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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

Primary host.
Secondary to vaccination; no known natural host.

a
b

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)

Chart from the Center


for Disease Control and
Prevention showing the
characteristic
distribution of smallpox
lesions.

Vi

Variola (Smallpox)

Smallpox on the hand: Notice how these lesions have


become confluent.

View Table

Variola (Smallpox)

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


same stage of development.

Vi

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
doctortvrao@gmail.com