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Author(s): Sandro Cinti, M.D., 2009

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Biopreparedness

              M1 Infectious Diseases Sequence
                        Sandro Cinti


Spring 2009
Stadium: 1000Faces, wikimedia commons
                                         4
Airplane: Gautherie, wikimedia commons
What is Bioterrorism?




                        5
•  Bioterrorism is the malevolent
   use of viruses, bacteria, fungi or
   toxins to produce death or
   disease in humans, animals or
   plants.




                                    6
Any Examples of Bioterrorism?




                                7
•  1360 – Plague victims bodies thrown over
             besieged city s walls
•  1763 – Europeans give smallpox infected
             blankets to Native Americans
•  1984 – Bhagwan Shree Rajneesh contaminates
             food with Salmonella to win election
•  1994 – Shoko Assahara group attack Tokyo
             subway with sarin gas
•  2001 – Anthrax




                                                                     8
                                     Admin-2000, wikimedia commons
The 1979 Sverdlovsk Anthrax Outbreak



                                                        Other images of
                                                       Sverdlovsk facility
                                                           removed




                                     See: http://www.semp.us/publications/biot_reader.php?BiotID=324




   UCLA Department of Epidemiology




                                                                                                  9
Why use biological weapons?




                              10
Why Use Biological Weapons?
•  Cheap-800 X less than nucs
•  Easy to acquire
  –  Dual use
  –  Web-based information
•  High Fatality
  –  100 kg anthrax could kill 3 million (OTA
     report, 1993)
•  High Panic factor
                                                11
What makes a good bioweapon?




                           12
USDA, HHS
            13
Category A Biological
                 Agents
•    Variola major (Smallpox)
•    Bacillus anthracis (Anthrax)
•    Yersinia pestis (Plague)
•    Francisella tularensis (Tularemia)
•    Botulinum toxin (Botulism)
•    Filoviruses and Arenaviruses (Viral
     hemorrhagic fevers)
                                           14
Anthrax- Bacillus anthracis



                                                      Cutaneous




                                       Usafe.af.mil               Gastrointestinal
Inhalational
                                                                                 15
 Sources Undetermined (All other images)
Anthrax
•  Spore former

•  Not transmissible person-person

•  Inhalational-high mortality (50-90%)
  –  2-3 IV antibiotics

•  Prophylaxis- ciprofloxacin, doxycycline-60
   days
                                            16
Tularemia


                                CDC
        Source Undetermined


        Cutaneous

• G(-) Coccobacillus
• 1-2 organisms can cause infection       Cornell University Medical College


• Not person-person spread
• Tx-aminoglycosides, cipro,
doxycycline
                                                                          17
Botulinum Toxin
•  Made by the bacterium Clostridium botulinum
•  Most toxic substance on earth - food poisoning
   ( 0.1 ug lethal dose)
•  Weaponizable and aerosolizable (air & food supplies)
•  BoTox also used to medically, anti-wrinkle
•  Secreted protein neurotoxin causing flaccid
   paralysis
•  Death due to asphyxiation
                                                        Image of Botox injection
                                                               removed




                                            Image available here: www.stylelist.com/blog/tag/anti-aging/

                             C. botulinum         Cosmetic improvements are NOT
      Source Undetermined                                   bioterrorism        18
Hemorrhagic Viruses
•  Ebola, Marburg, Yellow
   Fever, Lassa
•  Viral syndrome with
   hemorrhagic complications
•  High fatalities with Ebola
   (80%)                        Dr. Lyle Conrad, Joel G. Breman, CDC PHIL #7201




•  No treatments, few
   vaccines (YF)
•  Person-person spread

                                             Source Undetermined
                                                                   19
Plague-Yersinia pestis


                                                      Source Undetermined
        World Health Organization,
        CDC PHIL #463




                                     CDC PHIL #2047


                                        Bubonic



Source Undetermined




                                                                 20
Septicemic Plague




Source Undetermined   Source Undetermined




                                            21
Pneumonic Plague
•  Most likely form in BT
•  Mortality 80-90%
•  Person-person
   transmission
•  Tx- Streptomycin, IV
   ciprofloxicin or
   doxycycline                  Source Undetermined




•  Prophylaxis- oral cipro or
   doxy
                                                      22
18th century London newspaper

                                23
How would BT agents be
    disseminated?




                         24
•  Food

•  Water

•  Zoonotic

•  Aerosol

              25
How would a BT attack be
      detected?




                           26
Clues to a BT Attack
•  A large number of ill persons presenting at the
   same time with a similar disease, especially the
   following syndromes:
   o  Flaccid paralysis (botulinum toxin)
   o  Hemorrhagic fevers (Ebola, Lassa fever)
   o  Vesicular/pustular rash with considerable mortality
      (smallpox)
   o  Influenza-like illness associated with a widened
      mediastinum on chest X-ray and/or meningitis
      (anthrax)
   o  Pneumonia with painful lymphadenopathy (plague)
                                                            27
Clues to a BT Attack
•  Illness in animals and humans concurrently
•  A large number of unexplained deaths, especially
   in young healthy adults
•  A single case of an uncommon organism (e.g.,
   smallpox, pulmonary anthrax, Ebola)
•  Multiple disease entities presenting in one patient
•  An unusual disease presentation (e.g., pneumonic
   instead of bubonic plague)

                                                         28
Clues to a BT Attack
•  An unusual geographic distribution (e.g., Ebola in
   the U.S.)
•  An unusual seasonal pattern (e.g., influenza in
   summer)
•  An illness that fails to respond to usual
   antimicrobials or vaccines (e.g., engineered
   antibiotic/vaccine resistant anthrax)
•  Clusters of a similar illness in non-contiguous
   areas, domestic or foreign

                                                    29
36 yo female with rash and fever




                               30
Source Undetermined



                      31
Smallpox: Overview

•  1980 - Global eradication
•  Humans were only known
   reservoir
•  Person-to-person
   transmission (aerosol/
   contact)
•  Up to 30% mortality in
   unvaccinated
                               Source Undetermined




                                                     32
Smallpox:
              Clinical Features
•  Prodrome (incubation 7-17 days)
   –  Acute onset of fever, malaise, headache, backache,
      vomiting, occasional delirium
   –  Transient erythematous rash
•  Exanthem
   –  Begins face, hands, forearms
   –  Spread to lower extremities then trunk over ~ 7 days
                                      USAMRICD
   –  Synchronous progression: macules --> vesicles -->
      pustules --> scabs
   –  Lesions on palms /soles
                                                           33
Smallpox Enanthem

   Illustration of smallpox rash in
            throat removed




                                      34
Day 4
  Day 3




World Health Organization   World Health Organization
                                                        35
Day 5
                           Day 7




World Health Organization   World Health Organization
                                                        36
Day 8-9
                                 Day 10-14




World Health Organization
                            World Health Organization
                                                        37
World Health Organization   38
CDC PHIL # 131


                 39
Source Undetermined




                      40
SMALLPOX                  CHICKENPOX
FEVER                    2–4 days before the rash    At time of rash
RASH
Appearance               Pocks at same stage         Pocks in several stages
Development              Slow                        Rapid
Distribution             More pocks on arms & legs   More pocks on body
On palms & soles         Usually present             Usually absent
DEATH                    More than 10%               Very uncommon
       Source Undetermined




                                                                               41
World Health Organization
                            World Health Organization
                                                        42
•  Smallpox vaccine production using cows




     Source Undetermined



                                            43
44
CDC (All images)
45
Logical Images (All Images)
Normal Reactions




Source Undetermined    46
Staph Infection at Site




  Dr. V. Fulginiti
                          47
Erythema Multiforme



Dr. V. Fulginiti              Dr. V. Fulginiti                                Dr. V. Fulginiti




Arthur E. Kaye CDC ID#:3286   Arthur E. Kaye; J. Michael Lane, M.D. CDC PHIL #3318

                                                                                                 48
Accidental Inoculation



     Dr. H. Kempe               Dr. V. Fulginiti    Dr. V. Fulginiti


                                                   To sites of acne




     Dr. V. Fulginiti           Dr. V. Fulginiti


Diaper implantation                                                    49
Eczema Vaccinatum



Dr. H. Kempe




                  Arthur E. Kaye CDC PHIL #3305




Dr. H. Kempe                                      50
Generalized Vaccinia




                                             51
Dr. H. Kempe (All Images)
Progressive Vaccinia
Child with Hypogam Child with Hypogam             Lymphosarcoma




 Child with SCID                Child with SCID    Lymphoma




Dr. V. Fulginiti (All Images)                                 52
Vaccinia Keratitis




Dr. V. Fulginiti          Dr. V. Fulginiti




                                             53
Congenital Vaccinia




Source Undetermined                         Source Undetermined



                      3rd Trimester has the highest risk

                                                                  54
Contraindications to Vaccination
•    Pregnancy
•    Immunodeficiency
•    Eczema or Atopic Dermatitis
•    Active Skin Conditions
•    Active Eye Disease
•    Allergy to Components
•    Heart Problems
                                   55
Additional Source Information
                        for more information see: http://open.umich.edu/wiki/CitationPolicy

Slide 4: Stadium: 1000Faces, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:BigHousePacked.JPG; Airplane: Gautherie, Wikimedia
      Commons, http://commons.wikimedia.org/wiki/File:Bréguet_XIV_au_décollage_La_Ferté_Alais_1994.jpg
Slide 8: Admin-2000, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:40ef87e4e8.jpg, CC:BY-SA 3.0,
      http://creativecommons.org/licenses/by-sa/3.0/
Slide 9: UCLA Department of Epidemiology, School of Public Health, http://www.ph.ucla.edu/epi/bioter/sverd/sverd_fig3.html
Slide 13: USDA, HHS, http://www.selectagents.gov/resources/List%20of%20Select%20Agents%20and%20Toxins_111708.pdf
Slide 15: U.S. Air Forces in Europe, http://www.usafe.af.mil/direct/sg/anthrax/Pictures/anthrx22.jpg, Sources Undetermined (All other Images)
Slide 17: Lesion: Source Undetermined, Thumb: CDC, http://www.cdc.gov/Tularemia/Tul_Signssymptoms.html X-Ray: Cornell University Medical
      College
Slide 18: C. botulinum: Source Undetermined; Image of botox injection is available here: www.stylelist.com/blog/tag/anti-aging/
Slide 19: Dr. Lyle Conrad, Joel G. Breman, CDC PHIL #7201; Source Undetermined
Slide 20: (From left to right) Source Undetermined; World Health Organization, CDC PHIL #463; CDC PHIL #2047; Source Undetermined
Slide 21: Sources Undetermined
Slide 22: Source Undetermined
Slide 23: 18th century London newspaper
Slide 31: Source Undetermined
Slide 32: Source Undetermined
Slide 35: World Health Organization, http://www.who.int/emc/diseases/smallpox/slideset/ (All images)
Slide 36: World Health Organization, http://www.who.int/emc/diseases/smallpox/slideset/ (All images)
Slide 37: World Health Organization, http://www.who.int/emc/diseases/smallpox/slideset/ (All images)
Slide 38: World Health Organization, http://www.who.int/emc/diseases/smallpox/slideset/ (All images)
Slide 39: CDC PHIL # 131, http://emergency.cdc.gov/agent/smallpox/smallpox-images/smallpox1.htm
Slide 40: Source Undetermined
Slide 41: Source Undetermined
Slide 42: World Health Organization, http://www.who.int/emc/diseases/smallpox/slideset/ (All images)
Slide 43: Source Undetermined
Slide 44: CDC, http://emergency.cdc.gov/training/smallpoxvaccine/reactions/download_pocket_guide.htm
Slide 45: Logical Images (All Images), http://emergency.cdc.gov/training/smallpoxvaccine/reactions/tl_view.htm
Slide 46: Source Undetermined
Slide 47: Dr. V. Fulginiti
Slide 48: Dr. V. Fulginiti; Dr. V. Fulginiti; Dr. V. Fulginiti; Arthur E. Kaye CDC ID#:3286; Arthur E. Kaye; J. Michael Lane, M.D. CDC PHIL #3318
Slide 49: Dr. H. Kempe; Dr. V. Fulginiti; Dr. V. Fulginiti; Dr. V. Fulginiti; Dr. V. Fulginiti;
Slide 50: Dr. H. Kempe; Dr. H. Kempe; Arthur E. Kaye CDC PHIL #3305
Slide 51: Dr. H. Kempe (All Images)
Slide 52: Dr. V. Fulginiti (All Images)
Slide 53: Dr. V. Fulginiti; Dr. V. Fulginiti
Slide 54: Sources Undetermined

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04.15.09: Biopreparedness

  • 1. Author(s): Sandro Cinti, M.D., 2009 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution – Share Alike 3.0 License: http://creativecommons.org/licenses/by-sa/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
  • 2. Citation Key for more information see: http://open.umich.edu/wiki/CitationPolicy Use + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation License Make Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair.
  • 3. Biopreparedness M1 Infectious Diseases Sequence Sandro Cinti Spring 2009
  • 4. Stadium: 1000Faces, wikimedia commons 4 Airplane: Gautherie, wikimedia commons
  • 6. •  Bioterrorism is the malevolent use of viruses, bacteria, fungi or toxins to produce death or disease in humans, animals or plants. 6
  • 7. Any Examples of Bioterrorism? 7
  • 8. •  1360 – Plague victims bodies thrown over besieged city s walls •  1763 – Europeans give smallpox infected blankets to Native Americans •  1984 – Bhagwan Shree Rajneesh contaminates food with Salmonella to win election •  1994 – Shoko Assahara group attack Tokyo subway with sarin gas •  2001 – Anthrax 8 Admin-2000, wikimedia commons
  • 9. The 1979 Sverdlovsk Anthrax Outbreak Other images of Sverdlovsk facility removed See: http://www.semp.us/publications/biot_reader.php?BiotID=324 UCLA Department of Epidemiology 9
  • 10. Why use biological weapons? 10
  • 11. Why Use Biological Weapons? •  Cheap-800 X less than nucs •  Easy to acquire –  Dual use –  Web-based information •  High Fatality –  100 kg anthrax could kill 3 million (OTA report, 1993) •  High Panic factor 11
  • 12. What makes a good bioweapon? 12
  • 13. USDA, HHS 13
  • 14. Category A Biological Agents •  Variola major (Smallpox) •  Bacillus anthracis (Anthrax) •  Yersinia pestis (Plague) •  Francisella tularensis (Tularemia) •  Botulinum toxin (Botulism) •  Filoviruses and Arenaviruses (Viral hemorrhagic fevers) 14
  • 15. Anthrax- Bacillus anthracis Cutaneous Usafe.af.mil Gastrointestinal Inhalational 15 Sources Undetermined (All other images)
  • 16. Anthrax •  Spore former •  Not transmissible person-person •  Inhalational-high mortality (50-90%) –  2-3 IV antibiotics •  Prophylaxis- ciprofloxacin, doxycycline-60 days 16
  • 17. Tularemia CDC Source Undetermined Cutaneous • G(-) Coccobacillus • 1-2 organisms can cause infection Cornell University Medical College • Not person-person spread • Tx-aminoglycosides, cipro, doxycycline 17
  • 18. Botulinum Toxin •  Made by the bacterium Clostridium botulinum •  Most toxic substance on earth - food poisoning ( 0.1 ug lethal dose) •  Weaponizable and aerosolizable (air & food supplies) •  BoTox also used to medically, anti-wrinkle •  Secreted protein neurotoxin causing flaccid paralysis •  Death due to asphyxiation Image of Botox injection removed Image available here: www.stylelist.com/blog/tag/anti-aging/ C. botulinum Cosmetic improvements are NOT Source Undetermined bioterrorism 18
  • 19. Hemorrhagic Viruses •  Ebola, Marburg, Yellow Fever, Lassa •  Viral syndrome with hemorrhagic complications •  High fatalities with Ebola (80%) Dr. Lyle Conrad, Joel G. Breman, CDC PHIL #7201 •  No treatments, few vaccines (YF) •  Person-person spread Source Undetermined 19
  • 20. Plague-Yersinia pestis Source Undetermined World Health Organization, CDC PHIL #463 CDC PHIL #2047 Bubonic Source Undetermined 20
  • 21. Septicemic Plague Source Undetermined Source Undetermined 21
  • 22. Pneumonic Plague •  Most likely form in BT •  Mortality 80-90% •  Person-person transmission •  Tx- Streptomycin, IV ciprofloxicin or doxycycline Source Undetermined •  Prophylaxis- oral cipro or doxy 22
  • 23. 18th century London newspaper 23
  • 24. How would BT agents be disseminated? 24
  • 25. •  Food •  Water •  Zoonotic •  Aerosol 25
  • 26. How would a BT attack be detected? 26
  • 27. Clues to a BT Attack •  A large number of ill persons presenting at the same time with a similar disease, especially the following syndromes: o  Flaccid paralysis (botulinum toxin) o  Hemorrhagic fevers (Ebola, Lassa fever) o  Vesicular/pustular rash with considerable mortality (smallpox) o  Influenza-like illness associated with a widened mediastinum on chest X-ray and/or meningitis (anthrax) o  Pneumonia with painful lymphadenopathy (plague) 27
  • 28. Clues to a BT Attack •  Illness in animals and humans concurrently •  A large number of unexplained deaths, especially in young healthy adults •  A single case of an uncommon organism (e.g., smallpox, pulmonary anthrax, Ebola) •  Multiple disease entities presenting in one patient •  An unusual disease presentation (e.g., pneumonic instead of bubonic plague) 28
  • 29. Clues to a BT Attack •  An unusual geographic distribution (e.g., Ebola in the U.S.) •  An unusual seasonal pattern (e.g., influenza in summer) •  An illness that fails to respond to usual antimicrobials or vaccines (e.g., engineered antibiotic/vaccine resistant anthrax) •  Clusters of a similar illness in non-contiguous areas, domestic or foreign 29
  • 30. 36 yo female with rash and fever 30
  • 32. Smallpox: Overview •  1980 - Global eradication •  Humans were only known reservoir •  Person-to-person transmission (aerosol/ contact) •  Up to 30% mortality in unvaccinated Source Undetermined 32
  • 33. Smallpox: Clinical Features •  Prodrome (incubation 7-17 days) –  Acute onset of fever, malaise, headache, backache, vomiting, occasional delirium –  Transient erythematous rash •  Exanthem –  Begins face, hands, forearms –  Spread to lower extremities then trunk over ~ 7 days USAMRICD –  Synchronous progression: macules --> vesicles --> pustules --> scabs –  Lesions on palms /soles 33
  • 34. Smallpox Enanthem Illustration of smallpox rash in throat removed 34
  • 35. Day 4 Day 3 World Health Organization World Health Organization 35
  • 36. Day 5 Day 7 World Health Organization World Health Organization 36
  • 37. Day 8-9 Day 10-14 World Health Organization World Health Organization 37
  • 39. CDC PHIL # 131 39
  • 41. SMALLPOX CHICKENPOX FEVER 2–4 days before the rash At time of rash RASH Appearance Pocks at same stage Pocks in several stages Development Slow Rapid Distribution More pocks on arms & legs More pocks on body On palms & soles Usually present Usually absent DEATH More than 10% Very uncommon Source Undetermined 41
  • 42. World Health Organization World Health Organization 42
  • 43. •  Smallpox vaccine production using cows Source Undetermined 43
  • 47. Staph Infection at Site Dr. V. Fulginiti 47
  • 48. Erythema Multiforme Dr. V. Fulginiti Dr. V. Fulginiti Dr. V. Fulginiti Arthur E. Kaye CDC ID#:3286 Arthur E. Kaye; J. Michael Lane, M.D. CDC PHIL #3318 48
  • 49. Accidental Inoculation Dr. H. Kempe Dr. V. Fulginiti Dr. V. Fulginiti To sites of acne Dr. V. Fulginiti Dr. V. Fulginiti Diaper implantation 49
  • 50. Eczema Vaccinatum Dr. H. Kempe Arthur E. Kaye CDC PHIL #3305 Dr. H. Kempe 50
  • 51. Generalized Vaccinia 51 Dr. H. Kempe (All Images)
  • 52. Progressive Vaccinia Child with Hypogam Child with Hypogam Lymphosarcoma Child with SCID Child with SCID Lymphoma Dr. V. Fulginiti (All Images) 52
  • 53. Vaccinia Keratitis Dr. V. Fulginiti Dr. V. Fulginiti 53
  • 54. Congenital Vaccinia Source Undetermined Source Undetermined 3rd Trimester has the highest risk 54
  • 55. Contraindications to Vaccination •  Pregnancy •  Immunodeficiency •  Eczema or Atopic Dermatitis •  Active Skin Conditions •  Active Eye Disease •  Allergy to Components •  Heart Problems 55
  • 56. Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicy Slide 4: Stadium: 1000Faces, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:BigHousePacked.JPG; Airplane: Gautherie, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:Bréguet_XIV_au_décollage_La_Ferté_Alais_1994.jpg Slide 8: Admin-2000, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:40ef87e4e8.jpg, CC:BY-SA 3.0, http://creativecommons.org/licenses/by-sa/3.0/ Slide 9: UCLA Department of Epidemiology, School of Public Health, http://www.ph.ucla.edu/epi/bioter/sverd/sverd_fig3.html Slide 13: USDA, HHS, http://www.selectagents.gov/resources/List%20of%20Select%20Agents%20and%20Toxins_111708.pdf Slide 15: U.S. Air Forces in Europe, http://www.usafe.af.mil/direct/sg/anthrax/Pictures/anthrx22.jpg, Sources Undetermined (All other Images) Slide 17: Lesion: Source Undetermined, Thumb: CDC, http://www.cdc.gov/Tularemia/Tul_Signssymptoms.html X-Ray: Cornell University Medical College Slide 18: C. botulinum: Source Undetermined; Image of botox injection is available here: www.stylelist.com/blog/tag/anti-aging/ Slide 19: Dr. Lyle Conrad, Joel G. Breman, CDC PHIL #7201; Source Undetermined Slide 20: (From left to right) Source Undetermined; World Health Organization, CDC PHIL #463; CDC PHIL #2047; Source Undetermined Slide 21: Sources Undetermined Slide 22: Source Undetermined Slide 23: 18th century London newspaper Slide 31: Source Undetermined Slide 32: Source Undetermined Slide 35: World Health Organization, http://www.who.int/emc/diseases/smallpox/slideset/ (All images) Slide 36: World Health Organization, http://www.who.int/emc/diseases/smallpox/slideset/ (All images) Slide 37: World Health Organization, http://www.who.int/emc/diseases/smallpox/slideset/ (All images) Slide 38: World Health Organization, http://www.who.int/emc/diseases/smallpox/slideset/ (All images) Slide 39: CDC PHIL # 131, http://emergency.cdc.gov/agent/smallpox/smallpox-images/smallpox1.htm Slide 40: Source Undetermined Slide 41: Source Undetermined Slide 42: World Health Organization, http://www.who.int/emc/diseases/smallpox/slideset/ (All images) Slide 43: Source Undetermined Slide 44: CDC, http://emergency.cdc.gov/training/smallpoxvaccine/reactions/download_pocket_guide.htm Slide 45: Logical Images (All Images), http://emergency.cdc.gov/training/smallpoxvaccine/reactions/tl_view.htm Slide 46: Source Undetermined Slide 47: Dr. V. Fulginiti Slide 48: Dr. V. Fulginiti; Dr. V. Fulginiti; Dr. V. Fulginiti; Arthur E. Kaye CDC ID#:3286; Arthur E. Kaye; J. Michael Lane, M.D. CDC PHIL #3318 Slide 49: Dr. H. Kempe; Dr. V. Fulginiti; Dr. V. Fulginiti; Dr. V. Fulginiti; Dr. V. Fulginiti; Slide 50: Dr. H. Kempe; Dr. H. Kempe; Arthur E. Kaye CDC PHIL #3305 Slide 51: Dr. H. Kempe (All Images) Slide 52: Dr. V. Fulginiti (All Images) Slide 53: Dr. V. Fulginiti; Dr. V. Fulginiti Slide 54: Sources Undetermined