The deadly disease- samll pox

2. SMALL POX
MANEESHA M JOSEPH
IV BSc MLT
Govt MEDICAL COLLEGE
TRIVANDRUM

3. HISTORY
Smallpox is believed to originate as far back as 3,000 years ago in
India and Egypt
 Rameses V is believed to have had smallpox, due to the spots on his
mummified corpse. In 1525, Inca Emperor Huanya Capac died from
smallpox.
 Queen Elizabeth I was infected with smallpox, but survived.
 Queen Mary II of England was not as fortunate, and died from the
disease.
 In the 18th century, the city of Glasgow reported that 50% of the
children died before age 10, and of those, 40% died from smallpox.

4. In Europe, it was reported that 400,000 people died each year
from smallpox.
Because smallpox was so feared, it was used as a weapon of
war.
 In 1763, during the French and Indian war, the British gave
blankets infected with the smallpox virus to the Native Americans.
In 1796, Edward Jenner discovered that people who had been
exposed to cowpox, developed immunity to smallpox.
 Jenner used the thick pus from the cowpox virus and inoculated
the young man. Six weeks later, the boy was exposed to smallpox, but
did not become infected.

5. Even after the vaccine was discovered, there were problems with it
becoming contaminated. In 1861, children in Italy received a
vaccine that was contaminated with syphilis.
After several years of experimenting with ways to effectively
produce a non- contaminated vaccine, L.H. Collier discovered a way
to freeze dry the vaccine for commercial use.
World Health Organization (WHO) led an aggressive campaign to
rid the world of the disease.
 In 1980, they declared that smallpox had been eradicated.
The last reported case of naturally occurring smallpox in the U.S.
was in 1949, and, World wide, in Somalia in 1977.
Today there are 2 laboratories that hold a stock of smallpox virus,
one in the U.S., and one in Russia.

6. Statue of Sopona the West African god
thought to inflict the disease.
Rameses V

7. EPIDEMIOLOGY
Smallpox is no more, due to aggressive vaccination campaign by
WHO.
It is believed that the virus began in rodents, and as prehistoric man
killed and ate the rodents, the virus was passed on to humans. Once
humans became the new host, there was no stopping the deadly viruses
spread of devastation.
This was due to the fact that around 9000 BC humans began to
cultivate crops and settle into much larger communities. With larger
groups, the virus could move from person to person without exhausting
its supply of hosts.

8. The rate of new infections of smallpox depended on the size of
the community.
The more people there were, the more the virus spread. In its
most destructive state, 90% of smallpox victims died.

10. This transmission electron micrograph depicts a number of
smallpox virions. The "dumbbell-shaped" structure inside the
virion is the viral core, which contains the viral DNA;
Group: Group I (dsDNA)
Order: Unassigned
Family: Poxviridae
Subfamily: Chordopoxvirinae
Genus: Orthopoxvirus
Type species
Vaccinia virus
Species
Variola virus
VIRUS CLASSIFICATION
SMALL POX VIRUS

12. CAUSATIVE AGENT
Smallpox is caused by 2 variations of the virus variola.
 The deadliest form is Variola Major.
 This is the largest animal virus visible with light microscope apear
as smooth rounded rectangles.
It is the only virus that do not need a cell’s nucleus to replicate and
are larger than some bacteria.
 Variola Minor can leave large scars and can possibly cause
blindness.
Smallpox is a highly contagious disease with a long incubation
period, usually between 12-14 days.

13. The Variola virus is a member of the orthopoxvirus genus, which
also includes cowpox, camelpox, and monkeypox.
Smallpox is part of the poxviridae family, meaning it can infect both
vertebrates and invertebrates.
 The virions of the virus are enveloped externally and internally.
The Variola virus produces a double strand DNA dependent RNA.
This dsDNA replicates at a lower rate than an RNA virus.

14.  The RNA virus has the ability to edit out any mistakes during
polymerase replication, unlike DNA dependent viruses.
The smallpox virus is about 200-400 nanometers in size, and is
brick shaped.
The virus has 2 membranes ,The outer membrane is enveloped and
the inner membrane contains the double strand DNA dependent
RNA, along with multiple enzymes.
The dsDNA and the enzymes are used as the energy machinery in
the nucleic acid metabolism for the genome replication that occurs
in the cytoplasm. The genome is rather large in comparison to other
vital genomes, so reproducing in the lab is difficult.
The multiplication cycle starts by the virus binding to a host cycle

15. Once in the host cell, it will uncoat the exterior enveloped
virion, and then uncoats the inner enveloped virion.
 Now that the inner enveloped virion is uncoated, the dsDNA
uncoils along with multiple viral enzymes.
This process starts the replication of the genome that occurs in
the cytoplasm.
 This also makes smallpox unique in that replication usually
takes place in the nucleus, not the cytoplasm, since viruses
generally don’t have cytoplasm.
Once the DNA replicates to make a virion, the virion then
passes through the cell membrane and is enveloped
simultaneously and is then released to repeat the process.

17. TRANSMISSION
Transmission occurs through inhalation of airborne variola virus,
usually droplets expressed from the oral,nasal,or pharyngeal mucosa of
an infected person.
It is transmitted from one person to another primarily through
prolonged face-to-face contact with an infected person, usually within a
distance of 6 feet (1.8 m).
Can also be spread through direct contact with infected bodily fluids or
contaminated objects (fomites) such as bedding or clothing.

18. Rarely, smallpox has been spread by virus carried in the air in
enclosed settings such as buildings, buses, and trains.
The virus can cross the placenta, but the incidence
of congenital smallpox is relatively low.

19. Ninety percent or more of smallpox cases among unvaccinated
persons are of the ordinary type. In this form of the disease, by the
second day of the rash the macules become raised papules.
 By the third or fourth day the papules fill with an opalescent fluid
to become vesicles.
 This fluid becomes opaque and turbid within 24–48 hours, giving
them the appearance of pustules; however, the so-called pustules are
filled with tissue debris, not pus.
Ordinary smallpox generally produces a discrete rash, in which
the pustules stand out on the skin separately.
CLASSIFICATION OF SMALL POX
1) ORDINARY

20. The distribution of the rash is densest on the face; denser on the
extremities than on the trunk. The palms of the hands and soles of the
feet are involved in the majority of cases
2) MALIGNANT
In malignant-type smallpox (also called flat smallpox) the lesions
remain almost flush with the skin at the time when raised vesicles form in
the ordinary type.
 Malignant smallpox is accompanied by a severe prodromal phase that
lasts 3–4 days, prolonged high fever, and severe symptoms of toxemia.
The rash on the tongue and palate is extensive.
 Skin lesions mature slowly and by the seventh or eighth day they are
flat and appear to be buried in the skin.
 Unlike ordinary-type smallpox, the vesicles contain little fluid, are soft
and velvety to the touch, and may contain hemorrhages. Malignant
smallpox is nearly always fatal.

21. 3) HAEMORRHAGIC
Hemorrhagic smallpox is a severe form that is accompanied by
extensive bleeding into the skin, mucous membranes, and gastrointestinal
tract.
In hemorrhagic smallpox the skin does not blister, but remains smooth.
Instead, bleeding occurs under the skin, making it look charred and
black, hence this form of the disease is also known as black pox
In the early, or fulminating form, hemorrhaging appears on the second
or third day as sub-conjunctival bleeding turns the whites of the eyes
deep red.
Hemorrhagic smallpox also produces a dusky erythema, petechiae, and
hemorrhages in the spleen, kidney, serosa, muscle, and, rarely,
the epicardium, liver, testes, ovaries and bladder.

22. Patients in the late stage have significant thrombocytopenia;
however, deficiency of coagulation factors is less severe.
Fatality rate is high

23. The virus is acquired from inhalation (breathing into the lungs).
The incubation period lasts approximately 12 to 14 days.
 Once inhaled, variola virus invades the respiratory mucosa,
migrates to lymph nodes, and begins to multiply.
 A few days later, the virus enters the bloodstream and begins a
second wave of multiplication in the spleen, bone marrow, and
lymph nodes.
Finally, the virus reenters the blood in leukocytes, producing fever
and toxemia, and then spreads to the skin, intestines, lungs, kidneys,
and brain
PATHOLOGY

24. The pre-eruptive stage lasts approximately 2 to 6 days and is so
typical of smallpox that it must used for diagnosis. It is characterized
by sudden onset of high fever (102 F to 105 F), prostration, severe
headache, backache, pain in the limbs and abdomen.
 Over half of people with smallpox experience chills and vomiting.
Virus is most likely to be found in the blood in the first few days of
the pre-eruptive fever, particularly in severe infections
On day 4 to 6, the virus activity in the skin cells creates a rash that
starts as macules (flat, red lesions).
Typically, macules first appear on the forehead, then rapidly spread
to the whole face, the trunk, and lastly to distal portions of extremities.

25. After this, vesicles (raised blisters) form. Then, pustules appear in
two days.
Day 6 to 8: Lesions on mucous membranes have evolved into
papules and vesicles and broken down.
The virus particles are released, coughed, or sneezed into the
environment.
The patient is most infective at this time . Virus particles can
remain on such items as clothing, bedding, and surfaces for up to 1
week.
The infected person can be infectious for up to 3 weeks (until the
scabs fall off the rash).
Live virus can be present in the scabs.

26. Day 8 to 10: Fluid in the vesicles becomes opaque, giving them the
appearance of pustules; however, the so-called pustules are filled with
tissue debris, not pus
Day 10 to 20: Pustules mature, increase in size, become
umbilicated, and crusting begins
Day 21 to 28: With the exception of those embedded in the palms of
the hands and soles of the feet, most crusts have separated, leaving
depigmented or light-skinned scars.
The hemorrhagic variety of variola has a much higher death rate
(95%) than classic smallpox and leads to certain death more quickly,
5 or 6 days following the onset of rash.
Infected people often die before the pustules form

27. This variety is recognizable by certain types of bleeding sores in
mucous tissues.
In the flat or malignant form of smallpox, confluent vesicles
develop slowly, remain flat and velvety to the touch, appear fine-
grained, and may cause large areas of the epidermis to slough. It is
most often fatal form of smallpox.
In variola minor, rash erupts more slowly, with smaller vesicles
and rare umbilication or scarring.
Complications of smallpox arise most commonly in the respiratory
system and range from simple bronchitis to fatal pneumonia.

28. Other complications include permanent pitted scars, most notably
on the face and ocular complications .
Pustules can form on the eyelid, conjunctiva, and cornea.
Blindness results in approximately 35% to 40% of eyes affected
 In 2% to 5% of young children with smallpox, the smallpox viruses
reach the joints and bone, causing swollen joints, limit movement,
and arthritis may lead to malformed bones, flail joints, and stubby
fingers.

30. PATHOLOGIC FEATURES
Skin: Capillaries in the papillary dermis dilate, cells enlarge,
vacuolate, and degenerate.
Affected cells contain round or oval inclusion bodies, called Guarnieri's
bodies, that measure 2 to 8 µm, and compose of viral particles and
proteins; each body is the locus of viral replication and assembly.
Later, viral inclusions occupy large portions of cytoplasm.
Cells may lose normal orientation, condense, and detach. Cellular
degeneration spreads in the middle layer of the epidermis.
 Respiratory and Digestive Tracts: Smallpox can affect the epithelium
of the tongue, throat, trachea, gullet, and appendix
Necrosis begins in superficial cells, and then penetrates to form ulcers.
The trachea may have sharply defects 1 to 2 mm in diameter.

31. Lungs: Alveolar cells are swollen, mitotic, or degenerating with
accompanying bacterial growth.
Heart: Cardiac involvement in smallpox is not often but can include
hyperemia and small hemorrhages.
Liver: Endothelial cells become swollen and necrotic.
 Spleen: The spleen is enlarged and engorged with blood, and there
are small hemorrhages in the red and white pulp.
 Kidney: Pathologic changes in the kidney are most prominent in the
center (medulla). Tubular epithelial cells are swollen, degenerated, or
mitotic.

32. Testes: Foci of necrosis 1 to 3 mm in diameter form in the testes,
with focal hyperemia and hemorrhage.
Bone Marrow: Occasional necrosis and small hemorrhages are
seen in bone marrow. The cells become plastic with nuclear
degeneration.
Brain: Lesions are focally prominent in the cortex and white
matter of the cerebral hemispheres, brain stem, and spinal cord

34. Microscopically pox virus have characteristic cytoplasmic inclusions,
the most important of which are known as Guarnieri bodies and are the
sites of viral replication. Guarnieri bodies are readily identified in skin
biopsies stained with hematoxylin and eosin, and appear as pink blobs.
The diagnosis of an orthopoxvirus infection can also be made rapidly
by electron microscopic examination of pustular fluid or scabs. However,
all orthopoxviruses exhibit identical brick-shaped virions by electron
microscopy.
Definitive laboratory identification of variola virus involves growing
the virus on chorioallantoic membrane (part of a chicken embryo) and
examining the resulting pock lesions under defined temperature
conditions
LAB DIAGNOSIS

35.  Strains may be characterized by polymerase chain reaction (PCR)
and restriction fragment length polymorphism (RFLP) analysis.
 Serologic tests and enzyme linked immunosorbent assays (ELISA),
which measure variola virus-specific immunoglobulin and antigen
have also been developed to assist in the diagnosis of infection.
small pox on chorio allantoic membrane of -chick embryo

36. The earliest procedure used to prevent smallpox was inoculation (also
known as variolation)involved either nasal insufflation of powdered
smallpox scabs, or scratching material from a smallpox lesion into the
skin.
The current formulation of smallpox vaccine is a live virus
preparation of infectious vaccinia virus. The vaccine is given using a
bifurcated (two-pronged) needle that is dipped into the vaccine
solution.
 The needle is used to prick the skin (usually the upper arm) a
number of times in a few seconds.
TREATMENT

37. During the second week, the blister begins to dry up and a scab
forms. The scab falls off in the third week, leaving a small scar.
The antibodies induced by vaccinia vaccine are cross-protective for
other orthopoxviruses, such as monkeypox, cowpox, and variola
(smallpox) viruses.
Neutralizing antibodies are detectable 10 days after first-time
vaccination, and seven days after revaccination.
If successful, a red and itchy bump develops at the vaccine site in
three or four days. In the first week, the bump becomes a large blister
(called a "Jennerian vesicle") which fills with pus, and begins to
drain.

38. VACCINE ADMINISTRATION

39.  In the past, about 1 out of 1,000 people vaccinated shows
reactions including toxic or allergic reaction at the site of the
vaccination (erythema multiforme)
 spread of the vaccinia virus to other parts of the body, and to
other individuals.
 Based on past experience, it is estimated that 1 or 2 people in 1
million who receive the vaccine may die as a result of post
vaccinial encephalitis or severe necrosis in the area of vaccination
(called progressive vaccinia)
ADVERSE EFFECTS OF VACCINE

40. SMALLPOX CHICKENPOX
FEVER ONSET 2 to 4 days before rash At rash onset
RASH
Evolution Lesions at same stage Lesions appear in crops
Lesions evolve at same rate Lesions in different
stages
Distribution Rash centrifugal Rash centripetal
Rash on palms and soles Never on palms or soles
Development Slow Rapid
Pox don’t burst when probed Lesions burst when
probed
MORTALITY 30% Rare