Lecture 3: Plague

the disease that shaped history

The Great Plague in Constantinople (542 CE)

extract from Book II, chs. xxii-xxiv History of the Wars

by Procopius of Caesarea (c. 500 -560 CE)

Anno Domini 542. During these times there was a pestilence, by which the whole human race came near to being annihilated.

Now in the case of all other scourges sent from Heaven, some explanation of a cause might be given by daring men, such as the many theories propounded by those who are clever in these matters; for they love to conjure up causes which are absolutely incomprehensible to man, and to fabricate outlandish theories of natural philosophy knowing well that they are saying nothing sound but considering it sufficient for them, if they completely deceive by their argument some of those whom they meet and persuade them to their view. But for this calamity it is quite impossible either to express in words or to conceive in thought any explanation, except indeed to refer it to God.

It did not come in a part of the world, nor upon certain men, nor did it confine itself to any season of the year, so that from such circumstances it might be possible to find subtle explanations of a cause, but it embraced the entire world, and blighted the lives of all men, though differing from one another in the most marked degree, respecting neither sex nor age.

Did plague cause the Roman Empire

essentially to end?

Political and economic instability

already

Byzantine ‘golden age’ and Antiquity

was rendered powerless

Led to the Dark Ages of pre-modern

Europe

Boccacio’s Decameron

Florence – Boccacio lived through the 1348 Black death and described the plague society as a ‘loosening’

Of women’s morals

Of the social fabric of Florence

Camus’ Plague (1947)

La Peste – story of an Algerian port, Oran, suffering from an epidemic of bubonic plague. Quarantined, it becomes a prison of death and disease.

Plague is an analogy for other political and spiritual disease of the time

Characters respond differently to the events

The concept of a plague

Plague vs. plagues – not all caused by plague,

historically

Conjures up imagery of something devastating

No selective properties – universal illness

Pandemic, lethal and horrific

Let’s meet the true plague

Yersinia pestis

Identified by Alexander

Yersin (1894)

Gram negative bacterium

coccobacillus

Enterobacteriaceae

“safety pin” appearance

Most lethal bacterium known to mankind

WHO internationally notifiable diseases:

1. cholera

2. yellow fever

3. plague

• Plague, caused by Y. pestis, is the quintescential ‘pestilence’

• Main human forms:

– Bubonic is characterized by hemorrhaging lymph nodes which make big bumps

• Buboes – from the Greek bubo for groin

– Septacemic

• True ‘Black Death’

– Pnuemonic

• passed from human to human in droplet form (aerosol)

Ways to die from plague

#1 - BUBONIC

Flea-borne

Lymph nodes

Buboes

50 – 60% mortality rate (untreated)

• Pupuric plague – pupura (Latin) meaning

purple. Skin shows purple and red spots due

to subcutaneous bleeding.

• Extremities get severe septacemia and

gangrene, going black, hence Black Death

Ways to die from plague

#2 - SEPTICAEMIC

– from contact with infected tissues

– Mortality rate if untreated approaches 100%

#3 - PNEUMONIC

Bubonic becomes secondary pneumonic

Secondary pneumonic becomes primary

pneumonic

Sputum makes it highly contagious

Almost 100% fatal

Approximately 12% of cases of bubonic and primarysepticemic plague develop into secondary pneumonic plague.

So, approximately 1 in 10 chance of an out-of-control human-human epidemic

SCARY.

Flea-borne zoonotic disease

Fleas

(Insecta; Siphonaptera)

Flea transmission discovered by Simond (1898)

Yersinia pestis

Image: Xenopsylla chepsis (oriental rat flea) engorged with blood

Source: CDC Division of Vector-borne Infectious Disease

Primary vector of plague in most large plague epidemics in Asia, Africa, and South America.

Both male and female fleas can transmit the infection.

Wild or urban rodents maintain a reservoir

of Y. pestis that is transmitted by fleas -

sylvatic plague and urban plague

Humans are essentially an ‘accidental’ host

in a rodent epidemic

• Plague or black death is an infection of rodents

caused by Yersinia pestis and accidentially

transmitted to humans by the bite of infected fleas.

• The disease follows urban and sylvatic cycles and

is manifested in bubonic and pneumonic forms

How do the fleas actually transmit it?

Blocking fleas

1. Plague multiply in proventriculus (foregut)

2. Biofilm obstructs blood from midgut

3. Flea starves

4. Repeated biting

5. Regurgitation of bacteria

6. Flea dies

Increased

transmission

Blocking fleasClassic case:

Black rats and rat flea (Xenopsylla cheopis)

Plague multiply in proventriculus

Is it true?

Early-phase transmission can occur

0

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1 2 3 4 5 6 7 8 9 10

Days after flea infection

Tra

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Transmission begins

Early-phase transmission

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Days after flea infection

Tra

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Time to blocking

Transmission begins

Traditional ‘blocking’ mechanism

Evolutionary origin of plague

• Soil

• Relatives (abdominal pain):

– Yersinia pseudotuberculosis

– Yersinia enterocolitica

• Adopted plasmids

• Central Asia (Steppes)

Asian hosts

Marmots/tarabagan

Susliks

Gerbils

(anyone else used to have pet gerbils?)

Classic Transmission Cycle

RODENT

HOSTFLEA

Transmission Cycle

RODENT

HOST FLEA

HUMANS

pneumonic

carnivores

pets

pneumonic

environment?

The major Plagues

Pandemic #1: Justinian

• 6th century – Justinian plague

– Est. 100 million lives across Old World

– Supposedly started in 542 due to trade routes from a

small island

– More likely came through Egypt

• Largely restricted to Mediterranean coast

• Variant: ANTIQUA

• Still found in Africa & Central Asia

• Byzantine historian Procopius wrote that plague was killing 10,000 people in Constantinople every day

• Emperor Justinian I created new legislation to deal with inheritance suits resulting from plague deaths

• Justinian spent huge amounts of money for wars against the Vandals in Carthage and the Ostrogoths of Italy, and to build the Hagia Sophia

• Ultimately Italy fractured, Arabs won land wars, and the Western Roman Empire didn’t exist

• Long term effects on European and Christian history

Transmission Cycle:

black rat plague and black rat fleas?

RAT

HOST FLEA

HUMANS

Xenopsylla cheopis

Pandemic #2: The Black DeathThe Black DeathThe Black DeathThe Black Death

First, out of the blue, a kind of chilly stiffness troubled their bodies.

They felt a tingling sensation, as if they were being pricked by the

points of arrows.

The next stage was a fearsome attack which took the form of an

extremely hard, solid boil. In some people this developed under the

armpit and in others in the groin. As it grew more solid, its burning

heat caused the patients to fall into an acute and putrid fever, with

severe headaches. In some cases it gave rise to an intolerable stench.

In others it brought vomiting of blood. There was no known remedy

for the vomiting of blood. But from the fever it was sometimes

possible to make a recovery.

- de’ Mussis, French abbott, 1348

The Black DeathThe Black DeathThe Black DeathThe Black Death

Europe; 1347 – 1351

17 – 28 million deaths

(30 – 40% population)

Variant: MEDIEVALIS

Destruction of European feudal system

Intermittent outbreaks for 300 years

1665 Great Plague of London - 100,000 died

1666 “Great Fire” of London as disinfection –

70,000 of 80,000 homes destroyed

Newton fled London & invented ‘Calculus’

The Black DeathThe Black DeathThe Black DeathThe Black Death

The Black DeathThe Black DeathThe Black DeathThe Black Death

• The Black Death was one of the great epidemic scourges of mankind.

• It swept across Europe and Asia in a series of devastating pandemics during the Middle Ages.

• This disease was responsible for the death of one-third of the world's population at that time.

• Truly depressing for people – seen as inexplicable punishment – by GOD

• Christians blamed the Jews

– Tended to live in separate areas, thus initially appeared not to catch it

• Fear is useful for power and propaganda…

Napoleon in the pest house at Jaffa

Dental pulp from French graveyards

(9000 households in 1348;

1000 households in 1379)

It might not have been – records from earlier

suggest upto 1/3 of population were dead

around the mediterranean 6th century

Ecological explanation – transmission may

have been more efficient (next slide)

Why was Black Death worse than

Justinian Pandemic?

Transmission Cycle:

human fleas and pneumonic?

RODENT

HOST FLEA

HUMANS

pneumonic

Pulex irritans

Pandemic #3: Third Pandemic

• Yunan Province, China, 1855 – outbreak

– Muslim rebellion caused refugees to flee south

• Canton and Hong Kong, 1894

– 60,000 dead in a few weeks, 100,000 in 2 months

• Followed the shipping routes to all continents

– Ultimately killed 12 million in India and China

• Endemic in Hong Kong until 1929

• Variant: ORIENTALIS

• Rat-borne and rat fleas

Arrival in Chinatown,

San Francisco

• 1900 – Chinese Year of the Rat

– March 6 – dead man with buboes, quarantine ring in

Chinatown

– Samples taken and injected into rat, 2 guinea pigs, and a

monkey (Angel Island)

– March 10 – Chinatown quarantine lifted

– March 12 – 1 dead rat, 2 dead guinea pigs

– March 13 – 1 dead monkey

– Racism, commerce and public health…

Transmission CycleRAT

HOST FLEA

HUMANS

Rare

pneumonic

• In the United States, the last urban plague

epidemic occurred in Los Angeles in 1924-25.

• In 2002 two residents of New York City acquired

plague from New Mexico.

• What’s going on here?

Current USA distribution of plague

US: 10 – 20 cases/year

Incubation period: 1 – 6 days

Treatment:

Tetracycline antibiotics (7 days)

Global human plague activity (20th Century)

But did plague really arrive in the USA

in 1900?

• Has plague been in North America for a long time?

• Was monitoring fast enough?

• Does it matter?

Risks

• Rodent – flea relationships

– Fleas (263 species, 223 host-specific)

– Rodent hosts (217 species)

• Biological warfare?

Biological warfare and plague

• Pros: Man-to-man spread, deadly

• Cons: spread, antibiotics, loss of virulence, delivery

• Catapaulting corpses

• Japan bombed China with plague fleas

– Unit 731 in WWII

– Wheat and fleas dropped by air

• Genetic engineering for antibiotic resistance?

Avoiding it

(like the plague…)

• Awareness – seasonal and sporadic outbreaks

• Watch your pets.

• Sanitation (reduce rodent proximity) –

food/wood-piles etc

• Avoid human corpse catapaults and

bioterrorists

Controlling plague - management

• Sanitation

– Keep away fleas

– Don’t live with rodents

• There’s a reason people freak out about mice/rats

• Early detection, early response

• Treatment for individual patients

• Quarantine

GOOD BOOKS:

Plague – Wendy Orent; History of plague and biological warfare

The Barbary Plague – Marilyn Chase; Plague in San Francisco

FOR GENERAL REVIEWS:

Gage, K. L., and M. Y. Kosoy. 2005. Natural history of the plague: perspectives from

more than a century of research. Annual Review of Entomology 50:505-528.

Stenseth et al. 2008. Plague: past,present, and future. PLOS Medicine 5

FLEA-BLOCKING:

Eisen et al. 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, USA 103:15380-15385.

(THANKS TO DAN SALKELD FOR A LOT OF THESE SLIDES AND MATERIAL!!)

NEXT WEEK:

GUEST LECTURE

Dan Salkeld will talk about ecology and the

natural animal reservoirs of plague