COMPLICATIONS OF SMALLPOX VACCINATION VACCINIA

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COMPLICATIONS OF SMALLPOX VACCINATION (VACCINIA)

• Vincent A. Fulginiti, M.D.
• Professor Emeritus, Pediatrics
• University of Arizona
• University of Colorado

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(Classic cartoon lampooning smallpox vaccination)
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VACCINATIONNORMALSEQUENCE
Dixon
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VACCINATION COMPLICATIONS

• Non-infectious rashes-E.multiforme, variety of
  others
• Bacterial superinfectionStaph, strep,tetanus,
  
• Accidental inoculationself or from vaccinee,
  eczema vaccinatum
• Congenital vaccinia rare
• Generalized vaccinia often benign can progress
• Progressive vaccinia vaccinia necrosum, vaccinia
  gangrenosa, primarily in immunodeficient
• Post-vaccination encephalitis rare
• Miscellaneous hemolytic anemia, arthritis,
  osteo, pericarditis, myocarditis

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Non-specific rashes

• Erythema multiforme most common _at_ 7-14 days
  post primary sooner after revaccination-pruritic-
  ? Allergic vs toxic Macular rash intense
  perivaccinia Maculopapular Occasionally
  vesicular (differentiate from generalized
  vaccinia) Urticaria Rarely,
  Stevens-Johnson Syndrome

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ERYTHEMA MULTIFORME
COMMON, IMPRESSIVE, BUT BENIGN RARELY CAN SEE
STEVENS-JOHNSON SYNDROME
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DIAGNOSIS AND TREATMENT

• Diagnosis by clinical appearance
• Temporal association with vaccinia
• Rarely need consulatation to r/o other skin
  conditions

• Treatment is totally symptomatic
• Usually antihistamines suffice for most of these
  rashes
• With SJS, may need steroids. Locally (eye) and
  systemically

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Bacterial superinfection

• At one time, tetanus, syphilis, enteric were
  major complicating infections, especially with
  ritualistic poultices
• In recent times, staph and strep have
  predominated
• Can be accentuated by occlusive dressings
• Responds rapidly and completely to prompt,
  appropriate antimicrobial therapy

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STAPH ...AND STREP
Vesicular border with clearing central area -pure
staphylococcal
(Heaped up streptococcal infection -red color
is artifact of topical drug)
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ACCIDENTAL ADMINISTRATION

• Two major types of accidents Inadvertent I.M.
  Injection Oral ingestion
• To my knowledge, no adverse consequences from
  either accident, unless oral injury occurs from
  vaccine instrument during ingestion

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Accidental inoculation

• Autoinoculation or from a vaccinee
• Any part of body affected
• Serious keratitis, burns, and eczema vaccinatum
  (in last untreated may result in 30
  mortalitywith VIG, virtually zero)
• Traumatic/surgical woulds predispose
• Dermal infection/ disease may predispose
• Mucosal inoculation possible dental extraction
  sites, tonsillar lesions, rectal, laryngeal,
  esophageal

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Factors in Accidental Inoculation

• Common in very young infants/children
• Caretakers at risk
• Transfer often by hand to skin/mucosa
• Inflammatory eye disease predisposes to
  periorbital/corneal lesions (eye-rubbing)
• Bathing can result in autoinoculation

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EXAMPLES
INOCULATION INTO DIAPER RASH FROM VACCINATED
SIBLING AND PARENT
(VACCINIA KERATITIS)
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ECZEMA VACCINATUM
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ANOTHER EXAMPLE
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ACNE AND VACCINIA
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DIAGNOSIS

• Diagnosis usually obvious as lesions are
  identical to original vaccination
• Ocular lesions may be confused with herpes and
  other eye infections look for adjacent lesions,
  timing and hx of appropriate contact
• Wound/post surgical lesions may be confusing
  look for contact history
• Viral dx tests occasionally indicated

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TREATMENT

• For most lesions 0.6 ml/kg VIG sufficed
• Occasionally need up to 1-2 mg/kg
• Eczema vaccinatum, 1-5 ml/kg start with 1 and
  add to it if new lesions appear. The largest
  used was 10 ml/kg with massive lesions.
• Eye AVOID VIG use topical antivirals (human
  experience and animal work suggest that an Ag/Ab
  reaction occurs in the eye with VIG rx
• Thiosemicarbazone used occasionally not enough
  experience to judge efficacy

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Congenital vaccinia

• Rare event
• Greatest danger for pregnant susceptible is third
  trimester
• No congenital anomalies have been linked to
  maternal vaccination

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GENERALIZED VACCINIA

• Despite appearance, is generally benign
• Differs from eczema vaccinatum and progressive
  vaccinia
• Lesions normal and multiple, presumably
  bloodborne, and occur in healthy individual (as
  far as could be determined by prevailing
  immunologic methods at the time). Primary normal.
• Usually self-limited rarely recurrent every 4-6
  weeks up to one year

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Note that all lesions are normal and
non-progressive
GENERALIZED VACCINIA - BENIGN
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DIAGNOSIS TREATMENT

• Clinical picture characteristic verify with
  viral isolation or identification, p.r.n.
• Immunologic studies warranted with todays
  knowledge of range of defects
• Rx 0.6 ml/kg VIG (although most episodes
  self-limited, with repeat episodes may wish to
  give more or repeat course of rx
• Consider antivirals

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Progressive Vaccinia

• In immunolgically deficient primarily in
  cell-mediated immune deficiencies, but a few
  cases in hypogammaglobulinemia have been seen
  (immunologic studies not as sophisticated then as
  now)
• Progressive enlargement of primary, viremic
  spread to other parts of the body, each lesion
  expanding without limitation
• Fatal in most cases, a few survived

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PROGRESSIVE VACCINIA Note that the lesions have
no inflammation, and progress in size
without limitation. Child had severe combined
immunodeficiency (SCID) and despite rigorous and
extensive antibody and antiviral chemotherapy,
died with overwhelming viremia.
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PROGRESSIVE VACCINIA
Primary lesion in child with absent
cell-mediated immunity. Note vesicular edge
of advancing viral infection in the absence of
any inflammatory reaction
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PROGRESSIVE VACCINIA(Hypogammaglobulinemia with
concurrent viral infection shortly after
vaccination applied resulting in progressive
lesion)
This child underwent extensive antibody and
antiviral treatment without effect. When viral
load was reduced by amputation, therapy resulted
in cure and he is alive and well today.
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EMPIRIC THERAPY
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ADDITIONAL EXAMPLES
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ADDITIONAL EXAMPLES
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ANTIBODY CMI ABSENT
RX VIG, ISTC, SURGERY-Excision followed by
grafting, ANTIBIOTICS
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ADULT VACCINIA
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DIAGNOSIS TREATMENT

• VIROLOGIC DX
• IMMUNOLOGIC ASSESSMENT CRITICAL
• GENETIC TESTING
• FAMILY HISTORY

• VIG (ALSO PLASMA, EXCHANGE TRANSFUSION
• ANTIVIRAL RX IUDR INEFFECTIVE THEN
  THIOSEMICARBAZONES ? NOW (CIDOFOVIR?)
• CELL TRANSFER GVH RESULTED
• ? GENE THERAPY

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Post-vaccination encephalitis

• Rare 1 in 100,000 -500,000 vaccinations
• Sudden onset of headache,vomiting in second week
  after vaccination
• Convulsions, lethargy progressing to coma,
  paralysis, focal neurologic signs
• Cerebral edema evident with massive increased
  intracranial pressure
• Varies in severity and prognosis can be mild and
  self limited, or progressive and fatal. ?
  Autoimmune (anti virus-neural cell component)

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DIAGNOSIS TREATMENT

• Clinical diagnosis plus temporal association-
  usually in 2nd week after vaccination. Sxs
  include convulsions, lethargy, coma, paralysis,
  increased intracranial pressure focal
  neurologic signs in any combination.
• Compatible CSF findings
• Supportive care only

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REFERENCES-I
BEST OVERALL SOURCES Dixon CW, SMALLPOX,
1962, J A Churchill LTD, London This text is
the classic in smallpox and vaccinia. The author
did many of the original clinical studies of
this disease and his text is authoritative and
beautifully illustrated. Henderson DA,
Inglesby TV, Bartlett JG, et al Smallpox as a
Biological Weapon, JAMA 1999, 2812128-2136 A
concise summary of the disease and medical
and public health aspects of management in the
event of a bioterrorist attack Kempe CH
Studies on Smallpox and Complications of
Smallpox Vaccination E Mead Johnson Award
Address, Pediatrics 1960, 26 177-189. A
definitive report of the state of the art of the
time. Kempe CH, St Vincent L Variola and
Vaccinia Viruses WHO Expert Committee on
Smallpox, WHO Tech Report Series, 1964, 283,
665-692. Definitive information of the viruses
www.cdc.gov definitive website for up-to-date
information on smallpox GENERAL Anthony RL,
Douglass LT, Daniel RW, et al Studies of Variola
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Angulo JJ, Rodrgues-DA-Silva G, Rabello SI
Spread of Variola Minor in Households, Amer J
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Vincent L, Kempe CH Prophylaxis of Smallpox with
Methisazone, Amer J Epidemiol 1969, 96130-145
Breman JG, Arita I The Confirmation and
Maintenance of Smallpox Eradication, NEJM 1980,
3031263-73 Cohen J, Marshall E Vaccines for
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294498 Cruickshank JG, Bedson HS, Watson,
DH Electron Microscopy in the Rapid Diagnosis of
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Rao AR, St Vincent L, Kempe CH The Weeping
Mother, an unusal source of variola virus, Arch
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Den nis DT, Doberstyn EB, Awoke S Failure of
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1974, 2377-379 Downie AW, St Vincent L,
Meiklejohn G, Ratnakannan NR, Rao AR, Krishnan,
Kempe CH Studies on the Virus Content of Mouth
Washings in the Acute Phase of Smallpox, Bull
WHO 1961, 2541-71 Downie AW, Hobday TL, St
Vincent L, Kempe CH Studies of Smallpox Antibody
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Fulginiti VA, Vol II, Chapter 39, 1972
Fulginiti VA, Kempe CH, Hathaway WE, et al
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Fulginiti VA, Winograd LA, Jackson, M and Ellis
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Arch Ophtal 1965, 74539-44 Fulginiti, VA
Variola (smallpox). In Clinical Dermatology.
Demis, DJ et al, eds. Vol. 3, revised edition,
Unit 148, pp. 1-8. Harper Row, 1974.
(Revised for 2002 publication)
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REFERENCES II
Hobday TL, Rao AR, Kempe CH, Downie AW
Compariason of Dired Vaccine With Fresh Indian
Buffalo-Calf Lymph in Revaccination Against
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Fulginiti VA, Pierce CW, Githens JH, Pearlman DS,
Muschenheim F, Kempe CH Graft-vs-Host Reaction
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Yepke M Smallpox Transmission in Southern
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CH,Bowles G, Meikeljohn G, et al The Use of
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TECHNICAL REFERENCES
TECHNICAL REFERENCES Bedson S, Downie AW,
MacCallum FO, Stuart-Harris CH, VIRUS AND
RICKETTSIAL DISEASES OF MAN, Edward Arnold Ltd,
London Lennette, EH, Schmidt NJ, DIAGNOSTIC
PROCEDURES FOR VIRAL, RICKETTSIAL AND CHLAMYDIAL
INFECTIONS, 5TH ED., 1979, American
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Swain RHA, Dodds TC CLINICAL VIROLOGY, 1967,
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GJ, Merigan T, Buchanan RA ANTIVIRAL AGENTS AND
VIRAL DISEASES OF MAN, 1979Raven Press, New York,
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