Ocular Complications of Smallpox and Smallpox Vaccination

1
Ocular Complications of Smallpox and Smallpox
Vaccination

• Shmuel Shoham, MD
• Section of Infectious Diseases
• Washington Hospital Center
• Washington, DC.

2
Smallpox History

• Throughout history smallpox had been a dreaded
  disease
• 1960s Smallpox was endemic in 31 countries,10
  -15 million persons infected yearly and more than
  2 million died of each year

WHO
3
Smallpox History Clinical Manifestations

• Incubation period was about 12 days
• A pre-eruption phase lasting 3-4 days preceded
  the rash
• Lesions were synchronous
• Mortality sometimes exceeded 30 in unvaccinated
  patients

WHO
4
Smallpox History

• In the 1960s the WHO undertook a program to
  eradicate Smallpox worldwide
• 1980 WHO accepted the Final Report of the Global
  Commission for the Certification of Smallpox
  Eradication

WHO
5
Smallpox 2002

• CDC publishes Smallpox Response Plan and
  Guidelines
• Smallpox is clearly one of those biological
  agents that's very much on our mind and something
  that we're dealing with very, very aggressively
• Head of Homeland Security, Tom Ridge
• Post exposure containment of a terrorist-induced
  smallpox outbreak is unlikely to be successful.
  Widespread, voluntary vaccination before exposure
  will greatly reduce the number of victims
• Dean Boston University School of Public Health,
  William Bicknell

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Smallpox Ocular presentation

• Day 5 of Natural course of smallpox watery
  conjunctivitis
• 4 of patients developed ocular complications
• 77 corneal
• 23 conjunctival
• Monte 1911

CDC
7
Smallpox Ocular presentation

• Viral effect was limited to epithelium
• Hypopion/ulcers were common and occurred
  secondary to superinfection

CDC
8
Smallpox Ocular presentation

• Corneal opacification and phthisis bulbi occurred
  as complications.
• 100 years ago smallpox was responsible for 25 of
  blindness in Algeria
• Bruch 1909

Agarwal
9
Smallpox vaccine

• Live vaccinia virus
• Current stocks were produced over 30 years ago
• Routine vaccination ended in the United States in
  1972
• Does not confer lifelong protection
• Majority of worlds population is unvaccinated at
  this time

WHO
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Vaccination
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Ocular Complications of Smallpox Vaccination
United States 1968

• 14,168,000 total vaccinations given
• 143 cases of accidental infection of the eye
• mostly eyelids or conjunctiva
• Approximately 1 in 100,000 vaccinations
• 7 cases of keratitis
• Highest risk groups
• Vaccinated children
• Primary vaccinees
• Children who were contacts of vaccinees

Lane et al. NEJM 282 22 (1969)1201-7
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Smallpox vaccinationOcular Complications

• Transmission
• Auto-inoculation
• Contact contamination from others
• Spectrum of disease
• Lid infection
• Blepharitis
• Conjunctivitis
• Keratitis
• Anterior uveitis

Kempe Fenner F et al.Smallpox and its
eradication. World Health Organization 1988298.

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Ocular Vaccinia Outer surface of lid

• After several days of incubation a group of
  coalescing vesicles form in a zone of erythema.

Kempe Fenner F et al. Smallpox and its
eradication. World Health Organization
1988298.
.
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Ocular Vaccinia Outer surface of lid

• The lid becomes swollen
• At day 8-9 pre and post auricular lymphadenopathy
  develop /- constitutional symptoms

BR Jones System of Ophthalmology Duke-Elder 1974
.
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Ocular Vaccinia Outer surface of lid

• Vesicles turn to pustules

Frampton and Smith
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Ocular Vaccinia Outer surface of lid

• Crusting begins at 2 weeks
• Scabs form and ultimately fall off

System of Ophthalmology Duke-Elder 1974
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Ocular Vaccinia Outer surface of lid

• Red pitted scars are left that slowly become
  white and atrophic

System of Ophthalmology Duke-Elder 1974
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Ocular Vaccinia Blepharitis

• Lid margin ulcerates
• Palpebral conjunctiva is involved
• Scabs do not form
• Thickening of lid margin may persist after
  healing and lid architecture may be distorted
  permanently

BR Jones
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Smallpox vaccination conjunctivitis

• Typically secondary to infection of the lid or
  lid margin
• Most cases occur in contacts of vaccinees
• Ulcers form at the palpebral, and at times the
  bulbar conjunctiva

BR Jones
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Smallpox vaccination conjunctivitis

• Non-follicular, purulent conjunctivitis
• Conjunctival scrapings may show polymorphonuclear
  cells
• Inflammation lasts about 10 days
• 30 of patients may develop corneal complications

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Smallpox vaccination Keratitis

• Least common ocular complication
• 1.2 cases/1 million vaccinations
• Lane et al. NEJM 282 22 (1969)1201-7
• Onset pin head sized grayish, finely granular
  opacification of the epithelial cells
• Defect stains with fluorescein
• May stain with rose bengal

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Smallpox vaccination Keratitis

• Subepithelial keratitis
• Yellow opacities of the superficial stroma.
• Develop into grayish punctate subepithelial
  keratitis
• May persist for months or years

Jones and Al-Heussaini
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Smallpox vaccination Keratitis with ulceration

• Area of keratitis may break down into one or more
  ulcers to form finger-like projections
• Associated with long and painful course
• May simulate the appearance of herpes

Jones and Al-Heussaini
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Smallpox vaccination Keratitis with ulceration

• Complications
• Necrosis of the stroma
• Intracorneal abscess.
• Perforation

Jones and Al-Heussaini
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Smallpox vaccination Complications

• Ulceration may extend to involve large surfaces
• First time vaccinees and immunocompromised
  patients are at increased risk
• 2002 Vs. 1972
• More immunosupressed individuals
• More vaccinia naïve people in the general
  population

Ogg
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Smallpox vaccination Eczema Vaccinatum

• Dissemination of vaccinia virus among persons
  with
• Eczema
• History of eczema
• Other chronic or exfoliative skin disorders

Fenner F et al.Smallpox and its eradication.
World Health Organization 1988.
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Smallpox vaccination Eczema vaccinatum

• Generalized
• Local
• Primary vaccinees
• Contacts of vaccinees (30)
• Lane JID 1970122 303-9

John M. Leedom
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Treatment Vaccinia Immune Globulin (VIG)

• The immunoglobulin fraction of plasma from
  persons vaccinated with vaccinia vaccine
• May be Contraindicated in vaccinia keratitis
• Increased corneal scarring in experimental
  vaccinia keratitis
• Topical
• 250 mg dissolved in 2.5 ml sterile water Q 30
  minutes during waking hour

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Treatment Vaccinia Immune Globulin (VIG)

• Systemic
• 0.6 ml/kg of body weight IM in divided doses over
  a 24- to 36-hour period.
• Administered as early as possible after the onset
  of symptoms.
• Doses might be substantial (e.g., 42 ml for a
  person weighing 70 kg)
• Doses can be repeated, usually at intervals of
  2-3 days, until recovery begins (e.g., no new
  lesions)

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Treatment Topical antivirals

• Experimental keratitis
• Trifluorothymidine was superior to idoxuridine
• Improved efficacy on severity of keratitis
• Decreased positive cultures
• Hyndiuk Arch Ophthalmol 1976 Oct94(10)1785-6
• vidarabine
• More effective than idoxuridine
• Hyndiuk Arch Ophthalmol 1976 Aug94(8)1363-4

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Treatment Cidofovir
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Treatment Corticosteroids

• Animal studies
• Systemic cortisone led to increased viral
  multiplication and dissemination
• Predisposed rabbits to developing encephalitis
• Contraindicated in early infection
• Topical steroids are a useful adjunct in cases of
  stromal infiltration and uveitis

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Prevention

• Semi-permeable barrier at site of vaccination
• Co-administration of VIG with vaccination in high
  risk individuals
• Rigorous hand washing

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Request for VIG

• Centers for Disease Control and Prevention Drug
  Services, National Center for Infectious Diseases
  
  Mailstop D-09
  Atlanta, GA 30333
  Telephone [phone]
  Facsimile [phone]