BW-ch05.pdf

Plague

Chapter 5

PLAGUE

PATRICIA L. WORSHAM, P h D * ; THOMAS W. MCGOVERN, MD, FAAD † ; NICHOLAS J. VIETRI, MD ‡ ; and

ARTHUR M. FRIEDLANDER, MD §

INTRODUCTION

HISTORY

PLAGUE AND WARFARE

THE INFECTIOUS AGENT

EPIDEMIOLOGY

INCIDENCE

VIRULENCE DETERMINANTS

PATHOGENESIS

CLINICAL MANIFESTATIONS

DIAGNOSIS

TREATMENT

SUMMARY

* Deputy Chief, Division of Bacteriology, US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Maryland

21702

† Major, Medical Corps, US Army (Ret); Dermatologist, Fort Wayne Dermatology Consultants, 11123 Parkview Plaza Drive #203, Fort Wayne, Indiana

46845, and Assistant Clinical Professor of Dermatology, Indiana University School of Medicine, 1120 South Drive, Indianapolis, Indiana 46202

‡ Major, Medical Corps, US Army; Infectious Diseases Physician and Principal Investigator, Division of Bacteriology, US Army Medical Research In-

stitute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Maryland 21702; formerly, Infectious Diseases Fellow, Department of Medicine, Brooke

Army Medical Center, San Antonio, Texas

§ Colonel, Medical Corps, US Army (Ret); Senior Scientist, Division of Bacteriology, US Army Medical Research Institute of Infectious Diseases, 1425

Porter Street, Fort Detrick, Maryland 21702; and Adjunct Professor of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones

Bridge Road, Bethesda, Maryland 20814

Medical Aspects of Biological Warfare

INTRODUCTION

Plague, a severe febrile illness caused by the gram-

negative bacterium Yersinia pestis, is a zoonosis usually

transmitted by fleabites. Plague is foremost a disease

of rodents; over 200 species have been reported to be

infected with Y pestis . 1,2 Humans most often become

infected by fleabites during an epizootic event; less

frequently they are exposed to blood or tissues of

infected animals (including ingestion of raw or under-

cooked meat) or aerosol droplets containing the organ-

ism. 1,3 Humans or animals with plague pneumonia,

particularly cats, can generate infectious aerosols. 4,5

The resulting primary pneumonic plague is the most

severe and most frequently fatal form of the disease.

Pneumonic plague is of particular concern to the mili-

tary because it can also be acquired from artificially

generated aerosols.

In the 6th, 14th, and 20th centuries Y pestis caused

three great pandemics of human disease. The bubonic

form of Y pestis in humans is characterized by the

abrupt onset of high fever; painful local lymphade-

nopathy draining the exposure site (ie, a bubo, the

inflammatory swelling of one or more lymph nodes,

usually in the groin; the confluent mass of nodes, if

untreated, may suppurate and drain pus); and bac-

teremia. Septicemic plague can ensue from untreated

bubonic plague or without obvious lymphadenopathy

after a fleabite. Patients with the bubonic form of Y

pestis may develop secondary pneumonic plague,

which can lead to human-to-human spread by the

respiratory route. Cervical lymphadenitis has been

noted in several human plague cases, including many

fatal cases, and is often associated with the septicemic

form of the disease. However, it is possible that these

patients were exposed by the oral/aerosol route and

developed pharyngeal plague that progressed into

a systemic infection. 1,6-8 Cervical lymphadenopathy,

which is more common in patients from developing

countries, may result from flea bites on the neck or

face while sleeping on the dirt floors of heavily flea-

infested buildings. 9

During the past four millennia, plague has played a

role in many military campaigns. During the Vietnam

War, plague was endemic among the native popula-

tion, but US soldiers were relatively unaffected. The

protection of troops was attributable to the US mili-

tary’s understanding of the rodent reservoirs and flea

vectors of disease, the widespread use of a plague vac-

cine during the war, and prompt treatment of plague

victims with effective antibiotics. Mortality from

endemic plague continues at low rates throughout the

world despite the availability of effective antibiotics.

Deaths resulting from plague occur not because the

bacilli have become resistant but, most often, because

plague is not the differential diagnosis, or treatment

is absent or delayed.

The US military’s concern with plague is both as

an endemic disease and as a biological warfare threat.

To best prepare to treat plague in soldiers who are

affected by endemic disease or a biological agent at-

tack, military healthcare providers must understand

the natural mechanisms by which plague spreads

between species, the pathophysiology of disease in

humans, and the diagnostic information necessary to

begin treatment with effective antibiotics. No vaccine

is currently available for plague, although candidates

are in clinical trials. A better understanding of the

preventive medicine aspects of the disease will aid in

the prompt diagnosis and effective treatment necessary

to survive a plague attack.

Key terms in this chapter include enzootic and epi-

zootic. These terms refer, respectively, to plague that is

normally present in an animal community but occurs

in only a small number of animals, and to widespread

plague infections leading to death among susceptible

nest populations (ie, equivalent to an epidemic in a

human population). The death of a rodent causes the

living fleas to leave that host and seek other mammals,

including humans. Knowledge of these two concepts

helps to clarify how and when humans may be infected,

in either endemic or biological warfare scenarios.

HISTORY

The Justinian Plague (First Pandemic)

40% of Constantinople’s population, died during this

epidemic. 11,12 Repeated, smaller epidemics followed

this plague. 13

Procopius provided the first identifiable descrip-

tion of epidemic plague in his account of the plague

of the Byzantine Empire during the reign of Justinian

I (541–542 ce [the common era]), which is now consid-

ered the first great pandemic of the ce . 10 At the height

of the epidemic, more than 10,000 people died each

day. As many as 100 million Europeans, including

The Black Death (Second Pandemic)

The second plague pandemic, known as the Black

Death, brought the disease into the collective memory

of Western civilization. 13 Plague bacilli probably entered

Plague

Europe via the trans-Asian Silk Road during the early

14th century in fleas on the fur of marmots (a rodent

of the genus Marmota ). When bales of these furs were

opened in Astrakhan and Saray, hungry fleas jumped

from the fur seeking the first available blood meal,

often a human leg. 13-15 In 1346 plague arrived in Caffa

(modern Feodosiya, Ukraine) on the Black Sea. Caffa’s

large rat population helped spread the disease as they

were carried on ships bound for major European ports

such as Pera, a suburb of Constantinople, and Messina,

in Sicily. By 1348 plague had entered Great Britain at

Weymouth. 10

The Black Death probably killed 24 million people

between the years 1346 and 1352 and perhaps another

20 million by the end of the 14th century. 11 However,

some people believe that the plague persisted through

1720, with a final foray into Marseilles. During the 15th

through the 18th centuries, 30% to 60% of the popu-

lations of major cities, such as Genoa, Milan, Padua,

Lyons, and Venice, died of plague. 15

Failing to understand the plague’s epidemiology,

physicians could offer no effective treatment. Physi-

cians at the University of Paris theorized that a con-

junction of the planets Saturn, Mars, and Jupiter at

1:00 pm on March 20, 1345, corrupted the surrounding

atmosphere, which led to the plague. 11 Physicians rec-

ommended a simple diet; avoidance of excessive sleep,

exercise, and emotion; regular enemas; and abstinence

from sexual intercourse. 16 Although some people killed

cats and dogs because they were thought to carry

disease, rats seemed to escape attention. 11 Christians

blamed plague on Muslims, Muslims blamed it on

Christians, and both Christians and Muslims blamed

it on Jews or witches. 13

In 1666 a church rector in Eyam, Derbyshire, Eng-

land, persuaded the whole community to quarantine

itself when plague erupted there, but this was the worst

possible solution because the people then remained

close to the infected rats. The city experienced virtually

a 100% attack rate with 72% mortality. The average

mortality for the Black Death was consistently 70%

to 80%. 13,17

Accurate clinical descriptions of the Black Death

were written by contemporary observers such as

Giovanni Boccaccio in Decameron :

and black or purple spots appeared on the arms or

thighs or any other part of the body, sometimes a

few large ones, sometimes many little ones. 18

Marchionne di Coppo di Stefano Buonaiuti (1327–1385)

wrote in his memoir about the Black Death in Florence:

In the year of our Lord 1348 there occurred in the

city and contado of Florence a great pestilence, and

such was its fury and violence that in whatever

household it took hold, whosoever took care of

the sick, all the carers died of the same illness, and

almost nobody survived beyond the fourth day,

neither doctors nor medicine proving of any avail….

those symptoms were as follows: either between the

thigh and the body, in the groin region, or under the

armpit, there appeared a lump, and a sudden fever,

and when the victim spat, he spat blood mixed with

saliva, and none of those who spat blood survived.

Such was the terror this caused that seeing it take

hold in a household, as soon as it started, nobody

remained: everybody abandoned the dwelling in

fear, and led to another; some led into the city and

others into the countryside…. sons abandoned fa-

thers, husbands wives, wives husbands, one brother

the other, one sister the other. The city was reduced

to bearing the dead to burial…. 19

Some writers described bizarre neurological disor-

ders (which led to the term “dance of death”), followed

by anxiety and terror, resignation, blackening of the

skin, and death. The sick emitted a terrible stench:

“Their sweat, excrement, spittle, breath, [were] so

foetid as to be overpowering” [in addition, their urine

was] “turbid, thick, black, or red.” 11

The second great pandemic slowly subsided in Eu-

rope by 1720. The pandemic’s decline was attributed

to the replacement of the black rat ( Rattus rattus ) in the

area by the Norwegian rat ( Rattus norvegicus ), which

is a less efficient host; natural vaccination of animals

and/or humans by other Yersinia species or by less

virulent Y pestis strains; and other less plausible hy-

potheses. The theories are all flawed to some extent,

and the disappearance of plague from Europe remains

one of the great epidemiology mysteries. 3,8,20

The Third Pandemic

The symptoms were not the same as in the East,

where a gush of blood from the nose was a plain

sign of inevitable death, but it began both in men

and women with certain swellings [buboes] in the

groin or under the armpit. They grew to the size of

a small apple or an egg, more or less, and were vul-

garly called tumours. In a short space of time these

tumours spread from the two parts named all over

the body. Soon after this, the symptoms changed

The third, or modern, plague pandemic arose in

1894 in China and spread throughout the world as rats

and their fleas traveled via modern transportation. 13,17

In 1894 Alexandre JE Yersin discovered Y pestis and

satisfied Robert Koch’s postulates for bubonic plague. 6

The reservoir of plague bacilli in the fleas of the Sibe-

rian marmot was likely responsible for the Manchurian

pneumonic plague epidemic of 1910 through 1911,

Medical Aspects of Biological Warfare

which caused 50,000 deaths. 21 The modern pandemic

arrived in Bombay in 1898, and during the next 50

years, more than 13 million Indians died of rat-associ-

ated plague. 21,22

The disease officially arrived in the United States in

March 1900, when the lifeless body of a plague-infected

Chinese laborer was discovered in a hotel basement

in San Francisco, California. The disease subsequently

appeared in New York City and Washington state the

same year. 23,24 The plague appeared in New Orleans,

Louisiana, in 1924 and 1926. 24 The Texas Gulf Coast

and Pensacola, Florida, also saw the influx of plague.

Before 1925, human plague in the United States was a

result of urban rat epizootics. After general rat control

and hygiene measures were instituted in various port

cities, urban plague vanished—only to spread into ru-

ral areas, where virtually all cases in the United States

have been acquired since 1925. 25 Rodents throughout

the western United States were probably infected from

the San Francisco focus.

PLAGUE AND WARFARE

It is an axiom of warfare that battle casualties are

fewer than casualties caused by disease and nonbattle

injuries. 26 Y pestis can initiate disease both through

endemic exposure and as a biological warfare agent.

Medical officers need to distinguish likely from un-

likely cases of endemic disease and consider the pos-

sible biological warfare threat.

vaccinate US troops with the whole-cell killed plague

vaccine. No troops contracted plague, although they

served in known endemic areas. 27,28 Plague has since

disappeared from Hawaii.

Vietnam War

Endemic Disease

Plague entered Vietnam in Nha Trang in 1898 and

several pneumonic epidemics have occurred since

then. 21,29,30 Cases have been reported in Vietnam every

year since 1898, except during the Japanese occupa-

tion in World War II. 21 When French forces departed

Vietnam after the Indochina War, public health condi-

tions deteriorated, and plague flourished. The reported

plague incidence increased from 8 cases in 1961 to 110

cases in 1963, and to an average of 4,500 cases annually

from 1965 through 1969. 25,31-34 The mortality in clinically

diagnosed cases was between 1% and 5%. In untreated

individuals, it was higher (60%–90%). 21,32 However,

only eight American troops were affected (one case per

1 million human-years) during the Vietnam War. 34 The

low infection rate in the US troops was attributed to

insecticide use, vaccination of virtually all troops, and

a thorough understanding of plague’s epidemiology,

which led to insect repellent use, protective clothing,

and rat-proofed dwellings. 21,32 During this period,

two officers of the US Army Medical Service Corps,

Lieutenant Colonel Dan C Cavanaugh and Lieuten-

ant Colonel John D Marshall, studied plague ecology,

related plague epidemics to weather, described the

effects of high temperatures ( > 28°C) on the abilities

of fleas to transmit plague, developed serologic tests

for plague infection, and significantly contributed to

the field of plague vaccinology. 21,35

Plague has also afflicted armies in more recent times.

In 1745 Frederick the Great’s troops were devastated by

plague. Catherine the Great’s troops returned from the

Balkans with plague in 1769 through 1771. French mili-

tary operations in Egypt were significantly impeded by

plague in 1798, which caused them to abandon their

attack on Alexandria. The modern pandemic began in

China when its troops were deployed in an epidemic

plague area to suppress a Muslim rebellion. Military

traffic is responsible for the rapid plague spread to

nearly every country in Asia. 21

Endemic plague has not been a source of disease

and nonbattle injuries for the US military since the mid

20th century. During World War II and the Vietnam

War, US forces were almost free of plague. However,

the disease remains on and near military bases in

the western United States because the local mammal

populations are reservoirs of infection.

World War II

Endemic plague became established in Hawaii (on

the islands of Hawaii and Maui) in December 1899.

No evidence of the disease, however, in either rodents

or humans has been found on the islands of Oahu

or Kauai since the first decade of the 20th century. A

“small outbreak” occurred during World War II on

the island of Hawaii (in 1943) but was contained by

strict rat control measures that prevented any plague

spread to military personnel during the war in the

Pacific. 27 Official policy during World War II was to

Disease Threat on US Military Installations

Human exposure to plague on military installa-

tions may occur at home when pets bring in infected

rodents or fleas, at recreation areas with sick or dead

rodents and their infected fleas, or at field training

Plague

and bivouac sites. The consequences of plague at a

military installation include morbidity and mortality

of both humans and pets; loss of training and bivouac

sites; large expenditures of money, personnel, and

equipment to eliminate the plague risk; and the loss

of recreation areas. 25 Plague risk has been identified on

and near several US military installations (Exhibit 5-1).

For a description of relevant rodent/flea complexes

found in the United States see the Epidemiology sec-

tion of this chapter.

plague victims at the Genoese sailors. The Genoese

became infected with plague and fled to Italy. How-

ever, the disease was most likely spread by the local

population of infected rats, not by the corpses, because

an infected flea leaves its host as soon as the corpse

cools. 11 The 20th-century use of plague as a potential

biological warfare weapon is of concern and should

be considered, particularly if the disease appears in

an unlikely setting.

World War II

Plague as a Biological Warfare Agent

The first attempt at what is now called “biological

warfare” is purported to have occurred at the Crimean

port city of Caffa on the Black Sea in 1346 and1347. 11,21

During the conflict between Christian Genoese sailors

and Muslim Tatars, the Tatar army was struck with

plague. The Tatar leader catapulted corpses of Tatar

During World War II Japan established a secret bio-

logical warfare research unit (Unit 731) in Manchuria,

where pneumonic plague epidemics occurred from

1910 through 1911, 1920 through 1921, and 1927; a

cholera epidemic also spread in 1919. General Shiro

Ishii, the physician leader of Unit 731, was fascinated

by plague because it could create casualties out of

EXHIBIT 5-1

PLAGUE RISKS AT US MILITARY

INSTALLATIONS *

Plague-infected animals on the installation; human case

reported on post:

Fort Hunter Liggett, California

US Air Force Academy, Colorado †

Rocky Mountain Arsenal, Colorado

Vandenberg Air Force Base, California

White Sands Missile Range, New Mexico

Plague-infected animals or fleas in the same county but

not on the installation:

Bridgeport Naval Facility, California

Camp Roberts, California

Dyess Air Force Base, Texas

Fort Bliss, Texas

Fort Lewis, Washington

Sierra Army Depot, California

Tooele Army Depot, Utah

Umatilla Army Depot Activity, Oregon

Nellis Air Force Base, Nevada

No plague-infected animals or fleas on the installation or

in the county, but susceptible animals present:

Fort Huachuca, Arizona

Human case reported in the same county:

Edwards Air Force Base, Colorado ‡

FE Warren Air Force Base, Wyoming

Kirtland Air Force Base, New Mexico §

Peterson Air Force Base, Colorado

Plague-infected animals on the installation:

Dugway Proving Ground, Utah

Fort Carson, Colorado

Fort Ord, California

Fort Wingate Army Depot Activity, New Mexico

Marine Corps Mountain Warfare Training Center,

Bridgeport, California

Navajo Army Depot Activity, Arizona

Pueblo Army Depot Activity, Colorado

*Does not include military installations near Los Angeles and San Francisco, California, where urban plague cases and deaths were

common in the first quarter of the 20th century; no plague cases have occurred in these urban areas since the mid 1920s.

† Fatality: 18-month-old child died of pneumonic plague; rock squirrels and their fleas had taken up residence in the ducts of the

child’s on-base house.

‡ Two human cases in the same county in 1995; animal surveillance on base began in 1996.

§ Plague-infected animals in the county in 1995; last human case in the county in 1993; no animal surveillance on base since 1986.

Data sources: (1) Harrison FJ. Prevention and Control of Plague. Aurora, Colo: US Army Center for Health Promotion and Preventive

Medicine, Fitzsimons Army Medical Center; September 1995: 3–8. Technical Guide 103. (2) Data collected from Preventive Medicine

Officers on 30 military bases in the United States, March 1996.

Plik z chomika:

Inne pliki z tego folderu:

Inne foldery tego chomika: