Smallpox (Variola Virus)
- Smallpox is a life-threatening, acute, eruptive, contagious disease caused by variola virus.
- The disease is characterized by a febrile prodrome followed by the development of rash.
- Rash evolves in a characteristic fashion: macules → papules → vesicles → pustules; scabs form and fall off, leaving scars called pockmarks.
- There are two clinical forms of smallpox:
- Variola minor is a less common and less severe form of disease.
- Variola major is the more common and serious form of disease, of which there are five types.
- Ordinary smallpox
- Modified smallpox
- Flat smallpox
- Hemorrhagic smallpox
- Variola sine eruptione
- The last documented case of endemic smallpox was in Somalia in 1977.
- The last case in the United States was in the late 1940s.
- Smallpox was declared eradicated by the World Health Organization in 1979.
- Historically, in unvaccinated individuals, ordinary smallpox accounted for 90% of cases, hemorrhagic smallpox for 7% of cases, and flat and modified smallpox for the remainder.
- Modified smallpox was rare in unvaccinated individuals but accounted for 25% of cases of disease in vaccinated individuals.
- Prior to 1972, all U.S. children were vaccinated.
- Vaccines were produced from the vaccinia virus, a closely related orthopoxvirus to variola.
- Historically, the vaccine was prepared from virus grown on the skin of animals, and in some cases, the vaccine was contaminated with animal proteins, bacteria, and other viruses.
- Newer smallpox vaccines are developed from vaccinia clones grown in tissue culture and therefore are free of contamination from bacteria and other viruses.
- Due to concern for use of smallpox as an agent of bioterrorism, the U.S. Strategic National Stockpile still stores smallpox vaccine.
- The only currently U.S. Food and Drug Administration (FDA)-licensed smallpox vaccine, ACAM2000 (which replaced Dryvax®), is used for active immunization of persons determined to be at highest risk for infection.
- The Advisory Committee on Immunization Practices (ACIP) recommends smallpox vaccination for the following:
- Public health response teams responsible for investigating suspected smallpox cases
- Hospital-based health care teams responsible for assessing and caring for suspected smallpox cases
- Laboratory personnel who work with the virus that causes smallpox or other viruses similar to it
- Vaccine efficacy
- 95% efficacious in preventing disease if given prior to exposure
- May prevent smallpox or decrease severity if given 1 to 3 days after exposure
- May decrease severity of disease if given 4 to 7 days after exposure
- Vaccination is estimated to provide protective immunity for 3 to 10 years but may decrease the severity of disease for 10 to 20 years.
- Vaccine administration
- A skin abrasion is created using a bifurcated needle dipped in vaccine.
- The vaccinia vaccine is a live vaccine; thus the vaccine site should be loosely covered to prevent the spread of virus to others.
- After 3 to 4 days, a red pruritic papule appears at the vaccination site, which evolves into a vesicle followed by a pustule; after a few weeks, a scab forms, which then falls off leaving a scar.
- Contraindications to vaccine:
- Atopic dermatitis or exfoliative skin disorder
- Pregnancy or breastfeeding
- Close contact of someone who is pregnant, immunosuppressed, or has skin disease
- Allergy to vaccine component
- Moderate or severe acute illness
- Inflammatory eye disease
- Heart disease (myocardial infarction, stroke, cardiomyopathy, heart failure, or angina) or ≥3 risk factors for heart disease
- Age <1 year
- These contraindications may be reevaluated if smallpox is reintroduced into the population.
- Common adverse reactions to vaccination:
- Fever, swelling, lymphadenitis, and headache are seen in 2–16% of adults receiving the vaccine for the first time.
- A mild rash occurs in ~8% of cases.
- Less common vaccine reactions:
- Vaccinia keratitis and/or vision loss
- Accidental inoculation with blister formation
- Moderate to severe generalized rash
- Eczema vaccinatum
- Congenital or generalized vaccinia
- Progressive vaccinia/vaccinia gangrenosum
- Bacterial superinfection
- The virus infects the upper respiratory tract and replicates; rarely, primary infections can occur via skin, conjunctival, or placental routes.
- The virus enters the bloodstream (primary viremia) and is taken up by macrophages.
- Patient is asymptomatic during this time.
- Next, the virus enters the reticuloendothelial system where it continues to replicate.
- Secondary viremia occurs as the virus reenters the bloodstream and infects organs.
- Can cause epidermal necrosis and swelling
- Infections of the bone marrow, kidneys, liver, lymph nodes, spleen, and other organs result in coagulopathy and multiorgan system failure.
- Exact mechanisms of viral toxicity are not understood but may involve both viral cytopathic effects and inflammatory pathology.
- Variola virus is a member of the poxvirus family and Orthopox genus.
- Variola is a double-stranded DNA virus most commonly transmitted during face-to-face contact via respiratory aerosols or direct contact with infected skin lesions.
- Transmission of the virus via air in enclosed settings or via infected fomites is uncommon.
- Humans are the only vectors.
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