1. Presentation on
SMALLPOX

2. Smallpox
Smallpox is a serious, contagious and sometimes fatal disease.
There is no specific treatment for smallpox, and the only prevention is vaccination.
The name smallpox is derived from the latin word “spotted” and refers to the raised bumps that appear on the face and body of an infected person.
Smallpox is in the Orthopoxvirus genus of viruses.

3. 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.

4. 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.

5. Smallpox Travel
Smallpox was likely carried from Egyptian traders to India during the millennium B.C. where it became established as an endemic infection.
Epidemics of the disease can be found in the bible, and in ancient Greek and Roman literature.
From Asia and Africa smallpox spread with increasing frequency into less populous areas, and then into Europe.

6. Smallpox in the New World
In the early 16th century smallpox began to imported into the western hemisphere.
The Spanish inadvertently owe success in conquering the Aztec and Incas in Mexico to smallpox.
Smallpox arrived in North America via Canada, and Mexico.

7. 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.

8. Survival Rates with Variolation
Two to Three percent of variolated persons died of smallpox, became the source of a new epidemic, or developed other illnesses from the lymph of the donor such as tuberculosis or syphilis.
The case fatality rates were still ten times lower in those that were variolated compared to those with naturally occurring smallpox.
Side effects of variolation were the appearance of smallpox itself, but it would disappear after a week or so.

9. TAXONOMY FAMILY: POXVIRIDAE
SUBFAMILY: CHORDOPOXVIRINAE (infect vertebrates)
GENERA: ORTHOPOXVIRUS (variola, vaccinia, cowpox, monkeypox)
AVIPOXVIRUS (fowlpox)
CAPRIPOXVIRUS (sheep-pox)
LEPORIPOXVIRUS (myxoma)
PARAPOXVIRUS (milker’s nodule)
SULPOXVIRUS (swinepox)
2. SUBFAMILY: ENTOMOPOXVIRINAE (infect arthropods)

10. Transmission of Smallpox
Humans are the only natural host of smallpox and it is not known to be transmitted by insects or animals (no animal reservoir)
Transmission generally occurs from direct and fairly prolonged face-to-face contact (in order for infected spit particles to pass from one person to another)
Infected aerosols and air droplets spread in face-to-face contact with an infected person after fever has begun, esp. if symptoms include coughing
Smallpox can also be spread through direct contact with infected bodily fluids or contaminated objects (ie. Bedding and clothing)
In rare instances, smallpox can spread through the air of an enclosed area
Variola major renders infected people bedridden so spreading to the community is reduced
In variola minor, however, the symptoms are so mild that patients remain ambulatory during the infection phase and can spread the virus more widely

11. Pathogenesis of Smallpox
When studies were done on rabbits with rabbitpox to determine the cause of death the rabbits had extreme hypertension, leading to a shock-like syndrome, decreased urinary output and a rise in blood-urea and plasma potassium levels
Death seemed to be caused by lethal concentrations of potassium ion, which was possibly from the hypertension

12. Stages of Smallpox Incubation Period Prodrome Phase
Lasts on average days but can range from 7-17 days
Person is not contagious and exhibits no symptoms
Prodrome Phase
This is when initial symptoms develop and is also called the pre-eruptive stage
Begins abruptly with fever, malaise, headache, head and body aches, prostration, and often nausea and vomiting
Body Temperature rises to at least 101F and is often higher
Note that this severe febrile prodrome right before the onset of the rash is characteristic of smallpox and can be used to differentiate it from other rash illnesses
This phase lasts 2-4 days and is sometimes contagious

13. Stages of Smallpox: Rash Phase
When the first visible lesions appear the fever may start to go down
This is the most contagious period (the time when the saliva has the most virus in it)
Lasts 4 days
Rash emerges as small red spots on tongue and in mouth (about 24 hours before the appearance of rash on the skin)
Lesions in the mouth and pharynx enlarge and ulcerate quickly, releasing large amount of virus into the saliva
These spots develop into sores that break open and spread large amounts of virus into mouth and throat
The rash starts on the face as a few macules, known as herald spots, and spreads to the arms and the legs then to the hands and feet
The rash usually spreads to all parts of the body in just 24 hours
By the 3rd day of the rash the rash becomes raised bumps or papules
By the 4th day the bumps become vesicular, fill with a thick, opaque fluid and often have depression in center that looks like a bellybutton (this umbilication is a major distinguishing characteristic of smallpox especially from chickenpox)

14. Stages of Smallpox: Rash Phase
The rash of smallpox has a centrifugal distribution, meaning it is most dense on the face, and more dense on the extremities than on the truck
The palms of the hands and soles of the feet are involved in the majority of cases
These characteristics are important in differentiating smallpox from other causes of rash illness
Another differentiating characteristic of smallpox is that the lesions are all in the same stage of development on that part of the body (unlike chickenpox) these stages of development are: macules, papules, vesicles, and crusted lesions

15. When is a person contagious?
A person with smallpox is sometimes contagious with the onset of fever (the prodrome phase) but a person is most contagious with the onset of the rash
Luckily, by the time a person gets the rash they are so sick they can’t likely move around the community
An infected person is contagious until the last smallpox scab falls off

16. Clinical Diagnosis
There are 3 major criteria for diagnosing if a rash is indeed smallpox:
Prodrome that begins 1-4 days before rash onset and includes fever over 101F, and at least one of the following symptoms: prostrations, headache, backache, chills, vomiting, abdominal pains
Presence of classic smallpox lesions: firm, round, deep-seated vesicles or pustules
Lesions on the palms of the hands and/or soles of the feet
There are 5 minor criteria looked at for diagnosis of smallpox:
Lesions are centrifugal distribution
First lesions appear on the oral mucosa, face, or forearms
Patient appears toxic
Rash has slow evolution, each stage lasting 1-2 days
There are lesions on palms of the hands and/or soles of feet

17. Common conditions confused with Smallpox
Varicella (primary infection with varicella zoster virus)
Disseminated herpes zoster
Impetigo
Drug eruptions
Contact dermatitis
Erythema multiforme minor
Eyrthema multiforme (includes Steven Johnsons Syndrome)
Enteroviral infection esp. Hand, foot and mouth disease
Disseminated herpes simplex
Scabies and insect bites
Molluscum contagrosum

18. Outcomes of Infection:
Those who survive usually have scars
If eye involvement then blindness could occur
Recovery results in long lasting immunity to reinfection with variola virus; no evidence of chronic or recurrent infection with variola virus
In fatal cases death usually occurs b/w the 10th and 16th days of illness
The cause of death from smallpox is not exactly clear since the infection involves multiple organs; perhaps uncontrolled immune response as well as overwhelming viremia and soluble variola antigens

19. Treatment of Smallpox
Vaccine is administered up to 4 days after exposure to the virus and before the rash appears, provides protective immunity and can prevent infection or ameliorate the severity of the disease
There is really no effective treatment, other than the management of the symptoms
Adequate fluid intake (difficult)
Alleviation of pain and fever
Keeping skin lesions clean to prevent bacterial infection
Some compounds, such as Cidofovir, are under investigation as chemotherapeutic agents

20. Vaccination
In 1796, Edward Jenner demonstrated that immunity to smallpox could be produced by inoculating a human with material from a lesion on the udder of a cow (cowpox); Jenner called this material vaccine from vacca which is Latin for cow
At some time during the nineteenth century, the virus used for smallpox ceased to be cowpox and was changed to vaccinia
Vaccinia is in the same family has cowpox and smallpox but genetically different
In the early 1950s (150 years after Jenner’s vaccination came out) an estimated 50 million cases of smallpox occurred in the world each year, which feel to around million by 1967 b/c of vaccination

21. Vaccination
If vaccination is successful a red, itchy bump develops at the vaccine site in 3-4 days; this is caused by the vaccinia virus replicating in the basal cells of the epidermis producing a papule surrounded by erythema
In the first week the bump becomes a blister, fills with pus, and begins to drain
A person is considered protected with the development of a pustule like this at the vaccination site
During the second week the blister begins to dry and a scab forms; the scab then falls off leaving a scar
Most people experience the side effects of a sore arm, fever, and body aches and axillary lymphadenopathy (3-5 days after vaccination)
1st time vaccinators have a stronger reaction than those who are re-vaccinated
Because the virus is live it can be spread to other parts of the body or to other people so great care must be given to the vaccination site to prevent this

22. Vaccination
The vaccine provides a high level of immunity for 3-5 years and decreasing immunity thereafter
If a person is re-vaccinated the immunity lasts even longer
Studies show that even 30 years after a vaccination, while a person may not be protected against smallpox they have a less severe disease
The vaccine has been effective in preventing smallpox in 95% of people vaccinated
Evidence for a brisk cell-mediated immune response has also been detected
It is believed that healing of the vaccinia infection is associated with intact cell-mediated or T-cell and cytokine immune competence, and that viremia is defended by an intact antibody or B-cell immune competence
If the vaccine is given in 1-2 days after exposure to smallpox it is effective in preventing smallpox or mitigating the symptoms of those who have been exposed
The fatality rate among people vaccinated less than 10 years before exposure was 1.3%; it was 7% among those vaccinated years prior, and 11% among those vaccinated 20 or more years prior to infection; 52% of unvaccinated people died

23. Who Should Not Get the Vaccine?
The vaccine is contraindicated for:
Persons who have experienced a serious allergic reaction to a prior dose of vaccine or to a vaccine component
Persons with significant immunosuppression from any cause (HIV, transplant, receiving treatment for cancer) or anyone with an immunosuppressed person in their household
Pregnant women and persons with a pregnant person in the household
Breastfeeding women
Children under 12 months; in fact the Advisory Committee on Immunization Practices (ACIP) advises against non-emergency vaccination in children under 18
Persons with any heart problems, stroke or transient ischemic attack, high blood pressure, high cholesterol, or diabetes
Persons with any sort of skin condition
Persons with inflammatory eye diseases requiring steroid therapy

24. Eradication
26 October 1977 the last naturally occurring case of smallpox was recorded in Merka Somalia.
In 1978 two cases were reported. These were both from people working in labs with smallpox in England.

25. Eradication 1980: WHO formally declared that smallpox was dead.
The eradication of smallpox was one of the most important branches of modern medicine.
Jenner has been acknowledged as the father of immunology,

26. END OF PRESENTATION BY PRASANTH GROUP-4