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

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

                                                                      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
                                     treating                    –30 million cases, 12 million deaths
                                     plague                      –Cause and mode of transmission
                                     victims                      identified (Hong Kong 1894)

                      Yersinia pestis

                                                                      Pneumonic Plague
                                                                                    • 1910-1911
                            Alexandre Yersin
                                                                                    • L-T Wu identified
                                                                                      epidemiology of
                                                                                      the pneumonic
  Gram Negative                                                                       plague
  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

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

            Plague Bubos                        Role of the Macrophage
                                                                 • Phagocytosis: bind,
                                                                   engulf and destroy
                                                                    – digestive
                                                                    – oxidizing agents
                                                                     (NO, H2O2,
                                                                     Oxygen radicals)

      Role of the Macrophage
                                                  Plague Virulence Determinants
                         • Inflammation;
                           cytokines and
                           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

                                                      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

         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
• Fever, prostration, abdominal pain,
  shock and bleeding into skin
• Disseminated intravascular
• Multiple organ failure
                                        100% fatality if untreated

        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
                                            • 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

            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,
                                            • Insecticide use to control fleas
• Pneumonic Plague - Arizona, 1992.           when plague is present
• MMWR October 9, 1992                      • Flea control in pets

             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
                          • Plague is
                            endemic in
                            above 4,000
                            ft elevation

        US Plague Cases                     Prairie Dog Plague, Flagstaff,
• 10-20/year
   – 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

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

                                                       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.