MICROIMM Lec 19: The Black Death

What plague is ring around a rosie about?

The Black Death

What bacteria is responsible for the black plague?

Yersinia

Is Yersinia G+ or G-? What shape is it?

G- rod shaped bacterium

Name the 3 species of Yersinia that are pathogenic for humans

1. Y. enterocolitica

2. Y. pseudotuberculosis

3. Y. pestis

What does Y. enterocoliticia cause?

Yersiniosis: a rare cause of diarrhea and abdominal pain

What does Y. pseudotuberculosis cause in animals?

Primarily an animal pathogen that can cause tuberculosis-like symptoms in animals

What does Y. pseudotuberculosis cause in humans?

Enteritis (inflammation of small intestine)

What does Y. pestis cause?

Plague

Which two scientists discovered Yersinia pestis? When?

Discovered by Alexandre Yersin and Kitasato Shibasaburo in late 1800s

Define pestilence

a fatal epidemic disease

Yersinia pestis may cause death in __-__ days

2-4 days

How does Y. pestis cause death?

By sepsis and/or overwhelming pneumonia with respiratory failure

Is Y. pestis an efficient colonizer of humans?

No, does not colonize skin but goes immediately straight to target immune cells; very aggressive

What is the incubation period of Y. pestis?

3-7 days

Describe the symptoms of the plague

Fever, chills, swelling in neck/armpits/groin, death within days

High fever, delirium, mental deterioration, large blackish pustules that burst, vomiting of blood, bleeding in the lungs

Define buboes (where the name bubonic plague comes from)

Painful swellings of the lymph nodes in the armpits, legs, neck, or groin

What is the Plague of Justinian?

The first pandemic, caused by Yersinia pestis.

Who is the Plague of Justinian named after?

Eastern Roman Emperor Justinian

When did the Plague of Justinian start?

Started in the 6th century (541-542 AD)

Where did the Plague of Justinian spread to?

Spread to the Mediterranean, Italy, and throughout Europe

How many people died from the Plague of Justinian?

Estimated 100 million people, ~50% of the population

Was the Plague of Justinian a one-time event?

No, continued in cycles for another 200 years until ~750 AD then disappears for ~800 years

What is the Black Death?

The second pandemic; a medieval pandemic also caused by Yersinia pestis

Where did the Black Death originate and travel to?

Originated in Asia and spread to Europe

When did the Black Death occur?

Late 1340s

How many did the Black Death kill?

Reduced the global population from ~450 to 350 million

Killed 1/3 of Europe's total population (25 million)

What was the purpose of plague doctor mask?

Likely prevented transmission of the disease in its pneumonic phase (ie. coughing up infection)

What was the treatment for the Black Death back then?

- Bloodletting

- Putting frogs on swollen lymph nodes

What is the European Feudal System?

Political and social structure prevalent in Europe:

1. King (monarchy)

2. Nobles

3. Knights

4. Peasants

Where is a mass grave site for plague victims in East London located?

East Smithfield cemetery, close to Tower of London

What technique was used to sequence the bacterial sequence of Y. pestis in the remains?

Next-generation sequencing

Were the strains that caused Plague of Justinian and the Black Death the same?

No, different strains

When did the 3rd pandemic occur?

Mid 19th century (1850s)

Where did the 3rd pandemic originate from, and where did it spread?

Originated in China, and spread to all continents

When did the 3rd pandemic cease to be active?

1959

When did the 3rd pandemic reach San Francisco?

1900

How many deaths occurred due to the 3rd pandemic in China and India alone?

> 12 million

How did the infected rats transmit the disease to other countries?

Exchanged fleas with local wildlife

Plague mainly affects ____ and spreads through _____

Rodents, insects (fleas)

What event facilitated the movement of germs?

Increased international trade (ex. silk road)

How did rising urban populations contribute to spread of disease?

- Crowded neighbourhoods

- Accumulation of waste

- Unsanitary living conditions

What type of pathogen is Yersinia pestis?

Zoonotic

Explain how Y. pestis causes "blocking" in the flea

Biofilm formation in the flea's gut; causes "starving fleas"; causes regurgitation of organisms

Define the proventriculus

area between the crop and the gizzard (hind part of stomach). This stores and digestions food before heading to the gizzard.

How many cells does it take to be infected by Y. pestis?

Very low infective dose (~10 cells)

In which cells does Y. pestis survive and grow in?

Innate immune cells

Where does Y. pestis replicate?

In lymphoid organs (spleen, bone marrow, lymph nodes, liver)

Does Y. pestis grow intracellular or extracellular?

Can kill phagocytes and continue to grow extracellularly --> goes into bloodstream

What is the importance of having Y. pestis reside in the blood stream?

At the terminal stage of the disease, the blood contains high conc of bacterial cells; essential for transmission as fleas take a blood meal; part of infectious cycle

Y. pestis has massive growth in/ex vivo

In vivo

Name the 5 major virulence factors of Yersinia pestis

1. Type III secretion system

2. Phospholipase

3. Plasminogen activator --> clot buster

4. Yersiniabactin

5. Mutated LPS structure

Type III secretion system is found only in G+ or G-?

G- intracellular pathogens only

What does the Type III secretion system secrete?

Secretes virulence factors (called "effectors") directly into host cells across the host cell membrane

Explain the function of phospholipase

Enzyme toxin of Y. pestis: helps it survive in the midgut of fleas

Explain the function of plasminogen activator

Host protein: allows for dissemination of bacteria through bloodstream; clot buster

Define clot buster

ex. Plasminogen activator: clot-busting drug that breaks up blood clots to help restore blood flow; disseminates bacteria in blood

Explain the function of yersiniabactin

Iron-binding siderophore; bacteria siphons iron from host body

How many containment levels do we have?

1-4

Explain containment level 1

Bacteria is not really infectious

Give an example of a containment/BSL level 1 bacteria

- E.coli used in experiments

- Lactobacilli used to make cheese/yogurt

Name some examples of BSL-2

- Staphylococcus aureus

- E.coli that causes disease

Associated with causing human diseases

Name some examples of BSL-3 pathogens

- Yersinia pestis

- Tuberculosis mycobacterium

Explain how BSL2 and BSL3 differentiate

BSL3 pathogens cause severe disease

Define BSL4 pathogens

Cause hemorrhagic fevers, highest level of containment

Name some examples of BSL-4 pathogens

- Ebola

What is the function of having a mutated LPS structure in Y.pestis?

Immune system is less able to recognize LPS

In type III secretion systems, what membranes do the effectors penetrate in the host?

Host cell membrane, outer membrane, inner membrane

What do the effectors target in the host cell?

Function to "poison" the host cell signaling pathways

What did Y. pestis evolve from?

Y. pseudotuberculosis

Where is Y. pseudotuberculosis found?

Primarily an intestinal pathogen of animals and is found widely in the environment

Can Y. pestis survive in the animal intestine?

No, does not survive well. Can infect fleas and is hypervirulent in humans

What is pYV?

New virulence plasmid

All pathogenic Yersinia contain pYV which encode the .....

Type III secretion system

What is plasmid pFra?

Acquired by Yersinia: encodes for phospholipase D for survival in fleas

What is plasmid pPst?

Acquired by Yersinia: encodes plasminogen activator for dissemination/intracellular transmission in humans

The Y. pestis LPS molecule is weakly recognized by...

the innate immune system

What enzyme is responsible for modifying the Y. pestis LPS molecule?

Lipid A modifying enzyme

What are the 3 major forms of the disease?

1. Bubonic plague

2. Septicemic plague

3. Pneumonic plague

Which is the most common form of the disease?

Bubonic plague

What are the symptoms of bubonic plague?

Painfully swollen lympoh nodes ("buboes") in groin, armpits, and neck

Can develop into septicemic and pneumonic plague

What is the mortality % of bubonic plague if untreated?

40-60%

Define septicemic plague

Infection of the blood; presence of Y. pestis is systemic (in the blood)

Define bacteremia

presence of bacteria in the blood; overwhelming and progressive

Describe the symptoms of septicemic plague

Gangrene, disseminated intravascular coagulation

What is the mortality % of septicemic plague if untreated?

50-90%

What is the most dangerous form of plague?

Pneumonic plague

How does pneumonic plague transmit?

Transmission via aerosols directly into the lung, or spread to lungs from septicemic plague; through coughing (up blood)

The incubation period for pneumonic plague is long/short

Short

What is the mortality % of pneumonic plague if untreated?

95-100%, and treatment must be within first 24h of symptoms

What are the 4 transmission routes for human disease?

1. Flea bite

2. Inhalation from humans (pneumonic) or animals

3. Handling infected animals - skin contact, scratch bite

4. Ingesting infected meat

What is the most common transmission route?

Flea bite (historically, rat-borne urban epidemics)

What is the most common route of transmission nowadays?

Mostly wildlife associated plague with sporadic outbreaks

How many days does it take for culture and identification from bubo aspirate, sputum, blood (post-mortem)?

4 days (too long)

What methods are used to rapidly diagnosis?

Stains, rapid antigen tests, and PCR: identifies presence of bacteria quickly

What is the treatment for plague?

- Isolation of pneumonic plague patients

- Antibiotics

Define prophylaxis

use of a drug to prevent imminent infection of a person at risk; to exposed individuals

Plague is classified as a ______ agent

bioterrorism agent

The Centers for Disease Control and Prevention identify plague as a "category __" organism

A

Define a category A organism

- Can be easily disseminated or transmitted from person to person

- High mortality rates

- Have high potential for major public health impact

- Might cause public panic and social disruption

In 1346, the Mongol armies catapulted plague-ridden bodies over the city walls in ____

Caffa, Ukraine