• Smallpox

• Presentation by Nitika
• A0999323030

• (CONTENTS) slide 2
→ Introduction
→ Pathogenesis
→ Clinical Features
→ Differential Diagnosis
→ Laboratory Diagnosis
→ Prevention and Control
→ Treatment and Prophylaxis
→ Epidemiology
→ References
Slide 3
• SMALLPOX
• Smallpox is a highly contagious and
deadly disease caused by the
variola virus
→ It is an acute infectious diseass.
→ True origin of disease is not known but artifacts of third century BCE
shows evidence that is believed to be indicative of smallpox.
→

It was characterized by fever and a progressive skin rash that often led to
death. Smallpox was one of the most devastating diseases in human
history, killing millions of people around the world.

→ In 1796, Edward Jenner demonstrated that smallpox could be prevented

by inoculating a person with material from a cowpox lesion; this led to
the first smallpox vaccine.
→ The last case of smallpox in the United States was reported in Texas in
1949.
→ In 1966, the World Health Organization initiated an intensified global
smallpox eradication program.
→ The last indigenous case of smallpox on earth occurred in Somalia in
October 1977.
→ The World Health Assembly officially certified the global eradication of
 smallpox in May 1980.

Slide 4
• What causes small pox?
→ Smallpox is caused by variola virus.
→ It falls into the poxvirus family.
→ Poxvirus are the largest of all viruses
→ They form complex structures to protect large double stranded
Dna viral genomes.
→ And replicate in a unique way compared to other DNA viruses
→ Poxviruses replicate in the host cell cytoplasm which means
they must encode the enzyme required for messenger RNA and
DNA synthesis in their viral genome.

Slide 5

→ Poxviruses are large brick-shaped viruses with a double

stranded DNA genome.
→ Four orthopoxviruses are known to infect humans: variola,
vaccinia, cowpox, and monkeypox.
→ Variola virus infects only humans in nature.
→ Although animals can be infected with variola in laboratory conditions,
humans are the only natural host.
Slide 6
Transmission

Smallpox was primarily transmitted through

respiratory droplets, often spread by face-to
-face contact with an infected person.
The virus could also be transmitted by
direct contact with infected bodily fluids or
contaminated object.

After being inhaled variola virus replicates

in the upper respiratory tract without
causing any symptoms. Virus then infects
immune system cells called macrophages
which bring the virus into the lymphatic
system which then carries the virus to
lymph nodes and then virus spreads
through blood stream into liver spleen and
other organs.
Slide 7
• Types and Symptoms of Smallpox
→ There are two types of small pox
→ VARIOLA MAJOR
→ VARIOLA MINOR

Initial symptoms resembled flu,

including fever, headache, and
fatigue.
A characteristic rash developed,
progressing from macules to
papules and then pustules, leading
to scab formation.
Slide 8
Ordinary smallpox. Ordinary smallpox was the most common type of
smallpox and caused the symptoms described above. It caused about 85%
of cases. About 1 in 3 people with ordinary smallpox died.

Modified-type smallpox. People who had been vaccinated sometimes got

modified-type smallpox. This was similar to ordinary smallpox, but the rash
was less severe and didn’t last as long. Most people survived modified-type
smallpox.

Flat-type (malignant) smallpox. Flat-type smallpox caused more severe

initial symptoms than ordinary smallpox. The bumps from the rash merged
together and never got hard or fluid-filled. This made a flat, soft rash that
didn’t form scabs. Flat-type smallpox happened more often in children. It
was almost always fatal.

Hemorrhagic smallpox. Hemorrhagic smallpox was more common in

pregnant people. It caused severe initial symptoms. The rash usually didn’t
get hard and fluid-filled. Instead, the skin underneath it bled, causing it to
look black or burnt. It also caused internal bleeding and organ failure.
Hemorrhagic smallpox was almost always fatal.
Slide 9
VARIOLA MINOR

Variola minor, caused by different strains of variola, is a milder form of

smallpox.
most dense on the face
more dense on the extremities than on the trunk & on the extremities
more dense on the distal parts than on the proximal.
In general, the severity of the clinical picture parallels the extent of the rash.
Slide 10
DIAGNOSIS

Slide 11
• LABORATORY DIAGNOSIS
→ The diagnosis of smallpox requires a high index of suspicion because
the disease has been eradicated and its clinical presentation is similar
to other pox viruses.
→ Diagnosis of smallpox will be clinical initially, but followed by laboratory
confirmation.
→ Clinicians should use the CDC-developed tools to assess the likelihood
that patients with acute generalized vesicular or pustular rash illnesses
have smallpox.
→ Multiple tests will be used to evaluate for smallpox.
→ Polymerase chain reaction (PCR) testing will be an important
method
→ Electron microscopic examination of vesicular or pustular fluid or
scabs
→ Direct examination of vesicular or pustular material looking for
inclusion bodies (Guarnieri’s bodies)
→ Culture on egg chorioallantoic membrane
→ Tissue culture
→ Serology.
→ Definitive laboratory identification and characterization of the variola
virus requires several days

Slide 12
• Prevention & Control
 THE SMALLPOX VACCINE
→ Vaccinia virus
→ Protects against variola virus
→ Origins unknown
→ Live vaccine
→ Used in US until 1972
→ Immunity high for 3-5 years
→ Potentially protective much longer

Slide 13
• TREATMENT AND PROPHYLAXIS
→ The management of confirmed or suspected cases of smallpox
consists of supportive care, with careful attention to electrolyte and
volume status, and ventilatory and hemodynamic support. General
supportive measures include ensuring adequate fluid intake (difficult
because of the enanthem), alleviation of pain and fever, and keeping
skin lesions clean to prevent bacterial superinfection. 1-4, 6
→ Currently there are no FDA approved antiviral agents with proven activity
against smallpox in humans.

Slide 14
• EPIDEMIOLOGY
RESERVOIR
→

TRANSMISSION
→ Transmission of smallpox occurs through inhalation of airborne variola
virus, usually droplets expressed from the oral, nasal, or pharyngeal
mucosa of an infected person.
→ Most transmission results from direct face-to-face contact with an
 infected person.

COMMUNICABILITY
→ A person infected with variola virus is not infectious during the
incubation period or the first day or two of the prodromal stage of the
illness.
→ The patient becomes infectious with the first appearance of the rash,
which is often accompanied by lesions in the mouth and pharynx.
→ The virus can be transmitted throughout the course of the illness (i.e.,
until all crusts separate). Transmission is most frequent during the first
week of the rash, while most skin lesions are intact (i.e., vesicular or
pustular).
→ Natural transmission of smallpox in a population is relatively slow.
→ There is an interval of 2 to 3 weeks between each generation of cases.
Smallpox generally spreads less widely and less rapidly than does
varicella or measles, probably because transmission of variola virus
does not occur until the onset of rash and generally requires close face-
to-face contact for spread.

Slide 15
• REFERENCES
• Henderson DA, Inglesby TV, Bartlett JG, et al. Smallpox as a
biological weapon: medical and public health management.
Working Group on Civilian Biodefense. Jama. Jun 9
1999;281(22):2127-2137.
• CDC. Vaccinia (smallpox) vaccine: recommendations of the
Advisory Committee on Immunization Practices (ACIP).
MMWR 2001;50(No. RR-10):1–25.
• World Health Organization. Smallpox eradication: temporary
retention of variola virus stocks. Wkly Epidemiol Record
2001;19:142–5.
• Breman JG, Henderson DA. Diagnosis and management of
smallpox. N Engl J Med. Apr 25 2002;346(17):1300-1308.
• Sejvar JJ, Labutta RJ, Chapman LE, Grabenstein JD, Iskander
J, Lane JM. Neurologic adverse events associated with
smallpox vaccination in the United States, 2002-2004. Jama.
Dec 7 2005;294(21):2744-2750.
• Casey CG, Iskander JK, Roper MH, et al. Adverse events
associated with smallpox vaccination in the United States,
January–October 2003. JAMA 2005;294:2734–43.
• CDC. Notice to Readers: Supplemental recommendations on
adverse events following smallpox vaccine in the preevent
vaccination program: recommendations of the Advisory
Committee on Immunization Practices. MMWR
2003;52:282–84.
• Damon I. Orthopoxviruses: Vaccinia (Smallpox Vaccine),
Variola (Smallpox), Monkeypox, and Cowpox. In: Mandel GL,
Bennett JE, Dolin R, eds. Principles and practice of infectious
diseases. 6 ed. New York: Churchill Livingstone; 2005:1742-
1751.
• Casey CG, Iskander JK, Roper MH, et al. Adverse events
associated with smallpox vaccination in the United States,
January-October 2003. Jama. Dec 7 2005;294(21):2734- 2743.