Smallpox: Epidemiology, Diagnosis, Clinical Characteristics and Treatment

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Smallpox Epidemiology, Diagnosis, Clinical
Characteristics and Treatment

• Anthony Tomassoni, MD, MS, FACEP
• Geoff Beckett, PA-C, MPH
• Maine Bureau of Health
• (Most slides courtesy of Harvard Center for
  Public Health Preparedness and the Centers for
  Disease Control)

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Smallpox

• Smallpox is a severe, febrile, contagious,
  sometimes fatal disease caused by the virus
  variola that is characterized by a vesicular
  and pustular eruption.

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Why should we be concerned about smallpox?

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Why should we fear smallpox?

• Case fatality rate of 30
• No specific therapy
• Infectious dose is small
• Transmission rate of 110-20

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Why should we fear smallpox?

• Used in the past as a BW
• Smallpox invokes terror
• Weaponized stable in aerosol form
• Worldwide vaccination ended 1980

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Smallpox Repositories

• Atlanta, Georgia, USA Kotsovo,
  Novosibirsk, Russia

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September 11, 2001
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Anthrax Attacks 2001
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Smallpox

• Smallpox is a severe, febrile, contagious,
  sometimes fatal disease caused by the virus
  variola that is characterized by a vesicular
  and pustular eruption.

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variola

• Varius stained
• Varus mark

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small pockes

• pocke sac

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MICROBIOLOGY
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TAXONOMY

• Family Poxviridae
• Subfamily Chordopoxvirinae
• Genera Orthopoxvirus
• Species Variola

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Properties of Poxviruses

• Large virions
• Large genome, double-stranded DNA
• Cytoplasmic replication
• Enveloped
• Complex morphology

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Species of the genus Orthopoxvirus

• Camelpox
• Ectromelia
• Taterapox
• Raccoonpox
• Buffalopox

• Variola
• Vaccinia
• Vaccinia
• Cowpox
• Monkeypox

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Orthopoxviruses That Cause Cutaneous Lesions in
Man

• Variola major
• Vaccinia
• Cowpox
• Monkeypox

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MICROBIOLOGY

• Electron Micrograph of Variola Viruses

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VARIOLA MORPHOLOGY

• Ball-of-Knitting-Wool

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EPIDEMIOLOGY

• Variola major generally known as smallpox, is
  a severe, contagious, febrile disease
  characterized by a vesicular and pustular
  eruption.
• Variola minor known as alastrim or amaas,
  is a similar, albeit milder, illness with a lower
  mortality rate.

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EPIDEMIOLOGY

• Fatality Rates
• Variola major 30-50
• Variola minor 1

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EPIDEMIOLOGY
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EPIDEMIOLOGY

• No Animal Vectors or Reservoirs

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EPIDEMIOLOGY

• Contaminated Bedding and Clothing

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EPIDEMIOLOGY

• Contaminated Scab Material

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EPIDEMIOLOGY

• Hospital Spread of Smallpox

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Smallpox Hospitals
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EPIDEMIOLOGY

• Krankenhaus Meschede, Germany 1970

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EPIDEMIOLOGY

• Smallpox historically spreads through populations
  slower than measles or chickenpox.
• Patients spread smallpox primarily to household
  members and friends.
• Secondary cases are usually limited to family,
  friends and medical personnel attending the sick.

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EPIDEMIOLOGY

• Seasonal occurrence of smallpox is similar to
  measles and chicken pox.
• Highest incidence in winter and early spring.
• Orthopoxviruses prefer cold and dry to hot and
  humid.

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EPIDEMIOLOGYAge Distribution

• Age distribution of smallpox reflects overall
  population susceptibility.
• Historically affected mostly children because
  adults were protected by vaccination or previous
  infection.
• In areas without vaccination, smallpox affects
  all ages, but infants and the elderly are more
  affected as expected.

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EPIDEMIOLOGY

• Most infectious from onset of rash to the first 7
  10 days of the rash.

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PATHOGENESISPortal of Entry of Variola

• Respiratory tract
• Conjunctivae
• Inoculation
• Congenital

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PATHOGENESIS
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CLINICAL PRESENTATION

• High fever
• Chills and rigors
• Malaise
• Cephalgia
• Dorso-lumbar pain
• Myalgias
• Nausea and vomiting
• Prostration and delirium

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Classic Signs Symptoms

• Rash begins as macular, then quickly becomes
  maculopapular.
• Then evolve into vesicles and pustules
• Finally dried into scabs that fall off after 3-4
  weeks.

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Classic Smallpox Rash

• Centrifugal distribution
• Most dense on face and extremities
• Lesions appear during a 1 2 day period
• Lesions evolve at the same rate

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PATHOGENESIS

• Except for skin, mucous membranes, and reticulum
  cells, other organs are seldom involved.
• Secondary bacterial infection uncommon.
• Encephalitis sometimes ensues.
• Death most likely results from toxemia.

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Classification of Clinical Types of Variola Major

• Ordinary type
• Modified type
• Variola sine eruptione
• Malignant (flat) type
• Hemorrhagic type

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Classification of Variola Major

• Ordinary Type
• Confluent
• Semi-confluent
• Discrete

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Classification of Variola Major

• Ordinary Type Discrete

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Classification of Variola Major

• Ordinary Type Discrete

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Classification of Variola Major

• Ordinary Type Semi-Confluent

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Classification of Variola Major

• Ordinary Type Confluent

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Classification of Variola Major

• Modified Type

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Classification of Variola Major

• Variola sine eruptione

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Classification of Variola Major

• Flat (Malignant) Type

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Classification of Variola Major

• Hemorrhagic Smallpox

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Hemorrhagic Smallpox
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Hemorrhagic Smallpox
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Hemorrhagic Smallpox
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VARIOLA MINOR -- Alastrim
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3 Major Classifications of Smallpox Henderson
DA, et al. Consensus Statement Smallpox as a
Biological Weapon Medical and Public Health
Management. JAMA. 1999

• Classic
• Hemorrhagic
• Malignant (Flat)

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DIAGNOSIS of SMALLPOX

• Degree of suspicion
• Patient history
• Physical examination
• Laboratory confirmation

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NOTIFICATION

• The discovery of a single suspected case of
  smallpox must be treated as an international
  health emergency and be brought immediately to
  the attention of national officials through local
  and state health authorities.
• Consensus Statement Smallpox as a Biological
  Weapon, JAMA. 1999 281 2131.

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CLINICAL PRESENTATION

• High fever
• Chills and rigors
• Malaise
• Cephalgia
• Dorso-lumbar pain
• Myalgias
• Nausea and vomiting
• Prostration and delirium

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CLINICAL PRESENTATION
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DIFFERENTIAL DIAGNOSIS

• Variola (Smallpox)
• vs.
• Varicella (Chickenpox)

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Chicken pox Smallpox
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Classic Smallpox Rash

• Centrifugal distribution
• Most dense on face and extremities
• Lesions appear during a 1 2 day period
• Lesions evolve at the same rate

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Oral Lesions
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Lesions initially erupt on the face where they
remain most numerous.
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Smallpox Rash Progression

• Day 8 Day 15 Day 25
• Pustules Scabs
  Scars

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Last Case of Variola, Somalia, 1977

• Ali Maow Maalin Lesions on his palms

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Last Case of Variola Major in the World

• Rahima Banu
• Bhola Island, October 16, 1975

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Lesions on Palms and Soles
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Centripetal Rash
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All Lesions In Same Phase
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Summary Characteristics of Rash

• Occurs after several days of febrile illness
• Macules papules vesicles pustules
• All lesions appear over 1-2 days
• All lesions evolve synchronously
• Firm/nodular
• Centrifugal (especially face)
• Umbilications
• Early oral lesions (ulcerate)

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Laboratory Diagnosis

• Rule out chickenpox first
• Contact State Public Health Laboratory
• Collect appropriate specimens
• Remember BIOSAFETY!

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LABORATORY DIAGNOSIS
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LABORATORY DIAGNOSIS

• Electron Microscopy

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LABORATORY DIAGNOSIS

• Chorioallantoic Membrane Growth

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TREATMENT Supportive Care Is the Mainstay!

• Currently, there are no anti-viral drugs of
  proven efficacy. Although adefovir, dipivoxil,
  cidofovir and ribavirin have significant in vitro
  antiviral activity against poxviruses, their
  efficacy as therapeutic agents for smallpox is
  currently uncertain.
• Cidofovir is FDA-licensed and shows the most
  promise in animal models.

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TREATMENT

• No specific anti-viral therapy proven effective
  in clinical smallpox disease.
• Vaccinia vaccination by the 3rd day of exposure
  is helpful.
• Cidofovir by the 2nd day of exposure may be of
  benefit.

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Vistide (cidofovir)
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TREATMENT

• Vaccinia vaccination by the 3rd day of exposure
  is helpful.
• Vaccinations as late as day 7 post-exposure may
  attenuate the course of disease.

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Isolation of Patients

• Smallpox is transmissible from person-to-person
  by exposure to respiratory secretions (coughing),
  contact with pox lesions and by fomites (not
  efficient).
• Observe both Airborne and Contact Precautions, in
  addition to Standard Precautions, when smallpox
  is suspected or confirmed.

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Isolation

• C-door, negative pressure room with 6 to 12 air
  exchanges per hour and HEPA filtration of
  exhausted air
• Strict isolation from the onset of eruptive
  exanthem until all pox scabs have separated
  (generally 14-28 days)
• All entering the room should wear appropriate
  respiratory protection- minimum NIOSH N95
• Wear clean gloves and gowns for all patient
  contact.

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Cohort

• Cohort patients when isolation capacity is
  exceeded.
• All should receive smallpox vaccine or vaccine
  immune globulin within 3 days of exposure (if
  available) in case some are misdiagnosed with
  smallpox.

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Care provider Vaccination

• All healthcare workers providing direct patient
  care to persons with smallpox should be
  vaccinated.
• If vaccine is unavailable, then only staff who
  have received smallpox previously vaccine (e.g.,
  persons born before 1972 or persons who were in
  the military before 1989) should be caring for
  patients with smallpox.

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Infectious Waste

• Use of tracking forms, containment, storage,
  packaging, treatment and disposal methods should
  be based upon the same rules as all other
  regulated medical wastes.
• Investigation of the states capacity for
  disposal of this waste is needed

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Autopsy and Handling of Corpses

• Universal Precautions plus particulate
  respirators N95
• Follow O.S.H.A. guidelines for PPE/Decon.
• Instruments should be autoclaved or sterilized
  with a 10 bleach solution or other solutions
  approved by O.S.H.A.
• Surfaces should be decontaminated with a chemical
  germicide such as 10 hypochlorite or 5 phenol.

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Management of Exposed Persons

• An exposed person is defined as a person who has
  been in close personal contact with a patient
  with suspect or confirmed smallpox.
• same household with the case-patient
• face-to-face contact with the case AFTER the
  case developed febrile illness

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Quarantine

• All exposed persons should be placed in strict
  quarantine with respiratory isolation for 17 days
  after last contact
• If capacity is exceeded, quarantine of exposed
  persons in their home with a daily fever watch
  may be an alternative measure

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Vaccination Indications

• All exposed persons, including all household and
  face-to-face contacts of patients, should be
  vaccinated immediately, if vaccine is available.
• Additionally, all health care workers that might
  care for smallpox patients, emergency personnel
  who might transport patients, and mortuary staff
  should be vaccinated, if vaccine is available.

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Reporting

• Even an isolated suspect case must be reported
  immediately to the Maine Bureau of Health
  800-821-5821.
• Response plans are under active discussion. They
  are a work in progress.

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Our thanks to Anthony Carbone and the
for the use of their materials.