Lecture 31

Question 1

1. What is Plague caused by?
2. What was the Black Death?
3. What are some examples of the plague?

Answer 1

1. A bacterial disease caused by the Gram-negative, facultatively aerobic, rod-shaped bacterium Yersinia pestis, a member of the Enterobacteriaceae (Gammaproteobacteria). More human deaths than any other infectious disease except malaria and tuberculosis.
2. A disease of the lymphatic system. Yersinia pestis cells have a bipolar appearance; In culture, Yersinia Pestis grows slowly for an enteric bacterium, takes longer than 24 hours to form colonies.
3. Examples:
   
   1. 541 - started in Egypt and spread across Europe. Killed 60% of the population of North Africa, Europe, and Central and Southern Asia.
   2. 1346-1350: the black death, killed approx. 25-30% of the population of Europe.
   3. 1361-1362: Pestis secunda, a second wave of the plague in Europe, caught many of those who were missed by the Black Death.
   4. 1665-1666: The Great Plague of Europe
   5. 1855: Asian Plague, started in China.
   6. 1894: Southeast Asian Plague: started in the Yunan Province of China.
   7. 1900: Plague of San Francisco, introduced by rats.

Question 2

1. What are the symptoms of the plague?
2. What are fatality rates without treatment?

Answer 2

1. General malasise, high fever, highly painful lymph nodes (which many enlarge to be called buboes), septicemia, diffuse subcutaneous hemorrhage plus necrosis and gangrene producing dark skin at the extremities, shock.
2. 40-100% (depending on the disease); early diagnosis and treatment lowers the fatality rate for some types of the disease.

Question 3

1. Who was Alexandre Yersin?
2. Who was Shibasaburo Kitasato?
3. How do the two individuals differ in there approach to discovering the causative agent of plague?
4. What was the bacterium originally called?

Answer 3

1. Isolated and identified the causative agent of Plague, in 1894. A physcian/bacteriologist from the Pasteur Institute in Paris, while working in Hong Kong.
2. Another bacteriologist, from Japan, who was trained in Germany in the methods of Koch, was trying at the same time to identify the causative agent of plague.
3. Shibasaburo Kitasato isolated bacteria from patients, but described a mixed culture, whereas Yersin got the right orgnaism in pure culture.
4. Pasterurella pestis, but was renamed Yersinia pestis in honor of Yersin after he died in 1943.

Question 4

1. How did luck play a role in Yersin’s discovery?

Answer 4

1. Yersin sampled the bubo; Kitasato sampled blood and organs.
2. Kitasato had access to a hospital incubuator and so incubated his cultures at 37°C, the temp. o fthe human body, which favored the growth of pneumococcus, present due to a secondary infection.
3. Yersin did not have access to an incubuator and so grew his cultures at normal room temperature in Hong Kong, 28°C, which favors the growth of the plague bacterium

Question 5

1. How is plague transmitted?
2. What kind of disease is it?
3. How is normally passed to humans?

Answer 5

1. Commonly encountered as an infection of rats, ground squirrels, prairie dogs, and other rodents.
2. Plague is a zoonosis, primarily a disease of rodents.
3. The rat flea, Xenopsylla cheopis, serves as the vector between rodents and from rodents to humans. When a flea bites an infected rat, it ingests the bacterium from the rat’s blood, and the bacterium reproduces rapidly in the flea’s gut, blocking the flea’s gut, causing it to bite out of hunger or to regurgitate its gut contents to clear its gut; this introduces the bacterium at the sites where the flea bites.
4. I humans, plague most commonly occurs when fleas infected with Yersinia pestis bit humans who then develop the bubonic type of the disease. Human epidemics can occur after a mass die-off of rats. The fleas become hungry. because their natural hosts have died off. The fleas then find other hosts.

Question 6

1. What does the bacterium form?
   
   1. How does the bacteria benefit from this structure?

Answer 6

1. Forms a biofilm in the foregut of the flea.
   
   1. The ingested blood is pumped into the esophagus as flea tries to feed, but the biofilm blocks the ingestions of the blood. The pumped blood dislodges bacteria from the biofilm. The bacteria and blood are then regurgitated back into the bite wound. This introduces the bacteria into the host’s circulatory system.

Question 7

1. What is bubonic plague?
2. What is septicemic plague?
3. What is secondary pneumonic plague?
4. What is primary pneumonic plague?
5. How do these variations differ?

Answer 7

1. Typically is started by the bite by a flea infected with Y. pestis. The bite inoculates thousands of Y. pestis cells deep into the skin; the bacteria migrate to lymph nodes where they multiply; they then destroy the lymph node and escape into the bloodstream, where they continue reproducing.
2. Y. pestis septicemia without the prior formation of a visible bubo.
3. Spread of bacterium from lymph nodes to the bloodstream to the lungs.
4. Acquired by inhalation of respiratory droplets from person with secondary (or primary) pneumonic plague.
5. Bubonic and septicemic plague do not spread directly from person to person. Some people with bubonic plague or septicemic plague develop secondary pneumonic plague and they can then spread the disease by repiratory droplets through close contact to other people, who develop pneumonic plague.

Question 8

1. Where do the various forms of plague attack?

Answer 8

1. Places:
   
   1. Bubonic plague - in lymph nodes
   2. Septicemic - in bloodstream
   3. Secondary - from bloodstream to the lungs, highly transmissible.
   4. Primary - directly to the lungs, highly transmissible.

Question 9

Describe the progression of the disease.

Answer 9

1. When Y. pestis is present in infected fleas, the bacterium does not produce a capsular layer.
2. So, when an infected flea bites a human, introducing the bacterium into the body, most of the bacterial cells are phagocytosed and killed by the body’s leukocytes.
3. A few of the bacterial cells, however, survive phagocytosis and can grow in the phagosome, killing the phagocyte and releasing the bacteria.
4. During this time the bacteria produce a capsule that allows the released bacteria to resist phagocytosis by other phagocytes.
5. The bacterium produces several virulence factors, including protein-lipoprotein complexes (blocks phagocytosis) and a murein exotoxin (a respiratory inhibitor, blocks mitochondrial electron transport at quinon step).

Question 10

1. What is YopJ?
2. What does YopJ activate?
3. What do caspases trigger?

Answer 10

1. A protein that Y. pestis releases into the host cell (virulence factor).
2. Activates host-cell proteins called caspases.
3. Apoptosis, which leads to the break down of DNA in the nucleus, switching off and disintegrating the mitochondria and disrupting the human cell’s cytoplasmic membrane.

Question 11

1. What is the result of the series of events that lead to destruction and the release of the bacteria into the surrounding tissue?

Answer 11

1. The bacteria can now resist phagocytosis by leucocyte through the action of certain outer membrane proteins and the capsule. The cells quickly spread to the lymph nodes, which become hot, swollen, tender, and hemorrhagic. This gives the characteristic buboes responsible for the name of the disease.

Question 12

1. What happens a few hours after the colonization of the lymph nodes?
2. What does the patient develop?
3. What is the mortality rate of secondary pneumonic plague?
4. What happens to people who inhale the bacteria?
5. What happens if conditions are bad (severe overcrowding, malnutrition, and heavy flea infestation)?

Answer 12

1. The infection spills out into the bloodstream, leading to infection of the liver, spleen, lungs.
2. A severe bacterial pneumonia (secondary pneumonic plague), exhaling large numbers of bacteria into the air during coughing fits.
3. 50-100% even if treated.
4. Develop primary pneumonic plague. 90-100% of these individuals will die, even with treatment.
5. The epidemic of bubonic plague can shift to a predominately pneumonic form. Short incubation period of 1-3 days, versus 2-6 days for bubonic.

Question 13

1. Does the plague remain endemic today?
2. When was the last-rat caused epidemic in the U.S.?

Answer 13

1. Yes, plague is still endemic today, in many areas around the world. Epidemics from rats continue to occur in some developing countries, mostly rural areas. Plague remains endemic in ground squirrels and other rodents in the US West and Southwest.
2. Los Angeles in 1924-25.

Question 14

1. What are some treatments of plague?
2. What is the mortality rate of bubonic plague even with treatment?

Answer 14

1. Doxycycline, ciprofloxin; or other antibiotics such as tetracycline, streptomycin, gentamycin, or chloramphenicol. The earlier the diagnosis and antibiotic treatment, the better the prognosis.
2. 1-5%

Question 15

1. What are some preventions of plague?

Answer 15

1. Vaccination - formalin-killed whole cell vaccine or cell extract vaccine, generally given only to people working where plague is endemic. Not highly effective against the septicemic and pneumonic forms of the disease.
2. So, avoidance - avoid areas infested with rats, other rodents and their fleas; eliminate or reduce the animal reservoir.

Question 16

1. What is the potential use as a biological weapon?

Answer 16

1. Availability and ease of culture.
2. Capacity for mass production and aerosol dissemination.
3. Inhaled aerosolized Y. pestis would cause primary pneumonic plague.
4. High fatality rate for primary pneumonic plague, 1-3 days following exposure.
5. Potential for person-to-person spread of primary pneumonic plague, spreading rapidly through a population.