Lecture 3: Plague the disease that shaped history

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 primary
septicemic plague develop into secondary
pneumonic plague.
So, approximately 1 in 10 chance of an out-ofcontrol human-human epidemic
SCARY.
Yersinia pestis
Flea-borne zoonotic
disease
Fleas
(Insecta; Siphonaptera)
Flea transmission
discovered by
Simond (1898)
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.
2.
3.
4.
5.
6.
Plague multiply in proventriculus (foregut)
Biofilm obstructs blood from midgut
Flea starves
Repeated biting
Regurgitation of bacteria
Flea dies
Increased
transmission
Blocking fleas
Classic case:
Black rats and rat flea (Xenopsylla cheopis)
Plague multiply in proventriculus
Is it true?
Early-phase transmission can occur
Transmission efficiency
Early-phase transmission
Transmission begins
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
1
2
3
4
5
6
7
8
Days after flea infection
9
10
Traditional ‘blocking’ mechanism
Transmission efficiency
Transmission begins
4.5
4
Time to blocking
3.5
3
2.5
2
1.5
1
0.5
0
1
2
3
4
5
6
7
8
Days after flea infection
9
10
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
HOST
FLEA
environment?
RODENT
HOST
Transmission Cycle
FLEA
pneumonic
pets
HUMANS
carnivores
pneumonic
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
Xenopsylla cheopis
FLEA
HUMANS
Pandemic #2: The 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 Death
Europe; 1347 – 1351
17 – 28 million deaths
(30 – 40% population)
Variant: MEDIEVALIS
Destruction of European
feudal system
The Black Death
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 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)
Why was Black Death worse than
Justinian Pandemic?
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)
Transmission Cycle:
human fleas and pneumonic?
RODENT
HOST
Pulex irritans
FLEA
HUMANS
pneumonic
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 Cycle
RAT
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