The Black Death

Question 1

What is the incubation time for plagues?

Answer 1

2-6 days with death after 2-4 days

Question 2

What are the three plagues?

Answer 2

• The “Plague of Justinian”
• The “Black Death”
• The mid-19th century plague

Question 3

Who was named after the first pandemic?

Answer 3

Eastern Roman Emperor Justinian

Question 4

In what century did the first pandemic plague ‘had fun’

Answer 4

6th

Question 5

What bacteria caused the first pandemic plague?

Answer 5

Yersinia pestis

Question 6

What was the K/D of the first pandemic plague?

Answer 6

50% of the population dies with an estimation of 100 million people killed

Question 7

What is Yersinia?

Answer 7

• Gram-negative

- rod-shaped bacterium

Question 8

What are the 3 species of Yersinia that are pathogenic for humans?

Answer 8

Y. enterocolitica

• cause “Yersiniosis”
• a rare cause of diarrhea and abdominal pain

Y. pseudotuberculosis

• an animal pathogen
• cause tuberculosis-like symptoms in animals, enteritis in humans

Y. pestis
- the cause of the plague

Question 9

Who discovered Y. pestis?

Answer 9

Alexandre Yersin in 1894

Question 10

Where did pestis come from?

Answer 10

Pestilence (contagious or infectious epidemic disease)

Question 11

What is Y. pestis?

Answer 11

• an extraordinarily virulent pathogen
• may cause death in 2-4 days by sepsis and/or overwhelming pneumonia with respiratory failure
• not an efficient colonizer of humans

Question 12

What is the origin of the second pandemic plague?

Answer 12

• a medieval pandemic

- originated in Asia and reached Europe in the late 1340s

Question 13

What was the cause of the second pandemic plague?

Answer 13

Y. pestis

Question 14

What was the K/D of the second pandemic plague?

Answer 14

Reduced the global population from 450 million to 350 million

Question 15

What happens when medieval people had no idea what was causing all of the deaths (second pandemic)?

Answer 15

• many believed this was “God’s anger” or “Satan’s influence”
• persecution of strangers, minorities and witches
• European social order, family structure, agriculture, the military and the feuded system were destroyed

Question 16

What is the feudal system?

Answer 16

• political and social structure prevalent in Europe
• little opportunity for advancement
• a few people had everything, most had little
• the plague created vacant towns and farms
• position of authority need to be filled
• demand for physicians, clergy, and gravediggers
• provided new opportunities for the peasants

Question 17

Where is the third pandemic plague spawn point?

Answer 17

• China in the 1850s

- spread to all continents

Question 18

What is the K/D of the third pandemic plague?

Answer 18

more than 12 million deaths in China and India alone

Question 19

What happened when the third pandemic plague hits San Francisco in 1900?

Answer 19

• infected rats and then exchanged with fleas and local wildlife
• Y. pestis is now established in South Western U.S.

Question 20

Describe the pathogenesis fo Y. pestis

Answer 20

• organisms live in rodents and are transmitted by fleas
• a “zoonotic” pathogen
• causes “blocking” in the flea
• biofilm formation in the proventriculus
• “starving fleas”
• causes the regurgitation of bacteria
• very low infective dose ( about 10 cells)
• terminal stage of the disease, blood contains a high concentration of bacterial cells
• essential for transmission as fleas take a blood meal

Question 21

What are the major virulence factors of Y. pestis?

Answer 21

• LPS (septicemia)
• Phospholipase (survived in the flea)
• Plasminogen activator - clot buster (dissemination)
• Yersiniabactin - iron-binding siderophore
• Type 3 secretion (typical for Gram-negative intracellular pathogens)

Question 22

Describe what the type 3 secretion system is

Answer 22

• found in many Gram-negative pathogens (intracellular pathogen)
• secrete virulence factors (effectors) directly into host cells across the host cell membrane
• effectors function to ‘poison’ the host cell by targeting host cell signalling pathways

Question 23

Describe the evolution of Y. pestis

Answer 23

• evolved form Y. pseudotuberculosis
• acquired new virulence plasmids
• all pathogenic Yersinia contain pYV which encodes the type 3 secretion system
• Y. pseudotuberculosis is primarily an intestinal pathogen of animals and is found widely in the environment
• can infect the flea and is hypervirulent in humans, but does not survive well in the animal intestine

Question 24

What are the 3 major forms of a plague?

Answer 24

• bubonic plague
• septicemic plague
• pneumonic plague

Question 25

Describe what the bubonic plague is

Answer 25

• most common form, transmitted by flea bites
• painfully swollen lymph nodes (“buboes”) in groin, armpits and neck
• can develop into both septicemic and pneumonic plague
• 40-60% mortality if untreated

Question 26

Describe what the septicemic plague is

Answer 26

• presence of Y. pestis is systemic (in the blood)
• an overwhelming and progressive bacteremia
• flea bites can now pick up Y. pestis to transmit to a new host
• patients experience gangrene and disseminated intravascular coagulation (LPS mediated)
• 50-90% mortality if untreated

Question 27

Describe what the pneumonic plague is

Answer 27

• most dangerous
• transmission via aerosols directly into the lungs, or spread to lungs from septicemic plague
• short incubation
• the disease can pass directly from person to person through coughing (coughing up blood)
• 95-100% mortality if untreated, but treatment should be within the first 24h of symptoms

Question 28

What are the four routes for human disease?

Answer 28

• flea bites (most common)
• inhalation from humans (pneumonic) or animals
• handling infected animals - skin contact, scratch, bite
• ingesting infected meat

Question 29

Historically what would be the main route for human disease?

Answer 29

Rat-borne urban epidemics, but now it is mostly wildlife associated plague with sporadic outbreaks

Question 30

Describe the diagnosis, treatment and prevention for these plagues

Answer 30

• rapid diagnosis and treatment is essential
• culture and identification from bubo aspirate, sputum, blood (post-mortem) may take 4 days
• endemic regions - stains, the antigen test
• isolation of pneumonic plague patients
• outbreaks - insecticides to kill fleas treat human cases with appropriate antibiotics, prophylaxis to exposed individuals

Question 31

Delineate plagues as a bioterrorism agent

Answer 31

• the center for disease control and prevention identify plague as a “Category A” organism
• can be easily disseminated or transmitted from person to person
• result in high mortality rates and have the potential for major public health impact
• might cause public panic and social disruption

Question 32

How long does it take for Y. pestis to grow

Answer 32

2 days

Question 33

What are the 4 known historical incidents with plagues?

Answer 33

• Mongol armies catapulted plague-ridden bodies over the city walls in Caffa, Ukraine
• WW2, Unit 731 of the Japanese Imperial Army infected fleas and is released in China
• Larry Wayne Harris, an American “microbiologist” with suspect motive obtained Y. pestis through the mail (American Type Culture Collection)
• Aerosol release of 50 kg Y. pestis over the city of 5 million people

Question 34

Talk about the “modern plague”

Answer 34

• often thought to be extinct, the plague is very much alive
• found on all continents except Australia
• since Y. pestis is widespread in wildlife rodent reservoirs, plague cannot be eradicated
• about 1500 cases/year globally since 1965
• the last case reported in Canada in 1939
• more than 50% of cases reported in Southeastern Africa, especially Madagascar

Question 35

What happens to Y. pestis in the body

Answer 35

• initially survives and grows in innate immune cells
• replicates in lymphoid organs (spleen, bone marrow, lymph nodes, liver)
• lymph nodes - swelling - buboes
• kills phagocytes and continues to grow extracellularly