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Variola Virus

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Variola Virus
Photo Courtesy of CDC/Public Health Image Library1
January 2003
History
• Ancient scourge – many millions killed
• Global eradication in 1977
January 2003
Photo Courtesy of National Archives
January 2003
Photo Courtesy of World Health Organization2
January 2003
Bioweapon Potential
• Precedence
– Prior use in French-Indian War
– Produced by USSR
January 2003
Bioweapon Potential
• Reality of the risk
– Viral stocks exist
– Non-immune population
January 2003
Photo Courtesy of CDC3
January 2003
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
Photo Courtesy of World Health Organization4
January 2003
Epidemiology
• Aerosol route of transmission
– Likely in bioterrorism setting
January 2003
Virology
• Orthopoxviridae DNA Viruses
– Variola variants
• Variola major – high mortality
• Variola minor – low mortality, 20th Century
– Vaccinia
• Current smallpox vaccine
January 2003
Virology
• Orthopoxviridae DNA Viruses
– Other pox viruses
• Cowpox
• Monkeypox
January 2003
Pathogenesis
Virus contacts respiratory mucosa
Carried to lymph nodes
Primary viremia
Organ seeding
WBCs infected
Dermal invasion
Vesicle
Sepsis
January 2003
Clinical Features
• Incubation Stage
– Asymptomatic
– 10-12 days (range 7-17)
January 2003
Clinical Features
• Prodromal Stage
– Sudden nonspecific flu-like illness
•
•
•
•
High fevers
Headache
Backache
Prostration
– 2-5 days duration
January 2003
Clinical Features
• Eruptive Stage
– Characteristic rash
• Centrifugal location
• Grouping
• Depth of lesions
January 2003
Photo Courtesy of World Health Organization5
January 2003
Clinical Features
• Distribution of the rash
January 2003
Photo Courtesy of World Health Organization6
January 2003
Photo Courtesy of World Health Organization7
January 2003
Photo Courtesy of National Archives
January 2003
Photo Courtesy of National Archives
January 2003
Photo Courtesy of World Health Organization8
January 2003
Photo Courtesy of World Health Organization9
January 2003
Photo Courtesy of World Health Organization10
January 2003
Photo Courtesy of World Health Organization11
January 2003
Photo Courtesy of World Health Organization12
January 2003
Photo Courtesy of World Health Organization13
January 2003
Photo Courtesy of World Health Organization14
January 2003
Photo Courtesy of World Health Organization15
January 2003
Photo Courtesy of World Health Organization16
January 2003
Photo Courtesy of World Health Organization17
January 2003
Photo Courtesy of CDC/James Hicks18
January 2003
Photo Courtesy of CDC19
January 2003
Clinical Features
• Severity of the classical rash
– Discrete (<10% mortality)
– Semi-confluent (25-50%)
– Confluent (50-75%)
January 2003
Discrete Smallpox
Photo Courtesy of National Archives
January 2003
Semi-Confluent Smallpox
Photo Courtesy of World Health Organization20
January 2003
Confluent Smallpox
Photo Courtesy of National Archives
January 2003
Smallpox Complications
•
•
•
•
Eye infection or blindness
Arthritis
Encephalitis
Secondary bacterial infections
January 2003
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
Chickenpox
Photo Courtesy of World Health Organization21
January 2003
Monkey Pox
Photo Courtesy of CDC22
January 2003
Erythema Multiforme
Photo Courtesy of New England Journal of Medicine 23
January 2003
Generalized Vaccinia
Photo Courtesy of CDC24
January 2003
Generalized Vaccinia
Photo Courtesy of CDC25
January 2003
Molluscum Contagiosum
Photo Courtesy of American Academy of Pediatrics26
January 2003
Secondary Syphilis
Photo Courtesy of American Academy of Pediatrics27
January 2003
Hand-Foot-Mouth Disease
(Enterovirus Infection)
Photo Courtesy of American Academy of Pediatrics28
January 2003
Differential Diagnosis
• Chickenpox (varicella virus)
– Distribution of rash
– Grouping of lesions
• Asynchronous development
– Vesicle appearance
• Shallow
– Short Prodrome
January 2003
Chickenpox
Photo Courtesy of World Health Organization29
January 2003
Photo Courtesy of World Health Organization30
January 2003
smallpox
chickenpox
Photo Courtesy of World Health Organization31
January 2003
Chickenpox
Photo Courtesy of American Academy of Pediatrics32
January 2003
Chickenpox
Photo Courtesy of American Academy of Pediatrics33
January 2003
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
Modified Smallpox
Photo Courtesy of National Archives
January 2003
Flat (Malignant) Smallpox
Photo Courtesy of World Health Organization34
January 2003
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
Flat (Malignant) Smallpox
Photo Courtesy of World Health Organization35
January 2003
Hemorrhagic Smallpox
Photo Courtesy of World Health Organization36
January 2003
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
Meningococcemia
Photo Courtesy of American Academy of Pediatrics37
January 2003
Hemorrhagic Chickenpox
Photo Courtesy of American Academy of Pediatrics38
January 2003
Diagnosis
• Clinical
– Classic rash is sufficient in outbreak
setting
– Must have high index of suspicion
January 2003
Photo Courtesy of World Health Organization39
January 2003
Diagnosis
• Smallpox should be ruled out if:
– Classic rash is present
– Suspicious rash with severe systemic
illness
January 2003
Diagnosis
• From vesicle/pustule fluid
• Traditional confirmation
– Electron microscopy
– Culture
• Newer rapid tests
– PCR
– Immunohistochemistry
– Reference labs (e.g. CDC)
January 2003
Diagnosis
Photo Courtesy of CDC/Dr. Fred Murphy, Sylvia Whitfield40
January 2003
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
Post-Exposure Prophylaxis
• For exposure to aerosol or suspected
case
– Household or face-to-face contacts
January 2003
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
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
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
Vaccination
• Adverse Effects
– 3/100,000 vaccinees
• Death
– 1/million vaccinees historically
• Highest risk
– Infants
– Primary vaccinees
• Absolute contraindications
– None in outbreak setting
January 2003
Vaccination
• Relative contraindications
– Age <1 year old
– Pregnancy
– Immunocompromised
– Skin Disorders
• Eczema
• Atopic Dermatitis
– Contact with high-risk persons
January 2003
Vaccination
• Serious complications
– Encephalitis
•
•
•
•
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
Vaccination
• Mild complications
– Generalized vaccinia
– Autoinoculation
– VIG can treat or prevent
January 2003
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
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
Infection Control
• Nosocomial transmission
– All patients and staff in hospital with a
case should be vaccinated
• Quarantine may be necessary
January 2003
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