Black Death: Plague

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Black Death Plague
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Plague 1347-1351
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Black Death

• Killed 17-28 million Europeans
• 30-40 of the population

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Plague Memorial Vienna

• Monument to Immunity

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Plague Costume

• Early protective clothing for physicians treating
  plague victims

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Plague Pandemics

• Justinians Plague Middle East and
  Mediterranean basin 541-544
• The Black Death Europe 1347-1351
• Third pandemic 1855-1930
• 30 million cases, 12 million deaths
• Cause and mode of transmission identified (Hong
  Kong 1894)

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Yersinia pestis
Alexandre Yersin
Gram Negative Non-motile Non-spore forming
Paul-Louis Simond
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Pneumonic Plague

• 1910-1911 Manchurian outbreak
• L-T Wu identified epidemiology of the pneumonic
  plague

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Yersinia enterocolitica

• Infection from eating raw or undercooked pork
• Disease most often seen in small children
• Fever, abdominal pain, diarrhea
• In older children and adults can be confused with
  appendicitis

   
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Yersinia pseudotuberculosis
 

• An intestinal pathogen of rodents and birds
  sometimes infecting humans - survives in soil and
  water
• Causes septicemia, acute gastritis and
  pseudoappendicitis with lesions similar to
  intestinal tuberculosis
• 90 DNA homology with Y. pestis

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Yersinia pestis

• Evolved from Y. pseudotuberculosis between 1,500
  and 20,000 years ago
• Has lost function of 13 of Y.
  pseudotuberculosis genes
• Has gained virulence plasmids, ability to infect
  fleas

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Plague in Fleas

• Xenopsylla cheopis
• Acquires Yersinia in blood meal
• Yersinia infection confined to digestive tract
• Not transmitted transovarially
• Artificially infected larvae clear infection in
  24 hours

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Flea life cycle
60 days
Xenopsylla cheopis female
Xenopsylla cheopis male
4 days
7 days
24 days
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Plague in Fleas

• Yersinia multiplies in midgut
• Forms large mass of bacteria and a fibrinoid
  material biofilm
• Blocks proventriculus and prevents blood meals
  from getting to stomach - flea repeatedly
  attempts to feed
• Yersinia regurgitated into host

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Plague Vector Xenopsylla cheopsis
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Yersinia in Host

• Initially phagocytosed by PMNs and monocytes
• Grows intracellularly in monocytes and becomes
  resistant to phagocytosis
• Spreads from bite to regional lymph nodes -- bubo

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Plague Bubo
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Plague Virulence Determinants
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Yersinia in Host

• Spreads into bloodstream
• Removed by liver and spleen
• Eventually spreads to other organs
• Bacteremia allows for uptake by another feeding
  flea

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Lethality of Plague?

• Killing host generally thought to be
  counterproductive for a pathogen
• Killing host causes fleas to seek new host and
  spread disease
• Differential susceptibility of mammalian hosts
• Reversion to chronic disease

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Plague is a Zoonosis

• Plague arrived in North America (San Francisco)
  about 1900
• Many North American rodents experience massive
  die-offs (epizootics) after exposure
• Long term maintenance of plague is in enzootic
  (reservoir) hosts - kangaroo rats, deer mice,
  grasshopper mice

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Enzootic and Epizootic Reservoirs - US
Deer mouse
California ground squirrel
13-lined ground squirrel
Black-footed ferret
Prairie dog
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Animal Reservoirs United States
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Plague Epidemiology
Enzootic and Epizootic
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High Risk Groups in US

• Native Americans, especially Navajos
• Hunters
• Veterinarians and pet owners
• Campers and hikers

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Environmental Factors

• Increased rainfall
• Displacement of wildlife
• Deforestation
• Homes from which rodents cannot be excluded
• Human movement into endemic areas

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Bubonic Plague

• Acquired from flea bite
• Incubation period 2-6 days
• Fever, headache, tender lymph nodes, prostration
• Swollen lymph node(s) buboes
• 40-60 mortality if untreated

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Size of Flea
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Ulcerated Flea Bite
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Bubonic Plague
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Septicemic Plague

• Septicemia (bacteria in blood) in absence of
  swollen LN
• May be spread from bubonic plague
• Fever, prostration, abdominal pain, shock and
  bleeding into skin
• Disseminated intravascular coagulopathy
• Multiple organ failure

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Septicemic Plague
100 fatality if untreated
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Pneumonic Plague

• Spread from bubonic or acquired from domestic cat
• Incubation period 1-3 days
• Fever, cough, bloody sputum, difficulty in
  breathing, rapid shock and death
• Person-to-person spread
• 100 fatal if not treated immediately

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Pneumonic Plague
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Plague Diagnosis
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Treatment

• Yersinia pestis sensitive to antibiotics
  streptomycin, gentamycin, tetracyclines
• Isolation of patient and notification of public
  health personnel
• Death rates 15 with antibiotic therapy
  (pneumonic plague over 50)

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Case Studies

• Imported Plague - New York City, 2002. MMWR
  August 8, 2003
• Fatal Human Plague - Arizona and Colorado, 1996.
  MMWR July 11, 1997
• Pneumonic Plague - Arizona, 1992.
• MMWR October 9, 1992

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Prevention

• Monitoring of wild reservoir populations for
  plague
• Controlling rats in urban and rural areas
• Insecticide use to control fleas when plague is
  present
• Flea control in pets

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Prevention

• Prophylactic antibiotics for people exposed to
  fleas or tissues of infected animals
• No commercial vaccine in U. S.

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Plague in the 20th century

• Rats and infected fleas in the home primary
  source of disease
• Most cases in developing countries
• Worldwide 1,000-2,000 cases/year
• Last urban plague epidemic in Los Angeles in
  1924-1925.

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US Plague 1970-1997

• Plague is endemic in Arizona above 4,000 ft
  elevation

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US Plague Cases

• 10-20/year
• low 1 high 40 (1984 prairie dog and rock
  squirrel epizootic)
• 2000 6, none fatal
• 14 (1 in 7) fatal
• Usually acquired from wild animal via flea bite,
  contact with tissues, or contact with infected pet

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Prairie Dog Plague, Flagstaff, 2001

• 99 colonies observed
• 49 colonies experienced 99 mortality
  May-September 2001
• Y. pestis confirmed as cause of die offs at 19
  colonies

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Prairie Dog Plague, Flagstaff, 2001
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Plague in the Americas1994-1999

• Highest incidence Peru 1994
• 1,122 cases, 51 deaths
• El Niño
• Ecuador 1998
• 160 cases (estimate), 14 deaths
• Peru 1999
• 151 cases, 5 deaths

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World Plague Distribution
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Plague World Data
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Plague Case Fatality Data
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Plague in Madagascar

• 1983-1998 45 of plague cases in Africa have been
  in Madagascar
• Brought to county in 1898 by steamboat from India
• Multidrug resistant strain isolated

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Plague Bioterrorism

• Caffa (Feodosija, Ukraine) 1346
• Bodies of plague victims were catapulted over the
  city walls
• China WWII
• Japan released plague-infected fleas over several
  Chinese cities

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Plague Surveillance
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Plague Surveillance
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Plague Surveillance

• SUSPECTED PLAGUE SHOULD BE CONSIDERED IF THE
  FOLLOWING CONDITIONS ARE MET
• Clinical symptoms that are compatible with
  plague, i. e., fever and lymphadenopathy in a
  person who resides in or recently traveled to a
  plague-endemic area.
• If small gram-negative and/or bipolar-staining
  coccobacilli are seen on a smear taken from
  affected tissues, e.g.
• Bubo (bubonic plague)
• Blood (septicemic plague)
• Tracheal/lung aspirate (pneumonic plague)

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Plague Surveillance

• PRESUMPTIVE PLAGUE SHOULD BE CONSIDERED WHEN ONE
  OR BOTH OF THE FOLLOWING CONDITIONS ARE MET
• If immunofluorescence stain of smear or material
  is positive for the presence of Yersinia pestis
  F1 antigen.
• If only a single serum specimen is tested and the
  anti-F1 antigen titer by agglutination is 110.

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Plague Surveillance

• CONFIRMED PLAGUE IS DIAGNOSED IF ONE OF THE
  FOLLOWING CONDITIONS IS MET
• If a culture isolated is lysed by specific
  bacteriophage.
• If two serum specimens demonstrate a four fold
  anti-F1 antigen titer difference by agglutination
  testing.
• If a single serum specimen tested by
  agglutination has a titer of 1128 and the
  patient has no known previous plague exposure or
  vaccination history.
• Agglutination testing must be shown to be
  specific to Y. pestis F1 antigen by
  hemagglutination inhibition.