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

January 2003

Variola Virus

Photo Courtesy of CDC/Public Health Image Library1

January 2003

History

• Ancient scourge – many millions killed

• Global eradication in 1977

January 2003Photo Courtesy of National Archives

January 2003Photo 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 2003Photo 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 2003Photo 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 2003Photo Courtesy of World Health Organization5

January 2003

Clinical Features

• Distribution of the rash

January 2003Photo Courtesy of World Health Organization6

January 2003Photo Courtesy of World Health Organization7

January 2003Photo Courtesy of National Archives

January 2003Photo Courtesy of National Archives

January 2003Photo Courtesy of World Health Organization8

January 2003Photo Courtesy of World Health Organization9

January 2003Photo Courtesy of World Health Organization10

January 2003Photo Courtesy of World Health Organization11

January 2003Photo Courtesy of World Health Organization12

January 2003Photo Courtesy of World Health Organization13

January 2003Photo Courtesy of World Health Organization14

January 2003Photo Courtesy of World Health Organization15

January 2003Photo Courtesy of World Health Organization16

January 2003Photo Courtesy of World Health Organization17

January 2003Photo Courtesy of CDC/James Hicks18

January 2003Photo 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 Medicine23

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 2003Photo Courtesy of World Health Organization30

January 2003Photo Courtesy of World Health Organization31

smallpox

chickenpox

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 2003Photo 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