Smallpox

Aka: Smallpox, Small Pox, Variola, Vaccinia, Poxvirus, Orthopoxvirus, Cowpox, Variola major

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II. Epidemiology

  1. No natural source of Smallpox remains as of 1977
  2. Biological Weapon potential
  3. Outbreaks historically occurred in winter
    1. Same time as Varicella Zoster Virus and Measles

III. History

  1. British first used Smallpox as Biological Weapon
    1. French and Indian Wars 1754-1767
    2. Distributed contaminated blankets to Native Americans
  2. Edward Jenner demonstrated efficacy of Vaccine 1796
    1. Found milkmaids who had Cowpox did not get Smallpox
    2. Initiated Cowpox inoculation which prevented Smallpox
  3. Eradication of Smallpox completed in 1977
    1. Smallpox Vaccination discontinued
      1. United States: 1972
      2. Worldwide: 1980
    2. Most labs destroyed Variola virus samples by 1999

IV. Pathophysiology

  1. Variola Virus is a brick-shaped 200 nm member of Orthopoxvirus genus
  2. Cowpox is also a member of Orthopoxviruses

V. Types

  1. Standard Smallpox (90% of cases)
    1. Variola major (much more severe, lethal form)
    2. Variola Minor
  2. Severe variants
    1. Hemorrhagic Smallpox (more common in pregnant women)
    2. Malignant Smallpox

VI. Transmission

  1. Contagious only after onset of rash
    1. Infectious for first 7 to 10 days after rash
    2. Infectivity wanes after scabs form
    3. Only very low dose (few virions) needed for infection (highly contagious)
      1. Pandemic can be caused by 100 active cases
  2. Direct contact with oropharyngeal droplets or aerosols
  3. Contaminated clothing or linen
  4. Person to person transmission
    1. No animal or Insect hosts

VII. Symptoms

  1. Incubation Period of 7 to 17 days (usually 12-14 days)
  2. Viral prodrome (2-3 days before rash)
    1. High fever
    2. Rigors
    3. Malaise
    4. Myalgia
    5. Headache
    6. Backache
    7. Abdominal Pain
    8. Vomiting

VIII. Signs: Rash

  1. Timing
    1. Onset of rash within 2-4 days of fever
  2. Location
    1. Initial: Oropharynx, face (centrifugal)
    2. Next: Arms (esp. Forearms)
    3. Next: Remainder of extremities including legs
    4. Next: Palms and soles
    5. Later: Trunk
  3. Typical Smallpox Characteristics
    1. Initial: Maculopapular
    2. Next: Vesicles or Oral Ulcers within 1-2 days
    3. Next: Round, tense and embedded Pustules
    4. Next: Crusts or scabs form by 8-9 days of rash
    5. Last: Scars form with Sebaceous Gland destruction
  4. Hemorrhagic Smallpox Characteristics
    1. Initial: Dusky erythema
    2. Next: Petechiae
    3. Next: Hemorrhaging from skin and mucus membranes
  5. Malignant Smallpox Characteristics
    1. Initial: Slow confluence of lesions
    2. Next: Soft, flattened, velvety Vesicles form
    3. Next: Reddish fine-grained Skin Coloration
    4. Contrasts: No formation of Pustules or scabs

IX. Differential Diagnosis

  1. Varicella Zoster Virus (features of VZV listed)
    1. No lesions on palms or soles in VZV
    2. VZV with minimal prodrome; fever onset with rash
    3. Stages of maturation much faster in VZV
      1. Rash develops rapidly
      2. Scab forms within 7 days of rash
      3. Scab separates within 14 days of rash
    4. Trunk more involved in VZV than face or extremities
  2. Meningococcemia
    1. Contrast with Hemorrhagic or Malignant Smallpox
  3. Severe Acute Leukemia
    1. Contrast with Hemorrhagic or Malignant Smallpox

X. Labs: Used to identify epidemic

  1. Throat swab for PCR (preferred) or ELISA
  2. Obtain samples from possible source
    1. Open Vesicle with scalpel and dab with cotton swab
    2. Obtain scab sample with forceps
  3. Send sample in sealed Vacutainer (tape top)
  4. Encase Vacutainer in second, water proof container
  5. Send samples to high-containment labs (BL-4)
  6. Smallpox rapidly identified under electron microscopy

XI. Management: Emergently reduce transmission risk

  1. Patient Isolation at facility (home is preferred)
    1. Negative pressure room
    2. High-efficiency particulate air filtration
    3. Deceased patients should be cremated
      1. Vaccinate mortuary workers
  2. Protect all medical facility personnel
    1. Medical care by recently vaccinated persons only
    2. Immunize all hospital employees
    3. Furlough non-immunized employees
    4. Infectious precautions (Gloves and Mask)
    5. Contact public health immediately
    6. Decontamination
      1. Laundry in biohazard bags, autoclave, then launder
      2. Waste in biohazard bags and incinerate
      3. Room Decontamination per protocol
  3. Identify and immunize contacts of infection source
    1. Household or face-to-face contact with febrile source
    2. Isolate if fever >101 within 17 days of exposure
    3. Forced quarantine may be necessary

XII. Management: Medical

  1. See Prevention below (include Postexposure Prophylaxis)
  2. Symptomatic and supportive care
  3. Tecovirimat (TPOXX)
    1. Indicated in severe Vaccinia
    2. Dose: 600 mg orally twice daily for 14 days
    3. Interrupts virus transmission between cells
  4. Other agents with benefit
    1. Cidofovir (Vistide)
    2. Brincidofovir

XIII. Prognosis

  1. Variola major: 30% to 50% mortality rate in unvaccinated patients
  2. Variola Minor: 1-2% mortality rate
  3. Hemorrhagic Smallpox: Uniformly fatal by day 6 of rash
  4. Malignant Smallpox: Frequently fatal

XIV. Prevention

  1. Pre-exposure Smallpox Vaccination
    1. Immunity wanes after 5-10 years
    2. Those vaccinated 30 years ago are likely susceptible
    3. Routine Smallpox Vaccination stopped in U.S. 1972
  2. Post-exposure Prophylaxis
    1. Vaccinia Immune Globulin 0.6 ml/kg IM
      1. Must be given within 3 days (ideally within 24 hours)
    2. Smallpox Vaccination
      1. Must be given within 4 days of exposure (before symptoms) to be effective
      2. Contraindicated in pregnancy (risk of fetal Vaccinia) unless benefits outweight risks
  3. Variola Immunoglobulin (Vaccinia immune globulin)
    1. High risk patients, given within first 7 days
    2. Give in combination with post-exposure Vaccination
    3. Dose: 100 mg/kg IM
  4. Cidofovir
    1. May be efficacious if used within 2 days of exposure
    2. Indicated in significant exposure during pregnancy

XV. References

  1. Seeyave (2015) Crit Dec Emerg Med 29(5): 13-21
  2. Wilson (1991) Harrison's IM, McGraw-Hill, p. 709-11
  3. Breman (1998) N Engl J Med 339:556-9 [PubMed]
  4. Henderson (1999) JAMA 281:2127-37 [PubMed]
  5. Rathjen (2021) Am Fam Physician 104(4): 376-85 [PubMed]

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