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Variola Virus Photo Courtesy of CDC/Public Health Image Library1

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Presentation on theme: "Variola Virus Photo Courtesy of CDC/Public Health Image Library1"— Presentation transcript:

1 Variola Virus Photo Courtesy of CDC/Public Health Image Library1
January 2003

2 History Ancient scourge – many millions killed
Global eradication in 1977 January 2003

3 Photo Courtesy of National Archives
January 2003

4 Photo Courtesy of World Health Organization2
January 2003

5 Bioweapon Potential Precedence Prior use in French-Indian War
Produced by USSR January 2003

6 Bioweapon Potential Reality of the risk Viral stocks exist
Non-immune population January 2003

7 Photo Courtesy of CDC3 January 2003

8 Epidemiology No animal reservoir/vector Mortality 25-30%
Person-to-person transmission Via respiratory droplets Household and face-to-face contacts High risk of nosocomial spread Secondary attack rate 25-40% Up to 20 contacts infected per case January 2003

9 Photo Courtesy of World Health Organization4
January 2003

10 Epidemiology Aerosol route of transmission
Likely in bioterrorism setting January 2003

11 Virology Orthopoxviridae DNA Viruses Variola variants Vaccinia
Variola major – high mortality Variola minor – low mortality, 20th Century Vaccinia Current smallpox vaccine January 2003

12 Virology Orthopoxviridae DNA Viruses Other pox viruses Cowpox
Monkeypox January 2003

13 Pathogenesis Virus contacts respiratory mucosa Carried to lymph nodes
Primary viremia Organ seeding WBCs infected Dermal invasion Vesicle Sepsis January 2003

14 Clinical Features Incubation Stage Asymptomatic
10-12 days (range 7-17) January 2003

15 Clinical Features Prodromal Stage Sudden nonspecific flu-like illness
High fevers Headache Backache Prostration 2-5 days duration January 2003

16 Clinical Features Eruptive Stage Characteristic rash
Centrifugal location Grouping Depth of lesions January 2003

17 Photo Courtesy of World Health Organization5
January 2003

18 Clinical Features Distribution of the rash January 2003

19 Photo Courtesy of World Health Organization6
January 2003

20 Photo Courtesy of World Health Organization7
January 2003

21 Photo Courtesy of National Archives
January 2003

22 Photo Courtesy of National Archives
January 2003

23 Photo Courtesy of World Health Organization8
January 2003

24 Photo Courtesy of World Health Organization9
January 2003

25 Photo Courtesy of World Health Organization10
January 2003

26 Photo Courtesy of World Health Organization11
January 2003

27 Photo Courtesy of World Health Organization12
January 2003

28 Photo Courtesy of World Health Organization13
January 2003

29 Photo Courtesy of World Health Organization14
January 2003

30 Photo Courtesy of World Health Organization15
January 2003

31 Photo Courtesy of World Health Organization16
January 2003

32 Photo Courtesy of World Health Organization17
January 2003

33 Photo Courtesy of CDC/James Hicks18
January 2003

34 Photo Courtesy of CDC19 January 2003

35 Clinical Features Severity of the classical rash
Discrete (<10% mortality) Semi-confluent (25-50%) Confluent (50-75%) January 2003

36 Discrete Smallpox Photo Courtesy of National Archives January 2003

37 Semi-Confluent Smallpox
Photo Courtesy of World Health Organization20 January 2003

38 Confluent Smallpox Photo Courtesy of National Archives January 2003

39 Smallpox Complications
Eye infection or blindness Arthritis Encephalitis Secondary bacterial infections January 2003

40 Differential Diagnosis
Varicella (chickenpox) Monkeypox Drug eruptions Generalized vaccinia Multiple insect bites Molluscum contagiosum Secondary syphilis Viral exanthems (e.g. HHV-6, Cocksackie, etc) January 2003

41 Chickenpox Photo Courtesy of World Health Organization21 January 2003

42 Monkey Pox Photo Courtesy of CDC22 January 2003

43 Erythema Multiforme Photo Courtesy of New England Journal of Medicine23 January 2003

44 Generalized Vaccinia Photo Courtesy of CDC24 January 2003

45 Generalized Vaccinia Photo Courtesy of CDC25 January 2003

46 Molluscum Contagiosum
Photo Courtesy of American Academy of Pediatrics26 January 2003

47 Secondary Syphilis Photo Courtesy of American Academy of Pediatrics27
January 2003

48 Hand-Foot-Mouth Disease (Enterovirus Infection)
Photo Courtesy of American Academy of Pediatrics28 January 2003

49 Differential Diagnosis
Chickenpox (varicella virus) Distribution of rash Grouping of lesions Asynchronous development Vesicle appearance Shallow Short Prodrome January 2003

50 Chickenpox Photo Courtesy of World Health Organization29 January 2003

51 Photo Courtesy of World Health Organization30
January 2003

52 Photo Courtesy of World Health Organization31
smallpox chickenpox Photo Courtesy of World Health Organization31 January 2003

53 Chickenpox Photo Courtesy of American Academy of Pediatrics32
January 2003

54 Chickenpox Photo Courtesy of American Academy of Pediatrics33
January 2003

55 Non-Classical Rash Presentations
Modified variant of smallpox Seen in ~25% of cases who were previously vaccinated Much lower mortality, milder disease Harder to distinguish from chickenpox May be predominant form seen if cases appear in a vaccinated population January 2003

56 Modified Smallpox Photo Courtesy of National Archives January 2003

57 Flat (Malignant) Smallpox
Photo Courtesy of World Health Organization34 January 2003

58 Non-Classical Rash Presentations
Flat (Malignant) variant of smallpox 5-10% of smallpox cases in outbreak setting Severe systemic disease Flat, leathery lesions Lesions coalesce, no discrete pustules Mortality 97% May be associated with compromised hosts January 2003

59 Flat (Malignant) Smallpox
Photo Courtesy of World Health Organization35 January 2003

60 Hemorrhagic Smallpox Photo Courtesy of World Health Organization36
January 2003

61 Non-Classical Rash Presentations
Hemorrhagic variant of smallpox <5% of all cases Rapidly progressive fulminant illness Lesions become hemorrhagic before pustules form Predilection for pregnant women May be difficult to diagnose Differential diagnosis: Menigococcemia DIC Hemorrhagic Chickenpox January 2003

62 Meningococcemia Photo Courtesy of American Academy of Pediatrics37
January 2003

63 Hemorrhagic Chickenpox
Photo Courtesy of American Academy of Pediatrics38 January 2003

64 Diagnosis Clinical Classic rash is sufficient in outbreak setting
Must have high index of suspicion January 2003

65 Photo Courtesy of World Health Organization39
January 2003

66 Diagnosis Smallpox should be ruled out if: Classic rash is present
Suspicious rash with severe systemic illness January 2003

67 Diagnosis From vesicle/pustule fluid Traditional confirmation
Electron microscopy Culture Newer rapid tests PCR Immunohistochemistry Reference labs (e.g. CDC) January 2003

68 Diagnosis Photo Courtesy of CDC/Dr. Fred Murphy, Sylvia Whitfield40
January 2003

69 Management Isolation of suspected cases No effective antivirals
Supportive care Fluid, electrolyte balance Hemodynamic, ventilatory support Antibiotics for secondary infections +/- vaccination with smallpox vaccine January 2003

70 Post-Exposure Prophylaxis
For exposure to aerosol or suspected case Household or face-to-face contacts January 2003

71 Post-Exposure Prophylaxis
Vaccine Protective within 3-4 days of exposure Reduces incidence 2-3 fold Decreases mortality >50% Cidofovir Effective vs other poxviruses Nephrotoxic antiviral agent January 2003

72 Vaccination Vaccinia live virus vaccine U.S. stock
>20 years old, still viable 10 fold dilution still >95% effective Jennerian pustule = protection Photo Courtesy of CDC41 January 2003

73 Vaccination Efficacy 10 fold reduction 2o attack rate
Full protection for 3-10 years Modest protection from mortality up to 20 yr Multiple vaccinations boost duration January 2003

74 Vaccination Adverse Effects Death Highest risk
3/100,000 vaccinees Death 1/million vaccinees historically Highest risk Infants Primary vaccinees Absolute contraindications None in outbreak setting January 2003

75 Vaccination Relative contraindications Age <1 year old Pregnancy
Immunocompromised Skin Disorders Eczema Atopic Dermatitis Contact with high-risk persons January 2003

76 Vaccination Serious complications Encephalitis Progressive Vaccinia
1:300,000 primary vaccinees 25% mortality No treatment Often permanent neurological defects Progressive Vaccinia (a.k.a. vaccinia gangrenosum/necrosum) Untreated mortality near 100% Eczema vaccinatum History of eczema or chronic skin disorder 40% mortality in young children January 2003

77 Vaccination Mild complications Generalized vaccinia Autoinoculation
VIG can treat or prevent January 2003

78 Infection Control Isolation of Cases Contact precautions
Gloves, gowns Airborne precautions Negative pressure HEPA filtered room, N95 masks Home isolation an option Immunized persons should provide care January 2003

79 Infection Control Management of Case Contacts Period of infectiousness
Oral lesions all scabs Fever precedes rash Fever Isolation Contact identification Exposure to case after fever onset Face-to-face contact < 3 meters Immediate vaccination 17 day observation Isolate if > 38o January 2003

80 Infection Control Nosocomial transmission Quarantine may be necessary
All patients and staff in hospital with a case should be vaccinated Quarantine may be necessary January 2003


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