Dogs .............................................................................................................................................27

Livestock......................................................................................................................................27

Vector Infections.................................................................................................................................27

Obtaining a Diagnosis .................................................................................................................................30

Disease Ecology...........................................................................................................................................31

Domestic Cycle....................................................................................................................................31

Commensal Rats ........................................................................................................................31

Urban Epidemics........................................................................................................................32

Human Skin Parasites as Vectors...........................................................................................34

Pneumonic Plague.....................................................................................................................34

Sylvatic Cycle ......................................................................................................................................35

Classification of the Role of Wild Rodents ............................................................................35

Enzootic and Epizootic Cycles .................................................................................................38

Enzootic Hosts...................................................................................................................38

Epizootic Hosts..................................................................................................................39

Enzootic Plague.................................................................................................................39

Climate.........................................................................................................................................39

Metapopulations of Rodents....................................................................................................41

Reservoirs of Plague .................................................................................................................42

Fleas....................................................................................................................................43

Resistant Hosts .................................................................................................................44

Soil.......................................................................................................................................44

Carcasses and Tissues of Infected Animals ................................................................45
viii

Role of Carnivores .....................................................................................................................45

Survival of Y. pestis....................................................................................................................46

Points to Ponder...........................................................................................................................................46

Disease Prevention and Control................................................................................................................47

Treatment .............................................................................................................................................56

References Cited..........................................................................................................................................56

Glossary.........................................................................................................................................................71

Appendix 1. Common and Scientific Names for Species Cited ...........................................................77

Topic Highlight Boxes

1. The Three Plague Pandemics.....................................................................................................2

2. Stealth and Deception by Yersinia pestis .................................................................................7

3. Fleaborne Transmission of Y. pestis...........................................................................................8

4. Routes of Transmission of Y. pestis to Humans Associated with Infected Animals........20

5. Forms of Plague in Humans ......................................................................................................22

6. Plague and Cats ..........................................................................................................................28

7. Plague as a Biological Weapon ...............................................................................................48

8. Plague and the Conservation of Prairie Dogs and Ferrets ..................................................50

9. Using Vaccines to Fight Plague in Prairie Dogs and Black-Footed Ferrets......................54

Figures

1. Photograph showing Wright’s stain of Y. pestis in a blood smear 

showing its characteristic bipolar “safety pin” appearance................................................4

2. Photographs showing X. cheopis fleas immediately after feeding. 

A, uninfected flea and B, infected, blocked flea, C, diagram of 

the digestive tract of the flea......................................................................................................6

3. Map showing global distribution and natural foci of plague...............................................11

4. Map showing areas in United States where plague is found in animals, 

fleas, and humans.......................................................................................................................11

5. Graph showing human cases of plague, by region, 1954–2010 ..........................................12

6. Schematic representation of predicted waves of plague movement 

from the west coast of the United States eastward into the Great Plains........................17

7. Maps showing the spread of human cases of plague in the western 

United States, 1944–1993...........................................................................................................17

8. Diagram showing the Y. pestis transmission cycle and the progression 

from bubonic plague to pneumonic plague in humans. ......................................................31

9. Diagram showing general pathways of plague transmission for 

the domestic cycle .....................................................................................................................33
ix

10. Diagram showing the general pathways of transmission for the sylvatic 

cycle in North America..............................................................................................................36

11. Map showing areas where rodents are infected with Y. pestis and 

serve as sources of infection for other groups of wild and domestic 

animals and humans ..................................................................................................................37

12. Diagram showing routes of human exposure to Y. pestis....................................................38

13. Diagram showing trophic cascade model of plague. Climate may 

influence the incidence of plague by its influence on rodent and 

flea populations, as explained by the trophic cascade model............................................40

Tables

1. Timeline of important early events since the discovery of Y. pestis.....................................4

2. Taxonomy of Yersinia species.....................................................................................................5

3. Yersinia species pathogenic to humans ...................................................................................5

4. Virulence determinants of Y. pestis ...........................................................................................6

5. Classification systems of Y. pestis strains..............................................................................10

6. Major wild rodent hosts and flea vectors of natural plague foci .......................................13

7. Examples of the reemergence of human plague...................................................................16

8. Animals naturally infected with Y. pestis................................................................................18

9. Relative susceptibility of animal groups to infection and disease 

caused by Y. pestis and roles of animal groups as sources of 

human infection ..........................................................................................................................24

10. Prevalence of antibodies to Y. pestis in blood specimens from 

carnivores and omnivores in the western United States.....................................................26

11. Standard case definitions of plague........................................................................................30

12. Roles of hosts in maintaining plague in natural populations...............................................32

13. Modern outbreaks of pneumonic plague ...............................................................................35

14. Relative efficiency of early-phase transmission of Y. pestis

by fleas found on epizootic and enzootic hosts.....................................................................43

Words in bold type in the text, the topic highlight boxes, and the tables are defined in the Glossary.
x

Conversion Factors and Abbreviations

Inch/Pound to SI

Multiply By To obtain

Length

inch (in) 2.54 centimeter (cm)

foot (ft) 0.3048 meter (m)

mile (mi) 1.609 kilometer (km)

Area

acre 0.4047 hectare (ha)

Mass

pound, avoirdupois (lb) 0.4536 kilogram (kg) 

Temperature in degrees Celsius (°C) may be converted to degrees Fahrenheit (°F) as follows:

°F=(1.8×°C)+32

Temperature in degrees Fahrenheit (°F) may be converted to degrees Celsius (°C) as follows:

°C=(°F-32)/1.8

Micrometer, μm

Milliliter, mL
Plague

By Rachel C. Abbott and Tonie E. Rocke

“Plague is not an extinct medieval monster, and epidemics still happen frequently.” (Krasnov and others, 2006)

Synonyms

Black Death, bubonic plague, pneumonic plague, 

septicemic plague, pestis minor, peste, pestilential fever, 

pest

Overview

Plague is an acute infectious zoonotic disease caused 

by the highly virulent bacteria Yersinia pestis. Infections in 

humans most often result from the bites of fleas that feed on 

infected rodents, although person-to-person transmission can 

occur if the bacteria are inhaled. When someone is infected 

by Y. pestis and shows symptoms, the disease takes three main 

forms: bubonic, septicemic, and pneumonic. Without prompt 

antibiotic treatment, the mortality rate from bubonic plague

can be as high as 60 percent, and the pneumonic form is nearly 

100 percent lethal. Plague is broadly distributed around the 

world and is maintained by wild rodents and their fleas in natural foci or localized areas of infection. Outbreaks of plague 

develop periodically among susceptible rodents and can have 

severe impacts on the survival of threatened species of wild 

animals. Epidemics of plague continue among humans even 

in regions that have been unaffected for extended periods of 

time, prompting the World Health Organization (WHO) to 

identify plague as an emerging disease.

Background

Although the causative agent of plague, Yersinia pestis, 

was not identified until 1894, the disease is ancient, and the 

first descriptions of it may be found in the Bible. Passages 

in the book of Samuel describe a Philistine city in the 11th

century afflicted by dying mice and numerous deaths of its 

residents who suffered swellings in the groin and thighs (Zietz 

and Dunkelberg, 2004). In the first century A.D., an outbreak 

of plague causing buboes and a high death rate may have 

occurred in Libya, Syria, and Egypt as described by Rufus 

of Ephesus (Zietz and Dunkelberg, 2004). Although it is 

difficult to definitively attribute plague as the cause of these 

early epidemics, it is generally accepted that there have been 

three pandemics of plague, the most infamous being the Black 

Death (Box 1).

The 1894 discovery of the causative agent of plague at 

the onset of the plague epidemic in Hong Kong facilitated 

thorough research on this disease and resulted in rapid 

progress in the elucidation of the epidemiology of plague 

(table 1). Although the true cause of the Black Death and 

other ancient plagues may never be unequivocally determined, 

plague remains a real threat to both human and animal health. 

Epizootics of plague among threatened species of wildlife, 

epidemics causing numerous deaths and panic, and the threat 

of bioterrorism using the plague bacillus make Y. pestis not 

just a historical curiosity but a current menace.

Causative Agent

Plague is caused by Yersinia pestis, an oval-shaped 

bacteria that is unable to move on its own (“nonmotile”) 

and that is shaped between the coccus, or spherical, and the 

bacillus, or rod-shaped, forms, thus making it a “coccobacillus” 

bacteria. Scientists can sometimes distinguish one kind of 

bacteria from another by applying a purple stain, the Gram 

stain, to samples that contain bacteria; another chemical that 

removes the Gram stain from some kinds of bacteria is applied 

to the sample, and those bacteria that retain the purple stain 

are “Gram positive” while those that do not retain the stain 

are “Gram negative.” Y. pestis is Gram negative. A Wayson or 

Wright’s stain can be used to diagnose plague, and when it is 

applied to a sample that contains Y. pestis, it tends to collect in 

either end of the Y. pestis structure, revealing the characteristic 

“safety pin” appearance of the bacterium (fig. 1).
2 Plague

Box 1 The Three Plague Pandemics

The first plague pandemic struck in the sixth century A.D., around the year 540 in the Byzantine Empire, and is 

known as the Plague of Justinian, after the reigning emperor. The pandemic probably originated in Ethiopia or 

Egypt and spread to Constantinople when ships loaded with grain also carried rats and their fleas. Primarily of the 

bubonic form, the disease spread through the Mediterranean region into Europe, Central and Southern Asia, and 

Arabia (see map). It has been estimated that 50–60 percent of the population in the region died between the years 

541–700 (Perry and Fetherston, 1997; Gasper and Watson, 2001).

1

1

2

2

2

3 3

3

3

3

3

2 2

2

1

1

1 1

2

3

3

Justinian plague (5th–7th century)

Black Death (13th–15th century)

Modern plague (1870s onwards)

EXPLANATION

Routes followed by the three plague pandemic waves, labeled 1, 2, and 3. Circled numbers indicate the regions 

thought to be the origins of these pandemic waves. (Achtman and others, 1999)

The second pandemic is perhaps the most notorious. Known as 

the Black Death, the Great Pestilence, or the Great Plague, it 

arose in the 14th century and was responsible for killing onequarter to one-third of Europe’s population (Perry and Fetherston, 

1997; Poland and others, 1994; Butler, 1998; Gage, 1998; Gasper 

and Watson, 2001). This pandemic probably began in Central 

Asia and spread through trade routes into the Crimea. It arrived 

in the port city of Caffa, in present day Ukraine, on the Black Sea 

in 1346. Caffa was an Italian walled city established by Genoa 

as a port for its merchant ships. In 1345, Mongol troops besieged 

the city, but they were severely hampered in their attack by an 

epidemic of plague. A witness described soldiers dying “as soon 

as the signs of disease appeared on their bodies: swellings in 

the armpit or groin caused by coagulating humors, followed by a 

putrid fever;” almost all soldiers “fell victim to sudden death after 

contracting this pestilential disease, as if struck by a lethal arrow 

which raised a tumor on their bodies.” (Wheelis, 2002) 

In an example of biological warfare, the survivors catapulted the 

corpses into the city of Caffa, thereby infecting the inhabitants 

of the city, whether by direct contact with infectious material or 

flea bites (Wheelis, 2002). The plague spread from Caffa and the 

Crimea into the Mediterranean region on rat-infested ships, and 

subsequently throughout Europe by land travel. 

Outbreaks of plague, involving both the bubonic and pneumonic 

forms, continued sporadically throughout Europe for the next 

300 years. One of the last major outbreaks was the Great Plague 

of London in 1665. Despite lack of knowledge about the cause 

and mode of transmission of plague, preventive measures were 

instituted to control these outbreaks and limit the spread of the 

disease. Forty-day restrictions on travel were imposed to decrease 

the spread of the disease, giving rise to the term “quarantine.” 

Special protective clothing was developed for doctors to limit 

transmission. Because of its high mortality rate, plague had a lasting impact on European society. With the deaths of one-quarter 

to one-third of the population, most of who were peasants, the 
The Three Plague Pandemics 3

Bird’s beak mask

Black overcoat

Wide-brimmed hat

Cane

Red glass eyepieces

The Plague Doctor

1. The wide-brimmed black hat identified the wearer as a doctor 

and may have acted as a shield from infection.

2. Plague doctors wore bird’s beak masks to draw plague, which 

was believed to be spread by birds at the time, away from the 

patient. The beak of the mask was filled with fragrant herbs to 

overcome the foul air associated with the spread of plague, as 

well as to mask the stenches of corpses and ruptured buboes.

3. Red glass eyepieces were attached to the mask to protect the 

wearer from evil.

4. Plague doctors wore a long black overcoat tucked around the 

mask to avoid exposing any skin. It was often coated with suet 

or wax to make it resistant to sputum and other bodily fluids.

5. A wooden cane was used to direct other people nearby to move 

patients or themselves. It may also have been used to examine 

the patient.

6. Leather breeches were worn under the overcoat to protect the 

legs and groin from infection.

social structure changed dramatically, weakening the feudal 

system (Gage, 1998; Gasper and Watson, 2001). Culture, art, 

religion, and politics also changed because of plague (Stenseth 

and others, 2008).

The third pandemic, also known as the Modern Pandemic 

(Gage, 1998), began in China in 1855 in the south-central province of Yunnan and spread to Hong Kong and Canton by 1894, 

aided by movements of troops and refugees from a rebellion 

(Pollitzer, 1954; Perry and Fetherston, 1997). Steamships and 

trains spread the disease worldwide, reaching Bombay, India 

in 1896 and San Francisco in 1901 (see map). Many cities in 

Africa, Australia, Europe, Asia, North and South America were 

affected. Y. pestis disappeared from some areas, including 

Australia, after failing to become successfully established in 

maintenance cycles involving local fleas and animals (Poland 

and others, 1994).

Recently, the role of Yersinia pestis as the cause of the Black 

Death has been disputed (Duncan and Scott, 2005; Cohn, 2002; 

Twigg, 1984; Gilbert and others, 2004). Opponents believe 

other agents, such as anthrax (Twigg, 1984), a virus (Duncan 

and Scott, 2005), or typhus (Shrewsbury, 1970), were responsible for the pandemic based on what they see as significant 

inconsistencies in the epidemiology of the Black Death and 

present-day plague. They argue that the speed with which the 

disease spread across Europe, the lack of suitable rat species 

to spread the disease, the extremely high mortality, the long 

incubation period as evidenced by the successful 40-day quarantine period, and the directly infectious nature of the disease 

suggest the cause was an infectious agent other than Y. pestis

(Duncan and Scott, 2005; Twigg, 1995). Others have pointed out 

that plague caused by Y. pestis can have different symptoms 

and that the organism may have evolved since the Black Death 

in such a way that current epidemics do not exactly replicate 

what was recorded during the Middle Ages (Wood and others, 2003; Stenseth and others, 2008; Raoult and Drancourt, 

2002). Vectors other than fleas, such as lice, may have had a 

more prominent role in the transmission of ancient outbreaks 

of plague than is seen today (Drancourt and others, 2006; 

Houhamdi and others, 2006). In addition, the deoxyribonucleic 

acid (DNA) of Y. pestis has been identified by polymerase chain 

reaction (PCR) in the teeth of victims of the Black Death, leading researchers to conclude that these people suffered from 

septicemic plague, which probably caused their deaths (Drancourt and others, 1998; Raoult and others, 2000; Drancourt 

and Raoult, 2002). The anthrax bacillus was not found (Raoult 

and others, 2000). Y. pestis DNA has also been detected in the 

teeth (Drancourt and others, 2007; Drancourt and others, 2004) 

and skeletons (Wiechmann and Grupe, 2005) of victims of the 

Plague of Justinian. Subsequent testing of some of these bone 

and teeth samples by the use of a rapid diagnostic test (see 

Obtaining a Diagnosis) confirmed the presence of Y. pestis in 

skeletal remains (Bianucci and others, 2008; 2009). 
4 Plague

Table 1. Timeline of important early events since the discovery of Y. pestis.

[Sources: Zietz and Dunkelberg, 2004; Gage, 1998; Butler, 1998; Olsen, 1981]

Year Event

1894 Alexandre Yersin and Shibasaburo Kitasato independently find the plague bacterium in samples from humans and 

rats during the Hong Kong epidemic. Yersin is later credited with the discovery, because he correctly identified 

it as being Gram negative, whereas Kitasato described it as Gram positive. The organism is named Bacterium 

pestis.

1895 Wild rodents are confirmed as hosts of plague when wild marmots in Mongolia and Russia are found infected.

1896 Waldemar Haffkine develops a partially effective heat-killed vaccine and uses it during an outbreak in Bombay.

1897 Yersin proposes a link between rats and plague.

1897 Masanori Ogata in Taiwan suggests transmission of plague by flea bites.

1898 Paul-Louis Simond proposes the role of the flea in transmission of plague.

1900 The causative agent is renamed Bacillus pestis.

1900 The first human case in San Francisco occurs.

1902 The bacterium is found in commensal rats in the United States.

1905 William Glenn Liston provides proof of fleas as the vector of plague.

1908 Infected California ground squirrels are found in California.

1914 Charles James Martin and William Bacot describe transmission of Y. pestis by rat fleas, Xenopsylla cheopis, with 

blocked foreguts.

1923 The causative agent is renamed Pasteurella pestis.

1927 Ricardo Jorge identified wild living rodents as the reservoir of sylvatic plague.

1934 Ground squirrels and wood rats in United States are found to be infected in area outside of original focus. The first 

human case in the United States outside of California occurs and is associated with wild rodents.

1945 Insecticides (DDT) are used for first time to control an outbreak in Peru.

1946 Streptomycin is used for first time to treat cases of human plague and is shown to reduce the number of deaths 

caused by plague dramatically.

1963 Pierre Mollaret demonstrates experimental infection of animals in contact with contaminated soil.

1966–72 Killed vaccine used in soldiers in Vietnam is effective in preventing the bubonic form.

1970 The causative agent is renamed Yersinia pestis.

Figure 1. Wright’s stain of Y. pestis in a blood smear showing its 

characteristic bipolar “safety pin” appearance. (Photo courtesy of 

the Centers for Disease Control and Prevention.)

Originally classified in the family Pasteurellaceae, 

Y. pestis is now considered to be a member of the family 

Enterobacteriaceae, based on similarities to Escherichia coli

bacteria determined by studies of hereditary information 

contained in deoxyribonucleic acids (DNA) (table 2). The 

Enterobacteriacae are a large family of bacteria, and the 

Greek word “enteron” for “intestine,” used in the family 

name, indicates the location in the body where some of the 

bacteria in the family are found. Although the genus Yersinia

has 11 species, only 3 are pathogenic to humans: Y. pestis, 

Y. pseudotuberculosis, and Y. enterocolitica (table 3). Another 

species, Y. ruckeri, causes enteric redmouth disease in fish. 

Unlike Y. pseudotuberculosis, Y. enterocolictica, and other 

enterobacteria such as Salmonella typhi and E. coli, which 

are transmitted when feces are ingested in contaminated food 

and water (the fecal-oral route), Y. pestis has evolved the 

capability of transmission by arthropods, and it establishes 

infections in blood and lymphoid tissues.
Causative Agent 5

Table 2. Taxonomy of Yersinia species

Classification Designation

Kingdom Eubacteria

Phylum Proteobacteria

Class Gammaproteobacteria

Order Enterobacteriales

Family Enterobacteriaceae

Genus Yersinia

Species pestis, enterocolitica, pseudotuberculosis, 

frederiksenii, kristensenii, ruckeri, 

mollaretii, bercovieri, rohdei, aldovae, 

intermedia

Table 3. Yersinia species pathogenic to humans.

Species Disease Transmission route

Y. pestis Plague Flea bites, direct 

contact, airborne.

Y. enterocolitica Yersiniosis Foodborne.

Y. pseudotuberculosis Pseudoappendicitis Foodborne.

closely related to Y. pseudotuberculosis, a bacterium that can 

cause symptoms similar to those of tuberculosis in animals 

but mimics appendicitis in humans. The two kinds of bacteria 

have identical 16S rRNAs (Trebesius and others, 1998); 

they probably became separate species at least 12,000 years 

ago (Achtman and others, 1999, 2004; Achtman and Wagner, 

Genetic analysis has determined that Y. pestis is very 

2008). Y. pestis differs from Y. pseudotuberculosis by having 

two unique plasmids, pFra and pPla, that contain genes

enabling Y. pestis to infect and spread within mammalian 

hosts and produce a transmissible infection in fleas (table 4). 

Different genes are expressed in the corresponding host, 

often according to the body temperature of the host, 98.6°F 

in mammals and 82.4°F or lower in fleas. The products of 

these genes enable the bacteria to survive and multiply in 

both mammals and fleas, thereby completing its life cycle. 

In particular, several genes located on the Y. pestis plasmids 

enable the bacteria to evade the host immune response as it 

establishes infection (Box 2).

Although fleas were considered to play a key role in the 

transmission of Y. pestis early in the history of plague (Simond, 

1898), a mechanism was only first described in 1914, and it 

involved formation of a blockage in the flea’s foregut (fig. 2) 

that would lead to regurgitation of infectious bacteria and 

transmission to the host (Bacot and Martin, 1914). Foregut 

blockage is reported to occur readily in the Oriental rat flea 

(Xenopsylla cheopis), considered the primary vector of plague 

in Asia and Africa (Poland and Barnes, 1979). However, not 

all species of fleas develop foregut blockage from Y. pestis, yet 

many are still able to transmit Y. pestis (Box 3). Some species, 

such as one of the ground squirrel fleas (Oropsylla montana), 

rarely develop foregut blockage, although they act as the 

primary vectors of Y. pestis to humans and certain ground 

squirrels in North America (Craven and others, 1993).

An alternative mechanism, called early-phase 

transmission (Eisen and others, 2006), does not involve 

blockage of the flea foregut. Although earlier studies had 

also documented transmission by fleas without foregut 

blockage, this mechanism was not initially considered 

important (Burroughs, 1947). Upon laboratory infection, a 

ground squirrel flea, O. montana, was able to immediately 

transmit the bacteria after becoming infected in the absence 

of blockage formation (Eisen and others, 2006). This early 

transmission of the bacteria, within 1–4 days of infection, by 

O. montana is in sharp contrast to fleas that transmit plague 

only after the formation of foregut blockage, which does not 

typically occur until at least 5 days after infection. The rat 

flea, X. cheopis, typically develops foregut blockage even 

later, 12–16 days after infection. In early-phase transmission, 

the bacterial loads decline over time, thus leading to 

decreased transmission efficiency, the rate at which a 

vector is able to transmit an infection to a host, expressed 

as the number of infections per the number of attempts. 

Subsequent blood meals on infected hosts, however, can 

boost the levels of bacteria in the fleas, such as the ground 

squirrel flea O. montana, to allow potential transmission after 

each subsequent infectious blood meal. Fleas with foregut 

blockage, on the other hand, will starve and generally die 

within 5 days of becoming blocked, limiting the period of 

transmission. Early-phase transmission by fleas without 

foregut blockage may explain the rapid spread of plague 

during epizootics in prairie dogs or other rodents (Eisen and 

others, 2006). Early-phase transmission by the human flea 

(Pulex irritans), which rarely develops foregut blockage, 

could also explain the rapid spread of plague in the Middle 

Ages in areas of Europe where the rat flea X. cheopis was 

rare (Eisen and others, 2006). Subsequent work revealed that 

the rat flea X. cheopis can transmit Y. pestis as early as 1 day 

after infection without foregut blockage, and it transmits 

Y. pestis in the early phase with the efficiency of blocked fleas 

(Eisen, Wilder, and others, 2007). In addition, the rat flea 

X. cheopis maintains a constant transmission efficiency until 

the formation of foregut blockage (Eisen, Wilder, and others, 

2007).

Y. pestis has historically been classified into three 

biovars or subspecies, Antiqua, Mediaevalis, and Orientalis, 

according to biochemical characteristics (Devignat, 1951). 

Recently, a fourth biovar, Microtus, has been proposed 

(Zhou and others, 2004). Strains of Y. pestis, traditionally 

classified in the Mediaevalis biovar and obtained from 

plague foci associated with voles, rodents of the genus 

Microtus, in China, have been shown to have biochemical 

characteristics that distinguish them from other Mediaevalis 

strains (table 5). In addition, strains of Y. pestis within 

the Microtus biovar, although they are lethal to voles and 

other rodents, are not virulent in larger mammals including 

humans (Zhou and others, 2004). Other atypical strains of 

Y. pestis have been designated as Pestoides, and they differ 

from the other biovars biochemically (Anisimov and others, 

2004). Molecular analyses of Y. pestis strains from around 
Table 4. Virulence determinants of 

Mouth 

parts

Hindgut

Midgut/stomach Proventriculus

Esophagus

A.

C.

B.

Mouth 

parts

Hindgut

Midgut/stomach Proventriculus

Esophagus

A.

C.

B.

Figure 2. X. cheopis fleas immediately after feeding. 

A, uninfected flea and B, infected, blocked flea. The blockage of the 

proventriculus prevents ingested blood from reaching the stomach and 

interferes with the valvular function of the proventriculus. As the starving 

flea repeatedly tries to feed, blood sucked from the mammalian host 

fills the esophagus, mixes with bacilli, and is regurgitated back into the 

mammalian host. Eventually, the blocked flea dies from starvation and 

dehydration. (Photos by permission; Hinnebusch, 2010) C, diagram of the 

digestive tract of the flea.

Y. pestis.

[DNA, deoxyribonucleic acid. Temperatures are in degrees Celsius. Information obtained from Perry and Fetherston, 1997; Hinnebusch, 2005]

Virulence determinant Action on the host

Genes specifically required to infect the vertebrate host:

F1 capsular antigen (F1 or 

Caf1)

At 37°C, Y. pestis bacteria form large gel-like capsules to resist becoming engulfed and digested by the host’s 

white blood cells. This reaction does not develop in fleas.

Plasminogen activator (Pla 

protease)

At 37°C, destruction of blood clots acting to trap the bacteria enables Y. pestis to spread from the site of the 

fleabite systemically.

Yersinia outer proteins 

(Yops)

Activities that kill host cells and prevent host white blood cells from attacking the bacteria are required for 

virulence and growth within the liver and spleen. Suppression of the host’s immune system permits 

survival of Y. pestis within naïve host white blood cells during early infection.

V antigen (LcrV) Immunosuppressive activity stimulates host production of IL–10, a potent anti-inflammatory protein that 

leads to prevention of the formation of a mass of immune cells to surround the bacteria and allows Y. pestis

to maintain growth in visceral organs.

Yersiniabactin siderophore 

system (Ybt)

Part of the iron uptake system, it enables Y. pestis to acquire iron in blood, where availability is limited by the 

host’s iron-binding molecules.

pH 6 antigen Its fibrillar structure may facilitate entry of Y. pestis into naïve white blood cells and the delivery of Yops proteins into other white blood cells. These proteins help to prevent the host from developing an 

inflammatory response to infection.

Rough lipopolysaccharides 

(LPS)

A major component of the outer membrane of Y. pestis, they enable the bacteria to resist being destroyed by 

proteins found in the host’s blood.

Endotoxin A structural component of the bacteria that is released mainly when the bacteria are broken down; it causes 

signs and symptoms associated with septic shock.

Genes required to produce a transmissible infection in the flea:

Murine toxin (ymt) When first discovered, it was associated with the ability of the bacteria to cause disease in mammals, 

particularly mice (Ajl and others, 1955). Later, it was shown to enhance survival of Y. pestis, and other 

Gram-negative bacteria, in the flea midgut. It is not required for morbidity or mortality in mammals.

Pigmentation locus (Pgm) Named for the appearance of densely pigmented colonies of Y. pestis grown at 28°C on media containing 

hemin or Congo red dye, which was correlated with virulence. This region of DNA contains genes 

required for the formation of blockage in the flea proventriculus and the genes involved in iron uptake.

Hemin storage locus (Hms) It enables Y. pestis to synthesize a biofilm facilitating infection of the surface of spines in the proventriculus 

of the flea. This colonization allows Y. pestis to resist being swept into the midgut by the pumping action 

of the proventriculus and eventually block the proventriculus, thus permitting fleaborne transmission.

6 Plague
Stealth and Deception by Yersinia pestis 7

Box 2 Stealth and Deception by Yersinia pestis

 “...the symptoms of plague...reflect the combination of stealth and deception effects, which cause the 

host to ignore the mortal danger of ongoing systemic invasion.” (Brubaker, 2006)

Unlike other pathogens that do not kill their hosts to ensure transmission, Y. pestis is a highly virulent organism 

that can rapidly cause lethal disease in susceptible mammals. Y. pestis must reach high levels of bacteremia 

in the host, as much as 10 to 100 million organisms per milliliter of blood, for biting fleas to become infected 

(Hinnebusch, 2005). At the same time, Y. pestis must evade the host immune response to achieve these levels. 

Specific virulence factors (proteins which enable the bacteria to invade the host, elude the host immune 

response, and cause disease) allow Y. pestis to do just that.

As infected fleas feed, Y. pestis bacteria are deposited into the skin of the host. As few as 10 organisms can 

infect a susceptible host (Perry and Fetherston, 1997). The bacteria invade the lymphatic system and travel to 

regional lymph nodes, where severe inflammation results in the formation of buboes. This inflammatory response 

by the host may delay spread and multiplication of Y. pestis, but it generally does not block the disease process 

(Brubaker, 2006).

The bacteria then invade other host tissues. One virulence factor (Pla protease) facilitates the spread of Y. pestis

from the site of the fleabite by breaking down components of blood clots that act to trap the bacteria (Sodeinde 

and others, 1992), while another (F1 protein) blocks phagocytosis (the ingestion and destruction) of bacteria by 

white blood cells during the initial spread of bacteria through host tissues (Friedlander and others, 1995). With 

this increased tissue invasiveness, the bacteria spread systemically and colonize visceral organs, especially 

the liver and spleen. Within these organs, other virulence factors act to prevent the host immune system from 

responding to the infection.

A major contributor to the stealth of Y. pestis is its use of several other virulence factors that inhibit or prevent 

the host from mounting a defense against disease. Y. pestis uses a needlelike appendage to target a host’s white 

blood cells (Gendrin and others, 2010; Marketon and others, 2005). Using the needlelike appendage, Y. pestis 

injects proteins (Yops) directly into the host white blood cells. These proteins act to destroy immune functions of 

the host and prevent it from developing an inflammatory response that would inhibit or prevent further growth of 

the bacteria (Brubaker, 2006; Perry and Fetherston, 1997). Y. pestis can also inject into the host a different protein 

(V protein) that prevents the host from producing two of its own proteins that would be used to stimulate the formation of a mass of immune cells to surround the bacteria and prevent its growth (Nedialkov and others, 1997). In 

the case of plague, the host cells get a false message that tissue damage is under control, when, in fact, Y. pestis

bacteria are rapidly taking over visceral organs, particularly the liver and spleen, leading to loss of function.

Eventually, as organs are destroyed, Y. pestis bacteria spill out into the bloodstream, causing septicemia. The 

structure of the outer membrane of Y. pestis confers some protection to the bacteria. The rough outer membrane 

allows the bacteria to resist destruction by proteins found in the host’s blood (Porat and others, 1995). After the 

eventual death of the host from septicemia, infected fleas leave the carcass in search of new hosts for feeding. 

In this manner, the transmission cycle of Y. pestis is completed when these new hosts become infected.
8 Plague

Box 3 Fleaborne Transmission of Y. pestis

Day 0: Infection of the Flea

Fleas become infected by ingesting Y. pestis when they feed on a host mammal with at least 1 million bacteria 

per milliliter of blood (Engelthaler and others, 2000; Lorange and others, 2005).

Days 1–4: Early-Phase Transmission from 

Flea to Mammal

•	 Some species of fleas are able to transmit Y. pestis to a new 

mammal host as soon as 3 hours after becoming infected by 

what is now termed “early-phase transmission” (Eisen and 

others, 2006; Burroughs, 1947). Although the mechanism of 

this form of transmission is currently undetermined, mechanical transmission—that is, the bacteria do not invade the 

tissues of the flea or multiply—is unlikely because Y. pestis is 

unable to survive on the mouthparts of fleas for longer than 3 

hours (Bibikova, 1977).

•	 The location of the bacteria within the flea’s digestive tract is 

associated with the ability of the flea to transmit the infection 

to a host; esophageal infections are more readily transmitted than hindgut infections (Eisen and others, 2009; Eisen, 

Enscore, and others, 2007; Wilder, Eisen, Bearden, Montenieri, 

Gage, and Antolin, 2008; Wilder, Eisen, Bearden, Montenieri, 

and others, 2008).

•	 Early-phase transmission of Y. pestis to mammals continues 

in some fleas up to 4 days after they become infected (Eisen 

and others, 2006; Eisen, Wilder, and others, 2007; Eisen, 

Lowell, and others, 2007; Eisen, Holmes, and others, 2008; 

Eisen, Borchert, and others, 2008; Wilder, Eisen, Bearden, 

Montenieri, Gage, and Antolin, 2008; Wilder, Eisen, Bearden, 

Montenieri, and others, 2008). During this time, if the flea 

feeds on an uninfected host, the bacteria within the flea’s 

digestive tract may be pushed further into its gut, leading to 

decreased infection transmission efficiency (Eisen, Lowell, and 

others 2007; Wilder, Eisen, Bearden, Montenieri, Gage, and 

Antolin, 2008; Wilder, Eisen, Bearden, Montenieri, and others, 

2008).

•	 Some flea species, such as the cat flea (Ctenocephalides felis), 

rapidly eliminate Y. pestis in their feces making them poor 

transmitters (Eisen, Borchert, and others, 2008). In other fleas, 

Y. pestis multiplies within the digestive tract of the flea and 

forms dense clumps that are too big to pass into the hindgut.

Day 5 and Later: Transmission from Fleas with 

Blocked Foreguts to Mammals

•	 In some flea species, clusters of Y. pestis accumulate in the 

midgut and gradually extend into the proventriculus. The bacteria 

produce a biofilm to adhere to the surface of the spines lining the 

proventriculus, thus enabling them to resist being pumped into 

the midgut by the proventriculus (Jarrett, 2004; Hinnebusch and 

others, 2008).

•	 Between 3 and 9 days after the flea feeds on an infected host, the 

flea’s proventriculus becomes blocked by the mass of bacilli that 

may extend into the esophagus. This blockage prevents ingested 

blood from reaching the flea’s stomach and interferes with the 

valvular function of the proventriculus. Complete blockage of the 

proventriculus is not necessary for transmission of the bacteria 

from fleas to mammals; fleas with only partial obstruction can still 

transmit the bacteria.

•	 As the starving flea repeatedly tries to feed, blood sucked from 

the mammalian host fills the esophagus, mixes with bacilli, and is 

regurgitated back into the mammalian host. As many as 11,000 to 

24,000 bacilli may be regurgitated by the flea (Burroughs, 1947). 

Eventually, the blocked flea dies from starvation and dehydration, 

usually within 5 days (Burroughs, 1947).

Flea species that rarely develop foregut blockage, such as the ground 

squirrel flea O. montana, may continue to transmit the bacteria for long 

periods of time, especially after ingesting blood from additional infected 

hosts (Eisen, Lowell, and others, 2007).

For the rat flea X. cheopis, which can transmit Y. pestis both in the 

early-phase and after becoming blocked with equal efficiency, the period 

of potential transmission may be more than 1 month (Eisen, Wilder, and 

others, 2007; Engelthaler and others, 2000). Biofilm-induced blockages, 

or partial blockages, in fleas could be important for the maintenance of 

Y. pestis infections in fleas, allowing fleas to act as reservoirs of infection between transmission seasons (Gage and Kosoy, 2005; Vetter and 

others, 2010).
Fleaborne Transmission of Y. pestis 9

Transmission from Mammals to Fleas

•	 In a mammal, Y. pestis bacilli travel from the site of the flea bite to 

the regional lymph nodes, where they multiply rapidly and cause the 

formation of a bubo (swollen lymph node).

•	 The infection spreads into the bloodstream, and bacilli spread to the 

liver, spleen, and other organs, where they continue to multiply. The 

infection may progress to septicemic and pneumonic plague.

•	 High levels of bacilli in the blood increase the chances of infecting 

fleas that feed on the infected mammal. When the mammal dies, 

resident fleas depart to search for other hosts, including humans, 

thereby spreading the disease.

Plague infected male flea 28 days after feeding on an inoculated mouse. 

Photo from the Centers for Disease Control and Prevention (CDC). 
10 Plague

the world have further subdivided the biovars and Pestoides 

into eight populations of Y. pestis (Achtman and others, 

2004). However, these molecular groupings do not directly 

correspond to the biochemical characteristics associated with 

biovars, and different strains within a molecular grouping may 

have different biochemical characteristics. Historically, the 

original three biovars have been linked to the three plague 

pandemics. Recent evidence based on genotyping of strains 

indicates that the Orientalis biovar was involved in all three 

pandemics (Drancourt and others, 2004; Drancourt and 

others, 2007). Analysis of rRNA gene restriction patterns 

has divided strains of Y. pestis into 16 ribotypes (Guiyoule 

and others, 1994). Ribotypes B and O made up the majority 

of the strains studied and were associated with the biovars 

responsible for the three pandemics.

Geographic Distribution

Plague probably originated in Central Asia and has since 

spread worldwide. Natural foci of plague, “geographical areas 

in which reservoir and vector species coexist and in which 

the infection is common” (Biggins and Kosoy, 2001), occur 

on all inhabited continents, except Australia, in areas where 

populations of suitable rodent reservoirs and flea vectors are 

found (fig. 3). Appropriate climatic and landscape conditions 

must be present. In general, natural foci of plague occur 

between parallels 55°N and 40°S in tropical and subtropical

regions as well as warmer parts of temperate latitudes. 

Tropical foci tend to be in cooler, relatively dry upland areas, 

for example, the central highlands in Vietnam and Madagascar 

and mountains of Tanzania. Areas such as semideserts, 

steppes, savannas, and prairies have low annual precipitation 

or prolonged dry seasons that limit the growth of thick woody 

vegetation, and plague is found in these areas because they 

are suitable habitat for rodents and their fleas. Plague is not 

found in desert areas, which have few or no rodents and are 

excessively hot and dry, or in large forested areas. Natural foci 

of plague in animals are found in North and South America, 

Africa, Asia, and limited areas of southeastern Europe, and 

they cover only 6–7 percent of Earth’s dry land (Anisimov 

and others, 2004). In the United States, sylvatic plague is 

enzootic west of the 100th meridian (Cully and others, 2000), 

the historical boundary between the humid east and the dry 

west, where irrigation is required for successful agriculture 

(fig. 4). It is unclear why plague is nearly absent east of this 

line, because susceptible rodent species and flea vectors are 

present east of the line as well as west (Cully and Williams, 

2001; Cully and others, 2006). Plague is most prevalent in 

the southwest (New Mexico, Arizona, Colorado, Utah) and 

the Pacific region (California, Oregon, Nevada). Species of 

rodents, and their fleas, within these foci vary according to 

geographic region (table 6).

During the period 1954–2003, plague in humans was 

reported from 39 countries (Tikhomirov, 1999; World Health 

Organization, 2004). In the 1970s, most cases of plague 

in humans were reported from Asia, particularly Vietnam. 

However, more recently most cases occur in African countries 

(fig. 5), especially Madagascar. In the United States, human 

cases are most frequent in the Southwest (New Mexico, 

Arizona, Colorado, Utah) and the Pacific regions (California, 

Oregon, Nevada).

Table 5. Classification systems of Y. pestis strains.

[In the classification of bacteria, strains with sufficiently distinct characteristics (for example, chemical or molecular) are biovars, or considered a subspecies 

of a taxonomic species (Devignat, 1951). A ribotype is a grouping of bacteria within a species based on similarities in ribosomal ribonucleic acid (rRNA) 

(Guiyoule and others, 1994). Blank cells indicate there is no corresponding biovar or ribotype for the molecular grouping.]

Molecular 

grouping1

Biochemical characteristics

Biovar

Biochemical characteristics

Corresponding 

ribotypes Ability to 

reduce nitrate

Ability to 

ferment 

glycerol

Ability to 

reduce nitrate

Ability to 

ferment 

glycerol

Ability to 

ferment 

arabinose2

1.ANT Yes Yes Antiqua Yes Yes Yes F to O

2.ANT Varies Yes Antiqua Yes Yes Yes F to O

2.MED No Varies Mediaevalis No Yes Yes O and P

1.ORI Yes Varies Orientalis Yes No Yes A to G

0.PE4 No Yes Microtus3 No Yes No

0.PE1 No Yes

0.PE2 Yes Yes

0.PE3 Yes Yes

1

Achtman and others, 2004.

2, 3

 Zhou and others, 2004
Probable sylvatic foci

Countries reporting plague, 1970–2004

EXPLANATION

Figure 3. Global distribution and natural 

foci of plague. Natural foci of plague have 

become established in local rodent and 

flea populations on all inhabited continents 

except Australia. Sylvatic plague can act 

as a source of infection for humans. Since 

1954, plague in humans has been reported 

from more than 35 countries. (From http://

www.cdc.gov/ncidod/dvbid/plague/

resources/plagueFactSheet.pdf)

OREGON

CALIFORNIA

NEVADA

WASHINGTON

IDAHO

UTAH

ARIZONA

MONTANA

WYOMING

COLORADO

NEW MEXICO

NORTH

DAKOTA

SOUTH 

DAKOTA

NEBRASKA

KANSAS

OKLAHOMA

TEXAS

0 100 200 MILES

0 100 200 KILOMETERS

EXPLANATION

Counties with plague-positive

animal or flea samples

One human case randomly 

placed in county of exposure 

100°

100°

110°

110°

120°

120°

Geographic Distribution 11

Figure 4. Areas in the United States 

where plague is found in animals, fleas, and 

humans. In the United States, most counties 

with plague-positive animal or flea samples 

(1970–2009; shaded areas) are located west 

of the 100th meridian, where the infection 

is enzootic. Cases of plague in humans 

(1970–2007; dots) are most prevalent in the 

southwest and Pacific regions. (Map based 

on information from Ken Gage, CDC)
1954

0

1,000

2,000

Year

3,000

4,000

5,000

6,000

7,000

Africa

Americas

Asia

World

Number of cases

1957

1960

1963

1966

1969

1972

1975

1978

1981

1984

1987

1990

1993

1996

1999

2002

2005

2008

EXPLANATION

12 Plague

Figure 5. Human cases of plague, by region, 1954–2010. In the 1970s, most human cases of plague 

were reported from countries in Asia, particularly Vietnam. More recently, most cases are in African 

countries, especially Madagascar. War and political turmoil in Asian and African countries disrupted 

sanitation and medical services, contributing to the increased risk of transmission of Y. pestis from 

rodents to humans. (Data from World Health Organization, 2010; World Health Organization, 2000; 

World Health Organization, www.who.ing/whosis/whostat/2011/en/index.html)
Table 6. Major wild rodent hosts and flea vectors of natural plague foci.—Continued[Sources: Gage, 1998; Gratz, 1999]

Region

Wild rodent hosts Primary vectors

Common name Scientific name Common name 

North America

Southwest Prairie dog Cynomys species Prairie dog fleas Oropsy

Ground squirrel Spermophilus variegatus Ground squirrel fleas Oropsy

Spermophilus spilosoma Thrassi

Spermophilus lateralis Opisocr

Antelope ground squirrel Ammospermophilus leucurus OropsyChipmunk Tamias species HoplopWood rat Neotoma albigula Chipmunk fleas Eumolp

Neotoma mexicana Wood rat fleas Orchop

Deer mouse Peromyscus maniculatus Orchop

Peromyscus species Mouse fleas Malara

Aetheca Orchop

Pacific Coast Ground squirrel Spermophilus beecheyi Prairie dog fleas Oropsy

Spermophilus beldingi Ground squirrel fleas Oropsy

Spermophilus lateralis Thrassi

Chipmunk Tamias species OpisocrWood rat Neotoma fuscipes Oropsy

Neotoma cinerea Hoplop

Deer mouse Peromyscus maniculatus Chipmunk fleas Eumolp

Vole Microtus californicus Wood rat fleas Orchop

Microtus montanus Orchop

Mouse fleas Malara

Aetheca Orchop

West Ground squirrel Spermophilus elegans Prairie dog fleas Oropsy

Spermophilus armatus Ground squirrel fleas Oropsy

Spermophilus townsendi Thrassi

Prairie dog Cynomys species OpisocrFox squirrel Sciurus niger Oropsy

Hoplop
Table 6. Major wild rodent hosts and flea vectors of natural plague foci.—Continued [Sources: Gage, 1998; Gratz, 1999] Region Wild rodent hosts Primary vectors Common name Scientific name Common name 

North America (continued)

West (continued) Chipmunk fleas Eumolp

Wood rat fleas Orchop

Orchop

Mouse fleas Malara

Aetheca Orchop

South America

Commensal rat Rattus rattus Rat fleas Xenopsy

Rice rat Oryzomys species Wild rodent fleas Polygen

Cotton rat Sigmodon species PleochaSouth American field mouse Akodon speciesCane mouse Zygodontomys species

Bolomys lasiurusOryzomys species

Leaf-eared mouse Phyllotis species

Tree squirrel Sciurus stramineus

Wild cavies and domestic guinea 

pig

Cavia speciesGalea species

Africa

Multimammate mouse Mastomys species Gerbil fleas Xenopsy

Unstriped grass mouse Arvicanthis species Rat fleas Xenopsy

Swamp rat Otomys species XenopsyGerbil Tatera species Wild rodent fleas Dinopsy

Desmodillus speciesGerbillus species

Spring hare Pedetes capensisGroove-toothed cheek rat Pelomys species
Table 6. Major wild rodent hosts and flea vectors of natural plague foci.—Continued[Sources: Gage, 1998; Gratz, 1999]

Region

Wild rodent hosts Primary vectors

Common name Scientific name Common name 

Eurasia

Central Asia Gerbil Meriones species Gerbil fleas Xenopsy

Rhombomys opimus Nosopsy

Marmot Marmota species Coptop

Ground squirrel Spermophilus species Marmot fleas Oropsy

Voles Microtus species Rhadin

Eothenomys species Citellop

Callops

Ground squirrel fleas Citellop

Neopsy

Vole fleas Amphip

Rhadin

Vietnam and Myanmar1 Black rat Rattus rattus Rat fleas Xenopsy

Polynesian rat Rattus exulans XenopsyNorway rat Rattus norvegicusBandicoot rat Bandicota indicaForest rat Rattus nitidusHouse shrew2 Suncus murinus

India Indian gerbil Tatera indica Gerbil fleas Xenopsy

Rat Rattus species NosopsyBandicoot rat Bandicota bengalensis

Bandicota indica

Metad Millardia meltadaIndian field mouse Mus boodugaSpiny field mouse Mus platythrixIndian bush rat Golunda elliotiPalm squirrel Funambulus species

Java Polynesian rat Rattus exulans Rat fleas Xenopsy

Black rat Rattus rattus StivaliuWhite-bellied mountain rat Rattus niviventerMalayan wood rat Rattus tiomanicusHouse shrew2 Suncus murinus

1Hosts in Vietnam and Myanmar are generally considered to be commensal rather than sylvatic.2Nonrodent species, member of the Insectivora order. 
16 Plague

Patterns and Trends

Since the 1950s, two peaks have been noted in the 

number of human plague cases in the world (fig. 5). The 

first peak was during the 1960s and 1970s, primarily in 

Asia, especially Vietnam (Tikhomirov, 1999). The second 

peak began in the 1980s in African countries, particularly 

Mozambique and Madagascar (Tikhomirov, 1999). During 

both time periods, war and political unrest in these countries 

contributed to increased poverty among inhabitants and the 

disruption of sanitation and medical services, including rodent 

and flea control and surveillance, which increased the risk 

of transmission of Y. pestis from wild rodents to commensal 

rodents to humans.

Complacency can also contribute to decreased 

surveillance and control programs in areas where human 

cases of plague have not occurred for many years. Several 

epidemics of plague have occurred in regions unaffected 

by plague for extended periods of time (table 7), indicating 

reactivation of established foci or importation of Y. pestis from 

outside sources. In several of these outbreaks, natural events, 

such as drought, flooding, and earthquakes, contributed to the 

spread of plague into urban areas. In the Madagascan city of 

Mahajanga, plague was probably reintroduced when infected 

rats were inadvertently transported from the highlands, where 

plague is endemic, to urban markets. Y. pestis infection 

then spread to Asian house shrews, the dominant small 

mammal, and to people (Chanteau and others, 1998; World 

Health Organization, 2006). The infection is now enzootic 

among shrews and has caused several subsequent outbreaks 

among people in the city (World Health Organization, 2006). 

Although the source of the 2003 epidemic in Algeria is 

unknown, Y. pestis was detected 2 years later in rat fleas, X. 

cheopis, from rodents captured in and around houses, and 

it suggests the establishment of an enzootic cycle (Bitam 

and others, 2006). The potential for spread of the disease 

internationally from the port cities involved in these 

reemergent epidemics highlights the importance of timely and 

vigilant surveillance of Y. pestis infections in rodents and fleas 

for controlling its reoccurrence.

New strains of Y. pestis have also recently been 

discovered. In Madagascar, all strains of Y. pestis were 

classified as the Orientalis biovar, ribotype B until 1982 

(Guiyoule and others, 1997). Three other ribotypes, Q, R, 

and T, were obtained from human cases and rodents in the 

highlands of the country in 1982, 1983, and 1994, respectively 

(Guiyoule and others, 1997). The strain obtained in the 

outbreak of pneumonic plague in India in 1994 was identified 

as a new ribotype, designated S (Panda and others, 1996). The 

recent appearance of new biotypes may indicate evolution 

of Y. pestis over time. Whether or not these changes confer 

selective advantages to the bacteria remains unanswered.

In the United States, Y. pestis was first introduced on the 

west coast in San Francisco. A retrospective study of spatially 

and temporally unique plague cases sought to elucidate the 

route and speed at which plague initially spread eastward 

(Adjemian and others, 2007). Among cases of plague in 

humans, domestic animals, and wildlife from 1900 to 2005, 

cases representing the initial occurrence of plague in a specific 

region were found up until 1966. Thus, plague spread more 

Table 7. Examples of the reemergence of human plague.

[Period of silence refers to time since last outbreak of plague]

Date Country Period of 

silence

Number of 

deaths per 

number of cases

Contributing factors Reference

1989 Botswana 38 years 12/173 Increased rain led to rich harvest and an 

abundant rodent population that moved into 

villages.

Tikhmorov, 1999.

1991 Madagascar More than 

60 years

Not stated/41 Outbreaks were associated with Asiatic 

shrews.

Chanteau and others, 1998.

1994 India About 

30 years

54/876 Earthquake and flooding disrupted rat 

populations, causing increased rat contact 

with humans.

Tikhmorov, 1999.

1994 Mozambique More than 

15 years

3/226 Drought drove wild rodents into a village and 

increased hunting of rodents by villagers.

Barreto and others, 1995.

1996 Zambia More than 

30 years

26/319 Outbreak linked to flooding that drove rats 

into villages.

Tikhomorov, 1999; World Health 

Organization, 1997.

1997 Jordan More than 

80 years

Not stated/12 Outbreak of pharyngeal plague caused by 

consumption of camel meat.

Arbaji and others, 2005.

2003 Algeria More than 

50 years

1/18 Outbreak occurred at harvest time when rats 

entered a village searching for grain.

Bertherat and others, 2007.

2009 Libya 25 years 1/12 Outbreak from undetermined source in 

seminomadic community.

Tarantola and others, 2009.
Patterns and Trends 17

than 1,395 miles (mi) in just over 40 years, travelling at 

a speed of 28–54 mi per year, but it has not continued its 

spread beyond the 103rd meridian in the subsequent 60 

years (fig. 6) (Adjemian and others, 2007). It has become 

endemic in the southwest as well as in the Pacific region 

(fig. 4).

Plague has recently developed in new areas of the 

United States. In the 1990s, surveillance for Y. pestis

infection or exposure in rodents and carnivores revealed 

the spread of the bacteria to Montana, Nebraska, and 

North Dakota, states that were previously thought to 

be free of plague (Centers for Disease Control and 

Prevention, 1994). Plague was also identified in two fox 

squirrels and a roof rat in Dallas, Tex. in 1993, a site far 

removed from the known plague foci in western Texas, 

although animals that had developed antibodies against 

Y. pestis (were seropositive) have occasionally been 

observed east of the 100th meridian in that state (Centers 

for Disease Control and Prevention, 1994). A die-off of 

black-tailed prairie dogs from plague occurred in 1997 in 

Kansas, an area where plague had not been documented 

since 1950 (Cully and others, 2000). A plague epizootic 

also broke out recently in 2008 among prairie dogs in 

South Dakota (U.S. Geological Survey, 2008a), a site 

where plague had not previously been documented. 

Similarly, the eastward spread of human plague can be 

seen from 1944 through 1993 (fig. 7) (Centers for Disease 

Control and Prevention, 1994; Perry and Fetherston, 

1997). It is unknown if the distribution of plague will 

expand eastward in the future.

0 100 200 MILES

0 100 200 KILOMETERS

EXPLANATION

1920

1930

1940

1945

1950

1965

Predicted waves of plague, by year

1940

1945

1920

1930

1940 1945 1950

1965

1950

Figure 6. Predicted waves of plague movement from the west 

coast of the United States eastward into the Great Plains. 

(Based on Adjemian and others, 2007)

1944−1953 1954−1963 1964−1973

1974−1983 1984−1993

2

2

2

2

1 6

3

1 6

3 1

1

4

4 26

7

3 3

1

1

14

12

33 101

1

2

5

3

3

1

1

1

12

21

10 63

EXPLANATION

Plague cases

No plague cases

Figure 7. The spread of human cases 

of plague in the western United States, 

1944–93. Similar to the expansion of 

sylvatic plague, cases of human plague in 

the United States have spread eastward. 

(From Centers for Disease Control, 1994)
18 Plague

Species Susceptibility

In considering species susceptibility to Y. pestis, it is 

important to differentiate between susceptibility to infection

and susceptibility to disease. In this report, “plague” will be 

used to indicate clinical disease caused by infection with the 

bacteria Y. pestis. 

Human Infections

Humans are extremely susceptible to plague, and most 

cases result from transmission by flea bites. People also can 

become infected when they inhale infectious respiratory 

droplets, eat infected animals, are bitten or scratched by 

infected animals, and come into direct contact with infected 

tissues or fluids (Box 4). Most human cases present as one of 

three main forms: bubonic, septicemic, and pneumonic plague. 

Other less common forms include pharyngeal and meningeal

plague (Box 5). With appropriate and timely antibiotic 

treatment, most people usually recover. Forty to 60 percent of 

untreated cases of bubonic plague are likely to be fatal (Poland 

and Barnes, 1979), whereas untreated cases of septicemic and 

pneumonic plague are nearly 100 percent fatal and result from 

septic shock. In the United States, the average fatality rate is 

about 14 percent (Craven and others, 1993).

Wild and Laboratory Animal Infections

More than 200 species of mammals can be infected by 

Y. pestis (table 8), although not all species are susceptible to 

clinical disease (table 9). Susceptibility to morbidity and 

mortality caused by Y. pestis varies among both individuals 

and populations of a species.

Rodents

Rodents are the major group of animals infected by 

Y. pestis, and some species may act as reservoir or amplifying 

hosts for the organism. Some species, such as gerbils, 

marmots, deer mice, and California voles, demonstrate varied 

responses to infection by Y. pestis; some individuals suffer 

high bacteremias and death, while others survive after only 

mild illness. Within a population of hosts, certain individuals 

may be susceptible to disease while others are more resistant. 

Populations of the same species in different geographical 

locations may differ dramatically in their susceptibility to 

disease. Resistance within a population may be a result of 

genetic selection due to past exposure to plague. Northern 

grasshopper mice from Colorado, where plague is present, 

were much more resistant to disease than mice of the same 

species in a plague-free area of Oklahoma (Thomas and others, 

1988). Deer mice and California voles also show differences 

in susceptibility to plague in different populations (Quan and 

Kartman, 1956, 1962).

Other rodent hosts are more uniformly susceptible to 

plague and undergo dramatic die-offs during epizootics of 

plague. These hosts are often referred to as “amplifying hosts.” 

Colonies of prairie dogs, such as black-tailed prairie dogs and 

Gunnison’s prairie dogs, may be completely decimated by 

plague (Lechleitner and others, 1968; Rayor, 1985; Cully and 

others, 1997; Pauli and others, 2006). Other highly susceptible 

species include California ground squirrels and rock squirrels, 

although mortality rates appear to be lower in these species 

than in prairie dogs (Meyer and others, 1943; Lang, 2004). 

Occasional epizootics also occur in other prairie dog species, 

chipmunks, wood rats, ground squirrels, deer mice, and voles.

Among laboratory animals, guinea pigs are susceptible to 

disease, but they survive longer than mice (Poland and Barnes, 

1979; Gratz, 1999).

Shrews

The Asian house shrew, an insectivore, is susceptible to 

infection by Y. pestis, although it is moderately resistant to 

disease; none of 1,757 shrews examined for plague showed 

any gross abnormalities despite the presence of Y. pestis in 

their spleens (Marshall and others, 1967). In addition, serology 

revealed antibodies indicating prior exposure to Y. pestis

(Marshall and others, 1967). In Mahajanga, Madagascar, 

43 percent of house shrews caught after a plague epidemic 

in 1995 had antibodies against Y. pestis (Boisier and others, 

2002). Other species of shrews, such as tree shrews, have 

also been found to be seropositive against Y. pestis (Suntsov 

and others, 1997). In plague-endemic areas of North America, 

shrews are rarely captured and tested for evidence of Y. pestis

infection.

Table 8. Animals naturally infected with Y. pestis.

[Data represent relative numbers of species in each group and 

may not include all species ever found to have been infected. 

Data from Poland and Barnes, 1979; Pollitzer, 1954]

Group Number of species

Rodents More than 200

Carnivores 20

Lagomorphs 14

Insectivores 4

Artiodactyla 3

Primates 2

Marsupials 2
Species Susceptibility 19

Lagomorphs

At least 14 species of lagomorphs have been shown to 

be naturally infected by Y. pestis (Pollitzer, 1954). Rabbits and 

hares are extremely susceptible to disease caused by Y. pestis. 

During rodent epizootics, they may suffer high mortality. 

Pikas, in central Asia, are also important reservoir hosts for 

Y. pestis (Gage and Kosoy, 2005).

Ferrets and Polecats

Ferrets and polecats vary in their susceptibility to 

plague. Domestic ferrets, like many other carnivores, are 

fairly resistant; experimental infection of domestic ferrets by 

subcutaneous injection of Y. pestis failed to produce clinical 

signs in eight of eight ferrets (Williams and others, 1991). 

Animals that received higher doses of inocula developed 

antibodies against Y. pestis, whereas those that received low 

doses did not develop antibodies, or “seroconvert.” Similarly, 

two Siberian polecats also did not show clinical signs after 

experimental infection with low doses of Y. pestis; these 

animals did not seroconvert (Williams and others, 1991). In 

another experiment, 22 polecats were placed in pens where 

black-footed ferrets had either died of plague or were missing 

and presumed to be dead in underground burrows (Godbey 

and others, 2006). Only three polecats developed antibodies 

against Y. pestis; one of these animals died of plague. One 

animal that removed a plague-infected ferret carcass from its 

burrow did not develop antibodies to Y. pestis, a perhaps not 

surprising result considering very large numbers of plague 

bacteria typically appear to be required to infect animals by 

oral exposure (Butler and others, 1982).

In contrast, black-footed ferrets appear to be highly 

susceptible to plague. The first case was reported in 1993 in a 

captive animal in Wyoming after it was accidentally exposed 

to captive white-tailed prairie dogs (Williams and others, 

1994). Approximately 3–4 days later, the ferret died of plague. 

It was presumed to have been orally exposed, possibly by 

ingestion of an infected rodent. In a similar incident in 1995, 

30 captive ferrets were accidentally fed pieces of prairie dog 

meat infected with Y. pestis or meat that had come into contact 

with infected pieces (Godbey and others, 2006). Of these 

animals, 27 (90 percent) either died or went missing and were 

presumed to be dead in underground burrows; all the dead 

ferrets tested positive for plague and showed clinical signs, 

such as internal hemorrhages and congested lungs, consistent 

with plague (Godbey and others, 2006).

A subsequent study found that Siberian polecats are 

susceptible to plague following higher doses of Y. pestis in 

experimental infections; the mortality rate was 88 percent 

(or 29 of 33) (Castle and others, 2001). Only 6 of 33 polecats 

developed antibodies against Y. pestis and of these, 4 survived. 

Three of the surviving animals were reexposed to Y. pestis

by ingestion of an infected mouse, and they did not develop 

clinical disease, suggesting at least partial protection by the 

antibodies (Castle and others, 2001). Thus, polecats are 

susceptible to disease caused by Y. pestis, but the outcome 

of infection depends on the dose of Y. pestis and the route of 

exposure (flea bite or oral).

Other members of the weasel family (mustelids), such 

as badgers, striped and spotted skunks, pine marten, and 

long-tailed weasels, appear to be resistant to plague. However, 

they can be infected as demonstrated by the presence of 

antibodies against Y. pestis (Salkeld and Stapp, 2006; Dyer 

and Huffman, 1999; Hopkins and Gresbrink, 1982; Messick 

and others, 1983).

Carnivores

Wild carnivores produce antibodies to Y. pestis after 

infection but, with the exception of felids, rarely show 

clinical signs (Poland and others, 1994; Gage, 1998; Gasper 

and Watson, 2001) (table 10). Wild felids, on the other 

hand, are highly susceptible to plague. Among Canada lynx 

reintroduced to Colorado, 6 of 52 lynx that died showed 

evidence of infection by Y. pestis; 5 of these lynx died as a 

direct result of plague pneumonia (Wild and others, 2006). 

A bobcat that was found dead in Texas died of acute plague 

before it could develop antibodies (Tabor and Thomas, 1986). 

Surveillance studies for plague in wild felids have found some 

animals that developed antibodies against Y. pestis antigens, 

so not all infections are fatal (Paul-Murphy and others, 1994; 

Biek and others, 2002; Wild and others, 2006; Bevins and 

others, 2009).

Wild carnivores have also been implicated in the 

transmission of plague to humans in several cases. Coyote, 

gray fox, badger, bobcats, and mountain lions were reportedly 

the source of infection in humans who had direct contact with 

infected tissues or who inhaled infectious droplets (Poland 

and others, 1973; von Reyn, Barnes, Weber, Quan, and Dean, 

1976; Centers for Disease Control and Prevention, 1984; Gage 

and others, 1994; Wong and others, 2009).
20 Plague

Box 4 Routes of Transmission of Y. pestis to Humans Associated with Infected Animals

Most human cases of plague are transmitted from a bite from an infected flea. However, humans have 

become infected in other ways from contact with wild and domestic animals. In the United States, almost 

20 percent of human cases with identified sources result from contact with infected animals (Gage, 1998; 

Gage and others, 2000).

Transmission by Direct Contact with 

Infected Animals

Humans have become infected with Y. pestis after contact with 

the tissues of infected animals. In most cases, infection was 

transmitted through a break in the skin of the person. A 19-yearold male developed bubonic plague after skinning an infected 

bobcat (Poland and others, 1973); he had many hangnails and 

raw areas around his fingers, allowing penetration by Y. pestis. 

His friends, who also participated in the skinning, did not have 

any skin abrasions and did not become infected despite contact 

with the blood and tissues of the bobcat (Poland and others, 

1973). In another case, a man became infected after cutting 

his arm while skinning an infected bobcat (Centers for Disease 

Control and Prevention, 1984). Similarly, a young boy became infected with Y. pestis after skinning an infected coyote (von Reyn, 

Barnes, Weber, Quan, and Dean, 1976). The boy had a cut on his 

arm and a damaged nail bed that provided a route of entry for 

the bacteria. His friend, who had no cuts or abrasions, did not 

become infected. In all of these cases, Y. pestis was obtained 

from the wild animals, confirming their infection.

Numerous cases of bubonic plague in humans have resulted from 

contact with the tissues of infected rabbits, which are especially 

susceptible to plague. Most rabbit-associated cases occur in 

the winter, during hunting season when people become infected 

while skinning the rabbits and handling the tissues (Centers for 

Disease Control and Prevention, 2006; von Reyn, Barnes, Weber, 

and Hodgin, 1976; Centers for Disease Control and Prevention, 

1984; Kartman, 1960; Link, 1950). Buboes most often form in 

the armpit or elbow regions. In the United States, cottontail 

rabbits are most often involved in these cases; wild hares are 

associated with cases in South Africa (von Reyn, Barnes, Weber, 

and Hodgin, 1976). In China and Mongolia, bubonic plague is 

commonly seen in marmot hunters who skin infected animals 

(Tikhomirov, 1999; Kool, 2005).

Cases of plague in people in South American countries have 

been associated with guinea pigs, a common food (Ruiz, 2001; 

Gabastou and others, 2000). In those cases, plague may have 

been transmitted by direct contact of infectious tissues, or fluid, 

or both with broken skin when an infected guinea pig was killed, 

skinned, and cooked (Ruiz, 2001; Gabastou and others, 2000). 

Similarly, people may become infected when slaughtering and 

preparing domestic livestock, such as camels, goats, and sheep, 

for food (Christie and others, 1980).

A child may have become infected with Y. pestis either by direct 

contact with an infected rabbit or by being licked around the face 

and mouth by a dog who had handled an infected rabbit (Kartman, 

1960). The presence of cervical buboes implicated the mucous 

membranes of the mouth as the route of infection. However, 

a case-control study of dog-associated risk factors for human 

plague did not show any evidence supporting transmission by 

direct contact with an infected dog (Gould and others, 2008).

Transmission by Ingestion of an Infected 

Animal

Ingestion of meat from infected animals can cause pharyngeal 

plague in humans. In the Middle East, outbreaks of pharyngeal 

plague have occurred in people who ate raw camel meat (Arbaji 

and others, 2005; Bin Saeed and others, 2005; Christie and others, 

1980). In Jordan, 12 people developed pharyngeal plague with 

enlarged lymph nodes in the neck and fever after eating meat 

from the same infected camel; 10 of the people had eaten the 

meat raw (Arbaji and others, 2005). In Saudi Arabia, four people 

in a group who ate raw liver from an infected camel contracted 

pharyngeal plague (Bin Saeed and others, 2005). A fifth case of 

plague associated with this sick camel was that of a man who cut 

his arm while slaughtering the animal. None of the 31 people who 

ate the liver or meat cooked contracted pharyngeal plague (Bin 

Saeed and others, 2005). In addition to the risk of becoming infected with Y. pestis by direct contact with infected meat, people 

who eat raw or undercooked meat from infected animals increase 

their risk of developing plague. An experimental study showed 

that thorough cooking of ground beef inoculated with Y. pestis

would effectively decrease the probability and severity of disease 

in people who might eat it (Porto-Fett and others, 2009).
Routes of Transmission of Y. pestis to Humans Associated with Infected Animals 21

People may also become infected with Y. pestis by ingesting infected fleas during grooming activities (Bin Saeed 

and others, 2005; Conrad and others, 1968; Pollitzer, 1954; 

McGovern and others, 1997); members of some native South 

American cultures catch fleas and lice and crush them with 

their teeth.

Transmission by Inhalation of Infectious 

Droplets from an Infected Animal

Y. pestis can be transmitted by inhalation of infectious 

droplets and cause primary pneumonic plague. Since the 

1970s, numerous people have contracted pneumonic plague 

as a result of transmission from infected domestic cats 

(Gage and others, 2000; Centers for Disease Control and 

Prevention, 1994, 1992; Doll and others, 1994; Werner and 

others, 1984). The first wild carnivore-associated case of 

primary pneumonic plague was in 2007 in a wildlife biologist 

at Grand Canyon National Park, Ariz. (Wong and others, 

2009). The biologist performed a necropsy examination of 

a dead mountain lion with his bare hands and, presumably, 

without protective gear, such as a respirator or coveralls. Y. pestis

was most likely transmitted when the biologist inhaled infectious 

droplets that had become aerosolized during the necropsy. After 

developing fever, chills, and cough with bloody sputum, the biologist died 1 week after the necropsy. Tissue samples taken from 

the mountain lion’s liver and the lymph nodes below its jaw were 

positive for Y. pestis by polymerase chain reaction (PCR) analysis.

Probable modes of transmission in cases of plague in humans in the United States, 1970–95.

[Probable modes of transmission were identified for 294 of the 342 cases. Data from Gage, 1998]

Mode of transmission

Percentage 

of identified 

cases

Comment

Flea bite 79 Most of the people were probably exposed to infectious 

fleas from wild rodents, particularly rock squirrels and 

ground squirrels.

Direct contact with infected animals 19 Most of these people were hunters, trappers, and pet 

owners, and they were exposed to plague through 

contact with wild rabbits, domestic cats, wild 

carnivores, prairie dogs, and an Abert’s squirrel.

Inhalation 2 Most of these people were cat owners or veterinary staff 

who were exposed to cats with pneumonic plague.

Commensal rats 0 No cases of human plague associated with commensal 

rats have occurred in the United States since the 

1920s.

Human-to-human 0 The last case of human-to-human transmission of plague 

in the United States was in 1924.
Box 5 Forms of Plague in Humans

Bubonic Plague

Bubonic plague is the most common and well-known form of the 

disease. It most often results from the bite of an infected flea, but 

can also be contracted by exposure of open wounds to infective 

materials. Within 2 to 6 days after exposure to Y. pestis, patients 

develop symptoms of fever, headache, chills, muscle pain, and 

fatigue. Patients may also experience nausea, vomiting, and 

diarrhea. Lymph nodes near the site of exposure become swollen 

and extremely painful and are known as buboes, derived from 

“boubon,” the Greek word for groin. Most often, buboes develop 

in the groin area, but they can also occur in the lymph nodes in 

the armpits and neck, depending on the site of the flea bite or 

other exposure. In a study of pediatric cases, 70 percent of the 

children had buboes in the groin, whereas 17 percent had buboes 

in the neck, and 13 percent had buboes in the armpits (Mann and 

others, 1982). Antibiotic treatment of bubonic plague reduces the 

case fatality rate from 60 percent to less than 5 percent. Without 

treatment, the disease progresses rapidly, and the bacteria enter 

the bloodstream and cause secondary plague septicemia.

Septicemic Plague

Plague septicemia can be either primary or secondary to bubonic 

plague. Primary septicemic plague results when bacteria are 

transmitted directly into the bloodstream; patients have positive 

blood cultures without obvious swollen lymph nodes. Patients 

experience fever, chills, headache, malaise, and gastrointestinal 

symptoms similar to septicemias caused by other bacterial infections. Cell and tissue death, or necrosis, and gangrene of the extremities may develop as a result of blood clots. Without antibiotic 

treatment, the mortality rate ranges from 30 to 50 percent. 

Septicemic plague may progress to secondary pneumonic plague 

as the bacteria spread through the body to the lungs.

Pneumonic Plague

Primary pneumonic plague is the most uncommon form of plague 

in humans, accounting for only 2 percent of cases between 

1970–95 in the United States (Gage, 1998). Between 1–3 days 

after infection, patients develop a flulike illness that progresses 

rapidly to pneumonia with coughing, chest pain, and bloody sputum. Pneumonic plague, primary or secondary, has a high mortality 

rate, even with treatment, due to respiratory failure and shock. 

When antibiotic therapy is delayed more than 24 hours after the 

onset of symptoms, pneumonic plague is always fatal.

Patients become infected by inhaling bacteria found in respiratory 

droplets from infected individuals or animals. Person-to-person 

transmission of the disease requires prolonged, close contact at a 

distance of less than 6.5–10 feet with a person in the final stages 

of disease, when coughing produces profuse bloody sputum 

(Kool, 2005). In the United States, the last case of human-to-human 

transmission of pneumonic plague was in 1924. Instead, most 

cases of primary pneumonic plague in people result from contact 

with infected domestic cats, by inhalation of infectious droplets 

from a coughing or sneezing cat. In 2007, a wildlife biologist died 

of primary pneumonic plague after performing a necropsy exam on 

an infected mountain lion (Wong and others, 2009).

Pestis Minor

Pestis minor is a rare form of bubonic plague, most often seen in 

areas where plague is established. Symptoms of fever, inflamed 

lymph nodes, headache, and fatigue resolve without treatment 

within 1 week. This form is sometimes called “ambulatory” 

plague, because patients are generally not sick enough to need to 

lie down (Pollitzer, 1954).

Swollen, ruptured inguinal lymph node or 

bubo.

Gangrene.

22 Plague

Pneumonic plague.
Meningeal Plague

Acute meningitis caused by Y. pestis infection occurs rarely in 

0.2–7.0 percent of cases (Becker and others, 1987). Most cases 

seem to be in children and are secondary to bubonic plague; 

buboes in the armpits or neck may increase the risk of developing 

plague meningitis (Pollitzer, 1954; Martin and others, 1967; Becker 

and others, 1987; Landsborough and Tunnell, 1947). Patients 

develop symptoms of acute meningitis including fever, headache, 

a painfully stiff neck, delirium, and confusion 9–17 days after 

the onset of illness (Martin and others, 1967; Becker and others, 

1987; Landsborough and Tunnell, 1947; Pollitzer, 1954). Most 

patients have received some form of antibiotic treatment prior to 

developing meningitis, indicating that ineffective therapy due to 

choice of drug, duration, and dosage of treatment, and the onset 

of therapy may be important risk factors for plague meningitis 

(Pollitzer, 1954; Martin and others, 1967; Becker and others, 1987; 

Poland and Dennis, 1999). Y. pestis can spread to the central 

nervous system (CNS) during the intermittent presence of bacteria 

in the blood (Becker and others, 1987; Martin and others, 1967; 

Poland and Dennis, 1999). Commonly used antibiotics, such as 

tetracycline and streptomycin, do not cross the blood-brain barrier; thus, the amounts of antibiotics in the CNS are insufficient 

to inhibit the growth of Y. pestis. Chloramphenicol, which can 

cross the blood-brain barrier, is an effective treatment for plague 

meningitis.

Cutaneous Plague

Skin lesions associated with plague include ulcers or pustules 

at the site of inoculation. The spread of the bacteria in the blood 

may result in hemorrhages and bruising of the skin. Gangrene 

with associated skin manifestations can develop in severe infections and is the source of the name “Black Death.”

Pharyngeal Plague 

Inflammation of the pharynx from plague, or plague pharyngitis, 

can develop after consumption of infected meat or inhalation of 

infectious droplets (Arbaji and others, 2005; Christie and others, 

1980; Pollitzer, 1954; McGovern and others, 1997; Poland and 

Dennis, 1999; Laforce and others, 1971; Bin Saeed and others, 

2005). Large droplets (more than 5 micrometers in size) tend 

to settle in the tonsils or pharynx, causing cervical buboes and 

pharyngitis, whereas smaller particles permeate into the lower 

respiratory tract to cause primary pneumonic plague (Laforce 

and others, 1971). Symptoms of plague pharyngitis include fever, 

infected lymph nodes in the neck or below the jaw, sore throat, 

weakness, and headache, and the symptoms resemble those of 

streptococcal or viral pharyngitis but with more severely painful 

lymph nodes (Poland and Dennis, 1999; McGovern and others, 

1997).

Pharyngeal plague broke out in the Middle East in people who ate 

raw camel meat (Arbaji and others, 2005; Bin Saeed and others, 

2005; Christie and others, 1980). A group of six people in Nepal 

contracted pharyngeal plague when they inhaled infectious droplets from a patient with pneumonic plague (Laforce and others, 

1971). Indians of Ecuador have also developed plague pharyngitis 

as a result of catching and killing fleas and lice with their teeth 

(Pollitzer, 1954; McGovern and others, 1997). Plague pharyngitis 

may progress to pneumonia if infectious material from abscesses 

is aspirated (Arbaji and others, 2005; McGovern and others, 1997; 

Pollitzer, 1954).

All images are from the Center for Disease Control (CDC) with the 

exceptions of pneumonic plague and cutaneous hemorrhages, 

which are from the Center for Biologic Counterterrorism and 

Emerging Disease (CBC-ED).

Cutaneous hemorrhages. Gangrene, causing necrosis of the fingers. Swollen, ulcerated cervical 

lymph node.

Forms of Plague in Humans 23
24 Plague

Table 9. Relative susceptibility of animal groups to infection and disease caused by Y. pestis and roles of animal groups as sources of 

human infection.—Continued

Animal Susceptibility to Source of 

human infection Remarks

Infection Disease

Rodents

Rats Yes High Common Source of infectious fleas in epidemics.

Mice Yes Moderate Sometimes

Ground squirrels Yes High Common Most common source of infectious fleas for isolated cases 

in humans in the United States.

Prairie dogs Yes High Rare Epizootics in prairie dogs cause nearly 100 percent 

mortality.

Marmots Yes High Common Transmission by direct contact with infected tissues of 

marmots is common in hunters.

Guinea pigs Yes High Sometimes Transmission by human contact with or ingestion of 

infected guinea pig tissues.

Lagomorphs

Rabbits, hares Yes High Common Transmission by direct contact with infected tissues of 

rabbits and hares is common in hunters.

Pikas Yes High Rare

Insectivores

Shrews Yes High Common Most common source of infectious fleas in epidemics in 

port cities of Madagascar.

Mustelids

Black-footed ferret Yes High Not documented

Domestic ferret Yes Low Not documented

Polecats Yes Moderate Not documented

Badgers Yes Low Not documented

Skunks Yes Low Not documented

Weasels Yes Low Not documented

Carnivores

Coyote Yes Low Rare One case of transmission to a human by direct contact 

with infected tissues from a coyote.

Domestic dog Yes Low Sometimes Source of infectious fleas to pet owners.

Bobcat Yes High Rare Transmission by direct human contact with infected 

bobcat tissues.
Species Susceptibility 25

Table 9. Relative susceptibility of animal groups to infection and disease caused by Y. pestis and roles of animal groups as sources of 

human infection.—Continued

Animal Susceptibility to Source of 

human infection Remarks

Infection Disease

Carnivores (continued)

Mountain lion Yes High Rare First case of primary pneumonic plague from wildlife in a 

biologist who performed necropsy exam on an infected 

mountain lion carcass in 2007.

Domestic cat Yes High Common Numerous cases of bubonic and primary pneumonic 

plague in humans who had contact with infected cats.

Ungulates

Camel Yes Moderate Sometimes Transmission by direct human contact with or ingestion 

of infected camel tissues.

Goat Yes Moderate Sometimes

Sheep Yes Moderate Sometimes

Swine Yes Low Not documented

Deer Yes Low Not documented

Primates

Nonhuman Yes High Not documented

Humans Yes High Sometimes Pneumonic plague can be transmitted human-to-human.

Other

Birds No No No

Ungulates

Plague is relatively rare in wild ungulates. Deer, in 

general, are probably not highly susceptible to the disease, 

although several cases of fatal plague have been reported in 

mule deer (Edmunds and others, 2008; Thorne and others, 

1987) and in black-tailed deer (Jessup and others, 1989). 

One of the mule deer showed evidence of blood poisoning 

(septicemia), pneumonia, and inflamed lymph nodes 

(lymphadenitis) (Thorne and others, 1987). In three mule deer 

and one black-tailed deer, ocular lesions developed as a result 

of infection with Y. pestis (Edmunds and others, 2008; Jessup 

and others, 1989). The deer appeared to be blind and, in some 

cases, had bulging eyes. Examination of the eyes at necropsy 

showed widespread, severely inflamed tissue and dead tissue 

in both eyes and numerous Y. pestis bacteria (Edmunds and 

others, 2008; Jessup and others, 1989). The bacteria probably 

entered the eyes by the bloodstream.

One human case of plague was acquired from an infected 

pronghorn antelope during butchering (Poland and others, 

1994).

Wild boar can be infected by Y. pestis, as demonstrated 

by the presence of antibodies, but they do not suffer clinical 

disease. The infection is most likely acquired by ingestion of 

an infected rodent or other animal (Nelson and others, 1985).

Antibodies to Y. pestis were found in African buffalo 

(26 of 391 animals tested, or 6.6 percent) within 1 year of 

a plague epizootic among rodents in Zimbabwe Rhodesia 

(Gordon and others, 1979). Elephants (1 of 330 animals 

tested, or 0.3 percent) in the area were also found to be 

seropositive. No seropositive zebras or sable antelopes were 

found, although the numbers sampled were low (15 and 5, 

respectively).
26 Plague

Table 10. Prevalence of antibodies to Y. pestis in blood specimens from carnivores and omnivores in the western 

United States.

[The western United States includes California, Oregon, Arizona, Colorado, New Mexico, Utah, Wyoming, Idaho, Kansas, Texas, 

North Dakota, and South Dakota. These combined data from many studies are listed individually in Salkeld and Stapp, 2006]

Animal

Number of animals with 

Y. pestis antibodies per number of 

animals tested for Y. pestis antibodies

Percentage of tested 

animals with 

Y. pestis antibodies

Coyote 2458/17,403 14

Swift fox 54/117 46

Gray fox 10/81 12

Kit fox 0/1 0

Badger 621/1125 55

Raccoon 58/438 13

Fisher 0/1 0

Long-tailed weasel 19/339 6

American marten 29/91 32

Striped skunk 9/92 10

Spotted skunk 2/2 100

Ringtail cat 6/26 23

Bobcat 142/959 15

Canada lynx 2/39 5

Mountain lion 24/64 38

Black bear 117/523 22

Wild boar 18/23 74
Species Susceptibility 27

Nonhuman Primates

Nonhuman primates are highly susceptible to plague 

and exhibit symptoms similar to those seen in humans (Gage, 

1998).

Birds

Although birds are not susceptible to infection by 

Y. pestis, raptors may spread the organism by carrying 

infected fleas or prey to new areas (Poland and others, 1994).

Domestic Animal Infections

Cats

Domestic cats are highly susceptible to plague, and as 

many as 75 percent die if they are not treated (Eidson and 

others, 1991). Infected cats suffer from bubonic, septicemic, 

and pneumonic forms of plague, and they develop signs 

earlier than humans (Box 6).

Dogs

Domestic dogs are susceptible to infection by Y. pestis, 

although they are relatively resistant to clinical disease. Dogs 

show a brief, self-limiting, nonspecific, feverish illness after 

infection (Orloski and Eidson, 1995; Rust, Cavanaugh, and 

others, 1971). Dogs with plague may occasionally have 

oral lesions or infected lower jaw lymph nodes, or both, 

presumably as a result of ingesting infected rodents or rabbits 

(Orloski and Eidson, 1995). Y. pestis has been obtained from 

the throats of dogs experimentally infected by the oral route 

(Rust, Cavanaugh, and others, 1971); some dogs may briefly 

develop bacteremia, enabling the bacteria to be found in 

blood samples (Rust, Cavanaugh, and others, 1971). Infected 

dogs demonstrate an antibody response within 8 days that can 

last at least 11 months (Rust, Cavanaugh, and others, 1971).

Livestock

Camels, llamas, goats, and sheep are susceptible to 

plague, and they may be infected by fleas, or more rarely 

ticks, or by eating forage contaminated by infected rodents 

(Christie and others, 1980; Fedorov, 1960; Arbaji and others, 

2005). In experimental infections of camels with Y. pestis, 

susceptibility to plague was low; some animals injected 

with high doses of Y. pestis recovered after mild illness 

featuring buboes (Federov, 1960). Individual differences in 

susceptibility to disease were noted among the camels, and 

some animals died after infection. Presumably, more 

camels contract plague during rodent epizootics, when 

they are more frequently exposed to infected rodents 

(Federov, 1960). Camels often bed down for the night in 

soil loosened by rodent burrowing, thereby increasing 

their exposure to rodent fleas (Federov, 1960). Llamas, 

another camelid species, have been found infected with 

plague in the United States, and at least one llama in 

New Mexico apparently died of the disease (Centers for 

Disease Control and Prevention, unpublished data).

Domestic pigs have been experimentally infected 

with Y. pestis by ingestion of mice dead from plague 

(Marshall and others, 1972). All seven pigs in this study 

developed high levels of antibody against Y. pestis, 

indicating infection, but none developed clinical disease.

Horses and donkeys appear to be resistant to 

infection with Y. pestis.

Vector Infections

Fleas are the primary vector for the transmission 

of Y. pestis among rodents. Numerous genera and 

species of fleas have been demonstrated to be competent 

vectors, although their efficiency of transmission varies 

(table 6). The human flea (Pulex irritans) can also 

transmit Y. pestis (Blanc and Baltazard, 1941a; Gratz, 

1999). At least two other arthropod groups have been 

found to transmit Y. pestis under experimental conditions, 

although neither has been shown to be important vectors 

under natural conditions.

The human body louse (Pediculus humanus 

corporis) has been shown experimentally to transmit 

plague (Houhamdi and others, 2006; Ayyadurai and 

others, 2010). Lice became infected with Y. pestis after 

feeding on rabbits whose blood contained bacteria. 

Y. pestis multiplied within the lice and were excreted in 

the lice feces. Infected lice were then able to infect naïve 

rabbits, completing the transmission cycle. Body lice 

were also able to transmit Y. pestis to guinea pigs (Blanc 

and Baltazard, 1941b). The human head louse (Pediculus 

humanus capitis) has also been shown experimentally to 

transmit Y. pestis (Blanc and Baltazard, 1941b).

Ixodid (Hyalomma asiaticum asiaticum) and argasid

(Ornithodorus tartakovskyi) ticks were successfully used 

to infect camels with Y. pestis experimentally (Federov, 

1960). Other species of Ornithodorus ticks became 

infected with Y. pestis after feeding on infected mice. 

Although they maintained viable Y. pestis up to 1 year 

after the initial infectious blood meal, none of the ticks 

transmitted the infection to mice (Thomas and others, 

1990).
28 Plague

Box 6 Plague and Cats

Cats are the most common pet in the United States (American Veterinary Medical Association, 2007). Thirty-three percent of U.S. households own 

at least 1 cat, totaling 81 million owned cats (Conrad and others, 2005; Robertson, 2008). Unlike most other carnivores, cats are highly susceptible 

to plague and typically present with symptoms similar to those seen in infected humans. This increased susceptibility results from the lack of a 

strong immune response following infection by Y. pestis to block the development of observable signs. The microscopic examination of lesions 

in experimentally infected cats shows that the lesions are remarkably similar to those found in humans, suggesting a comparable mechanism 

of disease development (Watson and others, 2001). Several species of wild cats (lynx, mountain lion, and bobcat) are also known to be highly 

susceptible to plague (Wild and others, 2006; Tabor and Thomas, 1986).

Plague lesions in carnivores following experimental 

challenge with Y. pestis compared with human 

lesions. 

[Watson and others, 2001]

Form of 

plague Humans Cats Other carnivores1

Pneumonic Occurs Occurs Does not occur.

Septicemic Occurs Occurs Does not occur.

Bubonic Occurs Occurs Does not occur.

Death Yes Yes No.

1

Excluding black-footed ferrets, a carnivore that is highly 

susceptible to plague.

Bubonic

53%

Not confirmed

29%

Septicemic

8%

Pneumonic

 10%

Forms of feline plague in New Mexico, 1977–85 (from Eidson and 

others, 1991). The 35 (29 percent) unconfirmed cases did not have 

buboes or pneumonia, and blood cultures were not performed to 

confirm septicemia.

Like humans, domestic cats may suffer from bubonic, septicemic, 

and pneumonic plague, and the bubonic form is the most common. 

Although the disease is probably is transmitted to some cats by 

flea bites, it is thought that most transmission of Y. pestis to cats is 

through ingestion of infected rodents or rabbits. Cats experimentally 

exposed to Y. pestis by ingestion of an infected rodent had inflamed 

cranial and neck lymph nodes, similar to what is seen in naturally 

infected cats (Watson and others, 2001; Rust, Cavanaugh, and others, 

1971). Y. pestis also may invade cuts in the oral mucosa, and then 

spread to the local lymph nodes below the lower jaw and in the neck 

(Eidson and others, 1988; Orloski and Lathrop, 2003). Experimentally 

infected cats have developed severe inflammation of the lymph 

nodes, leading to complete disruption of the normal structure of the 

nodes and the escape of the bacteria into the bloodstream (Watson 

and others, 2001). Once Y. pestis enters the blood, septicemic plague 

occurs, and it may lead to secondary pneumonic plague.

Cats with primary and secondary septicemic plague exhibit severe 

observable signs. Primary pneumonic plague has not been documented in cats (Orloski and Lathrop, 2003), but secondary pneumonic 

plague is the second most common form in cats (Eidson and others, 

1988, 1991). Similar to humans, plague causes high mortality among 

cats; 33–38 percent die (Gage and others, 2000; Eidson and others, 

1991; Gasper and others, 1993), and the greatest risk of death is among 

cats with pneumonic plague (Eidson and others, 1991).

Plague in cats, particularly the pneumonic form, presents a serious 

risk of infection to humans associated with these cats, that is, their 

owners and veterinarians. Prior to 1977, no human case of felineassociated plague had been confirmed in the United States, although 

at least one case was suspected to have been acquired by contact with 

a cat (Kaufmann and others, 1981). From 1977 to 2006, 29 people in 

8 western States (New Mexico, Colorado, California, Arizona, Nevada, 

Oregon, Utah, and Wyoming) were diagnosed with cat-associated 

plague; at least 5 (17 percent) of these patients developed primary 

pneumonic plague (Gage and others, 2000; Hinckley and Gage, written 

communication). Cats with pneumonic plague present the most serious 

risk to humans because of the threat of acquiring primary pneumonic 

plague, the most lethal form, by inhaling infectious droplets from 

a coughing or sneezing cat. From 1993 to 1994, the proportion of 

human cases of primary pneumonic plague was significantly higher 

among cases acquired from cats than among cases from other sources 

(Centers for Disease Control and Prevention, 1994). People can also be 

infected by scratches and bites of infected cats, contacting infectious 
Plague and Cats 29

bodily fluids while examining or caring for sick cats, and burying dead 

cats (Gage and others, 2000). The claws of an infected cat may become 

contaminated with Y. pestis from contact with saliva or abscesses that 

contain the bacteria, either from itself or another cat (Weniger and 

others, 1984). In addition, claws may be contaminated with Y. pestis

from recent contact with an infected rodent (Weniger and others, 

1984), as could easily happen during hunting activities. Cats develop 

significant bacteremias, enabling them to infect fleas, which could, 

in turn, infect people or other animals (Rust, Cavanaugh, and others, 

1971). Although most cases of cat-associated plague have occurred 

in the United States, a few cases have been reported in South Africa 

(Thornton and others, 1975; Simpson, 1905), Argentina (Mall and 

O’Leary, 1945), and Brazil (Mall and O’Leary, 1945).

Cats that hunt and eat wild rodents or rabbits, especially in endemic 

areas, are at greatest risk of developing plague. Other risk factors for 

cats include exposure to dead rodents or rabbits and flea infestation 

(Orloski and Lathrop, 2003; Eidson and others, 1988). Because cat fleas 

(Ctenocephalides felis) are uncommon in plague endemic areas, the 

presence of fleas on a cat in these areas should alert the owner or 

veterinarian to the possibility of plague; the fleas would most likely 

be from a rodent and could potentially transmit plague (Eidson and 

others, 1988; Orloski and Lathrop, 2003). Cats may bring infected 

rodents—and their fleas—back to their homes, presenting a source of 

infection for people who then come into contact with these animals. 

Taking care of cats with plague poses a significant risk of infection 

to the attending veterinarian and staff, as well as their owners. Cat 

caretakers who take precautions, such as using a respirator, gloves, 

and eye protection; disinfecting equipment; and isolating infected 

cats, are taking effective measures to prevent disease transmission 

to themselves, other people, and other animals. Owners who prevent 

their cats from roaming and hunting are helping to prevent the potential transmission of diseases to people and other animals. Additional 

measures include not handling wild rodents and discouraging rodent 

nesting around homes by reducing food and shelter. Insecticides can 

be used to control fleas on pets.

Observable signs in cats with plague.

Form Signs

Bubonic Fever.

Lethargy.

Anorexia.

Enlarged lymph nodes (underneath the 

jaw and in the neck).

Septicemic Vomiting.

Diarrhea.

Elevated heart rate.

Weak pulse.

Respiratory distress.

Disseminated intravascular coagulopathy (DIC), a severe, potentially fatal, 

response to septicemia in which excessive clotting and bleeding develops. 

Pneumonic Fever.

Lethargy.

Anorexia.

Respiratory signs:

 dyspnea or shortness of breath;

 nasal discharge;

 coughing;

 sneezing.

Routes of exposure for cat-associated human plague 

cases in the United States, 1977–98.

[Adapted from Gage and others, 2000]

Type of 

exposure

State Form of 

plague Outcome

Bite or 

scratch

New Mexico Bubonic Recovered.1

New Mexico Bubonic Recovered.

New Mexico Bubonic Recovered.

New Mexico Bubonic Recovered.

New Mexico Bubonic Recovered.

Colorado Bubonic Recovered.1

Oregon Bubonic Recovered.

California Bubonic Recovered.1

Inhalation California Pneumonic Died.

Wyoming Pneumonic Recovered.1

Colorado Pneumonic Recovered.1

Utah Pneumonic Recovered.

Face-to-face 

contact

Colorado Pneumonic Died.

Arizona Bubonic Recovered.

Cared for sick 

cat

Nevada Septicemic Died.

Colorado Bubonic Died.

Colorado Bubonic Recovered.1

Colorado Bubonic Recovered.

New Mexico Bubonic Recovered.

California Bubonic Recovered.

Handled sick 

cat

California Bubonic Died.2

New Mexico Bubonic Recovered.

Arizona Bubonic Recovered.

1

Person infected was a veterinarian or veterinary technician.

2

Person buried a dead cat that had been sick.
30 Plague

Obtaining a Diagnosis

Human cases of plague are classified as suspect, 

presumptive, or confirmed, depending on published 

guidelines of diagnostic criteria (table 11). An initial 

diagnosis of plague can be made based on the symptoms 

and the exposure history of the person or animal. Tissue and 

fluid samples (blood, sputum, lymph node aspirates, and

nasopharyngeal swabs) can be used for visual identification 

of the bacteria as well as culture for definitive diagnosis. 

The organism can be seen in smears of these samples stained 

with Wayson or Giemsa stains or with Gram’s stain. Smears 

can also be analyzed using direct fluorescent antibody 

testing (anti-F1 antibody). Tissues from the liver, spleen, 

bone marrow, and swollen lymph nodes also can be analyzed 

following the death of the host by using autopsy or necropsy 

samples. A definitive diagnosis of plague can be made when 

Y. pestis colonies grow in specimen growth media that have 

been inoculated with tissue or body fluid from the patient. 

Colonies of Y. pestis are slow growing and take about 

2 days to become visible. They are opaque and smooth with 

irregular edges, and they have been described as having a 

“hammered-metal” appearance (Perry and Fetherston, 1997). 

The colonies can be presumptively identified as Y. pestis using 

biochemical tests and fluorescent antibody assays. Conclusive 

identification is made by lysis by a specific bacteriophage. 

Unfortunately, although biochemical testing can be done in 

many microbiological laboratories, the reagents required 

for fluorescent antibody assays and bacteriophage lysis tests 

often are available only in certain public health reference 

laboratories, such as the one at the Centers for Disease Control 

and Prevention (CDC). Polymerase chain reaction (PCR) 

testing, which targets multiple genes within a single sample, 

has also been used for identification of Y. pestis in patient 

and environmental specimens within 3–5 hours (Tomaso and 

others, 2003; Melo and others, 2003; Loïez and others, 2003; 

Woron and others, 2006; Riehm and others, 2011).

Plague can be diagnosed retrospectively by serological 

testing. A fourfold or greater change in the concentration of 

antibodies developed against Y. pestis F1 antigen detected by 

passive hemagglutination testing of paired serum samples 

indicates infection. The enzyme-linked immunosorbent assay 

(ELISA) is also commonly used to detect anti-F1 antibodies in 

serum.

Rapid diagnostic tests to detect F1 antigen in fluid samples drawn from buboes, serum, sputum, and urine are being 

developed (Chanteau and others, 2000; 2003; Ratsitorahina 

and others, 2000). These tests, known as “dipstick assays,” 

have been field tested in Madagascar and are at least as sensitive and specific as the standard ELISA and culture methods 

of diagnosis for humans. The dipstick test has the advantage 

of being able to be used at the bedsides of patients under field 

conditions and of giving a reliable result in 10–15 minutes. 

The dipstick assay can also be used with samples that have 

deteriorated, been contaminated, or that were obtained after 

antibiotic treatment was started in a patient.

Table 11. Standard case definitions of plague. 

[PCR, polymerase chain reaction. World Health Organization, 2006]

Case definition Criteria

Suspect plague Compatible observable signs and

Features consistent with possible exposure or infection by Y. pestis, such as contact with infected 

animals or humans, evidence of flea bites, living in or travelling to area with known plague.

Presumptive plague Meets the definition for a suspect case plus 

Putative new or reemerging focus: At least two of the four following:

Gram-negative or bipolar coccobacilli in stained material from a bubo, blood, sputum;

F1 antigen detection in a patient specimen;

Single blood sample is positive for anti-F1 antibodies without prior infection or vaccination;

PCR detection of Y. pestis in a patient specimen.

Known endemic focus: At least one of the following:

Gram-negative or bipolar coccobacilli in stained material from a bubo, blood, sputum;

Single blood sample is positive for anti-F1 antibodies without prior infection or vaccination;

PCR detection of Y. pestis in a patient specimen.

Confirmed plague Meets the definition for suspect case plus:

Bacteria identified as Y. pestis by physical appearance and two of the four following: phage lysis 

(destruction of the bacteria by specific viruses), F1 antigen detection, PCR, biochemical profile;

Fourfold change in concentration of antibodies to F1 antigen in paired blood samples;

Positive rapid diagnostic test to detect F1 antigen (in endemic areas when no other confirmatory 

test available).
Wild rodents

Sylvatic cycle

Wild rodents Human

Progresses

to

Bubonic plague

Primary 

pneumonic 

plague

Secondary 

pneumonic 

plague

Person-to-person

transmission

Flea Flea

Domestic rodents

Domestic cycle

Domestic rodents

Flea Flea

Disease Ecology 31

Figure 8. The Y. pestis transmission cycle and the progression from bubonic plague to pneumonic plague in 

humans. Y. pestis is transmitted between rodent hosts and flea vectors in two cycles: domestic and sylvatic. 

Humans can become infected by flea bites or by direct contact with infected rodents and other animals. 

Pneumonic plague can be transmitted person-to-person.

Similar rapid dipstick assays are being developed to 

detect anti-F1 antibodies in serum for use in the field as 

alternate tests to ELISA (Thullier and others, 2003; Rajerison 

and others, 2009); these tests are designed for use in humans 

and other mammals.

All human cases of suspected plague should be reported 

to the local public health department which will then notify 

the CDC and, if necessary, the WHO.

Disease Ecology

The basic life cycle of Y. pestis involves transmission 

between rodent hosts and flea vectors (fig. 8). Within 

this cycle, different species of rodents play different, 

although sometimes overlapping, roles depending on their 

susceptibility to disease. The specific rodent hosts involved 

in these cycles vary with geographic location. Rodents that 

suffer high mortality during epizootics present the greatest 

risk for human exposure. Nonrodent hosts are generally 

either susceptible or resistant to disease and can act to spread 

the infection to other locations or animals, although they 

are rarely thought to play a primary role in maintaining the 

disease in nature (table 12). For epidemiologic purposes, the 

cycle of plague can be divided into domestic and sylvatic 

cycles.

Domestic Cycle

The domestic cycle of plague involves the transmission 

of Y. pestis among rodents living with humans and can lead to 

outbreaks of disease in both human and animal populations 

(fig. 9).

Commensal Rats

The traditional epidemiological model of plague, thought 

to be responsible for the three pandemics, involves the 

transmission of Y. pestis among commensal rats by rat fleas 

and the accidental infection of humans by these same vectors. 

The primary species are the roof or black rat and the Norway 

or brown rat along with their fleas (Gage, 1998). 
32 Plague

Table 12. Roles of hosts in maintaining plague in natural populations.

Host type Host characteristics Host examples

Enzootic or maintenance rodent hosts Relatively resistant to disease California vole.

Low mortality Northern grasshopper mouse.

Long multiestrus breeding season with multiple litters Rock squirrel.

Successive multiple litters

High reproductive potential

Short natural life span

High replacement rate of individuals

Vector flea activity year round

Epizootic or amplification rodent hosts Low to moderate resistance to disease Prairie dogs.

High mortality Ground squirrels.

High density population to sustain outbreak

Resistant nonrodent hosts Robust immune response Ungulates (deer).

Illness rare Canids.

Susceptible nonrodent hosts High morbidity and mortality Humans.

Rapid proliferation of Y. pestis Primates.

Bubonic, pneumonic, septicemic plague Felids.

Ferrets.

The movement of these infected rats and their fleas had spread 

plague from central Asia or Africa throughout the world, 

causing the three pandemics. Although the Norway rat has 

largely displaced the black rat in many urban and port areas 

as a result of its aggressive nature, the black rat remains the 

dominant species in most rural areas of developing countries 

and is still, along with the rat flea, X. cheopis, the major 

source of infection in most of the world’s bubonic plague 

outbreaks (Gage, 1998). In the United States, no humans have 

contracted plague as a result of transmission from commensal 

rats since the 1920s (Gage, 1998).

Although commensal rats and their fleas have been 

responsible for causing epidemics (and pandemics) of bubonic 

plague among people, it has been generally accepted that, 

by themselves, rats are not able to maintain plague in an 

area indefinitely. Wild rodents that are relatively resistant 

to plague, as well as fleas that are able to transmit the 

bacteria, are thought to maintain the infection in established 

foci of plague from which commensal rodents can become 

periodically infected (Gage, 1998). However, modeling 

studies of plague in urban rats suggest the disease can also 

be maintained in their populations without introduction from 

another source (Keeling and Gilligan, 2000a, b; Durham and 

Casman, 2010). According to these models, plague circulates 

within rat populations when the proportion of susceptible rats 

is between 25 and 50 percent, and these circumstances pose 

little risk of causing an epidemic among humans (Keeling 

and Gilligan, 2000a, b). When the proportion of susceptible 

rats is greater than 80 percent, an epizootic occurs among the 

rats and human cases may result. Thus, plague may exist in 

an enzootic state within interconnected populations of rats for 

many years, allowing the disease to persist and surface among 

humans without introduction from an external source (Keeling 

and Gilligan, 2000a, b). Another modeling study concluded 

that enzootic plague in rats of a specified area depends on the 

“critical flea index,” a statistical tipping point related to the rat 

population. When flea density of the area is greater than the 

critical flea index, plague will become enzootic in urban rats 

(Durham and Casman, 2010).

Urban Epidemics

Human infections typically follow rodent acquisition of 

plague. When susceptible rodents die from plague, their fleas 

leave the carcasses in search of new hosts. Upon finding a 

new rodent or human host, the infection can be transmitted 

during the blood meal. Urban epidemics are generally 

preceded by numerous rodent deaths, often described as a 

“rat-fall,” because in ancient times dead rats would fall from 

the ceilings of houses, a phenomenon still observed in certain 

villages with thatched roof huts. The disease may be further 

transmitted from person to person by coughing and inhalation 

of infectious droplets, resulting in pneumonic plague.

A modern epidemic involving commensal rodents 

occurred in India in 1994 (Perry and Fetherston, 1997; 

Tikhomirov, 1999). According to one story of the outbreak, 

as a result of an earthquake, storage buildings for grain were 

damaged, attracting wild, plague-infected rodents into villages 

in the Maharashtra State. People complained of increased 
Domestic cats may become 

infected by rodents and can 

pass the infection to 

humans.

People develop bubonic 

plague after being bitten 

by infected fleas.

Infected fleas jump from 

dead rats to people in 

search of bloodmeal.

Numerous dead rodents 

indicate epizootic of plague.

Pneumonic plague 

spreads person-to-person 

through inhalation of 

infectious droplets.

Human ectoparasites, such as fleas 

and lice, may play an important role 

in transmission of Y. pestis in large 

epidemics.

Garbage dumps and 

damaged grain stores 

may attract wild rodents 

that pass the infection 

to domestic rodents.

Domestic dogs may carry 

infected fleas back to 

humans.

Disease Ecology 33

Figure 9. General pathways of plague transmission for the domestic cycle. Rats are the main rodent host in the domestic 

cycle of plague, although shrews are involved in some regions. Human cases are generally preceded by many dead 

rodents or “rat-fall.”
34 Plague

numbers of fleas and “rat fall” as susceptible local rats 

became infected and died. The disease spread to humans, who 

developed bubonic plague, and in some cases, it progressed to 

pneumonic plague. The disease was believed to then be spread 

by persons who traveled during the incubation period of their 

illness to another region, Surat. As the infected person(s) who 

had traveled to Surat became ill, they developed pneumonic 

plague and spread their infection to others. Transmission 

from infected rodents was also possible because previous 

flood damage had led to an increase in rodents attracted to the 

accumulation of garbage. Subsequent panic and flight among 

the residents of the city had the potential to spread the disease 

to a much wider region in India. Fortunately, the epidemic 

was contained with insecticides and prophylactic antibiotics, 

and it resulted in only 54 deaths (Perry and Fetherston, 1997; 

Tikhomirov, 1999). 

In Vietnam, fleas are scarce among wild rodents because 

of the humid tropical climate. Populations of the rat flea 

X. cheopis are able to survive on commensal rodents that 

live indoors where they are sheltered from rain. Because 

the density of rodents and their fleas required to maintain 

plague transmission is found only in human settlements, 

nearly all cases of human plague in Vietnam result from the 

domestic cycle (Suntsov and others, 1997) and are highly 

seasonal, depending on temperature and other climatic factors 

(Cavanaugh and Marshall, 1972). 

In Madagascar, a series of outbreaks of plague among 

humans occurred from 1995 to 1998 in the port city of 

Mahajanga. In the central highlands of Madagascar, plague 

has been present since its introduction by boats from India 

in 1898 (Chanteau and others, 1998), and the black rat is 

the primary reservoir (Boisier and others, 2002). Although 

the black rat is also found in Mahajanga, the Asian house 

shrew is the predominant small mammal in the city and is a 

common host for the rat flea, X. cheopis (Boisier and others, 

2002). Most cases of plague in these outbreaks were a result of 

transmission from commensal rats and shrews in the crowded 

and unsanitary conditions in some areas of the city (Boisier 

and others, 2002).

Human Skin Parasites as Vectors

Although most epidemics are generally blamed 

upon rat fleas, other human parasites that live on the skin 

(ectoparasites) can act as vectors (Blanc and Baltazard, 

1941a, b; Houhamdi and others, 2006; Laforce and others, 

1971). In 1967, bubonic plague broke out in Nepal; the 

disease probably was transmitted by the bites of human 

fleas. There was no evidence of a rodent epizootic, and strict 

quarantine measures resulted in distinct clustering of cases 

within households (Laforce and others, 1971). The human 

flea was also strongly associated with plague frequency 

among humans in specific areas of Tanzania, suggesting a 

role in plague epidemiology (Laudisoit and others, 2007). 

Human ectoparasites, such as fleas and lice, may have played 

a prominent role in the transmission of Y. pestis in large 

epidemics in the past, and they could possibly become a factor 

today in homeless or refugee populations and in bioterrorism 

events (Drancourt and others, 2006; Ayyadurai and others, 

2010). 

Pneumonic Plague

Progression of bubonic plague to the secondary pneumonic 

form can result in person-to-person transmission of the disease. 

Despite the common perception of being highly contagious, 

transmission of pneumonic plague actually requires prolonged, 

close contact of less than 6.4–9.6 feet (ft) (2–3 meters (m)) with 

a person in the final stage of disease who produces profuse 

bloody sputum when coughing (Kool, 2005; Gage, 1998; Perry 

and Fetherston, 1997). Pneumonic plague is transmitted by 

inhalation of infectious respiratory droplets, which cannot travel 

as far as finer aerosols; particles less than 5 micrometers in 

diameter pass into the lungs to cause primary pneumonic plague 

(Laforce and others, 1971).

In the early 1900s, two epidemics of pneumonic plague 

occurred in Manchuria among marmot hunters (Kool, 2005). 

The hunters became infected with Y. pestis after contact 

with infected marmot tissues, and they developed secondary 

pneumonic plague. Subsequent travel in crowded, poorly 

ventilated trains allowed person-to-person transmission, 

resulting in many cases of primary pneumonic plague. The 

epidemics followed the paths of the railroad tracks. Pneumonic 

plague broke out in the United States in 1919 and 1924 in which 

secondary pneumonic plague spread to 12 and 32 other people, 

respectively (Kool, 2005; Gage, 1998). No cases of personto-person transmission of plague in the United States have 

been documented since that time, although cases of primary 

pneumonic plague have occurred as a result of transmission 

from infected cats (domestic and wild), dogs, and laboratory 

accidents (Kool, 2005; Gage, 1998; Gage and others, 2000; 

Burmeister and others, 1962; Wong and others, 2009).

Modern epidemics of pneumonic plague have occurred 

in India (Tikhmorov, 1999; Perry and Fetherston, 1997; Gupta 

2007), the Democratic Republic of Congo (World Health 

Organization, 2005; Bertherat and others, 2011), Uganda 

(Begier and others, 2006), Madagascar (Ratsitorahina and 

others, 2000), and China (World Health Organization, 2009) 

(table 13). These outbreaks demonstrated the risk of spread 

is not as high as often perceived; the infection rate among 

people who had close contact with infected patients was 

only about 8 percent (Ratsitorahina and others, 2000; Begier 

and others, 2006). Modeling studies suggest the spread of 

pneumonic plague can be easily interrupted by public health 

interventions, such as by isolating ill people and treating them 

with antibiotics (Gani and Leach, 2004). In areas with limited 

resources and unsophisticated hospital facilities, transmission 

from infected patients to health care workers can be minimized 

by such simple procedures as examining the patient from 

behind to avoid face-to-face contact, limiting the contact time 

with infected patients, and providing well-ventilated wards 

(Kool, 2005).
Disease Ecology 35

Sylvatic Cycle

The ecology of plague among wild rodents is complex 

and not completely understood. Sylvatic plague, or the 

transmission of Y. pestis among “wild” rodents and their fleas 

(fig. 10), is present worldwide in what are known as natural 

foci of plague. Within these foci, numerous species of rodents 

and their fleas are infected with Y. pestis (fig. 11; table 6). 

Wild rodents can serve as sources of infection for other groups

of wild and domestic animals, as well as commensal rodents 

and humans. In the US, between 1970 and 1991, most cases 

(46 percent) of human plague were associated with ground 

squirrels and their fleas (Craven and others, 1993). Prairie 

dogs and rabbits were also important sources of infection 

(fig. 12).

Classification of the Role of Wild Rodents

Wild rodents have been classified in several ways, 

depending on their roles in the ecology of plague. In one 

system, wild rodents can be characterized as primary or 

secondary hosts of plague (Fenyuk, 1940). Primary hosts 

and their fleas are able to maintain plague in a focus without 

contributions from other hosts; secondary rodent hosts and 

their fleas are unable to maintain plague without the assistance 

of primary hosts, although they may act to disseminate the 

disease (Gage and Kosoy, 2005). Factors affecting whether 

or not a rodent species acts as a primary or secondary 

host include susceptibility to plague, population size and 

distribution, behavior, and habitat (Gage and Kosoy, 2005).

Related to primary and secondary hosts is the 

categorization of foci according to the number of rodent hosts 

involved in the maintenance of plague. Single species of 

rodents maintain plague in monohostal foci; polyhostal foci 

involve more than one species of host. While there are clearly 

polyhostal foci, such as susliks and pikas in Mongolia and 

susliks, gerbils, and jerboas in central Asia (Gage and Kosoy, 

2005), the designation of monohostal foci is more difficult. 

Although it is generally accepted that introduction of Y. pestis

from a wild rodent to commensal rats often precedes an 

epizootic in the rats, plague may be maintained in commensal 

rats in some areas without involvement of other hosts. In 

Madagascar, for example, rats in the rural areas are considered 

to be the primary host in a monohostal focus (Gratz, 1999).

Table 13. Modern outbreaks of pneumonic plague.

Date Country Number of 

cases

Number of 

deaths Comments Source

1994

1997

2002

2004

2005, 

2006

2009

India

Madagascar

India

Uganda

Democratic Republic 

of the Congo 

China

Hundreds

18

16

4

292

12

Numerous

8

4

3

102

3

An epidemic of bubonic plague developed into an 

outbreak of pneumonic plague, causing panic. 

The number of cases was poorly documented.

A healer, who cared for a person with bubonic 

plague that progressed to secondary pneumonic 

plague, developed primary pneumonic plague. 

Person-to-person transmission of plague among 

family members and attendees of funeral 

occurred.

The first documented case was bubonic plague in a 

person who had skinned a wild cat. This person 

developed secondary pneumonic plague and 

passed the infection to relatives.

Two patients with secondary pneumonic plague 

transmitted infection to two caregivers.

Pneumonic plague spread through workers at two 

separate diamond mines and caused mass panic.

The source of the outbreak was a marmot that had 

contact with the dog owned by the primary case.

Tikhomirov, 1999; Perry 

and Fetherston, 1997.

Ratsitorahina and others, 

2000.

Gupta and Sharma, 2007.

Begier and others, 2006.

World Health Organization, 

2005; Bertherat and 

others, 2011.

World Health Organization, 

2009.
Black-footed ferrets can become 

infected by consuming infected 

prairie dogs or by flea bites.

Domestic dogs can 

transport infected fleas 

back to humans.

Direct contact with infected 

animals by hunters and trappers 

provides exposure 

for human infection. Domestic cats can become 

infected by consuming infected 

rodents or by flea bites, and they 

can transmit the infection to 

humans.

Coyotes, swift foxes, 

and other predators can 

transport infected fleas 

long distances.

Y. pestis can survive in 

hibernating animals, causing 

acute disease enabling further 

transmission in the spring.

Grasshopper mice and other 

small rodents may play a role 

in spreading and maintaining 

plague among prairie dogs.

Wild rodents, such as chipmunks, wood rats, and mice, can 

enter domestic areas and present risk of infection to humans.

Y. pestis can survive in the 

soil and may be a source of 

infection for some animals.

Prairie dogs can become infected by flea 

bites, consuming infected carcases, and, 

possibly, inhaling the bacteria.

36 Plague

Figure 10. General pathways of transmission for sylvatic cycle in North America. Many species of wild rodents are 

involved in the sylvatic cycle of plague.
guinea pig mouse

mouse rat

gerbil

rat

gerbil

rat

bandicoot

rat

shrew

wood rat

prairie

 dog chipmunk

rock 

squirrel

ground squirrel

vole mouse

rat tree 

squirrel

rat

marmot

pika

jird

vole

ground squirrel

bandicoot

rat

Africa

India

Viet Nam

China

United States

South America

Disease Ecology 37

Figure 11. Areas where rodents are infected with Y. pestis and serve as sources of infection for other groups 

of wild and domestic animals and humans. The species of rodents involved in natural foci of plague vary by 

geographic region.
Close contact with person 

with pneumonic plague

Contact with infected 

domestic cat

Bites from infected fleas

Contact with tissues 

of infected wildlife

Consumption 

of infected 

animals or fleas

Bioterrorism Laboratory accidents

PLAGUE

38 Plague

Figure 12. Routes of human exposure to Y. pestis. Humans can become infected with Y. pestis from 

many sources.

Enzootic and Epizootic Cycles

In the United States, plague in wild rodents has 

traditionally been divided into two cycles affecting different 

rodent hosts: the enzootic cycle involving maintenance 

hosts and the epizootic cycle involving amplifying hosts 

(Gage and Kosoy, 2005; Poland and others, 1994). Enzootic, 

or maintenance, hosts are characterized as having a 

heterogeneous response to plague; some individuals are 

susceptible while others are resistant. Deer mice and voles 

have typically been classified as being enzootic hosts. 

Epizootic, or amplifying, hosts, on the other hand, are highly 

susceptible to plague and experience sporadic outbreaks 

resulting in high mortality. Prairie dogs, ground squirrels, 

chipmunks, and wood rats have been classified as epizootic 

hosts.

Enzootic Hosts 

Despite the persistence of this classification system, there 

has been little evidence to support the existence of enzootic 

hosts (Gage and Kosoy, 2005; Eisen and Gage, 2009; Stapp 

and others, 2008). A study of small rodents commonly 

occurring on prairie dog colonies found no evidence that 

they acted as long-term enzootic hosts of Y. pestis (Stapp 

and others, 2008). Northern grasshopper mice, thirteen-lined 

ground squirrels, deer mice, and kangaroo rats were trapped 

on prairie dog colonies in Colorado before, during, and after 

epizootics in prairie dogs. Only grasshopper mice were found 

to be seropositive during epizootics; other rodents were 

seropositive only after epizootics. There was no evidence of 

plague in rodents prior to epizootics.
Disease Ecology 39

Although grasshopper mice have many of the 

characteristics of an enzootic host (table 12), the evidence to 

validate their role in the maintenance of Y. pestis infections 

between epizootics is insufficient (Stapp and others, 2009; 

Stapp and others, 2008). Grasshopper mice do appear to be 

involved in the spread of plague epizootics among prairie 

dog colonies as revealed by a study of small rodents residing 

within and around prairie dog complexes in northern Colorado 

(Stapp and others, 2009). Epizootics in prairie dogs were 

more likely following years that grasshopper mice were 

more abundant (Stapp and others, 2009). Grasshopper mice 

harbored a wide range of flea species including O. hirsuta, a 

common prairie dog flea. Infestation of grasshopper mice by 

O. hirsuta increased dramatically during plague outbreaks, 

probably as fleas left dead prairie dogs in search of new 

hosts. The authors concluded high levels of O. hirsuta

on grasshopper mice may be a predictor of an impending 

outbreak of plague among prairie dogs. No other small rodents 

acted as hosts of O. hirsuta. Another flea species, Pleochaetis 

exilis, found almost exclusively on grasshopper mice, was 

found to be infected with Y. pestis by PCR analysis. This 

finding demonstrated that grasshopper mice develop sufficient 

bacteremia to infect fleas (Stapp and others, 2009). Typically, 

this level of bacteremia is lethal to the mice, and it occurs 

4–9 days after infection (Thomas and others, 1988). During 

this time period, grasshopper mice would have the opportunity 

to travel to other burrows and family groups (coteries) within 

the prairie dog colony, thereby spreading the disease by 

transporting infected fleas. Involvement of multiple coteries 

within a colony would result in a noticeable epizootic. These 

findings were supported by the results of a modeling study: 

the abundance of grasshopper mice on a prairie dog colony 

determined whether or not plague developed into an epizootic 

or remained at an enzootic level among prairie dogs (Salkeld 

and others, 2010).

Other studies have corroborated the suggestion that deer 

mice are not directly involved in maintenance of an enzootic 

cycle and transmission of Y. pestis to prairie dogs (Salkeld 

and Stapp, 2008a; Eisen, Holmes, and others, 2008). Deer 

mice often do not harbor enough of their primary flea species 

(A. wagneri) to be able to sustain the level of transmission 

needed for enzootic maintenance (Eisen, Holmes, and others, 

2008). In addition, deer mice appear to be an uncommon host 

for the prairie dog flea, O. hirsuta, and show little indication 

of exposure to infected fleas in this system (Salkeld and Stapp, 

2008a), although they might play a more significant role in 

areas where prairie dogs do not live or these mice carry more 

fleas. Thus, despite the search for enzootic hosts, no rodent 

species has been definitively identified as playing this role.

Epizootic Hosts 

On the other hand, certain rodent species are clearly 

epizootic hosts of plague. In the western United States, several 

species of prairie dogs undergo sporadic epizootics of plague 

and suffer nearly 100 percent mortality (Rayor, 1985; Cully 

and others, 1997; Pauli and others, 2006; Lechleitner and 

others, 1968; Ubico and others, 1988). Other rodent species 

that experience epizootics with significant die-offs include 

wood rats, California ground squirrels, and thirteen-lined 

ground squirrels (Barnes, 1982).

Enzootic Plague 

An alternative view is that the enzootic and epizootic 

cycles involve the same species of rodents but differ in 

other factors, such as rates of transmission of Y. pestis and 

the numbers of hosts infected depending on area, current 

environmental conditions, and the densities of rodent hosts 

and flea vectors (Eisen and Gage, 2009; Stapp and others, 

2009). Under certain conditions, Y. pestis may exist in a rodent 

population in an enzootic state, but under other conditions, the 

level of infection transforms into an epizootic.

Indirect evidence for enzootic plague in prairie dog 

colonies was obtained in a recent study of survival rates of 

black-footed ferrets at two reintroduction sites in Montana 

(Matchett and others, 2010). Ferret survival at these sites 

was poor, even in the apparent absence of epizootic plague 

in prairie dogs (Matchett and others, 2010). To determine if 

enzootic plague was present, prairie dog burrows were dusted 

with deltamethrin to control fleas at some locations but not 

others. Also, half the ferrets released at each location were 

vaccinated with F1–V vaccine to decrease their risk of plague 

infection (see Disease Prevention and Control below); the 

other half received a placebo. Survival rates of ferrets were 

higher on dusted locations than nondusted locations. Likewise, 

survival rates were higher in vaccinated ferrets compared 

to unvaccinated ferrets on nondusted locations, but there 

was no difference on dusted locations. The results of this 

study suggest that the presence of enzootic plague decreased 

ferret survival. The positive effects of flea control as well 

as vaccination on survival of ferrets suggest that fleas are 

required for transmission or maintenance, or both, of enzootic 

plague. Similarly, survival rates of prairie dogs were higher 

at dusted sites than nondusted sites in the absence of plague 

epizootics (Biggins and others, 2010).

Climate

Despite evidence of the maintenance of plague within 

populations of rodents, the factors that transform plague 

from an enzootic to an epizootic state and that act to maintain 

Y. pestis in an area during the period between epizootics are 

not well understood (Eisen and Gage, 2009; Gage and Kosoy, 

2005). One factor that may influence plague dynamics is 

climate, which can impact both host and flea populations, as 

explained by the trophic cascade model (fig. 13) (Collinge 

and others, 2005a; Enscore and others, 2002; Parmenter and 

others, 1999). An increase in rainfall provides the necessary 

moisture for increased primary productivity of the region, 

that is, plants become more abundant. The plentiful food 

supplies allow rodents to increase their populations, thereby 
Increase in soil moisture.

Increased rainfall

Increase in humidity 

levels in burrows.

Increase in flea reproduction 

and survival.

Increase in flea 

populations.

Increase in primary 

vegetation production.

Increase in abundance of 

food sources for rodents.

Increase in rodent 

abundance.

Increase in flea loads 

on rodents.

Greater probability of 

infectious fleas finding 

new susceptible hosts.

Increase in number of 

infected animals.

EPIZOOTIC

40 Plague

Figure 13. Trophic cascade model of plague. Climate may influence the incidence of plague by its 

influence on rodent and flea populations, as explained by the trophic cascade model.
Disease Ecology 41

increasing the numbers of potential plague hosts. The 

additional moisture in the soil also could have an effect 

on the local flea population. Because fleas are susceptible 

to desiccation, in moist years they are more successful in 

reproducing and surviving. The increase in flea numbers 

allows for increased transmission of Y. pestis when host 

densities are above a certain threshold (Davis and others, 

2004), leading to a greater incidence of plague in the rodents 

and, possibly, an epizootic of plague. With the larger rodent 

populations comes an increased risk of human exposure to 

plague through direct contact with infected animals or their 

fleas. Domestic animals would be similarly at increased risk, 

presenting a further risk to their owners and caretakers.

The effects of climate on the occurrence of plague have 

been documented in populations of wild rodents as well 

as in humans. Among black-tailed prairie dogs studied in 

Montana, time-lagged precipitation was strongly associated 

with the number of colony die-offs; high precipitation in April 

to July of the previous year was positively associated with 

the number of cases of plague (Collinge and others, 2005a; 

Snäll and others, 2008). Temperature was also important, and 

the optimal temperature range for plague transmission was 

80–95°F (Collinge and others, 2005a). Outside of this range, 

the temperature presumably had a negative effect on the fleas, 

which are susceptible to desiccation in hot weather. In addition, 

the ability of fleas to transmit Y. pestis is temperature related 

(Cavanaugh, 1971; Hinnebusch and others, 1998). Climatic 

variations associated with El Niño have been associated with 

extirpations of black-tailed prairie dog colonies in Colorado 

(Stapp and others, 2004). From 1969 to 2000, 75 percent of 

plague epizootics among prairie dogs happened during years 

of warmer and wetter winters attributed to El Niño events 

(Stapp and others, 2004). The 25 percent of extirpations not 

associated with El Niño events indicated that other factors 

may be important in the occurrence of epizootics of plague 

among prairie dogs (Stapp and others, 2004).

Similar results were obtained in studies assessing climate 

effects on the number of human cases in Arizona and New 

Mexico (Enscore and others, 2002; Parmenter and others, 

1999; Ben Ari and others, 2008, 2010). Increased late-winter 

precipitation was associated with a higher number of human 

cases of plague two years later (Enscore and others, 2002). In 

years following winter-spring precipitation of above-average 

levels in New Mexico, 60 percent more cases of human plague 

resulted (Parmenter and others, 1999). An optimal temperature 

range of 80–90°F in New Mexico or 85–95°F in Arizona 

was associated with increased numbers of cases in humans 

(Enscore and others, 2002). The use of broader regional 

climatic indices, the Pacific Decadal Oscillation (PDO) and 

El Niño Southern Oscillation (ENSO), for 13 western States 

showed that during 1950–2005, positive phases of the PDO, 

characterized by warmer and wetter conditions, corresponded 

to periods of increased numbers of cases of plague in humans, 

particularly when coincident with El Niño events (Ben Ari and 

others, 2008; 2010).

Climate effects on plague occurrence can also be seen 

in central Asia among great gerbils (Stenseth and others, 

2006; Kausrud and others, 2007). Warmer springs and 

wetter summers increase the fall prevalence of plague in the 

gerbils. Spring temperature is a primary environmental factor 

affecting plague prevalence in gerbils in Kazakhstan; a 1.8°F 

(1°C) increase in spring temperature may lead to a more than 

50 percent increase in the number of plague cases in gerbils 

the following spring (Stenseth and others, 2006). It has been 

proposed that climate influences plague in gerbils through its 

effects on fleas. The colder the spring, the lower the flea load

on gerbils and, with higher relative humidity in the summer, 

flea loads are higher on gerbils in the fall (Stenseth and others, 

2006). Thus, warmer springs and wetter summers provide a 

basis for higher incidence of plague in gerbils (Stenseth and 

others, 2006; Kausrud and others, 2007).

It should be kept in mind that the effects of climate on 

plague occurrence are regional and not, in general, broadly 

applicable for making predictions about the incidence of 

plague. The optimal temperatures for transmission of Y. pestis

may vary by latitude, with northern areas having a range 

of temperatures that are slightly lower than the range of 

temperatures in southern areas (Collinge and others, 2005a). 

The combined effects of El Niño and positive PDO events are 

stronger in the southwestern Unites States than in the western 

and northern areas (Ben Ari and others, 2010). Other factors, 

such as landscape features, regional variations in climate, 

and the timing and abundance of precipitation, can affect the 

plausibility of the trophic cascade model (Collinge and others, 

2005a; Cavanaugh and Marshall, 1972). For example, in areas 

of Vietnam with already high humidity, increased rainfall 

can decrease the incidence of plague in humans owing to 

flooding of rodent burrows and subsequent decreases in flea 

populations (Cavanaugh and Marshall, 1972). In Colorado, no 

association was detected between climate and the occurrence 

of plague in prairie dogs, possibly because the study site 

did not exhibit predictable seasonal precipitation patterns 

(Collinge and others, 2005a).

Metapopulations of Rodents

Related to the trophic cascade hypothesis of plague 

occurrence is the idea that abundance of rodents is a factor 

in influencing the transformation of enzootic plague into 

an epizootic. The concept of metapopulations of rodents 

has been used to model plague in populations of prairie 

dogs, gerbils, and rats (Davis and others, 2004, 2007, 2008; 

Keeling and Gilligan, 2000a, b; Stapp and others, 2004). 

A metapopulation can be defined as a group of distinct 

populations of the same species that interact at some level 

but are separated by unoccupied or unsuitable areas of 

habitat. Although individual populations may go extinct, the 

metapopulation is considered to be stable because of migration 

between populations. Seemingly isolated populations may, in 

fact, be connected.
42 Plague

In the natural foci of plague in central Asia, the great 

gerbil acts as the primary host of the disease and lives in 

family groups within distinct, permanent burrow systems that 

do not change appreciably in number, location, and size over 

time. In Kazakhstan, the gerbil population can be considered 

to be a metapopulation, and each burrow system is a distinct 

family grouping within the larger gerbil population (Davis 

and others, 2007, 2004). The occupancy rate of these burrows 

varies considerably over time (Davis and others, 2004; 

Kausrud and others, 2007). One study determined that at least 

30 percent of the burrows must be occupied for an epizootic 

of plague to occur (Davis and others, 2008). Evidently, this 

level of occupancy is enough to allow transportation of 

infectious fleas between burrow systems, which must occur to 

continue transmission of Y. pestis. This abundance threshold

may be the consequence of what is termed a “percolation 

phenomenon”; as the critical threshold is reached, isolated 

patches of burrow systems with their fleas become connected 

to form a continuous area in which infection can more readily 

be transmitted. This phenomenon results from the difference 

in scale between movements of infectious fleas between 

burrow systems and the immense size of the habitats used 

by the gerbils (Davis and others, 2008), and it reflects the 

significance of the spatial structure and abundance of the host 

population for predicting epizootic transmission (Eisen and 

Gage, 2009). A percolation phenomenon involving abundance 

of grasshopper mice may also be important in promoting 

epizootic spread of plague among prairie dogs. Results of 

a modeling study demonstrated that when the number of 

grasshopper mice reaches a critical threshold within a prairie 

dog colony where enzootic plague is present, the mice can act 

to spread plague between infected and susceptible coteries 

(Salkeld and others, 2010). 

The concept of metapopulations can also be applied to 

black-tailed prairie dogs (Stapp and others, 2004). In a study 

of the patterns of extinction of prairie dog colonies due to 

plague, the likelihood of extinction of a colony depended 

on the size and outcome of neighboring colonies, but it was 

not related to the distance between colonies (Stapp and 

others, 2004). Although colonies may appear to be isolated 

from distant neighbors, reduced vulnerability to the effects 

of plague was not seen, indicating that spatially separated 

colonies interacted (Stapp and others, 2004). However, the 

precise mechanisms of interaction among colonies that act to 

maintain and spread plague are unknown (Stapp and others, 

2004).

Landscape features have been found to influence 

plague occurrence among black-tailed prairie dogs in areas 

of urban Colorado and rural Montana (Collinge and others, 

2005b). Roads, lakes, and streams were found to decrease the 

occurrence of plague. These features may act as barriers to 

the spread of plague either by limiting the movement of hosts, 

or fleas, or both or by decreasing the quality of the habitat 

for these animals (Collinge and others, 2005b). Interestingly, 

urbanization by itself was not associated with the incidence of 

plague in prairie dogs (Collinge and others, 2005b), although 

increasing prairie dog density within colonies is associated 

with increases in adjacent urbanization (Johnson and Collinge, 

2004).

Comparison of plague dynamics in different species 

of prairie dogs has revealed factors that may influence the 

spread of plague and the survival of colonies (Cully and 

Williams, 2001). All five species of prairie dogs (black-tailed, 

white-tailed, Gunnison’s, Utah, and Mexican) are each highly 

susceptible to plague, but on a population basis, the responses 

to epizootics of plague differ among the species. These 

differences may possibly be explained by their varying social 

systems and colony densities (Cully and Williams, 2001). 

White-tailed prairie dogs are the least social species and live in 

low-density colonies. As a result of fewer contacts within their 

own species, the spread of Y. pestis through a white-tailed 

prairie dog colony is slower than in some other species, which 

could allow surviving prairie dogs to reproduce to replace 

the dead at a rate high enough to maintain the population. In 

contrast, black-tailed and Gunnison’s prairie dogs are more 

social and live in colonies up to 10 times as dense as those of 

white-tailed prairie dogs. The resulting increased transmission 

of Y. pestis by higher rates of flea exchange and direct contact 

may lead to an increased probability of black-tailed and 

Gunnison’s prairie dog colony extinction. In the Cimarron 

National Grasslands in Kansas, colonies of black-tailed 

prairie dogs infected with Y. pestis are widely scattered and 

are interspersed with uninfected colonies, indicating that a 

metapopulation structure may be important in this landscape; 

the rate of recolonization of extinct colonies is roughly equal 

to the rate of colony extinction caused by plague (Cully and 

Williams, 2001).

Reservoirs of Plague

Modeling studies on the relative importance of various 

modes of transmission of Y. pestis during epizootics in 

prairie dogs suggested that transmission from a short-term 

(2–3 weeks) infectious reservoir may be important in driving 

epizootics (Webb and others, 2006). Transmission by fleas 

with foregut blockage was apparently not efficient enough to 

sustain epizootics at flea loads typically seen on prairie dogs. 

Aerosol transmission appeared unlikely to drive epizootics 

because of the presumed rapid mortality of animals infected 

by this route; the number of infectious prairie dogs would 

not reach high enough levels to sustain the outbreak. In 

addition, based on experimental studies in guinea pigs (Meyer, 

1961), aerosol transmission resulting in pneumonic plague 

appears to be unlikely in prairie dogs. However, no data to 

test these hypotheses are currently available. Possible shortterm reservoirs of Y. pestis include resistant rodent species, 

infected carcasses, tissues, soil, and fleas without foregut 

blockage (Webb and others, 2006). These reservoirs may also 

be important in maintenance of Y. pestis in a focus during the 

periods between epizootics (Eisen and Gage, 2009; Drancourt 

and others, 2006).
Disease Ecology 43

Fleas 

Early-phase transmission of Y. pestis by fleas without 

foregut blockage may play an important role in driving 

epizootics of plague (Eisen and others, 2006; Eisen, Lowell, 

and others, 2007; Eisen and Gage, 2009; Webb and others, 

2006; Wilder and others, 2008a, b), because unblocked fleas 

may be able to remain infectious for the requisite 2–3 week 

period of a short-term reservoir (Eisen and Gage, 2009). Many 

of the flea species that are efficient early-phase transmitters 

are commonly found on rodent hosts that suffer high mortality 

during epizootics (table 14). Conversely, flea species that 

are inefficient early-phase transmitters are commonly found 

on hosts that do not experience epizootics or that suffer low 

mortality due to plague. Fleas have been proposed to be 

reservoirs of Y. pestis during enzootic periods (Gage and 

Kosoy, 2005; Salkeld and Stapp, 2008b; Hanson and others, 

2007; Wilder and others, 2008a; Wimsatt and Biggins, 2009). 

Among colonies of black-tailed prairie dogs in Montana, PCR 

analysis of fleas found an unexpectedly high prevalence of 

Y. pestis infection (57–63 percent of colonies) during a period 

of time without evidence of epizootic activity of plague, that 

is, decreasing colony size or increased flea activity (Hanson 

and others, 2007). Although an intriguing finding, this result 

and the use of PCR to detect Y. pestis in fleas have yet to be 

validated. Experimental studies of early-phase transmission 

by O. hirsuta, a major flea of black-tailed prairie dogs, found 

that these fleas are most efficient at transmitting Y. pestis

24 hours postinfection; they are relatively inefficient in the 

late phase after developing foregut blockage (Wilder and 

others, 2008a). Based on this early-phase efficiency, modeling 

studies predicted that a flea load of 11.6 fleas per host would 

be adequate to maintain plague at an enzootic level; a level of 

23.1 fleas per host would be sufficient to produce an epizootic 

of plague among the prairie dogs. Based on the natural level 

of about 12 fleas per prairie dog on average (Brinkerhoff 

and others, 2006), the authors concluded that plague may be 

maintained at an enzootic level among prairie dogs and their 

fleas (Wilder and others, 2008a). As more prairie dogs become 

infected and die, fleas will accumulate on the remaining 

prairie dogs until the threshold flea load is reached to cause 

an epizootic. A subsequent study of fleas on black-tailed 

prairie dogs in Colorado found the average number of fleas 

(O. hirsuta and P. simulans) per prairie dog increased from 

10.4 before epizootics to 18.9 during epizootics (Tripp and 

others, 2009). In addition, the greatest increases were seen on 

prairie dogs infested with Y. pestis-infected fleas compared to 

prairie dogs with uninfected fleas. These results support the 

idea that flea abundance may be important in the dynamics of 

plague epizootics.

Ecological characteristics of fleas are associated with 

their potential efficiency as vectors of Y. pestis. Using the 

percentage of fleas with foregut blockage in experimental 

infections as a measure of a flea’s ability to transmit Y. pestis

to a host, one study found flea species that are more abundant 

than others, which was expressed as the number of fleas per 

individual host, tend to be more efficient transmitters (Krasnov 

and others, 2006). Presumably, a high abundance of fleas 

can compensate for the high mortality of blocked fleas. This 

high abundance may not be needed by efficient early-phase 

transmitters, because they generally survive longer than 

blocked fleas (Eisen, Wilder, and others, 2007; Eisen, Lowell, 

and others, 2007). In the case of the rat flea, X. cheopis, which 

is able to transmit Y. pestis with equal efficiency both in the 

early phase and after becoming blocked (Eisen, Wilder, and 

others, 2007), abundance may influence its role in triggering 

epizootics (Eisen, Wilder, and others, 2007). When flea 

abundance and host density are high, epizootics may be 

propagated by early-phase transmission (Eisen, Wilder, and 

others, 2007).

Table 14. Relative efficiency of early-phase transmission of Y. pestis by fleas found on epizootic and enzootic hosts.

Flea species

Early-phase 

transmission 

efficiency

Primary host Role of host Reference

Xenopsylla cheopis

Oropsylla montana

Oropsylla hirsuta

Oropsylla tuberculata 

cynomuris

Aetheca wagneri

Ctenocephalides felis

High

High

High

High

Low

Low

Rat

California ground squirrel

Rock squirrel

Prairie dog

Prairie dog

Deer mouse

Cat

Epizootic

Epizootic

Epizootic

Epizootic

Enzootic

Other

Eisen, Wilder, and others, 2007; Eisen, 

Netter, and others, 2008.

Eisen and others, 2006; Eisen, Lowell, and 

others, 2007; Eisen, Netter, and others, 

2008.

Wilder, Eisen, Bearden, Montenieri, 

Gage, and Antolin, 2008; Wilder, Eisen, 

Bearden, Montenairi, Trip, and others, 

2008a.

Wilder, Eisen, Bearden, Montenairi, Trip, 

and others, 2008.

Eisen, Holmes, and others, 2008.

Eisen, Borchert, and others, 2008.
44 Plague

Flea vectors that are considered to be efficient 

transmitters of Y. pestis, based on the likelihood of developing 

foregut blockage, were also shown to have a narrower 

taxonomic range of hosts (Krasnov and others, 2006), tending 

to feed from only closely related species, and ensuring the 

persistence and transmission of disease to suitable hosts. Fleas 

that live only on a specific host animal, such as the prairie 

dog flea, O. hirsuta, which rarely forms blockages, may be 

important in the long-term persistence of Y. pestis in enzootic 

cycles within specific hosts, such as black-tailed prairie 

dogs (Krasnov and others, 2006; Wilder and others, 2008a). 

Switching hosts may affect the ability of a flea species to 

maintain its infection and transmit the bacteria to a new host 

(Eisen, Vetter, and others, 2008). In an experimental study, a 

ground squirrel flea (O. montana) and a rat flea (X. cheopis)

showed a higher prevalence of infection and higher bacterial 

loads after feeding on infected rat blood, compared to either 

rabbit or mouse blood (Eisen, Vetter, and others, 2008). If 

feeding on the blood of natural hosts also affects the duration 

of infection in fleas and their ability to transmit the bacteria, 

the range of hosts used by a flea species may affect the 

dynamics of plague epizootics (Eisen, Vetter, and others, 

2008). As an epizootic progresses and fleas move to alternative 

hosts, the rate of disease transmission may be affected.

Resistant Hosts 

Resistant hosts are unlikely to act as the short-term 

reservoir of Y. pestis infection (Eisen and Gage, 2009). For 

a host to be able to transmit the bacteria to fleas during a 

blood meal, the number of bacteria in its blood must reach a 

level of at least 10 million colony forming units per milliliter 

(Engelthaler and others, 2000). Colony forming units are a 

measure of the number of bacteria in blood that are able to 

survive and multiply. This high level of bacteremia is likely to 

favor survival and transmission to successive hosts of highly 

virulent strains of Y. pestis. However, animals with this many 

bacteria in their blood would not be able to survive as long 

as 2–3 weeks. Thus, resistant hosts having lower numbers of 

bacteria in their blood are not a source of infection for fleas, 

although they could potentially act as a vehicle for infectious 

fleas and transport the disease between disparate areas (see 

discussion below).

Although prairie dogs are highly susceptible to outbreaks 

of plague on a population level, individual animals do survive 

infection with Y. pestis. Studies of epizootics among blacktailed and Gunnison’s prairie dogs have found serological 

evidence of infection in surviving animals (Pauli and others, 

2006; Cully and others, 1997). Among the 5 percent of blacktailed prairie dogs that survived plague during an epizootic 

in Wyoming, half of them had antibodies to Y. pestis; of the 

1 percent surviving Gunnison’s prairie dogs affected by a 

plague epizootic in New Mexico, more than 40 percent of 

them were seropositive for Y. pestis. Acquired immunity to 

infection, rather than avoidance of infection, contributed 

to their survival (Pauli and others, 2006). Surviving prairie 

dogs can contribute to repopulation of colonies and may 

be important in the evolution of resistance to plague (Pauli 

and others, 2006). Among grasshopper mice experimentally 

infected with Y. pestis, a lower mortality rate was seen in mice 

descended from mice originating from a plague-endemic area 

in Colorado than those descended from mice obtained from 

a plague-free area in Oklahoma (Thomas and others, 1989), 

supporting the idea that populations may develop resistance to 

plague under natural conditions (Thomas and others, 1988).

In Central Asia, where the plague bacillus probably 

originated more than 12,000 years ago, Y. pestis has coevolved 

with rodents to produce distinct strains that occur in specific 

rodent species or geographic areas. Selective pressure has 

led to a balance between virulence of Y. pestis and resistance 

among rodent hosts. Rodent species that are less social or 

that have higher resistance to disease would be more likely to 

survive. The relationship between sociality of certain rodent 

species and their acquired resistance is evident. Marmots, the 

most social sciurid in Asia, are the most resistant to plague 

(Biggins and Kosoy, 2001). Similarly, populations of great 

gerbils, another highly social rodent, contain a high proportion 

of resistant animals (Biggins and Kosoy, 2001). In North 

America, where Y. pestis has been present for only about 

100 years, highly social prairie dogs are extremely susceptible 

to plague. With time, North American prairie dogs may 

develop resistance to plague as they coevolve with Y. pestis, 

similar to what has taken place in their Asian counterparts. 

Soil 

Another possible short-term reservoir of Y. pestis is 

soil. In 1894, Yersin reportedly obtained viable Y. pestis from 

soil in a house in which the residents had died of plague 

(Yersin, 1894). Y. pestis was also obtained from the burrow of 

a gerbil that died of plague; the burrow had been unoccupied 

by other rodents or fleas for 10–11 months (Karimi, 1963). 

Experimental work demonstrated survival of Y. pestis in 

autoclaved soil for 16 months (Mollaret, 1963). Transmission 

of Y. pestis to animals in contact with contaminated soil 

has also been successful in experimental situations (Indian 

Plague Commission, 1906; Mollaret, 1963). More recent 

experimental work showed that Y. pestis inoculated into 

sterilized soil, kept moist, survived and remained virulent 

for 40 weeks (Ayyadurai and others, 2008). Y. pestis has also 

survived in soil under natural conditions for at least 24 days 

(Eisen, Petersen, and others, 2008). In this case, blood from a 

plague-infected mountain lion contaminated soil in a sheltered 

location in Grand Canyon National Park, Ariz. Soil samples 

were collected 3 weeks after the mountain lion’s death, and 

virulent Y. pestis was obtained from the soil samples by mouse 

inoculation and cell culture. Although it is unclear how 

Y. pestis might survive long term in soils, several mechanisms 

have been proposed, including adherence to invertebrates

in the soil, invasion of single celled organisms, and survival 

within host tissues (Eisen and Gage, 2009). If virulent Y. pestis

is capable of long-term persistence in soil, it may be able 

to infect animals that burrow or forage in contaminated 

soil either by ingestion or inhalation, and soil may act as a 
Disease Ecology 45

reservoir of Y. pestis (Gage and Kosoy, 2005; Drancourt and 

others, 2006). Humans have contracted pneumonic plague by 

excavating plague corpses in Madagascar suggesting survival 

of Y. pestis in the soil (Ayyadurai and others, 2008).

Carcasses and Tissues of Infected Animals 

Carcasses and tissues of animals infected with Y. pestis

may also serve as short-term reservoirs of Y. pestis. Y. pestis

can be transmitted by the ingestion of infected animals 

by predation, scavenging, and cannibalism. Northern 

grasshopper mice are omnivores, and they frequently kill 

and eat other rodents (Thomas and others, 1989). In an 

experimental study, grasshopper mice were fed white mice 

infected with Y. pestis, and 35 percent of the grasshopper mice 

became infected (Thomas and others, 1989). Grasshopper 

mice naturally consume rodent carcasses on inhabited prairie 

dog colonies that may or may not be infected with Y. pestis. 

If the carcasses are infected, the mice may act to spread 

plague among neighboring prairie dog colonies (Boone and 

others, 2009). Y. pestis has survived for more than 2 months 

in carcasses of black-footed ferrets in burrows, subsequently 

infecting and causing the death of a Siberian polecat that 

scavenged the carcasses (Godbey and others, 2006). Y. pestis

may also be transmitted by cannibalism among rodents. 

Healthy rats were housed with infected rats dying of plague; 

rats that consumed the infected animals died of plague within 

2–5 days (Rust and others, 1972). Mice have also become 

infected experimentally by drinking water containing Y. pestis

(Butler and others, 1982) further demonstrating infection by 

ingestion of Y. pestis.

Role of Carnivores

The role of carnivores in the ecology of plague remains 

unclear. Based on serological studies, many species of North 

American carnivores are exposed to Y. pestis and are able to 

survive the infection (table 10). Carnivores can be infected by 

bites of infected rodent fleas or by consumption of infected 

prey during predation or scavenging (Perry and Fetherston, 

1997; Gasper and Watson, 2001; Poland and others, 1994). 

Carnivores that spend time in rodent burrows or colonies 

during hunting or scavenging may pick up infected fleas and 

transport them to distant rodent colonies. Evidence for such 

transport was found in a study of genotypes of Y. pestis in 

colonies of Gunnison’s prairie dogs in Arizona (Girard and 

others, 2004). The existence of similar genotypes in colonies 

separated by more than 6 mi (10 km) by habitat unsuitable 

for prairie dogs suggests distribution of plague-infected fleas 

by animals other than prairie dogs, such as predators or 

scavengers or both (Girard and others, 2004). Swift foxes 

and coyotes have been found to harbor flea species commonly 

found on prairie dogs: Pulex simulans and O. hirsuta (McGee 

and others, 2006; Harrison and others, 2003; Salkeld and 

others, 2007). A sizable proportion (24 percent) of swift 

foxes sampled in Colorado had antibodies to Y. pestis and 

harbored P. simulans, although none of the fleas were positive 

for Y. pestis when tested by PCR (Salkeld and others, 2007). 

Exposure of the foxes to Y. pestis was strongly associated with 

recent epizootics of plague among black-tailed prairie dogs 

in the area (Salkeld and others, 2007). Similarly, P. irritans

(commonly known as the human flea but abundant on swift 

foxes) and P. simulans and O. hirsuta (prairie dog fleas) were 

collected from swift foxes in Texas following an epizootic in 

black-tailed prairie dogs; none of the fleas were positive for 

Y. pestis by mouse inoculation (McGee and others, 2006). Oral 

transmission by consumption of infected prairie dogs probably 

plays an important role in exposing foxes and other carnivores 

to Y. pestis. In an experimental study, coyotes and foxes 

scavenged guinea pig carcasses from inhabited prairie dog 

colonies and from prairie dog colonies that had experienced 

a recent plague outbreak, most often within 2 days of being 

laid out (Boone and others, 2009). As a result of this behavior, 

carnivores could become infected with Y. pestis as well as 

pick up infected fleas and transport them to distant colonies. 

Infected fleas were regularly found on prairie dog carcasses 

1–2 days after the death of the animal (Boone and others, 

2009; Salkeld and others, 2007).

Humans have become infected with Y. pestis by direct 

contact with various carnivores, including coyotes, foxes, 

bobcats, mountain lions, and badgers, primarily while 

skinning animal carcasses (Gage and others, 1994; Wong and 

others, 2009), suggesting carnivore-to-carnivore transmission 

may also be possible. Felids are highly susceptible to plague, 

but other carnivores mount a strong immune response to 

Y. pestis, as evidenced by surveillance studies (Hopkins and 

Gresbrink, 1982; Thomas and Hughes, 1992; Messick and 

others, 1983; Clover and others, 1989; Biek and others, 2002; 

Dyer and Huffman, 1999; Ryan and others, 1992; Gese 

and others, 1997). Nonfelid carnivores appear relatively 

resistant to disease, and they probably do not develop 

bacteremia high enough to infect fleas (Rust, Cavanaugh, 

and others, 1971). The presence of virulent Y. pestis in the 

throats of experimentally infected dogs (Rust, Cavanaugh, 

and others, 1971) suggests the possibility of transmission 

to other carnivores, including members of the same species, 

through close contact during grooming, food begging, 

fighting, predation, and scavenging (Salkeld and Stapp, 2006). 

However, in a study assessing dog-associated risk factors for 

plague in humans, there was no evidence that direct contact, 

such as being licked by an infected dog, increased the risk of 

plague for humans (Gould and others, 2008). Transmission 

by inhalation is another possibility among social carnivores 

that share dens (Salkeld and Stapp, 2006). The differences 

between nutritional and health status of domestic dogs that 

were naturally or experimentally infected and wild carnivores 

may affect the susceptibility to infection and ability to transmit 

Y. pestis. It has been suggested that slower transmission among 

resistant hosts or hosts of lower population density, like 

carnivores, may contribute to the persistence of plague (Girard 

and others, 2004; Salkeld and Stapp, 2006), but further studies 

are needed to clarify their role in the ecology of plague.
46 Plague

Survival of Y. pestis

Y. pestis may be able to survive for prolonged periods 

of time in fleas. Infected prairie dog fleas (O. labis and 

O. tuberculata cynomuris) were collected from burrows in 

Colorado more than 1 year after an epizootic of plague had 

wiped out the colony (Lechleitner and others, 1968; Kartman 

and others, 1966). Apparently, the infected fleas overwintered 

and maintained the infection into the following spring.

Y. pestis may also be able to survive in the tissues of 

hibernating rodents and cause disease in the spring (Bižanov 

and Dobrokhotova, 2007; Pollitzer, 1954; Anisimov and 

others, 2005; Kartman and others, 1966). Experimental 

inoculation of ground squirrels (Bižanov and Dobrokhotova, 

2007; Pollitzer, 1954; Kartman and others, 1966), marmots 

(Pollitzer, 1954), and susliks (Pollitzer, 1954) during 

hibernation produced inapparent or latent infections with 

Y. pestis. Infected animals survived for several months 

during hibernation, but upon awakening in the spring, most 

animals developed bacteremias and died. In addition, a much 

higher (20x) experimental dose of Y. pestis was required to 

kill hibernating animals than normal experimental control 

animals (Kartman and others, 1966). Experimental studies of 

the effects of temperature on the virulence of Y. pestis have 

revealed a symbiotic relationship between the bacteria and 

the rodent host or flea host or both that enable the bacteria to 

persist asymptomatically while the host hibernates (Anisimov 

and others, 2005). During hibernation, marmots and ground 

squirrels typically have body temperatures of about 41°F 

(Ortmann and Heldmaier, 2000; Kauffman and others, 2004). 

When Y. pestis is grown at this temperature, the main virulence 

factors (Caf1, PsaA, Yops, Yscs, and Pla) become inhibited, 

making the organism less pathogenic (Han and others, 2005). 

At the same time, the host immune response is also muted 

during hibernation (Maniero, 2002; Prendergast and others, 

2002), facilitating survival of Y. pestis. When spring arrives, 

the temperature increases and the rodents awaken; they can 

then develop acute disease, thus enabling further transmission 

of Y. pestis.

Y. pestis may utilize many avenues of persistence to 

survive in enzootic foci and produce epizootics. These 

reservoirs likely vary geographically and seasonally and 

depend on numerous intertwining factors related to the host, 

vector, and environment. There exists a “...delicate balance 

between the enzootic and epizootic state ...[in which there 

is] ... a complex interaction of host and parasite within 

the framework of the environment, creating a dynamic 

equilibrium wherein minor changes in any of a multitude of 

influencing factors can tip the balance one way or the other” 

(Olsen, 1981).

Points to Ponder

“Plague has not been, and will not be soon, eradicated, despite the major advances made since the 

beginning of this century in the knowledge of the 

disease, in public health, and in therapy.” (Guiyoule 

and others, 1994) 

Numerous factors, including environmental and humancreated changes, have contributed to the reemergence of 

human cases of plague as well as increased activity within 

established foci of sylvatic plague. Regional as well as 

broader climatic trends have been used to predict plague 

activity in both rodents and humans (Enscore and others, 

2002; Parmenter and others, 1999; Ben Ari and others, 2008, 

2010; Stenseth and others, 2006; Kausrud and others, 2007). 

Global warming has been predicted to have varying effects 

on plague in the United States and Asia. In one study, climate 

change is apparently shifting the northern and southern 

limits of human plague cases in a northerly direction in the 

United States, with the result of increasing the potential for 

transmission in Wyoming and Idaho (Nakazawa and others, 

2007). At the same time, global warming may decrease cases 

of human plague in the Southwest by decreasing soil moisture 

and increasing temperatures that will negatively impact fleas 

and rodents as hypothesized in the trophic cascade model 

(Ben Ari and others, 2010). Plague prevalence in prairie dog 

colonies may decrease if global warming causes temperatures 

to increase above a level that would be detrimental to fleas 

(Snäll and others, 2009) or to transmission of Y. pestis by fleas 

(Cavanaugh, 1971; Hinnebusch and others, 1998). However, 

increases in the spring temperatures in central Asia are 

predicted to cause an increase in both the abundance of the 

primary host for plague, the giant gerbil, as well as the number 

of cases of infection in this host (Stenseth and others, 2006). 

Combined with changes in political structures and public 

health resources, these increases could lead to increased risk 

of plague among humans (Stenseth and others, 2006).

Humans may put themselves at risk of becoming infected 

with Y. pestis by encroaching on the sylvatic cycle of plague 

through expanded housing developments or recreational 

activities. In the western United States, ground squirrels and 

rock squirrels are common hosts of plague and suffer high 

mortality. These rodents readily adapt to human presence, 

often making their homes in rock walls, outbuildings, and 

refuse dumps, and their distribution corresponds to areas of 

higher risk of human exposure to Y. pestis (Eisen, Enscore, 

and others, 2007). These normally sylvatic species become 

peridomestic, thereby increasing the risk of transmission of 

Y. pestis to humans through direct contact with these rodents or 

their fleas.

The recent reemergence of plague in humans after 

prolonged periods of absence (table 7) highlights the 

importance of maintaining surveillance systems for monitoring 

plague activity in rodent populations. War and political unrest, 

natural disasters, as well as climatic trends affecting rodent 
Disease Prevention and Control 47

and flea populations, can underscore the need to be alert to 

increasing plague activity within specific areas. In addition, 

attention to controlling human ectoparasites, such as body 

lice or human fleas, may be warranted to limit outbreaks 

of plague among infested groups of refugees and homeless 

people (Drancourt and others, 2006; Ayyadurai and others, 

2010). This may become particularly important in the event of 

deliberate use of Y. pestis as a biological weapon (Box 7).

The effects of plague have serious impacts on the 

conservation of many wildlife species. Numerous rodent 

species designated as conservation concerns by the 

International Union for Conservation of Nature live in areas in 

the western United States that experience periodic outbreaks 

of plague. The black-tailed prairie dog, renominated for 

addition to the endangered species list in 2007, has recently 

suffered devastating epizootics of plague. The resulting 

population declines in prairie dogs have repercussions for 

the endangered black-footed ferret, which is also highly 

susceptible to plague and which preys almost solely on prairie 

dogs for food (Box 8).

Disease Prevention and Control

Wild carnivores are routinely used in surveillance 

programs as sentinels of plague activity, because they produce 

antibodies to Y. pestis after infection but, with the exception 

of felids, rarely suffer mortalities. A primary route of infection 

for carnivores is through ingestion of infected prey species, 

either by predation or scavenging. Thus, the antibody status 

of carnivores reflects the infection status of the rodent prey 

and helps to determine the level of plague infections in 

rodent populations, especially when the probability of new 

infections is low (Barnes, 1982). Sampling only a few rodenteating carnivores is equivalent to testing hundreds of rodents 

for infection (Gage and others, 1994). Carnivores used in 

surveillance programs include coyotes, badgers, raccoons, 

striped skunks, bobcats, and black bears (Hopkins and 

Gresbrink, 1982; Thomas and Hughes, 1992; Messick and 

others, 1983; Clover and others, 1989; Biek and others, 2002; 

Dyer and Huffman, 1999; Ryan and others, 1992; Gese and 

others, 1997). Wild boar and domestic dogs may also be useful 

as sentinel animals in plague surveillance systems (Nelson 

and others, 1985; Barnes, 1982; Rust, Miller, and others, 1971; 

Archibald and Kunitz, 1971). Surveillance of carnivores has 

been useful in documenting the spread of plague throughout 

the western United States and has detected the emergence 

of plague in previously unaffected areas (Gage and others, 

1994). Knowledge about the presence of plague is useful for 

predicting the level of risk to humans living in the area.

Monitoring the abundance of rodents in relation to 

climate variations may also be useful for predicting epizootics 

among particular species of rodents as well as increases in the 

expected number of human cases based on modeling studies 

(Enscore and others, 2002; Parmenter and others, 1999; 

Stenseth and others, 2006; Davis and others, 2008).

Residents of enzootic areas can minimize their risk of 

developing plague by controlling rodents and fleas (Centers 

for Disease Control and Prevention, 1996). Sources of food 

and shelter for rodents around homes can be eliminated, and 

access to homes by rodents can be prevented. People can 

avoid direct contact with sick or dead rodents. Domestic 

dogs and cats could potentially act as sources of infection for 

humans by transporting infected fleas into homes (Orloski and 

Eidson, 1995; Gould and others, 2008; Pollitzer, 1954; Poland 

and Barnes, 1979); regularly treating pets with flea controlling 

preparations and preventing their eating rodents can decrease 

the risk of infection. Severely ill cats may survive—and 

the risk to their owners may be mitigated—if they are seen 

promptly by a veterinarian. Veterinarians working in enzootic 

areas need to be aware of the risk of acquiring plague from 

infected cats. Gloves, eye protection, and respirators or masks 

are prudent precautions for veterinarians when examining 

potentially infected cats. Hunters and campers in enzootic 

areas can reduce their risk of infection by avoiding rodent 

nest areas and using insect repellents. Wearing gloves when 

handling dead animals, regardless of species, also reduces the 

risk of infection. 

Prophylactic treatment with tetracycline of people in 

close contact (within 6.5 ft or 2 m) (Centers for Disease 

Control and Prevention, 1996) with pneumonic plague patients, 

as well as people who have been exposed to infected fleas 

or who have had direct contact with body tissues and fluids 

of infected animals, is warranted within 6 days to minimize 

the risk of infection. Sulfonamides and trimethoprim-sulfa 

combinations can also be used for prophylaxis.

Control of outbreaks of plague among rodents living near 

humans is important for preventing human infections. The 

first step is the dusting of burrows with insecticides to kill the 

fleas transmitting the bacterium. Next, rodent control is useful 

for reducing the numbers of infected and susceptible animals. 

It is important to kill the fleas first; otherwise infected fleas 

may leave dying rodents and bite humans. Depending on the 

species of rodents involved and the location, trapping and 

rodenticides can be used.

Outbreaks among animals involving endangered species 

may have different considerations and may require different 

methods of control. Flea control is important and the use of 

vaccines may be helpful. Vaccines for use in prairie dogs and 

black-footed ferrets are being developed (Box 9).

Plague vaccines for humans were first used in the late 

1890s when a killed whole cell vaccine was used during 

on outbreak in Bombay. From 1946 until 1999, when the 

manufacturer discontinued production, an inactivated whole 

cell vaccine was available for use in the United States 

(Center for Infectious Disease Research and Policy, 2005). 

It appeared to be protective against bubonic plague, based 

on positive results among U.S. military personnel in the 

Vietnam War (Cavanaugh and others, 1974). The incidence 

of plague among soldiers was dramatically lower compared 

to the incidence among Vietnamese civilians, despite roughly 

equal rates of murine typhus, which was also transmitted by 
48 Plague

Box 7 Plague as a Biological Weapon

“...the intentional release of an infectious particle, be it a virus or bacterium, from the confines of a 

laboratory or medical practice must be formally condemned as an irresponsible threat against the whole 

human community.” (Lederberg, 1999)

Yersinia pestis has been used as a biological weapon since the 

14th century when Tartar forces heaved plague-infected corpses 

into the walled city of Caffa in 1346 (Koirala, 2006; Kirby, 2005; 

McGovern and others, 1997). Similar use of plague-infected bodies was employed by Russian forces against Sweden in the 18th 

century (Koirala, 2006; Kirby, 2005). During World War II, Japan 

expanded the use of plague as a biological weapon by exploiting 

the human flea, P. irritans, as a vector (McGovern and others, 

1997; Kirby, 2005). Unit 731 was formed as a secret biological 

warfare unit under the pretense of being a water purification 

unit (Kirby, 2005) to devise a bomb that could disseminate 

plague-infected fleas. The Uji bomb was designed to hold 30,000 

plague-infected fleas along with grain and rice to attract rodents. 

Upon detonation of the bomb in the air, the fleas and grain were 

dispersed over cities where they would eventually land with 80 

percent survival of fleas (McGovern and others, 1997; Kirby, 2005) 

In 1940, 2 of these bombs were dropped onto two Chinese cities, 

causing epidemics of bubonic plague among the inhabitants that 

killed 120 people in one city and 24 in the other (Kirby, 2005; 

Inglesby and others, 2000).

Further development of plague as a bioweapon by the United 

States and the U.S.S.R. in the 1950s and 1960s exploited aerosol 

transmission of Y. pestis to cause cases of primary pneumonic 

plague (Inglesby and others, 2000). The World Health Organization estimated that if 110 pounds of Y. pestis were released 

as an aerosol over a city of 5 million people, 150,000 people 

would develop pneumonic plague and 36,000 of them would die; 

Y. pestis could remain viable in an aerosol form for 1 hour and 

disperse up to 6.2 mi (World Health Organization, 1970). Testimony from a Soviet defector alleged that the U.S.S.R. continued 

to develop plague as a bioweapon in the 1970s and 80s, attempting to genetically engineer antibiotic resistant forms of Y. pestis

(Barry, 1993). Today, Yersinia pestis is classified as a Category A 

bioweapon based on its global distribution, ease of mass production, and potential to cause epidemics with high mortality, as well 

as incite panic among the populace.

Aerosol transmission of Y. pestis causes primary pneumonic 

plague associated with a high fatality rate, as well as subsequent 

person-to-person transmission that could spread the disease to 

a broader geographic range by secondary cases. Symptoms of 

pneumonic plague caused by use of a bioweapon would resemble 

those of other severe respiratory illnesses, and fever, dyspnea, 

and cough would develop 1–6 days after exposure (Inglesby 

and others, 2000; Koirala, 2006). The illness would progress to 

production of copious amounts of bloody sputum and sepsis, 

resulting in high mortality rates.

Rapid diagnosis of pneumonic plague is crucial to limiting the risk 

of deaths; when antibiotic therapy is delayed more than 24 hours 

after the onset of symptoms, pneumonic plague is always fatal. 

Unfortunately, early diagnosis of plague requires a large amount 

of suspicion, which authorities and medical personnel may not 

have in nonendemic areas. In addition, there are currently no 

effective warning systems for detecting aerosols of Y. pestis

(Inglesby and others, 2000). When plague is suspected, appropriate samples (blood, sputum, and nasopharyngeal swabs) should 

be taken for diagnostic testing. In addition to standard diagnostic 

methods, use of a newly developed onsite, rapid diagnostic test 

(RDT), based on antibodies to an antigen of Y. pestis, may help 

health workers diagnose cases of pneumonic plague in a timely 

manner to limit fatalities (Chanteau and others, 2003). Contacts 

who may need prophylactic antibiotics could then be identified, 

limiting spread of the disease

Although streptomycin is the drug of choice for treating plague, 

supplies of this antibiotic are limited in the United States. 

Alternative drugs that may be more appropriate for a widespread outbreak include gentamicin, which is widely available 

and cheap, as well as tetracycline and doxycycline (Inglesby 

and others, 2000). Unfortunately, standard antibiotics may not 

be effective if Y. pestis strains that are resistant to multiple 

antibiotics are genetically engineered for use as bioweapons. 

Antibiotic susceptibility testing of the Y. pestis strain during early 
Plague as a Biological Weapon 49

response to the epidemic would enhance effectiveness of treatment (Inglesby and others, 2000). In large outbreaks, preventive 

antibiotics are recommended for people who develop a fever of 

more than 101.3°F or new cough (Koirala, 2006). Basic methods to 

control person-to-person spread of the infection include the use of 

masks, gloves, gowns, and eye protection; isolation of cases for 

the first 48 hours of antibiotic treatment; and thorough disinfection of rooms, bedding, and clothing of patients (Inglesby and 

others, 2000).

Distinguishing a naturally occurring epidemic of pneumonic 

plague from one resulting from a bioweapon is important for 

assessing the potential for continued exposure from an identified source. Forensic analysis of Y. pestis obtained from human 

cases can link these cases of plague to environmental sources 

of Y. pestis (Lowell and others, 2005; Colman and others, 2009). 

Epidemiological clues pointing to plague as the result of a bioattack include an epidemic occurring in a nonenzootic location, lack 

of a previous epizootic among local rodents, and occurrence in 

people lacking the usual risk factors (Inglesby and others, 2000; 

Koirala, 2006). The size of an outbreak would depend on the 

virulence of the strain of Y. pestis used, the amount of bacteria 

released and method of release, as well as environmental conditions (Inglesby and others, 2000).

Characteristics and examples of diseases that can be used as bioterrorism agents.

[From Centers for Disease Control and Prevention, 2009]

Characteristics of diseases in category Examples of diseases in category

Category A

Easily disseminated or transmitted person-to-person Anthrax, botulism, plague, smallpox, tularemia, viral 

hemorrhagic fevers. Causes high mortality with potential for major public 

health impact

Might cause public panic and social disruption

Requires special action for public health preparedness

Category B

Moderately easy to disseminate Q fever, brucellosis, glanders, ricin toxin, epsilon toxin, 

staphylococcal enterotoxin B. Causes moderate morbidity and low mortality

Requires specific enhancements of Center for Disease 

Control and Prevention’s diagnostic capacity and 

surveillance

Category C

Emerging pathogens that could be engineered for mass 

dissemination

Nipah virus, hantavirus, tickborne encephalitis viruses, 

yellow fever, multidrug-resistant tuberculosis.

Ease of production and dissemination

Potential for high morbidity and mortality and major 

health impact
Box 8 Plague and the Conservation of Prairie Dogs and Ferrets

Five species of prairie dogs live in western North America, and 

their ranges extend from Canada to Mexico and from the Rocky 

Mountains to eastern Nebraska. Of these five, the black-tailed 

prairie dog is the most numerous and the only one to inhabit 

the Great Plains. In the early 1900s, when plague first arrived 

in North America, black-tailed prairie dogs occupied 98 million 

acres of grasslands in the Great Plains area, possibly numbering 

as many as 5 billion animals (Wuerthner, 1997; Hoogland, 2006b). 

Increasing use of these lands by ranchers and farmers led to the 

perception of prairie dogs as pests that competed with domestic 

livestock for forage or fed on grain crops. Programs for eradicating 

and controlling prairie dogs by the use of poisons were implemented, and recreational shooting of the animals became popular. 

Combined with loss of habitat to increasing human populations 

and agriculture, these programs led to drastic declines in prairie 

dog populations. Compounding human impacts on prairie dogs is 

the natural threat of plague, to which prairie dogs are highly susceptible, and they often suffer nearly 100 percent mortality during 

outbreaks (Rayor, 1985; Cully and others, 1997; Pauli and others, 

2006; Lechleitner and others, 1968; Ubico and others, 1988).

Utah prairie dog (NWHC).

Gunnison’s prairie dog (Andrew Hollander).

0 100 200 MILES

0 100 200 KILOMETERS

EXPLANATION

CANADA

MEXICO

Black-tailed prairie dog

White-tailed prairie dog

Utah prairie dog

Gunnison’s prairie dog

Mexican prairie dog

Black-footed ferret

50 Plague

Historical ranges of prairie dogs and the black-footed ferret in the 

western United States. (From Miller and Cully, 2001; blackfootedferret.org/

reintroduction)

cc $ ©
continued

Today, it is estimated that prairie dogs occupy only 1–2 percent 

of their former range (Proctor and others, 2006). Colonies are now 

much smaller and more widely dispersed than they were before 

human intervention, making individual colonies more vulnerable 

to extinction (Miller and Ceballos, 1994; Antolin and others, 2002; 

Proctor and others, 2006). The black-tailed prairie dog is thought 

to have been extirpated in Arizona sometime between 1930 and 

1960 (Underwood and Van Pelt, 2008), and it is currently being 

reintroduced to its original site in Arizona (Arizona Game and Fish 

Department, 2008). Of the five species of prairie dogs in North 

America, currently only one is listed as endangered, although 

petitions have been filed for listing others under the Endangered 

Species Act.

Prairie dogs play an important ecological role in grassland ecosystems and have been called “keystone species,” because they 

significantly influence ecosystems in ways that are not entirely 

replicated by other species and are disproportionate to their abundance (Power and others, 1996). Although the status of prairie 

dogs as keystone species has been debated, it is generally agreed 

that prairie dogs play a vital role in the grassland ecosystem by 

supporting a different set of species than those in areas that are 

not colonized (Stapp, 1998; Miller and Ceballos, 1994; Miller and 

others, 2000, 2007; Kotliar and others, 1999; Kotliar, 2000). Many 

species prey upon prairie dogs or use their burrows for shelter and 

protection from predators. Others take advantage of the effects of 

prairie dog grazing for nesting sites or feeding on nutritious young 

grasses. Prairie dog colonies serve various functions for several 

animals, including the highly endangered black-footed ferret, 

which depends on prairie dogs for almost 90 percent of its prey.

Status of prairie dogs under the Endangered Species Act.

[From U.S. Fish and Wildlife Service, 2010]

Common name Status Current distribution

Black-tailed prairie dog Not listed, although it has repeatedly 

been petitioned for listing under the 

Endangered Species Act

Colorado, Arizona, Kansas, Montana, 

North Dakota, Nebraska, New Mexico, 

Oklahoma, South Dakota, Texas, Wyoming.

Gunnison’s prairie dog Candidate in montane region Colorado, New Mexico, Arizona, Utah.

White-tailed prairie dog Not listed, although it has repeatedly 

been petitioned for listing under the 

Endangered Species Act

Wyoming, Colorado, Utah, Montana.

Utah prairie dog Threatened; it had been listed as an 

endangered species from 1973 to 1983

Utah.

Mexican prairie dog Endangered since 1970 Mexico.

White-tailed prairie dog (Rhonda Foley). Black-tailed prairie dog (J. Chipault, NWHC).

Plague and the Conservation of Prairie Dogs and Ferrets 51
52 Plague

Box 8 Plague and the Conservation of Prairie Dogs and Ferrets (continued)

Animals that are dependent on prairie dog colonies.

[From Kotliar and others, 1999. Obligate: almost totally dependent on prairie dogs for survival; strongly facultative: use one or more features of prairie dog colonies that have limited availability outside of colonies; weakly 

facultative: use features of prairie dogs colonies that are also abundant outside of colonies, use of colonies 

varies over time and area. Prey: prairie dogs serve as food source for predator; burrows: prairie dog burrows 

are used for shelter and protection from predators; nesting: short grass at colony sites is used as nesting ground; 

foraging: colony sites are used by animals feeding on vegetation and prey other than prairie dogs.]

Common name Dependency on prairie dog colonies Function

Black-footed ferret Obligate Prey, burrows.

Mountain plover Strongly facultative Nesting, foraging.

Burrowing owl Strongly facultative Burrows, foraging.

Golden eagle Weakly facultative Prey.

Ferruginous hawk Weakly facultative Prey.

Horned lark Weakly facultative Nesting, foraging.

Deer mouse Weakly facultative Nesting, foraging.

Northern grasshopper mouse Weakly facultative Nesting, foraging.

Swift fox Weakly facultative Prey.

The black-footed ferret was declared an endangered species 

when the Endangered Species Act was passed in 1973, and it had 

disappeared from the wild by the late 1970s (Biggins and Godbey, 

2003). However, a wild population was found on white-tailed prairie dog colonies in Meeteetse, Wyo. in 1981. These animals were 

carefully monitored until distemper spread through the colony 

and threatened its existence in 1985 (Williams and others, 1988). 

At the same time, plague broke out in the prairie dog colony 

(Ubico and others, 1988). The remaining ferrets were captured in 

1987 and placed in a captive breeding facility as part of a conservation plan. Since then, the population has expanded from the 

original 18 ferrets, and over 7,000 kits have been born in six North 

American breeding centers. Ferrets have been reintroduced into 

19 sites in 8 States, Mexico, and Canada, and several populations 

are now self-sustaining (Jachowski and Lockhart, 2009; World 

Wildlife Fund, 2009). Unfortunately, plague is a major impediment 

to these conservation programs. In addition to losing nearly all 

of their prey during an outbreak, ferrets are themselves highly 

susceptible to plague and suffer high mortality (Williams and 

others, 1994). The most recent outbreak of plague that threatened 

ferrets was in 2008 in prairie dogs in the Conata Basin in South 

Dakota, a region that had previously been free of plague and was 

the most successful reintroduction site for black-footed ferrets 

(U.S. Geological Survey, 2008a; U.S. Fish and Wildlife Service, 

2008). At sites where plague is thought to be enzootic, survival 

of reintroduced ferrets has been very poor (Matchett and others, 

2010). Conservation of black-footed ferrets depends on protecting 

both prairie dogs and ferrets from the effects of plague.

Efforts to battle plague in areas where ferrets have been 

reintroduced have focused on the use of insecticides to kill 

fleas. Dusting of burrows with deltamethrin has been shown 

to significantly reduce numbers of fleas both within burrows and on prairie dogs for at least 84 days after application 

(Seery and others, 2003). Because deltamethrin is waterproof, 

it can potentially remain active up to 8 months after application 

(Seery and others, 2003). Use of Pyraperm® in burrows killed 

fleas in a colony of Utah prairie dogs and immediately stopped 

epizootics of plague in 1998 and 2001 (Hoogland and others, 

2004). If plague can be controlled in prairie dogs, ferrets will also 

benefit. Another method of combating plague is vaccination; 

U.S. Fish and Wildlife Service (FWS)
Plague and the Conservation of Prairie Dogs and Ferrets 53

vaccines are currently being developed to protect both 

prairie dogs and ferrets from infection by Y. pestis (Box 9). 

Translocation of prairie dogs is also used to recolonize 

depleted areas or establish new colonies (Long and others, 2006).

Conservationists have argued that designation of prairie dogs as 

a keystone species is important in ensuring their conservation 

(Kotliar and others, 1999; Kotliar, 2000; Miller and Ceballos, 1994) 

and would emphasize the critical role prairie dogs play in the 

grassland ecosystem. Conservation of prairie dogs would have 

a beneficial influence on the preservation of other dependent 

species, particularly the black-footed ferret, which has shown significant population declines as a result of declines in prairie dog 

populations (Kotliar and others, 1999; Wuerthner, 1997). Although 

preserving prairie dogs in small widely distributed colonies may 

preserve them as a species, ecologically they will be functionally extinct (Miller and others, 2007; Proctor and others, 2006). 

Their persistence as a species depends on establishing equilibrium between extinction and recolonization (Roach and others, 

2001; Antolin and others, 2002). Effective management includes 

consideration of the ability of prairie dogs to repopulate colonies 

that become extinct (Roach and others, 2001; Antolin and others, 

2002; Wuerthner, 1997); the optimal distance between colonies 

has been estimated to be about 1.2–1.9 miles (Roach and others, 

2001; Milne, 2004). Appropriate distances for ferret dispersal are 

also a factor for consideration (Bevers and Hof, 1997). Landscape 

features that provide accessible dispersal routes around prairie 

dog colonies aid in the repopulation of colonies (Roach and others, 2001; Wuerthner, 1997; Antolin and others, 2002). In addition, 

prairie dog colonies that are large enough to act as sustainable 

prey bases benefit black-footed ferrets; to maintain a population of 200 adult ferrets requires a prairie dog complex covering 

16,000 acres (Bevers and Hof, 1997).

“By surviving 200 years of poisoning, plague, loss of habitat, 

and recreational shooting, prairie dogs have demonstrated that 

they can overcome formidable obstacles. With prudent conservation, the preservation of prairie dogs for future generations is 

eminently feasible” (Hoogland, 2006b, p. 52). The only factor not 

under human control in this statement is plague. Understanding 

the dynamics of plague will be vital for the conservation of both 

prairie dogs and black-footed ferrets. 

Background image, prairie dog town in fall, Wind Cave National Park (NP).

Burrowing owl and mountain plover, FWS.

Bobcat waiting at a prairie dog den entrance, ©Jim Braswell.

Prairie dog town with feral horses and coyote, Theodore Roosevelt NP.

Prairie dog town with pronghorn, Wind Cave NP, Jim Pisarowicz.
Box 9 Using Vaccines to Fight Plague in Prairie Dogs and Black-Footed Ferrets

Conservation of prairie dogs and black-footed ferrets depends on the ability to control 

the effects of plague on these species, both of which suffer high mortality rates from the 

disease (Lechleitner and others, 1968; Rayor, 1985; Cully and others, 1997; Pauli and others, 

2006; Ubico and others, 1988; Williams and others, 1994; Rocke and others, 2004, 2006; 

Rocke, Smith, Marinari, and others, 2008; Rocke, Smith, Stinchcomb, and others, 2008; 

Rocke, Pussini, and others, 2010). Although insecticides to control fleas, which are the 

vectors of Y. pestis, are useful in stopping plague outbreaks in prairie dog colonies, this 

practice is labor intensive, time consuming, and has detrimental effects on other insects 

(Cully and others, 2006). Preemptive methods to prevent infection may be more effective. 

Because the ecology of plague is so complex and incompletely understood, the only measure—other than pesticides—with potential prophylactic use is vaccination. Vaccines are 

being developed for use in prairie dogs and ferrets and have shown promise in successfully 

protecting these animals from infection with Y. pestis (Rocke and others, 2004, 2006; Rocke, 

Smith, Marinari, and others, 2008; Rocke, Smith, Stinchcomb, and others, 2008; Rocke, 

Pussini, and others, 2010; Rocke, Iams, and others, 2010; Mencher and others, 2004).

An injectable vaccine using proteins of Y. pestis virulence factors (proteins which enable the 

bacteria to invade the host, elude the host immune response, and cause disease), F1 and 

V, developed for use in humans by the U.S. Army Medical Research Institute for Infectious 

Disease (Heath and others, 1998), has been tested in black-footed ferrets (Rocke and others, 

2004, 2006; Rocke, Smith, Marinari, and others, 2008). In initial studies with older animals, 

69–86 percent of vaccinated animals survived infection with virulent Y. pestis injected 

under their skin, which mimics flea bites (Rocke and others, 2004, 2006). Subsequently, 

vaccination of ferret kits at 60 and 120 days of age was shown to fully protect animals (8 of 

8 animals) against infection by the oral route, that is, ingestion of Y. pestis-infected mice 

(Rocke, Smith, Marinari, and others, 2008), which is the most likely route of exposure in 

the field. Vaccinated ferrets developed significant numbers of antibodies to combat F1 and 

V antigens, and their antibodies persisted for at least 3 years, indicating the potential for 

long-lasting immunity (Rocke, Smith, Marinari, and others, 2008).

The F1–V vaccine may be useful in captive-breeding facilities for protecting animals against 

inadvertent exposure to Y. pestis from infected prairie dogs used as food (Williams and 

others, 1994; Castle and others, 2001). Beginning in 2008, all captive-born ferrets released 

into the wild have been given two doses of the F1–V vaccine to protect them against 

plague. Most recently, the vaccine has been used as an emergency intervention method 

to limit ferret infections during the plague outbreak in the Conata Basin of South Dakota 

(U.S. Geological Survey, 2008b). However, vaccination of wild ferrets in the field is difficult 

and time consuming. Management of the disease in prairie dogs may be easier and more 

effective for prevention of plague in ferrets.

Development of vaccines for use in prairie dogs has focused on an oral vaccine for use in 

the field; these vaccines use raccoon poxvirus (RCN) as a vector for infecting oral mucosa 

with antigens of Y. pestis. Initial studies used F1 antigen to stimulate a protective immune 

response in mice (Osorio and others, 2003). Subsequently, RCN–F1 vaccine was incorporated into sweet potato baits that were voluntarily consumed by prairie dogs (Mencher and 

others, 2004; Rocke, Smith, Stinchcomb, and others, 2008). Ingestion of a series of two 

RCN–F1 vaccine-laden baits provided prairie dogs with 40–50 percent protection against 

experimental infections with virulent Y. pestis injected under the skin (Mencher and others, 

2004; Rocke, Smith, Stinchcomb, and others, 2008). The vaccinated prairie dogs developed 

Black-footed ferret (NWHC).

FWS scientist sprays pesticide on a prairie dog

burrow to kill plague-carrying fleas 

(Randy Matchett, FWS).

54 Plague

USGS scientist injects a vaccine into a 

black-footed ferret (NWHC).
significant amounts of anti-F1 antibodies after vaccination, with higher numbers of antibodies in prairie dogs that survived the disease (Rocke, Smith, Stinchcomb, and others, 2008; 

Mencher and others, 2004).

In an effort to increase the effectiveness of the oral vaccine, the V gene was also incorporated into the viral vector. A truncated version of the gene (Vt) was used to avoid the 

immune impairment associated with the full V protein (Rocke, Iams, and others, 2010; 

Rocke, Pussini, and others, 2010). Both RCN–F1 and RCN–Vt vaccines were incorporated 

into sweet potato baits that were voluntarily consumed by prairie dogs. Survival rates of 

prairie dogs orally vaccinated with the RCN–F1/RCN–Vt combination were directly compared to rates in prairie dogs inoculated by injection with the F1–V vaccine previously studied in ferrets (Rocke, Pussini, and others, 2010). Although the numbers of antibodies against 

F1 and V were higher in the animals vaccinated by injection with the F1–V vaccine than 

in the animals that ingested the RCN–F1/RCN–Vt vaccine, 94 percent of the animals vaccinated with the RCN–F1/RCN–Vt vaccine survived compared to the 58 percent of animals 

vaccinated with the F1–V protein vaccine that survived (Rocke, Pussini, and others, 2010). 

Thus, the oral RCN–F1/RCN–Vt vaccines provided nearly full protection against injections of 

virulent Y. pestis replicating numerous flea bites. More recently a single vaccine containing both genes (RCN F1–Vt) has been shown to be equally effective even after prairie dogs 

consumed the baits one time (T. Rocke, unpub. data, 2010).

Vaccination status

RCN–F1/RCN-Vt F1–V Negative control

Survival rate, in percent

0

20

40

60

80

100

16 animals

12 animals

15 animals

Work continues in the development of suitable bait for vaccine delivery in the field that 

could be distributed by plane or vehicle. Protection of prairie dogs against plague would 

have several benefits. In addition to reducing mortality of the prairie dogs themselves, the 

source of bacteria for flea transmission to unvaccinated animals could be reduced. Use of 

an oral vaccine in the field could have the added benefit of immunizing small rodents that 

may be important in maintaining Y. pestis during periods between epizootics (Creekmore 

and others, 2002). Human exposure to Y. pestis could also be reduced. The ultimate goal 

would be to distribute the vaccine-laden baits in areas where black-footed ferrets are 

present. By preserving the prey of black-footed ferrets, as well as decreasing the source of 

infection for these animals, conservation of this species would be enhanced.

Survival rates in prairie dogs challenged with subcutaneous Y. pestis.

Using Vaccines to Fight Plague in Prairie Dogs and Black-Footed Ferrets 55

Black-tailed prairie dog (Dean Biggins, USGS 

Photo Gallery).

A variety of vaccine-laden oral baits (NWHC).
56 Plague

the vector of Y. pestis, the rat flea X. cheopis. Protection by 

the vaccine against the pneumonic form was not apparent. 

Currently, development of vaccines based on virulence factors 

of Y. pestis, F1 antigen and V antigen, is ongoing (Center for 

Infectious Disease Research and Policy, 2005; Titball and 

Williamson, 2001). Particular emphasis is being placed on 

protection against pneumonic plague for combatting potential 

bioterrorism events using airborne Y. pestis. Because the 

efficacy of potential vaccines cannot be rigorously tested 

in humans, other preventive measures can be employed to 

continue to minimize the risk of plague to vaccinated people.

Treatment

Prompt treatment of patients suspected of having plague 

infection is important because of the high mortality associated 

with delayed treatment. Untreated bubonic plague causes 

death in 40–60 percent of patients, and pneumonic plague is 

fatal within 48 hours of the first symptoms (Poland and Barnes, 

1979). Early treatment with antibiotics can reduce the mortality 

rate to less than 15 percent. Treatment for pneumonic plague 

is most effective when it is started within 24 hours of the first 

symptoms. Streptomycin is the drug of choice for treatment 

of plague (Poland and Dennis, 1999; Butler, 2009), and other 

effective antibiotics include gentamicin, chloramphenicol, 

tetracycline, and sulfonamides. Chloramphenical is especially 

useful in treating plague when it spreads to the meninges, (the 

membranes covering the brain and spinal cord), the pleura (the 

membrane surrounding the lungs), and the tissues surrounding 

the eyes, in conditions known as meningitis, pleuritis, and 

endophthalmitis, respectively (Poland and Barnes, 1979).

Recently, two strains of Y. pestis that are resistant to 

multiple drugs were obtained from cases of bubonic plague 

in humans in Madagascar (Galimand and others, 1997; 

Guiyoule and others, 2001); both patients recovered after 

treatment with trimethoprim-sulfamethoxazole. These strains 

of Y. pestis may have come into contact with other bacteria 

in the flea midgut that were resistant to multiple drugs. The 

Y. pestis then acquired DNA from the other bacteria through 

a process called “horizontal gene transfer”; the acquired 

DNA carried the genes for multidrug resistance, which was 

then conferred on the Y. pestis bacteria (Galimand and others, 

2006). If additional drug-resistant strains emerge, current 

antibiotic therapies to treat plague will become less effective, 

thus contributing to a major public health problem. Thorough 

surveillance of strains of Y. pestis can help to combat this 

threat, especially in light of the reemergence of plague.

References Cited

Achtman, M., Zurth, K., Morelli, G., Torrea, G., Guiyoule, A., 

and Carniel, E., 1999, Yersinia pestis, the cause of plague, 

is a recently emerged clone of Yersinia pseudotuberculosis: 

Proceedings of the National Academy of Sciences, v. 96, 

p. 14043–14048.

Achtman, M., Morelli, G., Zhu, P., Wirth, T., Diehl, I., 

Kusecek, B., Vogler, A.J., Wagner, D.M., Allender, C.J., 

Easterday, W.R., Chenal-Francisque, V., Worsham, P., 

Thomson, N.R., Parkhill, J., Lindler, L.E., Carniel, E., and 

Keim, P., 2004, Microevolution and history of the plague 

bacillus, Yersinia pestis: Proceedings of the National 

Academy of Sciences, v. 101, p. 17837–17842.

Achtman, M. and Wagner, M., 2008, Microbial diversity and 

the genetic nature of microbial species: Nature Reviews 

Microbiology, v. 6, p. 431–440.

Adjemian, J.Z., Foley, P., Gage, K.L., and Foley, J.E., 2007, 

Initiation and spread of traveling waves of plague, Yersinia 

pestis, in the western United States: American Journal of 

Tropical Medicine and Hygiene, v. 76, p. 365–375.

Ajl, S.F., Reedal, J.S., Durrum, E.L., and Warren, J., 1955, 

Studies on plague. I. Purification and properties of the 

toxin of Pasteurella pestis: Journal of Bacteriology, v. 70, 

p. 158–169.

Anisimov, A.P., Dentovskaya, S.V., Titareva, G.M., Bakhteeva, 

I.V., Shaikhutdinova, R.Z., Balakhonov, S.V., Lindner, B., 

Kocharova, N.A., Senchenkova, S.N., Holst, O., Pier, G.B., 

and Knirel, Y.A., 2005, Intraspecies and temperature-dependent variations in susceptibility of Yersina pestis to the 

bactericidal action of serum and to polymyxin B: Infection 

and Immunity, v. 73, p. 7324–7331.

Anisimov, A.P., Lindler, L., and Pier, G., 2004, Intraspecific diversity of Yersinia pestis: Clinical Microbiological 

Reviews, v. 17, p. 434–464.

Antolin, M.F., Gober, P., Luce, B., Biggins, D.E., Van Pelt, 

W.E., Seery, D.B., Lockhart, M., and Ball, M., 2002, 

The influence of sylvatic plague on North American wildlife 

at the landscape level, with special emphasis on blackfooted ferret and prairie dog conservation, Transactions of 

the 67th North American Wildlife and Natural Resources 

Conference: Wildlife Management Institute, p. 104–127.

Arbaji, A., Kharabsheh, S., Al-Azab, S., Al-Kayed, M., 

Amr, Z., Abu Baker, M., and Chu, M., 2005, A 12-case 

outbreak of pharyngeal plague following the consumption 

of camel meat, in north-eastern Jordan: Annals of Tropical 

Medicine and Parasitology, v. 99, p. 789–793.
References Cited 57

Archibald, W.S., and Kunitz, S.J., 1971, Detection of plague 

by testing serum of dogs on the Navajo reservation: Health 

Services and Mental Health Administration Health Reports, 

v. 86, p. 377–380.

Arizona Game and Fish Department, 2008, Black-tailed prairie 

dogs return to historical site in Arizona: accessed June 12, 

2009, at http://www.azgfd.gov/artman/publish/printer_975.

shtml.

American Veterinary Medical Association, 2007, Market 

research statistics: U.S. pet ownership—2007: accessed 

December 8, 2008, at http://www.avma.org/reference/

marketstats/ownership.asp.

Ayyadurai, S., Houhamdi, L., Lepidi, H., Nappez, C., 

Raoult, D., and Drancourt, M., 2008, Long-term persistence 

of virulent Yersinia pestis in soil: Microbiology, v. 154, 

p. 2865–2871.

Ayyadurai, S., Sebbane, F., Raoult, D., and Drancourt, M., 

2010, Body lice, Yersinia pestis Orientalis, and black death: 

Emerging Infectious Diseases, v. 16, no. 10. P. 892–893.

Bacot, A.W., and Martin, C.J., 1914, Observations on the 

mechanism of the transmission of plague by fleas: Journal 

of Hygiene, v. 13 (supp. 3), p. 423–439.

Barnes, A.M., 1982, Surveillance and control of bubonic 

plague in the United States: Symposia of the Zoological 

Society of London, v. 50, p. 237–270.

Barreto, A., Aragon, M., and Epstein, P., 1995, Bubonic plague 

outbreak in Mozambique, 1994: Lancet, v. 345, p. 983–984.

Barry, J., 1993, Planning a plague?: Newsweek, Feb. 1, 

p. 40–41.

Becker, T.M., Poland, J.D., Quan, T.J., White, M.E., 

Mann, J.M., and Barnes, A.M., 1987, Plague meningitis 

—a retrospective analysis of cases reported in the United 

States, 1970–1979: Western Journal of Medicine, v. 147, 

p. 554–557.

Begier, E., Asiki, G., Anywaine, Z., Yockey, B., Schriefer, M., 

Aleti, P., Ogen-Odoi, A., Staple, J.E., Sexton, C., Bearden, 

S., and Kool, J., 2006, Pneumonic plague cluster, Uganda, 

2004: Emerging Infectious Diseases, v. 12, p. 460–467.

Ben Ari, T., Gershunov, A., Gage, K., Snäll, T., Ettestad, P., 

Kausrud, K., and Stenseth, N., 2008, Human plague in the 

USA: the importance of regional and local climate: Biology 

Letters, v. 4, p. 737–740.

Ben Ari, T., Gershunov, A., Tristan, R., Cazelles, B., Gage, K., 

and Stenseth, N.C., 2010, Interannual variability of human 

plague occurrence in the western United States explained 

by tropical and north Pacific Ocean climate variability: 

American Journal of Tropical Medicine and Hygiene, v. 83, 

p. 624–632.

Bertherat, E., Bekhoucha, S., Chougrani, S., Razik, F., 

Duchemin, J., Houti, L., Deharib, L., Fayolle, C., 

Makrerougrass, B., Dali-Yahia, R., Bellal, R., Belhabri, L., 

Chaieb, A., Tikhomirov, E., and Carniel, E., 2007, Plague 

reappearance in Algeria after 50 years, 2003: Emerging 

Infectious Diseases, v. 13, p. 1459–1462.

Bertherat, E., Thullier, J., Shako, J.C., Koné, M.-L.,

Arntzen, L., Tomaso, H., Koyange, L., Formenty, P., 

Ekwanzala, F., Crestani, R., Ciglenecki, I., and 

Rahalison, L., 2011, Lessons learned about pneumonic 

plague diagnosis from 2 outbreaks, Democratic Republic of 

the Congo: Emerging Infectious Diseases, v. 17, p. 778–784.

Bevers, M., and Hof, J., 1997, Spatial optimization of prairie 

dog colonies for black-footed ferret recovery: Operations 

Research, v. 45, p. 495–507.

Bevins, S.N., Tracey, J.A., Franklin, S.P., Schmit, V.L., 

MacMillan, M.L., Gage, K.L., Schriefer, M.E., 

Logan, K.A., Sweanor, L.L., Alldredge, M.W., Krumm, C., 

Boyce, W.M., Vickers, W., Riley, S.P.D., Lyren, L.M., 

Boydston, E.E., Fisher, R.N., Roelke, M.E., Salman, M., 

Crooks, K.R., and VandeWoude, S., 2009, Wild felids as 

hosts for human plague, western United States: Emerging 

Infectious Diseases, v. 15, p. 2,021–2,024.

Bianucci, R., Rahalison, L., Massa, E.R., Peluso, A., 

Ferroglio, E., and Signoli, M., 2008, Technical note: a rapid 

diagnostic test detects plague in ancient human remains: 

an example of the interaction between archeological and 

biological approaches (southeastern France, 16th–18th 

centuries): American Journal of Physical Anthropology, 

v. 136, p. 361–367.

Bianucci, R., Rahalison, L., Peluso, A., Massa, E.R., 

Ferroglio, E., Signoli, M., Langlois, J.-Y., and Gallien, V., 

2009, Plague immunodetection in remains of religious 

exhumed from burial sites in central France: Journal of 

Archaeological Science, v. 36, p. 616–621.

Bibikova, V.A., 1977, Contemporary views on the 

interrelationships between fleas and the pathogens of human 

and animal diseases: Annual Review of Entomology, v. 22, 

p. 23–32.

Biek, R., Zarnke, R., Gillin, C., Wild, M., Squires, J., and Poss, 

M., 2002, Serologic survey for viral and bacterial infections 

in western populations of Canada lynx (Lynx canadensis): 

Journal of Wildlife Diseases, v. 38, p. 840–845.

Biggins, D., and Godbey, J., 2003, Challenges to 

reestablishment of free-ranging populations of black-footed 

ferrets: Comptes Rendus Biologies, v. 326, p. S104–S111.

Biggins, D., and Kosoy, M., 2001, Influences of introduced 

plague on North American mammals: implications from 

ecology of plague in Asia: Journal of Mammalogy, v. 82, 

p. 906–916.
58 Plague

Biggins, D.E., Godbey, J.L., Gage, K.L., Carter, L.G., and 

Montenieri, J.A., 2010, Vector control improves survival of 

three species of prairie dogs (Cynomys) in areas considered 

enzootic for plague: Vector Borne Zoonotic Disease, v. 10, 

p. 17–26.

Bin Saeed, A., Al-Hamdan, N., and Fontaine, R., 2005, 

Plague from eating raw camel liver: Emerging Infectious 

Diseases, v. 11, p. 1456–1457.

Bitam, I., Baziz, B., Rolain, J.-M., Belkaid, M., and Raoult, D., 

2006, Zoonotic focus of plague, Algeria: Emerging 

Infectious Diseases, v. 12, no. 12, p. 1975–1977.

Bižanov, G., and Dobrokhotova, N.D., 2007, Experimental 

infection of ground squirrels (Citellus pygmaeus Pallas) 

with Yersinia pestis during hibernation: Journal of Infection, 

v. 54, p. 198–203.

Blanc, G., and Baltazard, M., 1941a, Recherches 

expérimentales sur la peste: l’infection de la puce de 

l’homme, Pulex irritans L: Comptes Rendus de l’Académie 

des Sciences, v. 213, p. 813–16.

Blanc, G., and Baltazard, M., 1941b, Recherches 

expérimentales sur la peste: l’infection du pou de 

l’homme, Pediculus corporis de Geer: Comptes Rendus 

de l’Académie des Sciences, v. 213, p. 851.

Boisier, P., Rahalison, L., Rasolomaharo, M., Ratsihorahina, 

M., Mahafaly, M., Razafimahefa, M., Duplantier, 

J.-M., Ratsifasoamanana, L., and Chanteau, S., 2002, 

Epidemiologic features of four successive annual outbreaks 

of bubonic plague in Mahajanga, Madagascar: Emerging 

Infectious Diseases, v. 8, p. 311–316.

Boone, A., Kraft, J., and Stapp, P., 2009, Scavenging by 

mammalian carnivores on prairie dog colonies: implications 

for the spread of plague: Vector-Borne and Zoonotic 

Diseases, v. 9, p. 185–189.

Brinkerhoff, R.J., Markeson, A.B., Knouft, J.H., Gage, K.L., 

and Montenieri, J.A., 2006, Abundance patterns of two 

Oropsylla (Ceratophyllidae: Siphonaptera) species on 

black-tailed prairie dog (Cynomys ludovicianus) hosts: 

Journal of Vector Ecology, v. 31, p. 355–363.

Brubaker, R.R., 2006, Yersinia pestis and bubonic plague, in

Dworkin, M., Falkow, S., Rosenberg, E., Schleifer, K.-H., 

and Stackebrandt, E., eds., The Prokaryotes, a handbook 

on the biology of bacteria (3d ed.), vol. 6: Proteobacteria: 

Gamma Subclass: New York, Springer, p. 399–442.

Burmeister, R.W., Tigertt, W.D., and Overholt, E.L., 1962, 

Laboratory-acquired pneumonic plague: report of a case 

and review of previous cases: Annals of Internal Medicine, 

v. 56, p. 789–800.

Burroughs, A.L., 1947, Sylvatic plague studies: the vector 

efficiency of nine species of fleas compared with 

Xenopsylla cheopis: Journal of Hygiene, v. 45, p. 371–396.

Butler, T., 1998, Yersiniosis and plague, in Palmer, S.R., 

Soulsby, L., and Simpson, D.I.H., eds., Zoonoses: 

New York, Oxford University Press, p. 281–293.

Butler, T., 2009, Plague into the 21st century: Clinical 

Infectious Diseases, v. 49, p. 736–742.

Butler, T., Fu, Y.-S., Furman, L., Almeida, C., and Almeida, A., 

1982, Experimental Yersinia pestis infection in rodents after 

intragastric inoculation and ingestion of bacteria: Infection 

and Immunity, v. 36, p. 1160–1167.

Castle, K., Biggins, D., Carter, L., Chu, M., Innes, K., and 

Wimsatt, J., 2001, Susceptibility of the Siberian polecat to 

subcutaneous and oral Yersinia pestis exposure: Journal of 

Wildlife Diseases, v. 37, p. 746–754.

Cavanaugh, D.C., 1971, Specific effect of temperature on 

transmission of the plague bacillus by the Oriental rat flea, 

Xenopsylla cheopis: American Journal of Tropical Medicine 

Hygiene, v. 20, p. 264–273.

Cavanaugh, D.C., Elisberg, B.L., Llewellyn, C.H., 

Marshall, Jr., J.D., Rust, Jr., J.H., Williams, J.E., and 

Meyer, K. F., 1974, Plague immunization. V. indirect 

evidence for the efficacy of plague vaccine: Journal of 

Infectious Diseases, v. 129 (supp.), p. S37–S40.

Cavanaugh, D., and Marshall, J., 1972, The influence 

of climate on the seasonal prevalence of plague in the 

Republic of Vietnam: Journal of Wildlife Diseases, v. 8, 

p. 85–94.

Centers for Disease Control and Prevention, Bioterrorism 

agents/diseases: accessed April 16, 2009, at http://

emergency.cdc.gov/agent/agentlist-category.asp.

Centers for Disease Control and Prevention, 1984, 

Epidemiologic notes and reports winter plague—CO, WA, 

TX, 1983–1984: Morbidity and Mortality Weekly Report, 

v. 33, p. 145–8.

Centers for Disease Control and Prevention, 1992, Pneumonic 

plague—Arizona, 1992: Morbidity and Mortality Weekly 

Report, v. 41, p. 737–739.

Centers for Disease Control and Prevention, 1994, Human 

plague—US, 1993–1994: Morbidity and Mortality Weekly 

Report, v. 43, p. 242–246.
References Cited 59

Centers for Disease Control and Prevention, 1996, Prevention 

of plague: recommendations of the advisory committee on 

immunization practices (ACIP): Morbidity and Mortality 

Weekly Report, v. 45, p. 1–15.

Centers for Disease Control and Prevention, 2006, Human 

plague—four states, 2006: Morbidity and Mortality Weekly 

Report, v. 55, p. 940–943.

Center for Infectious Disease Research and Policy, 2005, 

US, UK, Canada to jointly test plague vaccines: accessed 

April 17, 2009, at http://www.cidrap.umn.edu/cidrap/

content/bt/plague/news/april2105plague2.html.

Chanteau, S., Rahalison, L., Ralafiarisoa, L., Foulon, J., 

Ratsitorahina, M., Ratsifasoamanana, L., Carniel, E., 

and Nato, F., 2003, Development and testing of a rapid 

diagnostic test for bubonic and pneumonic plague: Lancet, 

v. 361, p. 211–216.

Chanteau, S., Rahalison, L., Ratsitorahina, M., Mahafaly, 

Rasolomaharo, M., Boisier, P., O’Brien, T., Aldrich, J., 

Keleher, A., Morgan, C., and Burans, J., 2000, Early 

diagnosis of bubonic plague using F1 antigen capture 

ELISA assay and rapid immunogold dipstick: International 

Journal of Medical Microbiology, v. 290, p. 279–283.

Chanteau, S., Ratsifasoamanana, L., Rasoamanana, B., 

Rahalison, L., Randriambelosoa, J., Roux, J., and 

Rabeson, D., 1998, Plague, a reemerging disease 

in Madagascar: Emerging Infectious Diseases, v. 4, 

p. 101–104.

Christie, A., Chen, T., and Elberg, S., 1980, Plague in camels 

and goats: their role in human epidemics: Journal of 

Infectious Diseases, v. 141, p. 724–726.

Clover, J., Hofstra, T., Kuluris, B., Schroeder, M., Nelson, B., 

Barnes, A., and Botzler, R., 1989, Serologic evidence of 

Yersinia pestis infection in small mammals and bears from a 

temperate rainforest of north coastal California: Journal of 

Wildlife Diseases, v. 25, p. 52–60.

Cohn, S.K. Jr., 2002, The black death: end of a paradigm: 

The American Historical Review, v. 107, p. 703–738.

Collinge, S.K., Johnson, W.C., Ray, C., Matchett, R., Grensten, 

J., Cully, J.F., Gage, KL.., Kosoy, M.Y., Loye, J.E., and 

Martin, A.P., 2005a, Testing the generality of a trophiccascade model for plague: EcoHealth, v. 2, p. 102–112.

Collinge, S.K., Johnson, W.C., Ray, C., Matchett, R., Grensten, 

J., Cully, J.F., Gage, KL.., Kosoy, M.Y., Loye, J.E., and 

Martin, A.P., 2005b, Landscape structure and plague 

occurrence in black-tailed prairie dogs on grasslands of the 

western USA: Landscape Ecology, v. 20, p. 941–955.

Colman, R.E., Vogler, A.J., Lowell, J.L., Gage, K.L., 

Morway, C., Reynolds, P.J., Ettestad, P., Keim, P., 

Kosoy, M.Y., and Wagner, D.M., 2009, Fine-scale 

identification of the most likely source of a human 

plague infection: Emerging Infectious Diseases, v. 15, 

p. 1623–1625.

Conrad, F.G., LeCocq, F.R., and Krain, R., 1968, A recent 

epidemic of plague in Vietnam: Archives of Internal 

Medicine, v. 122, p. 193–197.

Conrad, P.A., Miller, M.A., Kreuder, C., James, E.R., 

Mazet, J., Dabritz, H., Jessup, D.A., Gulland, F., and 

Grigg, M.E., 2005, Transmission of Toxoplasma: clues from 

the study of sea otters as sentinels of Toxoplasma gondii

flow into the marine environment: International Journal of 

Parasitology, v. 35, p. 1155–1168.

Craven, R., Maupin, G., Beard, M., Quan, T., and Barnes, A., 

1993, Reported cases of human plague infections in the 

United States, 1970–1991: Journal of Medical Entomology, 

v. 30, p. 758–761.

Creekmore, T.E., Rocke, T.E., and Hurley, J., 2002, A baiting 

system for delivery of an oral plague vaccine to black-tailed 

prairie dogs: Journal of Wildlife Diseases, v. 38, p. 32–39.

Cully, J.F., Jr., Barnes, A.M., Quan, T.J., and Maupin, G., 1997, 

Dynamics of plague in a Gunnison’s prairie dog colony 

complex from New Mexico: Journal of Wildlife Diseases, 

v. 33, p. 706–719.

Cully, J.F., Jr., Biggins, D.E., and Seery, D.B., 2006, 

Conservation of prairie dogs in areas with plague in 

Hoogland, J.L., ed., Conservation of the black-tailed prairie 

dog: Washington D.C., Island Press, p. 157–168.

Cully, J.F., Jr., Carter, L.G., and Gage, K.L., 2000, New 

records of sylvatic plague in Kansas: Journal of Wildlife 

Diseases, v. 36, p. 389–392.

Cully, J.F., Jr., and Williams, E.S., 2001, Interspecific 

comparisons of sylvatic plague in prairie dogs: Journal of 

Mammalogy, v. 82, p. 894–905.

Davis, S., Begon, M., De Bruyn, L., Ageyev, V., Klassovskiy, N., 

Pole, S., Viljugrein, H., Stenseth, N., and Leirs, H., 2004, 

Predictive thresholds for plague in Kazakhstan: Science, 

v. 304, p. 736–738.

Davis, S., Klassovskiy, N., Ageyev, V., Suleimenov, B., 

Atshabar, B., Klassovskaya, A., Bennett, M., Leirs, H., 

and Begon, M., 2007, Plague metapopulation dynamics in 

a natural reservoir: the burrow system as the unit of study: 

Epidemiology and Infection, v. 135, p. 740–748.

Davis, S., Trapman, P., Leirs, H., Begon, M., and 

Heesterbeek, J.A.P., 2008, The abundance threshold for 

plague as a critical percolation phenomenon: Nature, 

v. 454, p. 634–637.
60 Plague

Devignat, R., 1951, Variétés de l’espèce Pasteurella pestis: 

Bulletin of the World Health Organization, v. 4, p. 247–263.

Doll, J.M., Zeitz, P.S., Ettestad, P., Bucholtz, A.L., Davis, T., 

and Gage, K., 1994, Cat-transmitted fatal pneumonic 

plague in a person who traveled from Colorado to Arizona: 

American Journal of Tropical Medicine and Hygiene, v. 51, 

p. 109–114.

Drancourt, M., Aboudharam, G., Signoli, M., Dutour, O., and 

Raoult, D., 1998, Detection of 400-year-old Yersinia pestis 

DNA in human dental pulp: an approach to the diagnosis of 

ancient septicemia: Proceedings of the National Academy 

of Sciences of the United States of America, v. 95, 

p. 12637–12640.

Drancourt, M., Houhamdi, L., and Raoult, D., 2006, Yersinia 

pestis as a telluric, human ectoparasite-borne organism: 

Lancet Infectious Diseases, v. 6, no. 4, p. 234–241.

Drancourt, M., and Raoult, D., 2002, Molecular insights 

into the history of plague: Microbes and Infection, v. 4, 

p. 105–109.

Drancourt, M., Roux, V., Dang, L.V., Tran-Hung, L., 

Castex, D., Chenal-Francisque, V., Ogata, H., Fournier, 

P.-E., Crubezy, E., and Raoult, D., 2004, Genotyping, 

Orientalis-like Yersinia pestis, and plague pandemics: 

Emerging Infectious Diseases, v. 10, p. 1585–1,92.

Drancourt, M., Signoli, M., Dang, L.V., Bizot, B., Roux, V., 

Tzortzis, S., and Raoult, D., 2007, Yersinia pestis Orientalis 

in remains of ancient plague patients: Emerging Infectious 

Diseases, v. 13, p. 332–333.

Duncan, C.J., and Scott, S., 2005, What caused the Black 

Death?: Postgraduate Medical Journal, v. 81, p. 315–320.

Durham, D.P., and Casman, E.A., 2010, Threshold conditions 

for the persistence of plague transmission in urban rats: Risk 

Analysis, v. 29, p. 1,655–1,663.

Dyer, N., and Huffman, L., 1999, Plague in free-ranging 

mammals in western North Dakota: Journal of Wildlife 

Diseases, v. 35, p. 600–602.

Edmunds, D., Williams, E., O’Toole, D., Mills, K., BoergerFields, A., Jaeger, P., Bildfell, R., Dearing, P., and Cornish, 

T., 2008, Ocular plague (Yersina pestis) in mule deer 

(Odocoileus hemionus) from Wyoming and Oregon: Journal 

of Wildlife Diseases, v. 44, no. 4, p. 983–987.

Eidson, M., Thilsted, J., and Rollag, O., 1991, Clinical, 

clinicopathologic, and pathologic features of plague in cats: 

119 cases (1977–1988): Journal of the American Veterinary 

Medical Association, v. 199, p. 1191–1197.

Eidson, M., Tierney, L., Rollag, O., Becker, T., Brown, T., and 

Hull, H., 1988, Feline plague in New Mexico: risk factors 

and transmission to humans: American Journal of Public 

Health, v. 78, p. 1333–1335.

Eisen, R.J., Bearden, S.W., Wilder, A.P., Montenieri, J.A., 

Antolin, M.F., and Gage, K.L., 2006, Early-phase 

transmission of Yersinia pestis by unblocked fleas as a 

mechanism explaining rapidly spreading plague epizootics: 

Proceedings of the National Academy of Sciences, v. 103, 

p. 15380–15385.

Eisen, R.J., Borchert, J.N., Holmes, J.L., Amatre, G., 

Van Wyk, K., Enscore, R.E., Babi, N., Atiku, L.A., 

Wilder, A.P., Vetter, S.M., Bearden, S.W., Montenieri, J.A., 

and Gage, K.L., 2008, Early-phase transmission of Yersinia 

pestis by cat fleas (Ctenocephalides felis) and their potential 

role as vectors in a plague-endemic region of Uganda: 

American Journal of Tropical Medicine and Hygiene, v. 78, 

p. 949–956.

Eisen, R.J., Eisen, L., and Gage, K.L., 2009, Studies of vector 

competency and efficiency of North American fleas for 

Yersinia pestis: state of the field and future research needs: 

Journal of Medical Entomology, v. 46, p. 737–744.

Eisen, R.J., Enscore, R.E., Biggerstaff, B.J., Reynolds, P.J., 

Ettestad, P., Brown, T., Pape, J., Tanda, D., Levy, C.E., 

Engelthaler, D.M., Cheek, J., Bueno, R., Jr., Targhetta, J., 

Montenieri, J.A., and Gage, K.L., 2007, Human plague in 

the southwestern United States, 1957–2004: spatial models 

of elevated risk of human exposure to Yersinia pestis: 

Journal of Medical Entomology, v. 44, p. 530–537.

Eisen, R.J., and Gage, K.L., 2009, Adaptive strategies of 

Yersinia pestis to persist during inter-epizootic and epizootic 

periods: Veterinary Research, v. 40, p. 1.

Eisen, R.J., Holmes, J.L., Schotthoefer, A.M., Vetter, S.M., 

Montenieri, J.A., and Gage, K.L., 2008, Demonstration of 

early-phase transmission of Yersinia pestis by the mouse 

flea, Aetheca wagneri (Siphonaptera: Ceratophylidae), and 

implications for the role of deer mice as enzootic reservoirs: 

Journal of Medical Entomology, v. 45, p. 1160–1164.

Eisen, R.J., Lowell, J.L., Montenieri, J.A., Bearden, S.W., 

and Gage, K.L., 2007, Temporal dynamics of earlyphase transmission of Yersinia pestis by unblocked fleas: 

secondary infectious feeds prolong efficient transmission 

by Oropsylla montana (Siphonaptera: Ceratophyllidae): 

Journal of Medical Entomology, v. 44, p. 672–677.

Eisen, R.J., Petersen, J.M., Higgins, C.L., Wong, D., Levy, C.E., 

Mead, P.S., Schriefer, M.E., Griffith, K.S., Gage, K.L, and 

Beard, C.B., 2008, Persistence of Yersinia pestis in soil 

under natural conditions: Emerging Infectious Diseases, 

v. 14, p. 941–943.
References Cited 61

Eisen, R.J., Vetter, S.M, Holmes, J.L., Bearden, S.W., 

Montenieri, J.A., and Gage, K.L., 2008, Source of host 

blood affects prevalence of infection and bacterial loads 

of Yersinia pestis in fleas: Journal of Medical Entomology, 

v. 45, p. 933–938.

Eisen, R.J., Wilder, A.P., Bearden, S.W., Montenieri, J.A., and 

Gage, K.L., 2007, Early-phase transmission of Yersinia 

pestis by unblocked Xenopsylla cheopis (Siphonaptera: 

Pulicidae) is as efficient as transmission by blocked fleas: 

Journal of Medical Entomology, v. 44, p. 678–682.

Engelthaler, D.M., Hinnebusch, B.J., Rittner, C.M., and 

Gage, K.L., 2000, Quantitative competitive PCR as a 

technique for exploring flea-Yersinia pestis dynamics: 

American Journal of Tropical Medicine and Hygiene, 

v. 62, p. 552–560.

Enscore, R.E., Biggerstaff, B.J., Brown, T.L., Fulgham, R.E., 

Reynolds, P.J., Engelthaler, D.M., Levy, C.E., Parmenter, R.R., 

Montenieri, J.A., Cheek, J.E., Grinnell, R.K., Ettestad, P.J., 

and Gage, K.L., 2002, Modeling relationships between 

climate and the frequency of human plague cases in the 

southwestern United States, 1960–1997: American Journal 

of Tropical Medicine and Hygiene, v. 66, p. 186–196.

Fedorov, V., 1960, Plague in camels and its prevention in the 

USSR: Bulletin of the World Health Organization, v. 23, 

p. 275–281.

Fenyuk, B.K., 1940, Ecological factors of plague focality: 

Zoolicheskii Zhurnal, v. 19, p. 349–351.

Friedlander, A.M., Welkos, S.L., Worsham, P.L., Andrews, G.P., 

Heath, D.G., Anderson Jr., G.W., Pitt, M.L.M., Estep, J., 

and Davis, K., 1995, Relationship between virulence and 

immunity as revealed in recent studies of the F1 capsule of 

Yersinia pestis: Clinical Infectious Diseases, v. 21, sup. 2, 

p. S178–S181.

Gabastou, J.-M., Proano, J., Vimos, A., Jaramillo, G., 

Hayes, E., Gage, K., Chu, M., Guarner, J., Zaki, S., 

Bowers, J., Guillemard, C., Tamayo, H., and Ruiz, A., 

2000, An outbreak of plague including cases with probable 

pneumonic infection, Ecuador, 1998: Transactions of the 

Royal Society of Tropical Medicine and Hygiene, v. 94, 

p. 387–391. 

Gage, K.L., 1998, Plague, in Collier, L., Balows, A., and 

Sussman, M., eds., Topley and Wilson’s Microbiology 

and Microbial Infections, 9th edition: New York, Oxford 

University Press, Inc., p. 885–906.

Gage, K.L., Dennis, D.T., Orloski, K.A., Ettestad, P., Brown, T.L., 

Reynolds, P.J., Pape, W.J., Fritz, C.L., Carter, L.G., and 

Stein, J.D., 2000, Cases of cat-associated human plague in 

the western US, 1977–1998: Clinical Infectious Diseases, 

v. 30, p. 893–900.

Gage, K.L., and Kosoy, M.Y., 2005, Natural history of plague: 

perspectives from more than a century of research: Annual 

Review of Entomology, v. 50, p. 505–528.

Gage, K.L., Montenieri, J.A., and Thomas, R.E., 1994, 

The role of predators in the ecology, epidemiology, 

and surveillance of plague in the United States, in

Halverson, W.S., and Crabb, A.C., eds., 16th Vertebrate 

Pest Conference, 16th, Lincoln, Neb., 1994, Proceedings: 

Davis, University of California, Vertebrate Pest Conference, 

p. 200–206.

Galimand, M., Carniel, E., and Courvalin, P., 2006, Resistance 

of Yersinia pestis to antimicrobial agents: Antimicrobial 

Agents and Chemotherapy, v. 50, p. 3233–3236.

Galimand, M., Guiyoule, A., Gerbaud, G., Rasoamanana, 

B., Chanteau, S., Carniel, E., and Courvalin, P., 1997, 

Multidrug resistance in Yersinia pestis mediated by a 

transferable plasmid: New England Journal of Medicine, 

v. 337, p. 677–680.

Gani, R., and Leach, S., 2004, Epidemiologic determinants 

for modeling pneumonic plague outbreaks: Emerging 

Infectious Diseases, v. 10, p. 608–614.

Gasper, P.W., Barnes, A.M., Quan, T.J., Benziger, J.P., 

Carter, L.G., Beard, M.L., and Maupin, G.O., 1993, 

Plague (Yersinia pestis) in cats: description of 

experimentally induced disease: Journal of Medical 

Entomology, v. 30, p. 20–26.

Gasper, P., and Watson, R., 2001, Plague and yersiniosis, in

Williams, E.S., and Barker, I.K., eds., Infectious diseases of 

wild mammals: Ames, Iowa State University, p. 313–329.

Gendrin, C., Sarrazin, S., Bonnaffé, D., Jault, J-M., 

Lortat-Jacob, H., and Dessen, A., 2010, Hijacking of 

the pleiotropic cytokine interferon-γ by the type III 

secretion system of Yersinia pestis: PLoS ONE, v. 5, 

e15242, available at http://dx.doi.org/ 10.1371/journal.

pone.0015242.

Gese, E.M., Schultz, RD.., Johnson, M.R., Williams, E.S., 

Crabtree, R.L., and Ruff, R.L., 1997, Serological survey 

for diseases in free-ranging coyotes (Canis latrans) in 

Yellowstone National Park, Wyoming: Journal of Wildlife 

Diseases, v. 33, p. 47–56.

Gilbert, M.T., Cuccui, J., White, W., Lynnerup, N., Titball, R., 

Cooper, A., and Prentice, M., 2004, Absence of Yersinia 

pestis-specific DNA in human teeth from five European 

excavations of putative plague victims: Microbiology, 

v. 150, p. 341–354.
62 Plague

Girard, J.M., Wagner, D.M., Vogler, A.J., Keys, C., 

Allender, C.J., Drickamer, L.C., and Keim, P., 2004, 

Differential plague-transmission dynamics determine 

Yersinia pestis population genetic structure on local, 

regional, and global scales: Proceedings of the National 

Academy of Sciences, v. 101, p. 8408–8413.

Godbey, J.L., Biggins, D.E., and Garelle, D., 2006, Exposure 

of captive black-footed ferrets to plague and implications 

for species recovery, in Roelle, J., Miller, B., Godbey, J., 

and Biggins, D., eds, Recovery of the black-footed ferret: 

progress and continuing challenges: U.S. Geological Survey 

Scientific Investigations Report 2005–5293, p. 233–237.

Gordon, D., Isaacson, M., and Taylor, P., 1979, Plague 

antibody in large African mammals: Infection and Immunity, 

v. 26, p. 767–769.

Gould, L.H., Pape, J., Ettestad, P., Griffith, K., and Mead, 

P., 2008, Dog-associated risk factors for human plague: 

Zoonoses and Public Health, v. 55, p. 448–454.

Gratz, N., 1999, Rodent reservoirs and flea vectors of natural 

foci of plague, in Plague manual: epidemiology, distribution, 

surveillance and control: World Health Organization, p. 63–96, 

available at http://www.who.int/csr/resources/publications/

plague/WHO_CDS_CSR_EDC_99_2_EN/en/.

Guiyoule, A., Gerbaud, G., Buchrieser, C., Galimand, M., 

Rahalison, L., Chanteau, S., Courvalin, P., and Carniel 

E., 2001, Transferable plasmid-mediated resistance 

to streptomycin in a clinical isolate of Yersinia pestis: 

Emerging Infectious Diseases, v. 7, p. 43–48.

Guiyoule, A., Grimont, F., Iteman, I., Grimont, P., Lefevre, M., 

and Carniel, E., 1994, Plague pandemics investigated by 

ribotyping of Yersinia pestis strains: Journal of Clinical 

Microbiology, v. 32, p. 634–641.

Guiyoule, A., Rasoamanana, B., Buchrieser, C., Michel, P., 

Chanteau, S., and Carniel, E., 1997, Recent emergence of 

new variants of Yersinia pestis in Madagascar: Journal of 

Clinical Microbiology, v. 35, p. 2826–2833.

Gupta, M.L., and Sharma, A., 2007, Pneumonic plague, 

northern India, 2002: Emerging Infectious Diseases, v. 13, 

p. 664–666.

Han, Y., Zhou, D., Pang, X., Zhang, L., Sone, Y., Tong, Z., 

Bao, J., Dai, E., Wang, J., Guo, Z., Zhai, J., Du, Z., 

Wang, X., Wang, J., Huang, P., and Yang, R., 2005, DNA 

microarray analysis of the heat- and cold-shock stimulons in 

Yersinia pestis: Microbes and Infection, v. 7, p. 335–348.

Hanson, D.A., Britten, H.B., Restani, M., and Washburn, L.R., 

2007, High prevalence of Yersinia pestis in black-tailed 

prairie dog colonies during an apparent enzootic phase of 

sylvatic plague: Conservation Genetics, v. 8, p. 789–795.

Harrison, R.L., Patrick, M.J., and Schmitt, C.G., 2003, Foxes, 

fleas, and plague in New Mexico: The Southwestern 

Naturalist, v. 48, no. 4, p. 720–722.

Heath, D.G., Anderson, G.W., Jr., Mauro, J.M., Welkos, S.L., 

Andrews, G.P., Adamovicz, J., and Friedlander, A.M., 1998, 

Protection against experimental bubonic and pneumonic 

plague by a recombinant capsular F1–V antigen fusion 

protein vaccine: Vaccine, v. 16, p. 1131–1137.

Hinnebusch, B.J., 2005, The evolution of flea-borne 

transmission in Yersinia pestis: Current Issues in Molecular 

Biology, v. 7, p. 197–212.

Hinnebusch, B.J., 2010, Plague in the 21st century: global 

public health challenges and goals, in Georgiev, V.St., 

ed., National Institue of Allergy and Infectious Diseases, 

NIH: Volume 3: Intramural Research, Infectious Disease: 

New York, Springer, p. 87–94.

Hinnebusch, B.J., and Erickson, D.L., 2008, Yersinia pestis 

biofilm in the flea vector and its role in the transmission 

of plague: Current Topics in Microbiology and 

Immunology, v. 322, p. 229–48.

Hinnebusch, B.J., Fischer, E.R., and Schwan, T.G., 1998, 

Evaluation of the role of the Yersinia pestis plasminogen 

activator and other plasmid-encoded factors in temperaturedependent blockage of the flea: Journal of Infectious 

Diseases, v. 178, p. 1406–1415.

Hoogland, J.L., 2006a, Demography and population dynamics 

of prairie dogs, in Hoogland, J.L., ed., Conservation of the 

black-tailed prairie dog: Washington D.C., Island Press, 

p. 27–52.

Hoogland, J.L., 2006b, Introduction: why care about prairie 

dogs?, in Hoogland, J.L., ed., Conservation of the blacktailed prairie dog: Washington D.C., Island Press, p. 1–4.

Hoogland, J.L., Davis, S., Benson-Amram, S., Labruna, D., 

Goossens, B., and Hoogland, M.A., 2004, Pyraperm 

kills fleas and halts plague among Utah prairie dogs: 

Southwestern Naturalist, v. 49, p. 376.

Hopkins, D.D., and Gresbrink, R.A., 1982, Surveillance 

of sylvatic plague in Oregon by serotesting carnivores: 

American Journal of Public Health, v. 72, p. 1295–1297.

Houhamdi, L., Lepidi, H., Drancourt, M., and Raoult, D., 

2006, Experimental model to evaluate the human body 

louse as a vector of plague: Journal of Infectious Diseases, 

v. 194, p. 1589–1596.

Indian Plague Commission, 1906, Indian Plague Commission: 

Journal of Hygiene, v. 6, p. 509.
References Cited 63

Inglesby, T.V., Dennis, D.T., Henderson, D.A., Bartlett, 

J.G., Ascher, M.S., Eitzen, E., Fine, A.D., Friedlander, 

A.M., Hauer, J., Koerner, J.F., Layton, M., McDade, J., 

Osterholm, M.T., O’Toole, T., Parder, G., Perl, T.M., 

Russell, P.K., Schoch-Spana, M., and Tonat, K., 2000, 

Plague as a biological weapon: medical and public health 

management: Journal of the American Medical Association, 

v. 283, p. 2281–2290.

Jachowski, D.S., and Lockhart, J.M., 2009, Reintroducing 

the black-footed ferret Mustela nigripes to the great plains 

of North America: International Union for Conservation 

of Nature/Species Survival Commission, Small Carnivore 

Specialist Group, Small Carnivore Conservation Journal, 

Special Issue: The Americas, v. 41, p. 58–64.

Jarrett, C.O., Deak, E., Isherwood, K.E., Oyston, P.C., 

Fischer, E.R., Whitney, A.R., Kobayashi, S.D., DeLeo, F.R., 

and Hinnebusch, B.J., 2004, Transmission of Yersinia pestis

from an infectious biofilm in the flea vector: Journal of 

Infectious Diseases, v. 190, p. 783–792.

Jessup, D.A., Murphy, C.J., Kock, N., Jang, S., and Hoefler, L., 

1989, Ocular lesions of plague (Yersina pestis) in a blacktailed deer (Odocoileus hemionus columbianus): Journal of 

Zoo and Wildlife Medicine, v. 20, p. 360–363.

Johnson, W.C., and Collinge, S.K., 2004, Landscape effects on 

black-tailed prairie dog colonies: Biological Conservation, 

v. 115, p. 487–497.

Karimi, Y., 1963, Natural preservation of plague in soil: 

Bulletin de la Societe de Pathologie Exotique et de ses 

Filiales, v. 56, p. 1183–1186.

Kartman, L., 1960, The role of rabbits in sylvatic plague 

epidemiology, with special attention to human cases in New 

Mexico and use of the fluorescent antibody technique for 

detection of Pasteurella pestis in field specimens: Zoonoses 

Research, v. 1, p. 1–27.

Kartman, L., Goldenberg, M.I., and Hubbert, W.T., 1966, 

Recent observations on the epidemiology of plague in the 

United States: American Journal of Public Health, v. 56, 

p. 1554–1569.

Kauffman, A.S., Paul, M.J., and Zucker, I., 2004, Increased 

heat loss affects hibernation in golden-mantled ground 

squirrels: American Journal of Physiology, Regulatory, 

Integrative and Comparative Physiology, v. 287, 

p. R167–R173.

Kaufmann, A.F., Mann, J.M., Gardiner, T.M., Heaton, F., 

Poland, J.D., Barnes, A.M., and Maupin, G.O., 1981, 

Public health implications of plague in domestic cats: 

Journal of the American Veterinary Medical Association, 

v. 179, p. 875–878.

Kausrud, K.L., Viljugrein, H., Frigessi, A., Begon, M., 

Davis, S., Leirs, H., Dubyandkiy, V., and Stenseth, N.C., 

2007, Climatically driven synchrony of gerbil populations 

allows large-scale plague outbreaks: Proceedings of the 

Royal Society B, v. 274, p. 1963–1969.

Keeling, M.J., and Gilligan, C.A., 2000a, Bubonic plague: a 

metapopulation model of a zoonosis: Proceedings of the 

Royal Society B, v. 267, p. 2219–2230.

Keeling, M.J., and Gilligan, C.A., 2000b, Metapopulation 

dynamics of bubonic plague: Nature, v. 407, p. 903–906.

Kirby, R., 2005, Using the flea as a weapon: Army Chemical 

Review, p. 30–35, available at http://www.wood.army.mil/

chmdsd/pdfs/Jul-Dec%202005/Kirby.pdf.

Koirala, J., 2006, Plague: disease, management, and 

recognition of act of terrorism: Infectious Disease Clinics 

of North America, v. 20, p. 273–287.

Kool, J., 2005, Risk of person-to-person transmission of 

pneumonic plague: Clinical Infectious Diseases, v. 40, 

p. 1166–1172.

Kotliar, N.B., 2000, Application of the new keystonespecies concept to prairie dogs: how well does it work?: 

Conservation Biology, v. 14, p. 1715–1721.

Kotliar, N.B., Baker, B.W., and Whicker, A.D., 1999, A critical 

review of assumptions about the prairie dog as a keystone 

species: Environmental Management, v. 24, p. 177–192.

Krasnov, B.R., Shenbrot, G.I., Mouillot, D., Khokhlova, I.S., 

and Poulin, R., 2006, Ecological characteristics of flea 

species relate to their suitability as plague vectors: 

Oecologia, v. 149, p. 474–481.

Laforce, F.M., Acharya, I.L., Stott, G., Brachman, P.S., 

Kaufman, A.F., Clapp, R.F., and Shah, N.K., 1971, Clinical 

and epidemiological observations on an outbreak of plague 

in Nepal: Bulletin of the World Health Organization, v. 45, 

p. 693–706.

Landsborough, D., and Tunnell, N., 1947, Observations on 

plague meningitis: British Medical Journal, v. 1, p. 4–7.

Lang, J.D., 2004, Rodent-flea-plague relationships at the 

higher elevations of San Diego County, California: Journal 

of Vector Ecology, v. 29, p. 236–247.

Laudisoit, A., Leirs, H., Makundi, R.H., van Dongen, S., 

Davis, S., Neerinckx, S., Deckers, J., and Libois, R., 2007, 

Plague and the human flea, Tanzania: Emerging Infectious 

Diseases, v. 13, p. 687–693.

Lechleitner, R.R., Kartman, L., Goldenberg, M.I., and 

Hudson, B.W., 1968, An epizootic of plague in Gunnison’s 

prairie dogs (Cynomys gunnisoni) in south-central Colorado: 

Ecology, v. 49, p. 734–743.
64 Plague

Lederberg, J., 1999, Epilogue, in Lederberg, J., ed., Biological 

weapons: limiting the threat: Cambridge, Mass., MIT Press, 

p. 321–329.

Link, V., 1950, Plague epizootic in cottontail rabbits: Public 

Health Reports, v. 65, p. 696.

Loïez, C., Herwegh, S., Wallet, F., Armand, S., Guinet, F., and 

Courcol, R.J., 2003, Detection of Yersinia pestis in sputum 

by real-time PCR: Journal of Clinical Microbiology, v. 41, 

p. 4873–4875.

Long, D., Bly-Honness, K., Truett, J.C., and Seery, D.B., 2006, 

Establishment of new prairie dog colonies by translocation, 

in Hoogland, J.L., ed., Conservation of the black-tailed 

prairie dog: Washington, D.C., Island Press, p. 188–209.

Lorange, E.A., Race, B.L., Sebbane, F., and Hinnebusch, B.J., 

2005, Poor vector competence of fleas and the evolution 

of hypervirulence in Yersinia pestis: Journal of Infectious 

Diseases, v. 191, p. 1907–1912.

Lowell, J.L., Wagner, D.M., Atshabar, B., Antolin, M.F., 

Vogler, A.J., Keim, P., Chu, M.C., and Gage, K.L., 

2005, Identifying sources of human exposure to plague: 

Journal of Clinical Microbiology, v. 43, p. 650–656.

Mall, A.A., and O’Leary, S.B., 1945, Plague in the Americas 

[publication no. 225]: Washington, D.C., Pan American 

Sanitary Bureau, p. 45, 65, 98.

Maniero, G.D., 2002, Classical pathway serum complement 

activity throughout various stages of the annual cycle of a 

mammalian hibernator, the golden-mantled ground squirrel, 

Spermophilus lateralis: Developmental and Comparative 

Immunology, v. 26, p. 563–574.

Mann, J.M., Shandler, L., and Cushing, A.H., 1982, Pediatric 

plague: Pediatrics, v. 69, p. 762–767.

Marketon, M.M., DePaolo, R.W., DeBord, K.L., Jabri, B., and 

Schneewind, O., 2005, Plague bacteria target immune cells 

during infection: Science, v. 309, p. 1739–1741.

Marshall, J.D., Harrison, D.N., Murr, J.A., and 

Cavanaugh, D.C., 1972, The role of domestic animals in 

the epidemiology of plague. III. Experimental infection of 

swine: Journal of Infectious Diseases, v. 125, p. 556–559.

Marshall, J.D., Quy, D.V., Gibson, T.C., Dung, T.C., and 

Cavanaugh, D.C., 1967, Ecology of plague in Vietnam I. 

Role of Suncus murinus: Proceedings of the Society for 

Experimental Biology and Medicine, v. 124, p. 1083–1086.

Martin, A.R., Hurtado, F.P., Plessala, R.A., Hurtado, E.G., 

Chapman, C.E., Callahan, E.L., and Brutsché, R.L., 1967, 

Plague meningitis—a report of three cases in children and 

review of the problem: Pediatrics, v. 40, p. 610–616.

Matchett, M.R., Biggins, D.E., Carlson, V., Powell, B., and 

Rocke, T., 2010, Enzootic plague reduces black-footed 

ferret (Mustela nigripes) survival in Montana: Vector-Borne 

and Zoonotic Diseases, v. 10, p. 27–35.

McGee, B.K., Butler, M.J., Pence, D.B., Alexander, J.L., 

Nissen, J.B., Ballard, W.B., and Nicholson, K.L., 2006, 

Possible vector dissemination by swift foxes following a 

plague epizootic in black-tailed prairie dogs in northwestern 

Texas: Journal of Wildlife Diseases, v. 42, p. 415–420.

McGovern, T.W., Faad, M.D., and Friedlander, A.M., 1997, 

Plague in Sidell, F.R., Takafuji, E.T., and Franz, D.R., 

eds., Medical aspects of chemical and biological warfare: 

Washington, D.C., Borden Institute, p. 479–502, available 

at http://www.bordeninstitute.army.mil/published_volumes/

chembio/Ch23.pdf.

Melo, A.C., Amleida, A.M.P., and Leal, N.C., 2003, 

Retrospective study of a plague outbreak by multiplex-PCR: 

Letters in Applied Microbiology, v. 37, p. 361–364.

Mencher, J.S., Smith, S.R., Powell, T.D., Stinchcomb, D.T., 

Osorio, J.E., and Rocke, T.E., 2004, Protection of blacktailed prairie dogs (Cynomys ludovicianus) against 

plague after voluntary consumption of baits containing 

recombinant raccoon poxvirus vaccine: Infection and 

Immunity, v. 72, p. 5502.

Messick, J., Smith, G., and Barnes, A., 1983, Serologic testing 

of badgers to monitor plague in southwestern Idaho: Journal 

of Wildlife Diseases, v. 19, p. 1–6.

Meyer, K.F., 1961, Pneumonic plague: Bacteriological 

Reviews, v. 25, p. 249–261.

Meyer, K.F., Holdenried, R., Burroughs, A.L., and Jawetz, E., 

1943, Sylvatic plague studies: IV. inapparent, latent sylvatic 

plague in ground squirrels in central California: Journal of 

Infectious Diseases, v. 73, p. 144–157.

Miller, B.J., and Ceballos, G., 1994, The prairie dog and biotic 

diversity: Conservation Biology, v. 8, p. 677–681.

Miller, B.J., and Cully, J.F., Jr., 2001, Conservation of blacktailed prairie dogs (Cynomys lubovicianus): Journal of 

Mammalogy, v. 82, p. 889–893.

Miller, B.J., Reading, R.P., Biggins, D.E., Detling, J.K., 

Forrest, S.C., Hoogland, J.L., Javersak, J., Miller, S.D., 

Proctor, J., Truett, J., and Uresk, D.W., 2007, Prairie dogs: 

an ecological review and current biopolitics: Journal of 

Wildlife Management, v. 71, p. 2801–2810.

Miller, B., Reading, R., Hoogland, J., Clark, T., Ceballos, G., 

List, R., Forrest, S., Hanebury, L., Manzano, P., Pacheco, J., 

and Uresk, D., 2000, The role of prairie dogs as a keystone 

species: response to Stapp: Conservation Biology, v. 14, 

p. 318–321.
References Cited 65

Milne, S.A., 2004, Population ecology and expansion 

dynamics of black-tailed prairie dogs in western 

North Dakota: Grand Forks, University of North Dakota, 

MS thesis.

Mollaret, H.H., 1963, Experimental preservation of plague in 

soil: Bulletin de la Societe de Pathologie Exotique et de ses 

Filiales, v. 56, p. 1168–1182.

Mueller, C.A., Broz, P., Müller, S.A., Ringler, P., 

Erne-Brand, F., Sorg, I., Kuhn, M., Engel, A., and Cornelis, 

G.R., 2005, The V-antigen of Yersinia forms a distinct 

structure at the tip of injectisome needles: Science, v. 310, 

p. 674–676.

Nakazawa, Y., Williams, R., Peterson, A.T., Mead, P., Staples, 

E., and Gage, K.L., 2007, Climate change effects on plague 

and tularemia in the United States: Vector-Borne and 

Zoonotic Diseases, v. 7, p. 529–540.

Nedialkov, Y.A., Motin, V.L., and Brubaker, R.R., 1997, 

Resistance to lipopolysaccharide mediated by the Yersinia 

pestis V antigen-polyhistidine fusion peptide: amplification 

of interleukin-10: Infection and Immunity, v. 65, 

p. 1196–1203.

Nelson, J., Decker, R., Barnes, A., Nelson, B., Quan, T., 

Gillogly, A., and Phillips, G., 1985, Plague surveillance 

using wild boar and wild carnivore sentinels: Journal of 

Environmental Health, v. 47, p. 306–309.

Olsen, P.F., 1981, Sylvatic plague, in Davis, J.W., Karstad, 

L.H., and Trainer, D.O., eds., Infectious diseases of wild 

mammals: Ames, Iowa State University Press, p. 232–243.

Orloski, K., and Eidson, M., 1995, Yersinia pestis infection 

in three dogs: Journal of the American Veterinary Medical 

Association, v. 207, p. 316–318.

Orloski, K., and Lathrop, S., 2003, Plague: a veterinary 

perspective: Journal of the American Veterinary Medical 

Association, v. 222, p. 444–448.

Ortmann, S., and Heldmaier, G., 2000, Regulation of body 

temperature and energy requirements of hibernating 

Alpine marmots (Marmota marmota): American Journal 

of Physiology, Regulatory, Integrative and Comparative 

Physiology, v. 278, p. R698–R704.

Osorio, J.E., Powell, T.D., Frank, R.S., Moss, K., Haanes, E.J., 

Smith, S.R., Rocke, T.E., and Stinchcomb, D.T., 2003, 

Recombinant raccoon pox vaccine protects mice against 

lethal plague: Vaccine, v. 21, p. 1231–1238.

Panda, S.K., Nanda, S.K., Ghosh, A., Sharma, C., Shivaji, S., 

Kumar, G.S., Kannan, K., Batra, H.V., Tuteja, U., Ganguly, 

N.K., Chakrabarty, A., and Chandra, H.S., 1996, The 

1994 plague epidemic of India: molecular diagnosis and 

characterization of Yersinia pestis isolates from Surat and 

Beed: Current Science, v. 71, p. 794–799.

Parmenter, R.R., Yadav, E.P., Parmenter, C.A., Ettestad, P., 

and Gage, K.L., 1999, Incidence of plague associated 

with increased winter-spring precipitation in New Mexico: 

American Journal of Tropical Medicine and Hygiene, v. 61, 

p. 814–821.

Paul-Murphy, J., Work, T., Hunter, D., McFie, E., and 

Fjelline, D., 1994, Serologic survey and serum biochemical 

reference ranges of the free-ranging mountain lion (Felis 

concolor) in California: Journal of Wildlife Diseases, v. 30, 

p. 205–215.

Pauli, J., Buskirk, S., Williams, E., and Edwards, W., 2006, 

A plague epizootic in the black-tailed prairie dog (Cynomys 

ludovicianus): Journal of Wildlife Diseases, v. 42, p. 74–80.

Perry, R., and Fetherston, J., 1997, Yersinia pestis—etiologic 

agent of plague: Clinical Microbiology Reviews, v. 10, 

p. 35–66.

Poland, J.D., and Barnes, A.M., 1979, Plague, in Steele, J.H., 

ed., CRC Handbook series in zoonoses: Boca Raton, Fla., 

CRC Press, p. 515–597.

Poland, J.D., Barnes, A.M., and Herman, J.J., 1973, Human 

bubonic plague from exposure to a naturally infected 

wild carnivore: American Journal of Epidemiology, v. 97, 

p. 332–337.

Poland, J.D., and Dennis, D.T., 1999, Diagnosis and 

clinical manifestations, in Plague manual: epidemiology, 

distribution, surveillance and control: World Health 

Organization, p. 43–53, available at http://www.who.int/

csr/resources/publications/plague/WHO_CDS_CSR_

EDC_99_2_EN/en/index.html.

Poland, J.D., Quan, T.J., and Barnes, A.M., 1994, Plague, 

in Beran, G., and Steele, J., eds, Handbook of zoonoses, 

section A, bacterial, rickettsial, chlamydial, and mycotic 

zoonoses: Boca Raton, Fla., CRC Press, p. 93–112.

Pollitzer, R., 1954, Plague: Geneva, World Health 

Organization, 698 p.

Porat, R., McCabe, W.R., and Brubaker, R.R., 1995, 

Lipopolysaccharide-associated resistance to killing of 

yersiniae by complement: Journal of Endotoxin Research, 

v. 2, p. 91–97.

Porto-Fett, A.C., Juneja, V.K., Tamplin, M.L., and 

Luchansky, J.B., 2009, Validation of cooking times and 

temperatures for thermal inactivation of Yersinia pestis 

strains KIM5 and CDC–A1122 in irradiated ground beef: 

Journal of Food Protection, v. 72, p. 564–571.

Power, M.E., Tilman, D., Estes, J.A., Menge, B.A., Bond, W.J., 

Mills, L.S., Daily, G., Castilla, J.C., Lubchenco, J., and 

Paine, R.T., 1996, Challenges in the quest for keystones: 

BioScience, v. 46, p. 609–620.
66 Plague

Prendergast, B.J., Freeman, D.A., Zucker, I., and Nelson, R.J., 

2002, Periodic arousal from hibernation is necessary 

for initiation of immune responses in ground squirrels: 

American Journal of Physiology. Regulatory, Integrative 

and Comparative Physiology, v. 282, p. R1054–R1062.

Proctor, J., Haskins, B., and Forrest, S.C., 2006, Focal 

areas for conservation of prairie dogs and the grassland 

ecosystem, in Hoogland, J.L., ed., Conservation of the 

black-tailed prairie dog: Washington, D.C., Island Press, 

p. 232–247.

Quan, S.F., and Kartman, L., 1956, The resistance of Microtus 

and Peromyscus to infection by Pasteurella pestis: 

Transactions of the Royal Society of Tropical Medicine and 

Hygiene, v. 50, no. 1, p. 104–105.

Quan, S.F., and Kartman, L., 1962, Ecologic studies of wild 

rodent plague in the San Francisco Bay area of California: 

VIII: Zoonoses Research, v. 1, p. 121–124.

Rajerison, M., Dartevelle, S., Ralafiarisoa, L.A., Bitam, I., 

Tuyet, D.T.N., Andrianaivoarimanana, V., Nato, F., and 

Rahalison, L., 2009, Development and evaluation of 

two simple, rapid immunochromatographic tests for the 

detection of Yersinia pestis antibodies in humans and 

reservoirs: PLoS Neglected Tropical Diseases, v. 3, e421, 

available at http://dx.doi.org/10.1371/journal.pntd.0000421.

Raoult, D., Aboudharam, G., Crubezy, E., Larrouy, 

G., Ludes, B., and Drancourt, M., 2000, Molecular 

identification by “suicide PCR” of Yersinia pestis as 

the agent of Medieval Black Death: Proceedings of the 

National Academy of Sciences, v. 97, p. 12800–12803.

Raoult, D., and Drancourt, M., 2002, Cause of black death: 

Lancet, v. 2, p. 459.

Ratsitorahina, M., Chanteau, S., Rahalison, L., 

Rasifasoamanana, L., and Boisier, P., 2000, Epidemiological 

and diagnostic aspects of the outbreak of pneumonic plague 

in Madagascar: Lancet, v. 355, p. 111–113.

Rayor, L., 1985, Dynamics of a plague outbreak in Gunnison’s 

prairie dog: Journal of Mammalogy, v. 66, p. 194–196.

Riehm, J.M., Rahalison, L., Scholz, H.C., Thoma, B., Pfeffer, 

M., Razanakoto, L.M., Dahouk, S.A., Neubauer, H., and 

Tomaso, H., 2011, Detection of Yersinia pestis using 

real-time PCR in patients with suspected bubonic plague: 

Molecular and Cellular Probes, v. 25, p. 8–12.

Roach, J.L., Stapp, P., Van Horne, B., and Antolin, M.F., 2001, 

Genetic structure of a metapopulation of black-tailed prairie 

dogs: Journal of Mammalogy, v. 82, p. 946–959.

Robertson, S.A., 2008, A review of feral cat control: Journal of 

Feline Medicine and Surgery, v. 10, p. 366–375.

Rocke, T.E., Iams, K.P., Dawe, S., Smith, S.R., Williamson, J.L., 

Heisey, D.M., and Osorio, J.E., 2010, Further development 

of raccoon poxvirus-vectored vaccines against plague 

(Yersinia pestis): Vaccine, v. 28, p. 338–344.

Rocke, T.E., Mencher, J., Smith, S.R., Friedlander, A.M., 

Andrews, G.P., and Baeten, L.A., 2004, Recombinant 

F1–V fusion protein protects black-footed ferrets (Mustela 

nigripes) against virulent Yersinia pestis infection: Journal 

of Zoo and Wildlife Medicine, v. 35, p. 142–146.

Rocke, T.E., Nol, P., Marinari, P., Kreeger, J., Smith, S., 

Andrews, G.P., and Friedlander, A.M., 2006, Vaccination as 

a potential means to prevent plague in black-footed ferrets, 

in Roelle, J.E., Miller, B.J., Godbey, J.L., and Biggins, D.E., 

eds., Recovery of the black-footed ferret: progress and 

continuing challenges: U.S. Geological Survey Scientific 

Investigations Report, 2005–5293, p. 243–247.

Rocke, T.E., Pussini, N., Smith, S.R., Williamson, J., Powell, B., 

and Osorio, J.E., 2010, Consumption of baits containing 

raccoon pox-based plague vaccines protects black-tailed 

prairie dogs (Cynomys ludovicianus): Vector-Borne and 

Zoonotic Diseases, v. 10, p. 53–58.

Rocke, T.E., Smith, S., Marinari, P., Kreeger, J., Enama, J., 

and Powell, B., 2008, Vaccination with F1–V fusion protein 

protects black-footed ferrets (Mustela nigripes) against 

plague upon oral challenge with Yersinia pestis: Journal of 

Wildlife Diseases, v. 44, p. 1–7.

Rocke, T.E., Smith, S., Stinchcomb, D., and Osorio, J., 2008, 

Immunization of black-tailed prairie dog against plague 

through consumption of vaccine-laden baits: Journal of 

Wildlife Diseases, v. 44, p. 930–937.

Ruiz, A., 2001, Plague in the Americas: Emerging Infectious 

Diseases, v. 7 (supp.), p. 539–540.

Rust, J.H., Jr., Cavanaugh, D.C, O’Shita, R., and Marshall, J.D., 

Jr., 1971, The role of domestic animals in the epidemiology 

of plague. I. Experimental infection of dogs and cats: 

Journal of Infectious Diseases, v. 124, p. 522–526.

Rust, J.H., Jr., Harrison, D.N., Marshall, J.D., Jr., and 

Cavanaugh, D.C., 1972, Susceptibility of rodents to oral 

plague infection: a mechanism for the persistence of plague 

in inter-epidemic periods: Journal of Wildlife Diseases, v. 8, 

p. 127–133.

Rust, J.H., Jr., Miller, B.E., Bahmanyar, M., Marshall, J.D., 

Jr., Purnaveja, S., Cavanaugh, D.C., and Hla, U.S.T., 1971, 

The role of domestic animals in the epidemiology of plague. 

II. Antibody to Yersinia pestis in sera of dogs and cats: 

Journal of Infectious Diseases, v. 124, p. 527–531.

Ryan, C.P., Hughes, P.E., and Matsumoto, G., 1992, Plague 

surveillance in Los Angeles county: American Journal of 

Public Health, v. 82, p. 897.
References Cited 67

Salkeld, D.J., Eisen, R.J., Stapp, P., Wilder, A.P., Lowell, J., 

Tripp, D.W., Albertson, D., and Antolin, M.F., 2007, The 

potential role of swift foxes (Vulpes velox) and their fleas 

in plague outbreaks in prairie dogs: Journal of Wildlife 

Diseases, v. 43, p. 425–431.

Salkeld, D.J., Salathe, M., Stapp, P., and Jones, J.H., 2010, 

Plague outbreaks in prairie dog populations explained 

by percolation thresholds of alternate host abundance: 

Proceedings of the National Academy of Sciences, v. 107, 

p. 14247–14250.

Salkeld, D.J., and Stapp, P., 2006, Seroprevalence rates and 

transmission of plague (Yersinia pestis) in mammalian 

carnivores: Vector-Borne and Zoonotic Diseases, v. 6, 

p. 231–239.

Salkeld, D.J., and Stapp, P., 2008a, No evidence of deer mouse 

involvement in plague (Yersinia pestis) epizootics in prairie 

dogs: Vector-Borne and Zoonotic Diseases, v. 8, p. 331–337.

Salkeld, D.J., and Stapp, P., 2008b, Prevalence and abundance 

of fleas in black-tailed prairie dog burrows: implications 

for the transmission of plague (Yersinia pestis): Journal of 

Parasitology, v. 94, p. 616–621.

Seery, D.B., Biggins, D.E., Montenieri, J.A., Enscore, R.E., 

Tanda, D.T., and Gage, K.L., 2003, Treatment of blacktailed prairie dog burrows with deltamethrin to control fleas 

(Insecta: Siphonaptera) and plague: Journal of Medical 

Entomology, v. 40, p. 718.

Shrewsbury, J.F.D., 1970, A history of plague in the British 

Isles: Cambridge, England, Cambridge University Press, 

665 p.

Simond, P.L., 1898, La propagation de la peste: Annals 

Institute Pasteur, v. 12, p. 626–686.

Simpson, W.J., 1905, A treatise on plague: Cambridge, 

England, Cambridge University Press.

Snäll, T., Benestad, R.E., and Stenseth, N.C., 2009, Expected 

future plague levels in a wildlife host under different 

scenarios of climate change: Global Change Biology, v. 15, 

p. 500–507.

Snäll, T., O’Hara, R.B., Ray, C., and Collinge, S.K., 2008, 

Climate-driven spatial dynamics of plague among prairie 

dog colonies: American Naturalist, v. 171, p. 238–248.

Sodeinde, O.A., Subrahmanyam, Y.V.B.K., Stark, K., Quan, T., 

Bao, Y., and Goguen, J.D., 1992, A surface protease and the 

invasive character of plague: Science, v. 258, p. 1004–1007.

Stapp, P., 1998, A reevaluation of the role of prairie dogs 

in great plains grasslands: Conservation Biology, v. 12, 

p. 1253–1259.

Stapp, P., Antolin, M.F., and Ball, M., 2004, Patterns of 

extinction in prairie dog metapopulations: plague outbreaks 

follow El Niño events: Frontiers in Ecology and the 

Environment, v. 2, p. 235–240.

Stapp, P., Salkeld, D.J., Eisen, R.J., Pappert, R., Young, J., 

Carter, L.G., Gage, K.L., Tripp, D.W., and Antolin, M.F., 

2008, Exposure of small rodents to plague during epizootics 

in black-tailed prairie dogs: Journal of Wildlife Diseases, 

v. 44, p. 724–730.

Stapp, P., Salkeld, D.J., Franklin, H.A., Kraft, J.P., Tripp, D.W., 

Antolin, M.F., and Gage, K.L., 2009, Evidence for the 

involvement of an alternate rodent host in the dynamics 

of introduced plague in prairie dogs: Journal of Animal 

Ecology, v. 78, p. 807–817.

Stenseth, N.C., Atshabar, B.B., Begon, M., Belmain, S.R., 

Bertherat, E., Carniel, E., Gage, K.L., Leirs, H., and 

Rahalison, L., 2008, Plague: past, present, and future: 

PLoS Medicine, v. 5, p. 9–13.

Stenseth, N.C., Samia, N.I., Viljugrein, H., Kausrud, K.L., 

Begon, M., Davis, S., Leirs, H., Dubyanskiy, V.M., Esper, 

J., Ageyev, V.S., Klassovskiy, N.L., Pole, S.B., and Chan, 

K.-S., 2006, Plague dynamics are driven by climate 

variation: Proceedings of the National Academy of Sciences, 

v. 103, p. 13110–13115.

Suntsov, V., Huong, L.T.V., Suntsova, N., and Gratz, N., 1997, 

Plague foci in Viet Nam: zoological and parasitological 

aspects: Bulletin of the World Health Organization, v. 74, 

p. 117–123.

Tabor, S., and Thomas, R., 1986, The occurrence of plague 

(Yersina pestis) in a bobcat from the trans-Pecos area of 

Texas: The Southwestern Naturalist, v. 31, p. 135–136.

Tarantola, A., Mollet, T., Gueguen, J., Barboza, P., and 

Bertherat, E., 2009, Plague outbreak in the ligyan Arab 

Jamahiriya: Eurosurveillance, v. 14, no. 26, available 

at http://www.eurosurveillance.org/ViewArticle.

aspx?Article=19258.

Thomas, C., and Hughes, P.E., 1992, Plague surveillance 

by serological testing of coyotes (Canis latrans) in 

Los Angeles County, California: Journal of Wildlife 

Diseases, v. 28, p. 610–613.

Thomas, R.E., Barnes, A.M., Quan, T.J., Beard, M.L., 

Carter, L.G., and Hopla, C.E., 1988, Susceptibility 

to Yersinia pestis in the northern grasshopper mouse 

(Onychomys leucogaster): Journal of Wildlife Diseases, 

v. 24, p. 327–333.
68 Plague

Thomas, R.E., Beard, M.L., Quan, T.J., Carter, L.G., 

Barnes, A.M., and Hopla, C.F., 1989, Experimentally 

induced plague infection in the northern grasshopper 

mouse (Onychomys leucogaster) acquired by consumption 

of infected prey: Journal of Wildlife Diseases, v. 25, 

p. 477–480.

Thomas, R.E., Karstens, R.H., and Schwan, T.G., 1990, 

Experimental infection of Ornithodoros spp. ticks (Acari: 

Argasidae) with Yersinia pestis: Journal of Medical 

Entomology, v. 27, p. 720–728.

Thorne, E.T., Quan, T.J., Williams, E.S., Walthall, T.J., and 

Daniels, D., 1987, Plague in a free-ranging mule deer from 

Wyoming: Journal of Wildlife Diseases, v. 23, p. 155–159.

Thornton, D.J., Tustin, R.C., Piennar, W.N., and Bubb, J.D., 

1975, Cat bite transmission of Yersinia pestis infection to 

man: Journal of the South African Veterinary Association, 

v. 46, p. 165–169.

Thullier, P., Guglielmo, V., Rajerison, M., and Chanteau, S., 

2003, Short report: serodiagnosis of plague in humans 

and rats using a rapid test: American Journal of Tropical 

Medicine and Hygiene, v. 69, p. 450–451.

Tikhomirov, E., 1999, Epidemiology and distribution of 

plague, in Plague manual: epidemiology, distribution, 

surveillance and control: World Health Organization, 

p. 11–41, available at http://www.who.int/csr/resources/

publications/plague/WHO_CDS_CSR_EDC_99_2_EN/en/.

Titball, R., and Williamson, E.D., 2001, Vaccination 

against bubonic and pneumonic plague: Vaccine, v. 19, 

p. 4175–4184.

Tomaso, H., Reisinger, E.C., Sascha, A.D., Frangoulidis, 

D., Rakin, A., Olfert, L., and Neubauer, H., 2003, Rapid 

detection of Yersinia pestis with multiplex real-time PCR 

assays using fluorescent hybridization probes: FEMS 

Immunology and Medical Microbiology, v. 38, no. 2, 

p. 117–126.

Trebesius, K., Harmsen, D., Rakin, A., Schmelz, J., and 

Heesemann, J., 1998, Development of rRNA-targeted 

PCR and in situ hybridization with fluorescently labelled 

oligonucleotides for detection of Yersinia species: Journal 

of Clinical Microbiology, v. 36, p. 2557–2564.

Tripp, D.W., Gage, K.L., Montenieri, J.A., and Antolin, M.F., 

2009, Flea abundance on black-tailed prairie dogs (Cynomys 

ludovicianus) increases during plague epizootics: VectorBorne and Zoonotic Diseases, v. 9, p. 313–321.

Twigg, G., 1984, The Black Death: a biological reappraisal: 

London, Batsford Academic and Educational.

Twigg, G., 1995, Bubonic plague: doubts and diagnosis: 

Journal of Medical Microbiology, v. 42, p. 383–385.

Ubico, S.R., Maupin, G.O., Fagerstone, K.A., and 

McLean, R.G., 1988, A plague epizootic in the white-tailed 

prairie dogs (Cynomys leucurus) of Meeteetse, Wyoming: 

Journal of Wildlife Diseases, v. 24, p. 399–406.

Underwood, J.G., and Van Pelt, W.E., 2008, A proposal 

to reestablish the black-tailed prairie dog (Cynomys 

ludovicianus) to southern Arizona, Nongame and 

Endangered Wildlife Program Draft Technical Report: 

Phoenix, Arizona Game and Fish Department., available 

at http://www.azgfd.gov/artman/uploads/draftblacktailedprairiedogreestablishment.pdf.

U.S. Fish and Wildlife Service, 2008, Actions underway in 

response to the plague outbreak in Conata Basin, South 

Dakota: accessed May 14, 2009, at http://www.fws.gov/

mountain-prairie/pressrel/08-41.htm.

U.S. Fish and Wildlife Service, 2010, Species report: accessed 

June 4, 2010, at http://ecos.fws.gov/tess_public/pub/

SpeciesReport.do.

U.S. Geological Survey, 2008a, Ouch! Taking a shot at 

plague: vaccine offers hope for endangered ferrets in plague 

outbreak: accessed May 15, 2009, at http://www.usgs.gov/

newsroom/article.asp?ID=1976.

U.S. Geological Survey, 2008b, Protecting black-footed ferrets 

and prairie dogs against sylvatic plague: accessed June 1, 

2009, at http://www.nwhc.usgs.gov/publications/fact_sheets/.

Vetter, S.M., Eisen, R.J., Schotthoefer, A.M., Montenieri, J.A., 

Holmes, J.L., Bobrov, A.G., Bearden, S.W., Perry, R.D., 

and Gage, K.L., 2010, Biofilm formation is not required for 

early-phase transmission of Yersinia pestis: Microbiology, 

v. 156, p. 2216–2225.

von Reyn, C.F., Barnes, A.M., Weber, N.S., Quan, T., and 

Dean, W.J., 1976, Bubonic plague from direct exposure 

to a naturally infected wild coyote: American Journal of 

Tropical Medicine and Hygiene, v. 25, p. 626–629.

von Reyn, C.F., Barnes, A.M., Weber, N.S., and Hodgin, U.G., 

1976, Bubonic plague from exposure to a rabbit: a 

documented case, and a review of rabbit-associated plague 

cases in the United States: American Journal of 

Epidemiology, v. 104, no. 1, p. 81–87.

Watson, R.P., Blanchard, T.W., Mense, M.G., and Gasper, P.W., 

2001, Histopathology of experimental plague in cats: 

Veterinary Pathology, v. 38, no. 2, p. 165–172.

Webb, C.T., Brooks, C.P., Gage, K.L., and Antolin, M.F., 

2006, Classic flea-borne transmission does not drive plague 

epizootics in prairie dogs: Proceedings of the National 

Academy of Sciences, v. 103, p. 6236–6241.
References Cited 69

Weniger, B.G., Warren, A.J., Forseth, V., Shipps, G.W., 

Creelman, T., Gorton, J., and Barnes, A.M., 1984, Human 

bubonic plague transmitted by a domestic cat scratch: 

Journal of the American Medical Association, v. 251, 

p. 927–928.

Werner, S.B., Weidmer, C.E., Nelson, B.C., Nygaard, GS., 

Goethals, RM.., and Poland, J.D., 1984, Primary plague 

pneumonia contracted from a domestic cat as South Lake 

Tahoe, Calif: Journal of the American Medical Association, 

v. 251, p. 929–931.

Wheelis, M., 2002, Biological warfare at the 1346 siege of 

Caffa: Emerging Infectious Diseases, v. 8, p. 971–975.

Wiechmann, I., and Grupe, G., 2005, Detection of Yersinia 

pestis DNA in two early medieval skeletal finds from 

Aschheim (Upper Bavaria, 6th century A.D.): American 

Journal of Physical Anthropology, v. 126, p. 48–55.

Wild, M.A., Shenk, T.M., and Spraker, T.R., 2006, Plague 

as a mortality factor in Canada lynx (Lynx canadensis) 

reintroduced to Colorado: Journal of Wildlife Diseases, 

v. 42, p. 646–650.

Wilder, A.P., Eisen, R.J., Bearden, S.W., Montenieri, J.A., 

Gage, KL.., and Antolin, M.F., 2008, Oropsylla hirsuta 

(Siphonaptera: Ceratophyllidae) can support plague 

epizootics in black-tailed prairie dogs (Cynomys 

ludovicianus) by early-phase transmission of Yersinia pestis: 

Vector-Borne and Zoonotic Diseases, v. 8, no. 3, p. 359–367.

Wilder, A.P., Eisen, R.J., Bearden, S.W., Montenieri, J.A., 

Tripp, D.W., Brinkerhoff, R.J., Gage, K.L., and Antolin, 

M.F., 2008, Transmission efficiency of two flea species 

(Oropsylla tuberculata cynomuris and Oropsylla hirsuta) 

involved in plague epizootics among prairie dogs: 

EcoHealth, v. 5, no. 2, p. 205–212.

Williams, E.S., Mills, K., Kwiatkowski, D., Thorne, E.T., and 

Boerger-Fields, A., 1994, Plague in a black-footed ferret 

(Mustela nigripes): Journal of Wildlife Diseases, v. 30, 

p. 581–585.

Williams, E.S., Thorne, E.T., Quan, T.J., and Anderson, S., 

1991, Experimental infection of domestic ferrets (Mustela 

putorius furo) and Siberian polecats (Mustela eversmanni) 

with Yersinia pestis: Journal of Wildlife Diseases, v. 27, 

no. 3, p. 441–445.

Williams, E.S., Thorne, E.T., Appel, M.J.G., and Belitsky, 

D.W., 1988, Canine distemper in black-footed ferrets 

(Mustela nigripes) from Wyoming: Journal of Wildlife 

Diseases, v. 24, p. 385.

Wimsatt, J., and Biggins, D.E., 2009, A review of plague 

persistence with special emphasis on fleas: Journal of Vector 

Borne Diseases, v. 46, p. 85–99.

Wong, D., Wild, M.A., Walburger, M.A., Higgins, C.L., 

Callahan, M., Czarnecki, L.A., Lawaczeck, E.W., 

Levy, C.E., Patterson, J.G., Sunenshine, R., Adem, P., 

Paddock, C.D., Zaki, S.R., Petersen, J.M., Schriefer, 

M.E., Eisen, R.J., Gage, K.L., Griffith, K.S., Weber, I.B., 

Spraker, T.R., and Mead, P.S., 2009, Primary pneumonic 

plague contracted from a mountain lion carcass: Clinical 

Infectious Diseases, v. 49, p. E33–E38.

Wood, J.W., Ferrell, R.J., and Dewitte-Avińa, S.N., 2003, The 

temporal dynamics of the fourteenth-century black death: 

new evidence from English ecclesiastical records: Human 

Biology, v. 75, p. 427–448.

World Health Organization, 1970, Health aspects of 

chemical and biological weapons: Geneva, World Health 

Organization, p. 98–109, available at http://www.who.int/

csr/delibepidemics/biochem1stenglish/en/.

World Health Organization, 1997—Bubonic plague in 

Zambia: accessed May 15, 2009, at http://www.who.int/csr/

don/1997_01_31b/en/.

World Health Organization, 2000, Plague, in WHO Report on 

Global Surveillance of Epidemic-prone Infectious Diseases: 

Geneva, World Health Organization, p. 25–31, available at 

http://www.who.int/csr/resources/publications/surveillance/

WHO_Report_Infectious_Diseases.pdf.

World Health Organization, 2004, Human plague in 2002 and 

2003: Weekly Epidemiological Record, v. 79, p. 301–306.

World Health Organization, 2005, Plague in the Democratic 

Republic of the Congo—update 3: accessed August 17, 

2009, at http://www.who.int/csr/don/2005_03_09/en/index.

html.

World Health Organization, 2006, International meeting on 

preventing and controlling plague: the old calamity still has 

a future: Weekly Epidemiological Record, v. 81, p. 278–284.

World Health Organization, 2009, Plague in China: 

accessed August 17, 2009, at http://www.who.int/csr/

don/2009_08_11/en/index.html.

World Health Organization, 2010, Human plague: review 

of regional morbidity and mortality, 2004–2009: Weekly 

Epidemiological Record, v. 85, p. 40–45.

World Wildlife Fund, 2009, WWF Helps Masked Bandit 

Return to Prairies: accessed October 9, 2009, at 

http://wwf.ca/newsroom/?4760.

Woron, A.M., Nazarian, E.J., Egan, C., McDonogh, K.A., 

Cirino, N.M., Limberger, R.J., and Musser, K.A., 2006, 

Development and evaluation of a 4-target multiplex realtime polymerase chain reaction assay for the detection and 

characterization of Yersinia pestis: Diagnostic Microbiology 

and Infectious Disease, v. 56, p. 261–268.
70 Plague

Wren, B.W., 2003, The Yersiniae—a model genus to study 

the rapid evolution of bacterial pathogens: Nature Reviews 

Microbiology, v. 1, p. 55–64.

Wuerthner, G., 1997, Viewpoint: the black-tailed prairie dog—

headed for extinction?: Journal of Range Management, 

v. 50, p. 459–466.

Yersin, A., 1894, La peste bubonique a Hong Kong: Annales 

de l’Institut Pasteur, v. 8, p. 662–667.

Zhou, D., Tong, Z., Song, Y., Han, Y., Pei, D., Pang, X., 

Zhai, J., Li, M., Cui, B., Qi, Z., Jin, L., Dai, R., Du, Z., 

Wang, J., Guo, Z., Wang, J., Huang, P., and Yang, R., 2004, 

Genetics of metabolic variations between Yersinia pestis

biovars and the proposal of a new biovar, microtus: Journal 

of Bacteriology, v. 186, p. 5147–5152.

Zietz, B.P., and Dunkelberg, H., 2004, The history of the 

plague and the research on the causative agent Yersinia 

pestis: International Journal of Hygiene and Environmental 

Health, v. 207, no. 2, p. 165–178.
Glossary 71

Glossary

Bolded terms within the definition of a term are in the 

glossary.

16S rRNA A small portion of the ribosomal RNA of bacteria 

used in studies of the evolution of a species, because it is 

nearly identical among members of a species of bacteria.

A

abundance threshold The minimum population of a species 

of rodent above which an epizootic of plague may occur.

acute Sharp or severe, such as an illness with a sudden onset 

and a relatively short course.

aerosol Fine mist of microscopic solid or liquid particles 

suspended in air or gas.

amplifying host A host in which disease agents, such as 

viruses, increase in number.

antibody A protein formed in the body of a vertebrate that 

is used by the immune system to identify and neutralize the 

effects of foreign invading proteins, called antigens, such as 

bacteria and viruses.

antigen Any foreign substance (generally proteins) to which 

the body reacts by producing antibodies. Antigens may be 

soluble substances such as toxins, particulate matter such as 

pollen, or microorganisms such as bacteria and viruses.

argasid ticks Eight-legged arthropods of the family 

Argasidae characterized by their soft, membranous external 

shells; also called “soft ticks.”

aspirate The substance or material obtained by suctioning of 

fluids from a cavity.

arthropod An invertebrate belonging to the phylum 

Arthopoda, including insects, spiders, and crustaceans. 

Arthropods are covered by a hard exoskeleton and are 

characterized by a segmented body, jointed legs, and many 

pairs of limbs.

B

bacillus (bacilli, plural) Any rod-shaped bacteria that can 

be found in many different taxonomic groups of bacteria.

bacteria (bacterium, singular) Microscopic, unicellular 

organisms that have distinct cell membranes and lack a distinct 

nucleus surrounded by a nuclear membrane.

bacteremia The presence of bacteria in the blood.

bacterial load The number of bacteria within the vector; 

the number of Y. pestis within a flea.

bacteriophage A virus that infects a bacterium.

biofilm A mass of microorganisms in which cells are 

adhered to each other, or to a surface, or both.

bioterrorism The use of biological agents, such as 

pathogenic organisms or agricultural pests, for terrorist 

purposes.

biovar In the classification of bacteria, strains with 

sufficiently distinct characteristics (for example, chemical, 

molecular) to be considered a subspecies of a taxonomic 

species.

bioweapon Any weapon usable in biological warfare and 

bioterrorism.

birds Warm-blooded vertebrates with wings and feathers, 

although the wings are poorly developed in some flightless 

species. Birds belong to the taxonomic class Aves.

bubo An enlarged and inflamed lymph node, particularly in 

the armpit or groin, due to infection with Y. pestis or other 

organisms, such as those causing gonorrhea, tuberculosis, or 

syphilis.

bubonic plague A severe bacterial disease of humans due 

to infection by Y. pestis; acute regional enlargement and 

inflammation of lymph nodes (buboes) is typical of this most 

common form of plague in humans.

C

cannibalism The act of any species consuming members of 

its own kind.

carnivore Mammals with teeth and other body adaptations 

for feeding on flesh; primarily species belonging to the order 

Carnivora such as wolves, bears, raccoons, weasels, civets, 

hyenas, and tigers.

clinical signs Readily observable indications of a disease or 

injury.

coccobacillus A type of rod-shaped bacteria intermediate 

between the coccus (spherical) and bacillus (elongated) forms.

commensal Living with or near people and depending on 

humans, at least partially, for food and shelter.

contagious Capable of being transmitted from animal to 

animal.
72 Plague

critical threshold The level, such as numbers or density of 

animals, above which a particular event, such as an epizootic

of plague, occurs suddenly. Below the threshold, the event 

does not occur.

culture The growing of bacteria, other microorganisms, or 

cells in a specially prepared nutrient medium.

D

desert An area that receives almost no precipitation, less 

than 10 inches (250 millimeters) per year, or that loses more 

than is received; vegetation is sparse to almost nonexistent.

die-off A sudden dramatic decline of a population of animals 

or plants caused by natural events such as weather or disease.

direct fluorescent antibody test A laboratory test using 

antigen-specific antibodies labeled with fluorescent dye to 

detect the presence of microorganisms.

disease An abnormal condition of an animal or plant that 

causes specific signs or symptoms.

DNA (deoxyribonucleic acid) A nucleic acid found mainly in 

the chromosomes that contains the hereditary information of 

organisms and some viruses.

domestic Pertaining to an environment managed by humans.

E

emerging disease A disease that has newly appeared or 

increased in frequency of occurrence, or both, within the 

past three decades, or threatens to increase in the near future 

relative to populations affected, geographic distribution, or 

magnitude of effects.

endemic A disease that commonly is present within a human 

population or a geographical area or pertaining to such a 

disease.

endophthalmitis Inflammation involving the eye cavities 

and their adjacent structures.

enteric redmouth disease A bacterial infection of fish 

caused by Yersinia ruckeri. Infected fish have bleeding under 

the skin around the mouth, fins, and eyes. Bleeding also 

occurs on internal organs, such as the intestine and swim 

bladder. The disease can cause severe economic losses in the 

trout farming industry.

enzootic An animal disease that commonly is present within 

a population or a geographical area or pertaining to such a 

disease.

epidemic An outbreak of disease affecting a 

disproportionately large number of humans within a 

population, community, or region during a period of time or 

pertaining to such an outbreak.

epidemiology The study of factors affecting the frequency 

and distribution of disease within populations.

epizootic An outbreak of disease affecting a greater number 

of animals than normal, typically involving many animals 

in the same region at the same time or pertaining to such an 

outbreak.

extinction The end of a species or other taxon when there 

are no surviving members of the group.

extirpation Local extinction; a species (or other taxon) 

ceases to exist in a particular area, but survives elsewhere.

F

fatality rate The ratio of deaths within a designated 

population with a particular disease, over a specified period of 

time.

fecal-oral route A route of transmission of disease, in 

which pathogens are passed from individual to individual by 

ingestion of feces.

felid Mammals within the family Felidae (for example, 

domestic cats, lion, tiger, leopard, lynx, cheetah, and many 

other wild cats).

flea Small, wingless, bloodsucking insect within the order 

Siphonaptera with laterally compressed body and legs adapted 

for jumping.

flea load The number of fleas infesting an animal.

fluorescent antibody test A laboratory test utilizing 

fluorescent dyes as stains for the detection of antibody against 

specific pathogens.

foci (focus, singular) A geographically localized area in 

which plague is maintained indefinitely by specific rodents

and their fleas.

foregut The esophagus and proventriculus of the flea.

G

gene The biologic unit of heredity consisting of a specific 

sequence within a DNA molecule that determines a particular 

characteristic of an organism by controlling production of a 

specific protein.

genera (genus, singular) (plural of genus) A low-level 

taxonomic rank used in the classification of living and fossil 

organisms.
Glossary 73

genotype The genetic makeup of a cell, an organism, or an 

individual, usually with reference to a specific character under 

consideration.

genotyping The process of determining the genotype of an 

individual by the use of biological tests, including PCR and 

DNA sequencing.

genus A taxonomic group of similar species; similar genera

are grouped into families.

Gram-negative Referring to the inability to retain the purple 

dye when treated by Gram’s stain for differentiating bacteria

into two major groups (Gram-negative and Gram-positive).

ground squirrels Typically, burrowing small rodents of the 

family Sciuridae, but this term often also includes species 

in other genera such as chipmunks and prairie dogs. Ground 

squirrels in the United States include the thirteen-lined ground 

squirrel, rock squirrel, and antelope ground squirrel.

H

heterogeneous Made up of parts with dissimilar 

characteristics or properties.

hibernation A state of inactivity and metabolic depression 

in animals, characterized by lower body temperature, slower 

breathing, and lower metabolic rate to conserve energy, 

especially during winter when food is scarce.

horizontal gene transfer Any process in which an organism 

incorporates genetic material from another organism without 

being the offspring of that organism.

host An organism that harbors or nourishes microbes, 

viruses, and parasites on or in itself.

I

incidence The probability of a new case of a specific 

disease developing in a population at risk during a specified 

time period.

incubation period The time interval required for the 

development of disease; the time between the invasion of the 

body by a disease agent and the appearance of the first clinical

signs.

infection The invasion by and reproduction of 

microorganisms in body tissues.

inguinal Related to the groin, the junction between the 

abdomen and thighs.

inocula (inoculum, singular) The antigenic material 

introduced into an animal to produce immunity or disease.

insecticide A pesticide used against insects.

insectivore An animal that feeds primarily on insects.

ixodid ticks Arthropods of the family Ixodidae that 

are important for disease transmission; includes ticks 

of the genera Dermacentor, Amblyomma, Ixodes, and 

Haemaphysalis; also known as “hard ticks.”

J

K

L

lagomorph Mammal within the order Lagomorpha (rabbits, 

hares, and pikas).

latent Dormant or concealed; a latent infection refers to the 

situation in which a disease condition is not apparent.

latitude The location of a place on Earth north or south of 

the equator.

louse Small, wingless, usually flattened insect that is 

parasitic on animals, or plants, or both and derives its nutrition 

by feeding on host blood or other body components; true 

lice infest animals, including humans, and transmit several 

important diseases.

lymphadenitis Inflammation of lymph nodes.

lymphadenopathy Disease (infection, autoimmune disease, 

or tumor) of the lymph nodes, often used synonymously with 

“swollen/enlarged lymph nodes.”

lymphoid tissues Immune system tissues, such as bone 

marrow, thymus, lymph nodes, tonsils, and spleen

lysis Refers to the death of a cell by breaking of the cellular 

membrane, causing the contents to spill out.

M

maintenance host An organism that keeps a disease agent 

in existence in nature and provides a source of infections to 

susceptible hosts. (See reservoir.)

mammal Warmblooded vertebrate animal that possesses hair 

during some part of its life and suckles it young.

mandibular Related to the mandible or lower jaw bone.

meningeal Related to the meninges, the membranes 

covering the brain and spinal cord.

meningitis Inflammation of the meninges, the membranes 

covering the brain and spinal cord.
74 Plague

metapopulation A group of spatially separated populations 

of the same species that interact at some level.

monohostal Describing maintenance of plague in a focus by 

a single rodent species.

morbidity A diseased condition, or the severity or incidence 

of a disease.

mortality Susceptible to death; death.

mortality rate The ratio of deaths (in general or due to a 

specific cause) in a specific population over a particular period 

of time.

mouse inoculation Injection of material suspected of 

containing a disease-causing agent into a mouse; development 

of disease in the mouse confirms the presence of the pathogen

in the sample.

mustelid A member of the weasel family (Mustelidae), 

carnivorous animals such as weasel, wolverine, otter, marten, 

badger, ferret, and mink.

N

nasopharyngeal swab A sample of fluid obtained by passing 

a sterile instrument up the nostril to the portion of the pharynx 

above the soft palate.

necrotizing panophthalmitis Severe inflammation of all the 

eye structures leading to death of the tissues.

O

ocular Related to the eye.

P

pandemic An epidemic of infectious disease that is 

spreading through human populations across a large region, 

such as a continent or worldwide.

parasitism An association between two species in which 

one (the parasite) benefits from the other (the host), often by 

obtaining nutrients and shelter.

passive hemagglutination testing A laboratory test in which 

red blood cells are coated with soluble antigen; the red blood 

cells then clump in the presence of antibodies specific for the 

antigen.

pathogen Typically, a microorganism capable of inducing 

disease, but broadly including all disease-inducing agents.

pathogenic The ability to cause disease.

PCR (polymerase chain reaction) A laboratory technique 

used to generate millions or more copies of a particular DNA

sequence.

peridomestic Pertaining to living in and around human 

habitations.

pharyngeal Pertaining to the pharynx, the 

musculomembranous passage between the mouth and the 

larynx and esophagus.

pika Short-eared, small rabbit-like mammals within the 

order Lagomorpha; also referred to as coney or rock rabbit.

plasmid A piece of DNA found in bacteria independent of 

the chromosomal DNA.

pleuritis Inflammation of the pleura, the membrane 

surrounding the lungs and lining the thoracic cavity.

pneumonic Pertaining to the lungs or pneumonia.

polyhostal Describing maintenance of plague in a focus by 

more than one rodent species.

population A group of organisms inhabiting a specific area 

or possessing a specific trait.

prairie Mainly in North America, the part of the temperate 

latitude grasslands characterized by level-to-rolling terrain, 

deep fertile soil, moderate rainfall, and a predominance of 

grasses, herbaceous plants, and shrubs, rather than trees.

predation The characteristic of preying on other animals as a 

source of food.

predator An animal that preys on other animals as a source 

of food.

prevalence The total number of cases of a disease in a 

population at a given time.

prevalent Widely or commonly occurring.

primary productivity The rate at which sunlight is used by 

plants to convert carbon dioxide (CO2) to organic compounds 

used by animals as food.

prophylactic Preventing the spread of disease.

protozoa One-celled animals with recognizable nucleus, 

cytoplasm, and cytoplasmic structures, such as amoebas, 

ciliates, flagellates, and sporozoans.

protein An essential component of living cells that is made 

of chains of amino acids and contains carbon, hydrogen, 

nitrogen, oxygen, and sometimes sulfur.
Glossary 75

proventricular blockage Obstruction of the proventriculus

by the aggregation and adherence of Y. pestis within its interior 

space.

proventriculus The valve that connects the midgut to the 

esophagus of a flea.

Q

R

raptor Synonymous with birds of prey; including hawks, 

owls, falcons, and eagles, that feed on flesh.

regurgitation The flow of stomach contents back into the 

esophagus and mouth.

reservoir The host that maintains the disease agent in nature 

and provides a source of infection to susceptible hosts. (See

maintenance host.)

resistant Pertaining to the ability of a microorganism to 

remain unaffected by an antimicrobial agent or the ability of 

an animal to remain either uninfected by a disease-causing 

organism or disease-free despite becoming infected.

ribotype A grouping of bacteria within a species based on 

similarities in rRNA. (See also 116 rRNA.)

RNA (ribonucleic acid) A nucleic acid found mainly in the 

cytoplasm of cells that functions principally in the production 

of proteins. It differs from DNA by having a single chain 

rather than a double chain of nucleotides and containing the 

sugar ribose instead of deoxyribose.

rodent A diverse group of mammals characterized by incisor 

teeth that grow throughout life and that must be worn away 

by cutting and gnawing hard materials. Species within the 

order Rodentia include squirrels, mice, rats, voles, chipmunks, 

gophers, lemmings, beaver, porcupines, and many others.

rodenticide Toxic substances used to kill rodents.

rRNA gene restriction pattern A molecular tool used to 

type strains of bacteria by analyzing the number and size of 

fragments of rRNA obtained after enzymatic digestion. (See 

also 116 rRNA and RNA.)

S

savanna A tropical grassland characterized by small, widely 

spaced trees, where most rain falls during one season of the 

year.

scavenging Feeding on dead or decaying matter.

scavenger An animal that feeds on dead carcasses, other 

carrion, and refuse (such as vultures, crows, hyenas, and 

jackals).

semidesert An extremely dry area characterized by sparse 

vegetation.

sentinel A susceptible animal or population that is monitored 

for the appearance or recurrence of a pathogen or antibodies 

against the pathogen as part of a disease surveillance system.

septicemia Blood poisoning; persistence of pathogenic

microorganisms, or their toxins, or both in the blood.

septic shock A sudden drop in blood pressure caused by 

severe infection, especially with gram-negative bacteria, and 

marked by low blood pressure, coldness of the skin, increased 

heart rate, anxiety, and death in some cases.

seroconvert To develop detectable specific antibodies in the 

blood serum in response to immunization or infection.

serological testing The diagnostic identification of 

antibodies in the serum, the liquid portion of blood.

serum The pale liquid that separates from the blood when it 

is allowed to clot completely.

species A population of organisms whose members are 

able to breed among themselves and produce fertile offspring. 

More precise determinations of species are based on similarity 

of DNA. (See also strain.)

sputum Material, such as mucus or phlegm, that is coughed 

up from the lungs, bronchi, and trachea, into the mouth.

steppe A vast semiarid grass-covered plain, found in 

southeast Europe and Siberia.

strain A genetically or biochemically distinguishable 

subtype of a microorganism.

subcutaneous Under the skin.

subspecies A taxonomic category subordinate to a species, 

whose members differ morphologically from other members 

of the species but remain capable of interbreeding with them.

subtropical The region in each hemisphere between the 

tropical and temperate regions.

surveillance The systematic collection, analysis, and 

interpretation of data pertaining to the occurrence of specific 

diseases for the purpose of monitoring morbidity and 

mortality trends.

susceptible Pertaining to the ability of an animal to become 

infected by a disease-causing organism or to develop disease 

after becoming infected.
76 Plague

sylvatic Existing normally in the wild, not in the human 

environment.

symbiotic Living together in symbiosis, the close 

association of two unlike organisms with varying degrees of 

benefit, or harm, or both to the participants.

T

taxonomy The systematic principles and procedures of 

grouping and arranging organisms into a hierarchical order.

temperate latitudes Latitudes of the globe that lie between 

the tropics and the polar circles that exhibit seasonal 

temperature patterns.

translocation Human capture of wildlife at one geographic 

area and its transportation and release at a different geographic 

area.

transmission The spread of infectious agents from one 

individual to another by direct and indirect means, such as 

through contaminated environment or inanimate objects.

transmission efficiency The rate (infections per number of 

attempts) at which a vector is able to transmit an infection to 

a host.

trophic cascade Trophic level refers to an animal’s position 

in the food chain. In plague ecology, precipitation and 

temperature have a cascading effect on plague occurrence by 

influencing the plant productivity of an area, which in turn 

affects the populations of rodents and fleas that further affect 

the transmission of plague.

tropical Geographically, the zone on either side of the 

equator, bounded by the Tropic of Cancer (23°27’ North 

latitude) and the Tropic of Capricorn (23°27’ South latitude); 

climatically hot and humid for most of the year.

U

ungulate Mammals having hooves. The even-toed hoofed 

species (Artiodactyla) include deer, antelope, cattle, and 

sheep; the odd-toed hoofed mammals (Perissodactyla) include 

horses, tapirs, and rhinoceroses.

V

vaccine A biological preparation containing an antigen, a 

molecule that stimulates the immune system, that is used to 

establish immunity to a disease.

vector An insect or other living organism that carries and 

transmits a disease agent from one animal to another.

vertebrate An animal that has a backbone, such as 

mammals, birds, amphibians, and fish.

virulence The degree or ability of a pathogenic organism 

to cause disease. The disease-producing ability of a 

microorganism, generally indicated by the severity of the 

infection in the host and the ability of the agent to invade or 

cause damage or both to the host’s tissues.

W

X

Y

Z

zoonotic Pertaining to a disease that can be transmitted from 

animals to humans, and vice versa.
Appendix 1. Common and Scientific Names for Species Cited 77

Appendix 1. Common and Scientific Names for Species Cited

Common name Scientific name

Abert’s squirrel Sciurus aberti

African buffalo Syncerus caffer

American marten Martes americana

Antelope ground squirrel Ammospermophilus leucurus

Asian house shrew Suncus murinus

Badger (American) Taxidea taxus

Bandicoot rat Bandicota indica

Bandicota bengalensis

Black bear Ursus americanus

Black-footed ferret Mustela nigripes

Black rat Rattus rattus

Black-tailed deer Odocoileus hemionus

Black-tailed prairie dog Cynomys ludovicianus

Bobcat Lynx rufus

Burrowing owl Athene cunicularia

California ground squirrel Spermophilus beecheyi

California vole Microtus californicus

Camel Camelus species

Canada lynx Lynx canadensis

Cane mouse Zygodontomys species

Bolomys lasiurus

Oryzomys species

Chipmunk Tamias species

Cotton rat Sigmodon species

Cottontail rabbit (mountain) Sylvilagus nuttallii

Coyote Canis latrans

Deer mouse Peromyscus species, including P. maniculatus

Domestic cat Felis catus

Domestic dog Canis lupus familiaris

Domestic ferret Mustela putorius furo

Domestic guinea pig Cavia porcellus

Domestic pig Sus scrofa

Donkey (ass, burro) Equus asinus

Elephant (African) Loxodonta africana

Ferruginous hawk Buteo regalis

Fisher Martes pennanti

Forest rat Rattus nitidus

Fox (red, kit) Vulpes species

Fox squirrel Sciurus niger

Gerbil (jird, great gerbil) Meriones species

Rhombomys opimus

Tatera species

Desmodillus species

Gerbillus species
78 Plague

Common name Scientific name

Goat Capra hircus

Golden eagle Aquila chrysaetos

Gray fox Urocyon cinereoargenteus

Great gerbil Rhombomys opimus

Groove-toothed cheek rat Pelomys species

Ground squirrel Spermophilus species including

S. variegatus

S. spilosoma

S. beecheyi

S. lateralis

S. beldingi

S. elegans

S. armatus

S. townsendi

Citellus species

Guinea pig Cavia porcellus

Gunnison’s prairie dog Cynomys gunnisoni

Hare Lepus species

Horned lark Eremophila alpestris

Horse Equus caballus

House shrew Suncus murinus

Indian bush rat Golunda ellioti

Indian field mouse Mus booduga

Indian gerbil Tatera indica

Jerboa Family Dipodidae

Kangaroo rat (Ord’s) Dipodomys ordii

Kit fox Vulpes macrotis

Leaf-eared mouse Phyllotis species

Llama Lama glama

Long-tailed weasel Mustela frenata

Lynx (Canada) Lynx canadensis

Malayan wood rat Rattus tiomanicus

Marmot Marmota species

Metad or soft-furred field rat Millardia meltada

Mexican prairie dog Cynomys mexicanus

Mountain lion Puma concolor

Mountain plover Charadrius montanus

Mule deer Odocoileus hemionus

Multimammate mouse Mastomys species

Northern grasshopper mouse Onychomys leucogaster

Norway or brown rat Rattus norvegicus

Palm squirrel Funambulus species

Pika Ochotona species
Appendix 1. Common and Scientific Names for Species Cited 79

Common name Scientific name

Pine marten Martes martes

Polynesian rat Rattus exulans

Prairie dog Cynomys species

Pronghorn antelope Antilocapra americana

Rabbit (cottontail, Old World) Sylvilagus species

Oryctolagus species

Raccoon Procyon lotor

Rat Rattus species

Rice rat Oryzomys species

Ringtail cat Bassariscus astutus

Rock squirrel Spermophilus variegatus

Roof or black rat Rattus rattus

Sable antelope Hippotragus niger

Sheep Ovis aries

Siberian polecat (Steppe) Mustela eversmanii

South American field mouse Akodon species

Spiny field mouse Mus platythrix

Spotted skunk Spilogale putorius

Spring hare Pedetes capensis

Striped skunk Mephitis mephitis

Suslik Spermophilus species

Swamp rat Otomys species

Swift fox Vulpes velox

Thirteen-lined ground squirrel Spermophilus tridecemlineatus

Tree shrew (common) Tupaia glis

Tree squirrel Sciurus stramineus

Unstriped grass mouse Arvicanthis species

Utah prairie dog Cynomys parvidens

Vole Microtus species, including

M. californicus

M. montanus

Eothenomys species

White-bellied mountain rat Rattus niviventer

White-tailed prairie dog Cynomys leucurus

Wild boar Sus scrofa

Wild cavies Cavia species

Galea species

Wood rat Neotoma species, including

N. albigula

N. mexicana

N. fuscipes

N. cinerea

Zebra Equus species




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