iv. The Black Plague (Yersinia Pestis)

Question 1

What type of bacteria is the Black Plague?

Answer 1

Gram negative bacteria

Question 2

Microbial Pathogenesis: The 5 Challenges:

Answer 2

1. Maintain a reservoir
2. Gain access to new host
3. Adherence
4. Mechanisms of disease causation
5. Exiting from one host, entering another or returning to reservoir

Question 2

Microbial Pathogenesis: The 5 Challenges:
1. Maintain a reservoir:

Answer 2

1. Maintain a reservoir: human, animal or environ source in which microbe can exist & can be transmitted - rodents (plague), contaminated animal products (leather, wool - anthrax) to human = ZOONOTIC infection (zoonosis) [Rodents, gerbils -> zoonosis]

Question 3

Microbial Pathogenesis: The 5 Challenges:

2. Gain access to new host:

Answer 3

2. Gain access to new host: Portal of entry (skin, mucous membrane, resp tract, GIT); Mode of transmission (contact, traumatic/parenteral inoculation, vector-borne, inhalation, ingestion) - Vector = living creature that transmits infection from 1 host to another eg, mosquito, flea, tick [vector = flea; entry via inoculation due to vector bite]

Question 4

Microbial Pathogenesis: The 5 Challenges:

4. Mechanisms of disease causation:

Answer 4

4. Mechanisms of disease causation: adherence, invasion (agressins), toxins (exo/endo), immunologically-mediated damage (cytokines, superantigens, hypersensitivity-mediated rxns) [evade host defence - Fraction 1 Ag, low calcium response plasmid, V & W antigens, intracellular survival; invasion of tissues (buboes, lungs etc.); toxins (exotoxin - murine exotoxin;
   endotoxin [LPS]; immunological damage (inflamm cytokines)]

Question 5

Microbial Pathogenesis: The 5 Challenges:

5. Exiting from one host, entering another or returning to reservoir:

Answer 5

[Human-human; animal-human; flea to animal/human returning to reservoir (rodents)]

Question 6

History of Plague:

3 documented pandemics in recent history: (3)

Answer 6

1. 6th century (541-75 AD) - Justinian plague
2. 14th century (1347-17th C AD)
3. 1860 (China) -> 1894 (Hong Kong) -> SE Asia, India, Africa & Americas

Question 7

Yersinia Pestis as an agent of bioterrorism:

Historically =

Answer 7

Long history as bio-weapon, ancient china used infected animal carcasses to contaminate enemy water supply

Question 8

Yersinia Pestis as an agent of bioterrorism:

1346/7:

Answer 8

Genoese possession of Caffa (trade emporium on Crimean peninsula) - now Feodosiya, Ukrainian. Mongolian army withering from plague & their general catapulted infected human corpses over city wall - Genoese traders fled, transferring plague via ships into S. Europe

Question 9

Yersinia Pestis as an agent of bioterrorism:

WW2:

Answer 9

WW2: Japanese army weaponised plague by breeding & releasing infected flees into Manchuria & performing dissection &/or vivisection on victims

Question 9

Yersinia Pestis as an agent of bioterrorism:

Post WW2:

Answer 9

Post WW2: both US & USSR had significant bio-weaponisation programs using plague

Question 10

Yersinia Pestis as an agent of bioterrorism:

Today:

Answer 10

Today, Y. Pestis is classified as category A agent for possible bioterrorism attacks (aerosolised pneumonic plague = most significant threat)

Question 11

Bacteriology & Properties: (2)

Answer 11

• Gram -ve bacillus.
• Obligate pathogen (cant survive freely in environment), unable to replicate in nature outside host (flea/mammal), survive drying for few days, survival prolonged in
  dried blood & secretions.

Question 11

The Plague Cycle: Zoonosis:

Answer 11

Question 12

Pathogenesis:

Virulence factors: (3)

Answer 12

• Temp-dependant coagulase (<30 degrees); Fraction 1 antigen (capsular glycoprotein - 37 degrees), low calcium response at 37 deg mediated
• By 70 kb plasmid is important for adaptation to IC environ; V & W antigens (maintain bacteriostasis & aid IC survival); Yersinia OMPs (Yops)
• Type E & K important for virulence; Other - antigen 4 or pH 6 antigen; pigment production; LPS endotoxin; plasmid-encoded murine exotoxin
  (Lethal only to mice & rats)

Question 13

Pathogenesis:

Fleas are ____ blooded -> ingestion of organism from blood of suitable reservoir result in clotting of flood in flea’s ________ (foregut) -> blood containing many organisms regurgitated during subsequence feeding attempts -> perpetuation of infection cycle -> F1 Ag enables organism to evade _______ when produced at 37 deg -> immune evasion -> Intracellular survival negotiated by ‘low calcium response’ and V & W Ags

Answer 13

cold
proventriculus
phagocytosis

Question 14

What are the plague syndromes? (4)

Answer 14

Bubonic
Septicaemic
Pneumonic
Uncommon

Question 15

Plague Syndromes:
Bubonic:

Answer 15

Fever, painful lymphadenopathy (bubo)

Question 16

Plague Syndromes:
Septicaemic:

Answer 16

Septicaemic: Bacteraemia often occurs in bubonic plague (40% of cases). Severe illness: fever, rapid shock & death w/in days

Question 17

Plague Syndromes:
Pneumonic:

Answer 17

Pneumonic: primary or secondary to bacteraemia spread in bubonic/septicaemic plague. Cough, bloody vomit, ± bubo (depending on primary or secondary)

Question 18

Plague Syndromes:
Uncommon: (2)

Answer 18

Uncommon:

• Pharyngeal: painful, inflames pharynx, local lymphadenopathy
• Meningitis: fever, nuchal rigidity, usually with bubo

Question 19

How do you diagnose the Black Plague? (3)

Answer 19

• Bubo aspirates; blood cultures; sputum (? Pneumonic); CSF (? Meningeal)
• Microscopy (Wayson, Giemsa/Gram stains); culture
• Serology or PCR

Question 20

What is the treatment for the Black Plague? (4)

Answer 20

• Untreated, case fatality rate > 50%
• Antibiotics eg. Aminoglycosides; doxycycline; fluoroquinolones
• Supportive therapy
• Infection prevention & control (as appropriate)

Question 21

What is the prevention for the Black Plague?

Answer 21

Surveillance, public education, rodent & flea control, chemoprophylaxis for close contact with plague pneumonia & indv exposed in lab accidents; infection prevention & control