Presentation on 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.

Smallpox

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.

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.

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.

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.

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.

TAXONOMYTAXONOMY

FAMILY: FAMILY: POXVIRIDAEPOXVIRIDAE

1.1. SUBFAMILY: SUBFAMILY: CHORDOPOXVIRINAE CHORDOPOXVIRINAE (infect vertebrates)(infect vertebrates)

GENERA: GENERA: ORTHOPOXVIRUS (variola, vaccinia, cowpox, monkeypox)ORTHOPOXVIRUS (variola, vaccinia, cowpox, monkeypox) AVIPOXVIRUS (fowlpox)AVIPOXVIRUS (fowlpox)

CAPRIPOXVIRUS (sheep-pox)CAPRIPOXVIRUS (sheep-pox)

LEPORIPOXVIRUS (myxoma)LEPORIPOXVIRUS (myxoma)

PARAPOXVIRUS (milker’s nodule)PARAPOXVIRUS (milker’s nodule)

SULPOXVIRUS (swinepox)SULPOXVIRUS (swinepox)

2. SUBFAMILY: 2. SUBFAMILY: ENTOMOPOXVIRINAEENTOMOPOXVIRINAE (infect arthropods) (infect arthropods)

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

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

Stages of Smallpox

Incubation Period Lasts on average 12-14 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

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)

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

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

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

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

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

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

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 10-15 million by 1967 b/c of vaccination

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

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 11-20 years prior, and 11% among those vaccinated 20 or more years prior to infection; 52% of unvaccinated people died

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

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.

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,

END OF PRESENTATION BY

PRASANTHGROUP-4