Plague History and Terminology

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Questions and Answers

What term describes a disease that is always present at relatively stable levels in a human population?

Endemic (correct)

Epidemic

Zoonosis

Pandemic

Which of the following is true about an epidemic?

It is a disease that is always present.

It involves unusually high incidence of disease spreading rapidly. (correct)

It indicates a stable level of incidence.

It is restricted to non-human animal populations.

What is the definition of a pandemic?

A disease that only affects animals.

An epidemic occurring in a single country.

A disease restricted to a small geographic area.

An epidemic spanning multiple continents. (correct)

Which genus causes the plague?

Yersinia Signup and view all the answers

Which of the following is a known reservoir host for Yersinia pestis?

Rattus norvegicus Signup and view all the answers

What type of organism is primarily responsible for transmitting Yersinia pestis?

Flea Signup and view all the answers

What characteristic does Yersinia pestis exhibit in clinical specimens?

It shows pleomorphism. Signup and view all the answers

What is an epizootic?

A high incidence of disease in non-human animals. Signup and view all the answers

What year does the first historical account of plague date back to?

541 CE Signup and view all the answers

Which historical figure provided account of the plague outbreak in the Byzantine Empire?

Procopius Signup and view all the answers

What symptom involved a swelling in multiple areas of the body?

Bubonic swelling Signup and view all the answers

What were the two distinct conditions that developed in patients suffering from plague according to Procopius?

Deep coma and violent delirium Signup and view all the answers

What city did the plague reach after spreading from Pelusium?

Constantinople Signup and view all the answers

Which of the following was NOT a cause of death for those suffering from the plague?

Improper medication Signup and view all the answers

What characterizes septicemic plague in terms of plague organism density?

It exhibits very high densities at approximately 10^7/ml. Signup and view all the answers

What physical symptom was noted to appear as black pustules about the size of a lentil?

Bubonic swelling Signup and view all the answers

What significant event did the plague lead to among the sufferers as described by Procopius?

Suicidal tendencies Signup and view all the answers

Which symptom is not commonly associated with septicemic plague?

Production of watery sputum Signup and view all the answers

What does acral necrosis refer to in the context of septicemic plague?

Blackening of the extremities. Signup and view all the answers

Which form of plague can be transmitted from person to person?

Pneumonic plague Signup and view all the answers

What is the initial symptom of primary pneumonic plague?

Intense headache with malaise Signup and view all the answers

What is the recommended timeframe for starting antibiotic therapy for pneumonic plague?

Within 4 hours of symptom onset Signup and view all the answers

Which condition is NOT considered a complication of bubonic plague?

Acral necrosis Signup and view all the answers

What is the mortality rate trend in pneumonic plague compared to other forms?

It is higher than both primary and secondary forms. Signup and view all the answers

What is the primary function of the Type III secretion system in Y.pestis?

To facilitate the transfer of toxins directly into target cells Signup and view all the answers

Which protein is primarily involved in adhering to and invading epithelial cells in Y.pestis?

YadBC Signup and view all the answers

Yop proteins serve as what type of factors in the virulence of Y.pestis?

Effector proteins Signup and view all the answers

What role does the plasminogen activator play in the virulence of Y.pestis?

Facilitates blood clot dissolution and inhibits chemotaxis Signup and view all the answers

Which Yop protein disrupts the cytoskeleton to inhibit phagocytosis?

YopH Signup and view all the answers

What is the effect of YopE on phagocytosis?

Inhibits phagocytosis and reactive oxygen species generation Signup and view all the answers

What impact does the loss of the yadBC gene have on Y.pestis virulence?

It significantly reduces virulence for bubonic plague only Signup and view all the answers

Which of the following is NOT a characteristic of V antigen (LcrV)?

Promotes the generation of reactive oxygen species Signup and view all the answers

What is the mechanism by which YopJ inhibits pro-inflammatory responses?

It blocks NF-kB signaling. Signup and view all the answers

What cellular component does YopT disrupt to impair leukocyte function?

Actin filaments Signup and view all the answers

Why is the adaptive immune system compromised when the innate immune system is disrupted by Y.pestis?

It relies on phagocytic cell activity for activation. Signup and view all the answers

Which of the following antibiotics is recommended as a first-line treatment for Y.pestis in the absence of sensitivity information?

Gentamicin Signup and view all the answers

What is the primary mode of transmission for Yersinia pestis?

Bite from an infected flea. Signup and view all the answers

What unique biological characteristic does Y.pestis possess compared to its closest relative, Y.pseudotuberculosis?

It is transmitted via arthropod vectors. Signup and view all the answers

What physiological change occurs in fleas when they ingest Y.pestis from an infected host?

Bacteria multiply and form a biofilm. Signup and view all the answers

Which treatment approach is warranted for pulmonary or advanced cases of Y.pestis infection?

Intravenous administration of antibiotics. Signup and view all the answers

Study Notes

Plague History

Plague was first recorded in 541 CE in Pelusium, Egypt
The plague spread to Alexandria, Egypt and rapidly expanded through the Byzantine Empire
Plague reached the capital, Constantinople, within a year
Sources of information about the plague include:
- Procopius, Court Archivist to the Emperor Justinian
- Syriac Church Historians John of Ephesus and Evangrius Scholasticus

Plague Terminology

Endemic: Always present in a population at relatively stable levels
Enzootic: Like endemic, but in non-human animal populations
Epidemic: Increased incidence of a disease in humans, spreading rapidly
Pandemic: An epidemic spanning multiple continents
Zoonosis: A disease that spreads naturally from animals to humans
Epizootic: An “epidemic” among non-human animals.
Vector: A living intermediary, usually an arthropod, that transmits a pathogen from one organism to another

Plague - General

Plague is an ancient disease caused by Yersinia pestis
Plague is currently endemic in many parts of the world
There have been three historically recorded pandemics
- 1st Century CE (Plague of Justinian)
- 14th Century CE (European Black Death, wiped out 1/4 to 1/3 of the population)
- Began in China in 1860 (3rd pandemic)
Alexandre Yersin isolated the plague organism in Hong Kong in 1894

Plague - Reservoirs and Vectors

Rats are the reservoir hosts for Yersinia pestis
- Important rat species for transmission to humans include:
  - Domestic black rat (Rattus rattus)
  - Brown sewer rat (Rattus norvegicus)
Plague is reported in Africa, and the southwest United States
Other reservoir hosts include:
- Ground squirrels
- Prairie dogs
The vector for Y. pestis is the flea, Xenopsylla cheopsis

Plague - Microbiology

Yersinia pestis is a small Gram-negative coccobacillus
Yersinia pestis exhibits pleomorphism (different shapes) in clinical specimens
Yersinia pestis grows aerobically on many common nutrient agars

Plague - Septicemic Plague

“Septicemic plague” refers to a particular acute clinical syndrome with high densities of plague organisms in the blood
Septicemic plague is characterized by:
- Fever
- Rigors
- Malaise
- Headache
- Nausea, diarrhea and vomiting
- Abdominal pain
The duration of the disease is shorter compared to bubonic plague

Plague - Septicemic Plague - Clinical Manifestations

Septicemic plague causes acral necrosis:
- “Acral” meaning “of the extremities”
- Blackening of the extremities may be a reason why plague became known as “Black Death”
Acral necrosis is also seen with pneumonic plague

Plague - Pneumonic Plague

“Pneumonic” denotes an infection in the lungs
Pneumonic plague can be either:
- Primary: lungs are the main focus of infection
- Secondary: infection spreads to the lungs after initial bubonic or septicemic presentation
Initial symptoms include:
- Intense headache
- Malaise
- Fever
- Vomiting
- Prostration
Patients often have impaired consciousness
Patients show minimal classical pneumonia symptoms
There is often production of watery, blood-tinged sputum
Mortality rate for both primary and secondary pneumonic plague are very high
Patients require antibiotic therapy within 4 hours of symptom onset
Pneumonic plague is the only type that is transmissible from person-to-person
- Transmission occurs via infected droplets
- Close contact with a patient experiencing a productive cough
- Cool and humid environments enable airborne infection
Epidemics of pneumonic plague have occurred in Manchuria (1911)

Plague - Less Common Plague Manifestations

Plague meningitis:
- Often a complication of inadequately treated bubonic plague
- May be associated with axillary buboes
- Bacteremia may be the route of spread
- Symptoms include:
  - Fever
  - Headache
  - Neck stiffness
  - Vomiting
- Higher mortality rate than uncomplicated bubonic plague
Pharyngeal or tonsillar plague:
- Transmitted via direct contact with respiratory secretions of the throat
- Rarely occurs in developed countries

Plague - Virulence Factors

Yersinia pestis produces potent toxins
Features a Type III secretion system that injects toxins directly into target cells
The type III system contains three kinds of proteins:
- Structural: form the system’s components
- Effector: the actual toxins
- Chaperones: proteins that protect the effector proteins before and during secretion

Plague - Virulence Factors/Toxins

yadBC: Gene that encodes two proteins, likely involved in adherence and invasion of epithelial cells
Plasminogen activator: A membrane serine protease that activates host plasminogen
- Can dissolve blood clots
- Inhibits chemotaxis of PMN
V antigen (LcrV): A multifunctional virulence factor
- Facilitates the transfer of other effector proteins across the Type III secretion system
- Links to pore formation on target cells
- Is translocated into target leukocytes where it exerts immunomodulatory effects
Yop (Yersinia Outer Proteins): The primary group of effector proteins
- There are six known Yop proteins:
  - YopE: Inhibits reactive oxygen species generation and phagocytosis
  - YopH: Disrupts cytoskeleton to inhibit phagocytosis; disrupts PI3K pathway; down-regulates ROI production, IL-12 production, TNF-alpha and IL-1B
  - YopO/YopA: Disrupts actin-based cytoskeletal system; inhibits MAP kinase and NF-kB signaling systems; limits proinflammatory cytokine release; causes apoptosis in macrophages
  - YopT: Disrupts actin filaments and inhibits cell migration

Plague - Yersinia toxins and Immune System Targets

Yersinia toxins target phagocytic cells of the innate immune system
Yops disrupt intracellular signaling and the cytoskeleton to block leukocyte activation and phagocytosis
Inactivation of the innate immune system compromises the adaptive immune system
Plague causes death by overwhelming the immune system

Plague - Treatment

Therapy should begin as quickly as possible
Antibiotic sensitivity screening, when possible
First-line drugs if sensitivity information isn’t available:
- Streptomycin
- Gentamycin
- Chloramphenicol
- Tetracycline
- Doxycycline
Intravenous administration is preferred for pulmonary or advanced cases
Prophylactic antibiotics are recommended for patient contacts

Plague - Transmission

When Xenopsylla cheopsis feeds on a Y.pestis-infected host, the organisms multiply in the flea gut
Y. pestis can form biofilms within the flea’s proventriculus, leading to blockage
Blockage prevents the flea from swallowing a blood meal, causing it to bite repeatedly and regurgitate Y.pestis back into the host

Plague - Evolutionary Origins

Y. pestis is distinct from other enterobacteriaceae because it is not transmitted via ingestion
Y. pestis is most closely related to Y. pseudotuberculosis, which causes a benign enteric disease
Genetic analysis shows a strong similarity between Y. pestis and Y. pseudotuberculosis
The two species likely diverged relatively recently

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Description

Explore the historical context of the plague, from its first recorded instance in 541 CE to its spread through the Byzantine Empire. This quiz also covers essential terminologies related to the plague, helping you understand concepts like endemic, epidemic, and zoonosis.