Black Death Plague

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					       Black Death: Plague




Plague Spread by Biological Warfare
                                             Plague 1347-1351
• Caffa was a Genoese port on the Black
  Sea in Mongol territory
• Mongol army besieging Caffa suffered
  from plague
• Catapulted dead bodies into the city
• Plague spread to city residents; those
  who fled carried the plague with them to
  Europe




• Killed 17-28
  million Europeans    Black Death
• 30-40% of the
  population                                               Plague
• Conflicting                                             Memorial
  studies on
  recovery of Y.
                                                           Vienna
  pestis DNA from
  supposed plague
  victims




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                                                                      Plague Pandemics
               Plague Costume
                                                              • Justinian’s Plague : Middle East and
                                   • Early                      Mediterranean basin 541-544
                                     protective               • The Black Death: Europe 1347-1351
                                     clothing for
                                                              • Third pandemic 1855-1930
                                     physicians
                                     treating                    –30 million cases, 12 million deaths
                                     plague                      –Cause and mode of transmission
                                     victims                      identified (Hong Kong 1894)




                      Yersinia pestis

                                                                      Pneumonic Plague
                                                                                    • 1910-1911
                                                                                      Manchurian
                                                                                      outbreak
                            Alexandre Yersin
                                                                                    • L-T Wu identified
                                                                                      epidemiology of
                                                                                      the pneumonic
  Gram Negative                                                                       plague
  Non-motile
  Non-spore forming

                                          Paul-Louis Simond




           Yersinia enterocolitica                               Yersinia pseudotuberculosis
• Infection from eating raw or
                                                              • An intestinal pathogen of rodents and
  undercooked pork
                                                                birds sometimes infecting humans -
• Disease most often seen in small                              survives in soil and water
  children                                                    • Causes septicemia, acute gastritis and
• Fever, abdominal pain, diarrhea                               “pseudoappendicitis” with lesions similar
• In older children and adults can be                           to intestinal tuberculosis
  confused with appendicitis                                  • ~ 90% DNA homology with Y. pestis




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                 Yersinia pestis                             Plague in Fleas
   • Evolved from Y.
     pseudotuberculosis between                     • Xenopsylla cheopis
     1,500 and 20,000 years ago                     • Acquires Yersinia in blood meal
                                                    • Yersinia infection confined to
   • Has lost function of ~13% of Y.
                                                      digestive tract
     pseudotuberculosis genes
                                                    • Not transmitted transovarially
   • Has gained virulence plasmids,                 • Artificially infected larvae clear
     ability to infect fleas                          infection in 24 hours




                   Flea life cycle
                        ~60 days
                                                             Plague in Fleas
                                                    • Yersinia multiplies in midgut
Xenopsylla
cheopis female
                                     Xenopsylla
                                     cheopis male
                                                    • Forms large mass of bacteria and a
                                                      fibrinoid material = biofilm
   7 days                            4 days
                                                    • Blocks proventriculus and prevents
                                                      blood meals from getting to
                                                      stomach - flea repeatedly attempts
                                                      to feed
                                                    • Yersinia regurgitated into host
                        24 days




        Plague Vector: Xenopsylla                            Yersinia in Host
                cheopsis
                                                    • 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 Bubos                        Role of the Macrophage
                                                                 • Phagocytosis: bind,
                                                                   engulf and destroy
                                                                   pathogen
                                                                    – digestive
                                                                     enzymes
                                                                     (lysozyme,
                                                                     proteases)
                                                                    – oxidizing agents
                                                                     (NO, H2O2,
                                                                     Oxygen radicals)




      Role of the Macrophage
                                                  Plague Virulence Determinants
                         • Inflammation;
                           produces
                           cytokines and
                           chemokines
                           that attract
                           WBC and
                           allow them to
                           enter the
                           infection site




          Yersinia in Host
                                                  Lethality of Plague?
•   Spreads into bloodstream                • Killing host generally thought to be
•   Removed by liver and spleen               counterproductive for a pathogen
•   Eventually spreads to other organs         – Killing host causes fleas to seek
                                                new host and spread disease
•   Bacteremia allows for uptake by
                                               – Differential susceptibility of
    another feeding flea                        mammalian hosts
                                               – Reversion to chronic disease




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                                                      Enzootic and Epizootic Reservoirs - US

      Plague is a Zoonosis
• Plague arrived in North America (San
  Francisco) about 1900
• Many North American rodents
  experience massive die-offs (epizootics)                                   California ground squirrel
                                                                                                                   Deer mouse
                                             13-lined ground squirrel
  after exposure
• Long term maintenance of plague is in
  enzootic (reservoir) hosts - kangaroo
  rats, deer mice, grasshopper mice
                                                                  Black-footed ferret
                                                                                                          Prairie dog




                                                                        Plague Epidemiology

    Animal Reservoirs – United States

                                                        Enzootic and Epizootic




    High Risk Groups in US                                  Environmental Factors
• Native Americans, especially                   • Increased rainfall
  Navajos                                        • Displacement of wildlife
• Hunters                                           –Deforestation
• Veterinarians and pet owners                   • Homes from which rodents cannot
                                                   be excluded
• Campers and hikers
                                                 • Human movement into endemic
                                                   areas




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         Bubonic Plague                         Size of Flea
• 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




       Ulcerated Flea Bite                   Bubonic Plague




       Septicemic Plague                   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
                                        100% fatality if untreated




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        Pneumonic Plague                           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




         Plague Diagnosis
                                                         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%)




            Case Studies                                 Prevention
• Imported Plague - New York City,
  2002. MMWR August 8, 2003                 • Monitoring of wild reservoir
                                              populations for plague
• Fatal Human Plague - Arizona and
                                            • Controlling rats in urban and rural
  Colorado, 1996. MMWR July 11,
                                              areas
  1997
                                            • Insecticide use to control fleas
• Pneumonic Plague - Arizona, 1992.           when plague is present
• MMWR October 9, 1992                      • Flea control in pets




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             Prevention                       Plague in the 20th century
• Prophylactic antibiotics for people       • Rats and infected fleas in the home
  exposed to fleas or tissues of              primary source of disease
  infected animals                          • Most cases in developing countries
• No commercial vaccine in U. S.            • Worldwide 1,000-2,000 cases/year
                                            • Last urban plague epidemic in Los
                                              Angeles in 1924-1925.




                          US Plague
                          1970-1997
                          • Plague is
                            endemic in
                            Arizona
                            above 4,000
                            ft elevation




        US Plague Cases                     Prairie Dog Plague, Flagstaff,
• 10-20/year
                                                        2001
   – low = 1; high = 40 (1984; prairie
    dog and rock squirrel epizootic)        • 99 colonies observed
   –2000 = 6, none fatal                    • 49 colonies experienced >99%
• 14% (1 in 7) fatal                          mortality May-September 2001
• Usually acquired from wild animal         • Y. pestis confirmed as cause of die
  via flea bite, contact with tissues, or     offs at 19 colonies
  contact with infected pet




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Prairie Dog Plague, Flagstaff,         Plague in the Americas
            2001                            1994-1999
                                   • Highest incidence Peru 1994
                                     –1,122 cases, 51 deaths
                                     –El Niño
                                   • Ecuador 1998
                                     –160 cases (estimate), 14 deaths
                                   • Peru 1999
                                     –151 cases, 5 deaths




  World Plague Distribution                   Plague World Data




     Plague – Case Fatality Data
                                        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 Surveillance
        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




       Plague Surveillance                             Plague Surveillance
                                              SUSPECTED PLAGUE SHOULD BE
                                                 CONSIDERED IF THE FOLLOWING
                                                 CONDITIONS ARE MET:
                                              1. 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.
                                              2. 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)




                                                       Plague Surveillance
       Plague Surveillance                    CONFIRMED PLAGUE IS DIAGNOSED IF
                                                  ONE OF THE FOLLOWING CONDITIONS
                                                  IS MET:
PRESUMPTIVE PLAGUE SHOULD BE                  1. If a culture isolated is lysed by specific
   CONSIDERED WHEN ONE OR                         bacteriophage.
   BOTH OF THE FOLLOWING                      2. If two serum specimens demonstrate a four
   CONDITIONS ARE MET:                            fold anti-F1 antigen titer difference by
1. If immunofluorescence stain of smear           agglutination testing.*
                                              3. If a single serum specimen tested by
   or material is positive for the presence       agglutination has a titer of >1:128 and the
   of Yersinia pestis F1 antigen.                 patient has no known previous plague
2. If only a single serum specimen is             exposure or vaccination history.*
   tested and the anti-F1 antigen titer by    *Agglutination testing must be shown to be
   agglutination is >1:10.*                       specific to Y. pestis F1 antigen by
                                                  hemagglutination inhibition.




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