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What term describes a disease that is always present at relatively stable levels in a human population?
Which of the following is true about an epidemic?
What is the definition of a pandemic?
Which genus causes the plague?
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Which of the following is a known reservoir host for Yersinia pestis?
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What type of organism is primarily responsible for transmitting Yersinia pestis?
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What characteristic does Yersinia pestis exhibit in clinical specimens?
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What is an epizootic?
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What year does the first historical account of plague date back to?
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Which historical figure provided account of the plague outbreak in the Byzantine Empire?
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What symptom involved a swelling in multiple areas of the body?
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What were the two distinct conditions that developed in patients suffering from plague according to Procopius?
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What city did the plague reach after spreading from Pelusium?
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Which of the following was NOT a cause of death for those suffering from the plague?
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What characterizes septicemic plague in terms of plague organism density?
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What physical symptom was noted to appear as black pustules about the size of a lentil?
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What significant event did the plague lead to among the sufferers as described by Procopius?
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Which symptom is not commonly associated with septicemic plague?
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What does acral necrosis refer to in the context of septicemic plague?
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Which form of plague can be transmitted from person to person?
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What is the initial symptom of primary pneumonic plague?
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What is the recommended timeframe for starting antibiotic therapy for pneumonic plague?
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Which condition is NOT considered a complication of bubonic plague?
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What is the mortality rate trend in pneumonic plague compared to other forms?
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What is the primary function of the Type III secretion system in Y.pestis?
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Which protein is primarily involved in adhering to and invading epithelial cells in Y.pestis?
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Yop proteins serve as what type of factors in the virulence of Y.pestis?
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What role does the plasminogen activator play in the virulence of Y.pestis?
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Which Yop protein disrupts the cytoskeleton to inhibit phagocytosis?
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What is the effect of YopE on phagocytosis?
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What impact does the loss of the yadBC gene have on Y.pestis virulence?
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Which of the following is NOT a characteristic of V antigen (LcrV)?
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What is the mechanism by which YopJ inhibits pro-inflammatory responses?
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What cellular component does YopT disrupt to impair leukocyte function?
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Why is the adaptive immune system compromised when the innate immune system is disrupted by Y.pestis?
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Which of the following antibiotics is recommended as a first-line treatment for Y.pestis in the absence of sensitivity information?
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What is the primary mode of transmission for Yersinia pestis?
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What unique biological characteristic does Y.pestis possess compared to its closest relative, Y.pseudotuberculosis?
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What physiological change occurs in fleas when they ingest Y.pestis from an infected host?
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Which treatment approach is warranted for pulmonary or advanced cases of Y.pestis infection?
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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)
- Important rat species for transmission to humans include:
- 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
- There are six known Yop proteins:
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.
