SMALLPOX

A DEAD DISEASE
Dr.T.V.Rao MD
 Small Pox - Variola
Variola - Small pox
• WHO 1977 ended
• 8th May 1980 WHO declares Global
eradication
• Most Fatal – Small pox Variola Major
• Non fatal - Alastrim – Variola minor
• Vaccine – Virus – Cow pox used for
vaccination
• Vaccina – Viral vector.
 Origin of Smallpox
• The name Variola was first used in the 6th
century. Derived from the Latin word
varius (spotted) or varus (pimple).
• Anglo-Saxons in the 10th century used the
word poc or pocca (bag or pouch) to
describe an exanthemous disease,
possibly smallpox.
• In the 15th century, the English used the
prefix small to distinguish variola the
smallpox from syphilis, the great pox.
First Case of Smallpox
• There is no animal
reservoir, and no
human carriers.
• First certain evidence
comes from the
mummified remains of
Ramses. (1157 B.C.)
• Written descriptions
did not appear until
the 10th century in
Southwestern Asia.
 History of Variolation and
Vaccine
• Known that survivors became immune to
the disease.
• As a result, physicians intentionally
infected healthy persons with smallpox
organisms.
• Variolation is the act of taking samples
(pus from pustules or ground scabs) from
patients whose disease had been benign,
and introducing it into others through the
nose or skin.
 Species of the Genus Orthopoxvirus

Species Animals Infected Host Range Geographic Range

Variola Human Narrow Formerly worldwide

Vaccinia Human,a cow, pig, buffalo, rabbit, etc. Broad Worldwideb

Cowpox Rodent,a cow, human, cat, etc. Broad Europe

Monkeypox Squirrel,a monkey, ape, human Broad Western and central Africa

Ectromelia Mouse, mole Narrow Europe

Camelpox Camel Narrow Africa and Asia

Taterapox Gerbil Narrow Western Africa

Volepox Vole ? United States

Raccoonpox Raccoon ? United States

Skunkpox Skunk ? United States

Uasin Gishu Horse Medium Eastern Africa

a
Primary host.
b
Secondary to vaccination; no known natural host.
http://books.nap.edu/html/variola_virus/ch2.html#TopOfPage
SMALLPOX
• Genus Orthopoxviruses
Smallpox, monkey pox,
cowpox,vaccinia
• DNA Virus
• 200 nm brick
shaped
• Smallpox-person to
person spread via
respiratory
secretions/direct
contact
• Spread best in low
humidity/temperature
 CHARACTERISTICS SHARED BY
SPECIES OF ORTHOPOXVIRUS :
- The largest and most complex viruses
- Virons particles can be seen with a light
microscope

- They contain a linear genome of a single

double-stranded DNA
- They replicate in the cytoplasm of the
host cell,
DNA synthetic machinery
(including DNA-dependent RNA
polymerase

- Serological cross-reactivity
- Produce a hemagglutininin antigen (HA)
 Guarnieri's bodies or
Elementary bodies
• Inclusion
bodies: type A
and type B
• Virions have a
brick-like shape
and are present
in
2 forms, both
are infectious
 Vaccinia Virus – Electron micrographs

A. Non- enveloped virion (surface of outer membrane with tubular elements)

C. Thin section of non-enveloped virion (biconcave core)
B. Enveloped virion, found in extracellular medium
D. Viral core, released after treatment of virions with Nonidet
Fenner,F. et al. Smallpox and Its Eradiction. Genevea, Switzerland:WHO. 1998:1460
 Variola virus
• Brick shaped,cosists
of double layered
membrane which
surrounds –
Biconcave –Nucleoid
congaing DNA core
• Either side lens
shaped lateral body
300 x 200 x 100 nm
 Physical characters
• Remain viable for months at
room temperature
• Resists 50% Glycerin and 1 %
phenol
• Inactivated by formalin and
oxidizing agents
 Antigenic structure
• Nearly 20 antigen
• Heat liable and stable antigens
• Cultured on Chorioallontoic membrane of 11
– 13 days old chick embryo
• Variola pocks are small shiny, white convex
non necrotic, non hemorrhagic
• Variola pocks are larger irregular flat grayish
necrotic lesions some are hemorrhagic
• Tissue culture on Monkey kidney, Hela cells
Virus spread by respiratory route
 Variola (Smallpox)
Smallpox is an acute exanthematous disease caused
by infection with the poxvirus variola.

The significant clinical features include:

 Three-day prodromal illness characterized by

fever, headache, backache, and vomiting.
 Generalized centrifugal rash that follows prodrome
 Begins centrally then spreads to the
extremities and face
 Rapid succession of papules, vesicles, pustules,
umbilication, and crusting over a 14-day period.

Prior vaccination may alter the clinical presentation

of smallpox. The following description applies to the
classic presentation in unvaccinated individuals.
 Variola (Smallpox) Vie

A macular red rash may precede the appearance of the papules,

which are deep and firm to palpation. Papules soon vesiculate,
forming a circumscribed, elevated lesion that contains clear
fluid.

Central umbilication of the pustule is characteristic of smallpox.

A second important distinguishing characteristic of smallpox
is that all of the lesions at a given time are in the same stage
of development. That is, at any one point in time the lesions are all
papules or vesicles or pustules. Bacterial infection of the lesions can occur,
producing localized abscesses and cellulitis.
Variola (Smallpox) Vi

Chart from the Center

for Disease Control and
Prevention showing the
characteristic
distribution of smallpox
lesions.
 Variola (Smallpox) View Table

Smallpox on the hand: Notice how these lesions have

become confluent.
 Variola (Smallpox) Vi

Smallpox in a child: Notice that all lesions are in the

same stage of development.
 Small pox
• Last case Saiban Bibi Assam 24
may 1977
• Patients are source of infection
• Close contacts
• Single crop centrifugal distribution
• Macules – Papules – Vesicles –
Pustules
 Pathogenesis of Smallpox
• The portal of entry for smallpox is the
respiratory tract or inoculation on the skin
• Excretions from the mouth and nose, rather
than scabs, are the most important source of
infectious virus
• Studies have shown that primary infection in
the nose or mouth do not produce a “primary
lesion” that ulcerates and releases virions
onto the surface
 Clinical Features
• Rash stages of development
– All lesions in one region at same stage
– Starts macular, then papular
– Deep, tense vesicles by Day 2 of rash
– Turns to round, tense, deep pustules
– Pustules dry to scabs by Day 9
– Scabs separate
 Clinical Features
• Scarring
– From separated scabs
– Fibrosis, granulation in sebaceous
glands
– Pink, depressed pock marks
– Prominent on face, usually >5
lesions
– Permanent
 Clinical Features
• Complications
– Sepsis/toxemia
• Usual cause of death
• Associated with multiorgan failure
• Usually occurs during 2nd week of illness
– Encephalitis
• Occasional
• Similar to demylination of measles,
Varicella
 Clinical Features
• Complications
– Secondary bacterial infections uncommon
• Staphylococcus aureus cellulitis
– Responds to appropriate antibiotics
• Corneal ulcers
– A leading cause of blindness before 20th Century
– Conjunctivitis rare
• During 1st week of illness
A disfiguring Disease
 Epidemiology
• Infectious Materials
– Saliva
– Vesicular fluid
– Scabs
– Urine
– Conjunctival fluid
– Possibly blood
 Epidemiology
• Infectious Materials
– Saliva
– Vesicular fluid
– Scabs
– Urine
– Conjunctival fluid
– Possibly blood
 Diagnosis
• Clinical diagnosis
– Sufficient in outbreak setting
– >90% have classical syndrome
• Prodrome followed by rash
– Rarely, variants can be difficult to recognize
• Hemorrhagic – mimics meningococcemia
• Malignant – more rapidly fatal
• Sine eruptione – prodrome without rash
• Partially immune – milder, often atypical
 Diagnosis
• Traditional confirmatory methods
– Electron microscopy of vesicle fluid
• Rapidly confirms if orthopoxvirus
– Culture on chick membrane or cell culture
• Slow, specific for variola
• Newer rapid tests
– Available only at reference labs (e.g. CDC)
– PCR, RFLP
 Laboratory Diagnosis of Smallpox
• Culture on Egg chorioallantoic membrane (CA): classical
method; poxvirus grow on CA
• Direct examination of vesicle or pustular material:
aggregations of virus may be seen in certain cytoplasm upon
staining
• Tissue culture: growth in cultured cells
• EM: negative staining is used to visualize characteristic large
brick shape of poxvirus
– Relatively rapid
– Can distinguish orthopox viruses from other viral agents
– Cannot differentiate between variola and vaccinia viruses
– May not be as sensitive as PCR-Based methods
 Laboratory Diagnosis of Smallpox
• PCR Based method: In North America a positive test is
considered diagnostic for vaccinia virus unless medical
or epidemiologic evidence suggests otherwise
• With slight modifications to the fluorescently labeled
probe, this assay can also be used to detect variola virus
– Family specific primers are used first, then subgroup-specific
primers are used if the former is not successful in producing PCR
product
• DNA Probes: Assays using immobilized oligonucleotides
in a microarray have been developed to identify and
discriminate among orthopoxviruses
• In situ hybridization of formalin-fixed tissues
• Serology: Classical methods such as complement
fixation and gel precipitation commonly were used in the
past; experimental enzyme-linked immunoassays are
currently being evaluated
 Diagnosis
• Differential Diagnosis
– Chickenpox (varicella)
• Vesicles shallow, in crops, varied stages
• Centripetal, spares palms/soles
– Other orthopox viruses
• Monkeypox – only in Africa, monkey contact
• Vaccinia – after exposure to vaccine
• Cowpox – rare, only in UK
 Prevention
• Vaccination - History
– Introduced by Jenner
• Inoculated boy with pustular fluid from cowpox
• 1st immunization using virus of similar disease
• Initially passed arm-to-arm
– Also passed syphilis, hepatitis
• Eventually passed calf-to-calf on scarified leg
• Immunity not lifelong
 Prevention
• Vaccine – modern times
– Vaccinia virus
• Related to cowpox and variola
• Source – calf lymph
• Now cell culture methods available
• Strains
– Lister used by WHO for eradication campaign
– New York Board of Health only U.S. strain
– Newer more attenuated Japanese strain
Jenner vaccinating
Vaccination for Small Pox
Vaccinating for Smallpox
Prevention
Vaccinating for Smallpox
• Program Created by Dr.T.V.Rao MD
for benefit of many in the world for
Historical perception on a Dead
Disease
• Email
• [email protected]