Lecture 16-1 Smallpox

Poxvirus

pox = blistering skin lesions

Virion: Complex, ovoid or brick shaped
Largest known animal virus
Surface ridges or “tubules”
Internal core and lateral bodies

Genome: Linear double-stranded DNA molecule
Genome encodes for 150-250 different virus proteins

Variola Major

Ancient disease, mortality 10-30%

Variola Minor

less severe form, mortality 1%

Transmission

Humans only host, no resevoirs

>Aerosols
>Direct physical contact via vesicles
>Fomites (bedding and clothing)

Pathogenesis

Infection of the oropharynx via infected aerosols→ virus spreads to the regional lymph nodes → Asymptomatic primary viremia via infected monocytes/macro-phages on day ¾ → virus spreads to spleen, bone marrow, other lymph nodes, + small blood vessels of skin + oropharyngeal mucosa→ secondary viremia on day 8-12 after primary infection→ onset of clinical signs and symptoms →Vesicles on skin and oropharynx appear on day 14

Clinical disease

•Incubation period average 12-14 days, range 7-17 days

•Initial symptoms begin abruptly with fever (> 101F), headache, malaise, nausea, and vomiting
>Prodrome phase that appears before onset of rash, lasts 2-4 days, and person may be infectious

•Rash emerges as small red spots on tongue and in mouth, ~24 hours before appearance of rash on skin
>Lesions ulcerate fast→ release large # of virus into saliva
>Time during clinical disease when person is most infectious, lasts 4 days

•Rash appears on face as few macules → spreads to arms/legs→ hands/feet, → all parts of body in 24 hours (centrifugal distribution)

Rash day 3, macules → papules

Rash day 4, papules → vesicles fwith thick, opaque fluid that has infectious virus
>Vesicles often have depression in center (umbilication) (diff between chicken pox vs small pox)

•Fever rises again, remains high until scabs form on vesicles→ pustules
>Pustules are raised, round, and firm to touch, mature + reach max size by day 7-10

Rash day 10, pustules form a crust, and most scab over on rash day 14

•3 weeks after onset of rash, site of each lesion is depigmented and eventually becomes pitted scar due to destruction of sebaceous gland of skin

 •In fatal cases, death occurs between days 10-16
>Cause of death not clear, but may involve
1. Multiple organ failure due to immunopathogenesis
2. Over-whelming viremia and soluble virus antigens
3. Secondary bacterial infection and sepsis

Vaccine (Origin)

Variolation: traced to the Middle East, practice of injecting powdered smallpox scabs under the skin, intent was aesthetic

Vaccube

smallpox vaccine virus is called Vaccinia

Not the og cowpox or variola (smallpox), but a hybrid from mixing both during early vaccination programs

Multipuncture vaccine with bifurcated needle, vesicle → pustule events

HIGHEST rates of adverse reactions

Honorable Gentleman

1. Symptoms of smallpox are obvious so smallpox can be diagnosed without laboratory tests

2. Patients are most infectious for only a short time after initial clinical symptoms appear

3. There are no carriers/carrier states

4. An effective vaccine has been available for over 200 years (and it can be freeze-dried)

5. There is herd immunity to smallpox

Two repositories of smallpox in the world

Centers for Disease Control, Atlanta

Vector State Research Center for Virology and Biotechnology, Koitsovo (Siberia), Russia

Some countries didn’t participate in the WHO eradication program  (North Korea)

Should the lab virus be destroyed? [BONUS]

Pros:
•Prevent accidental release of virus from two isolation facilities
•Prevent terrorists from acquiring virus as an agent of biological warfare
•Entire genome has been sequenced + sequences now exist in plasmids for study

Cons:
•May need a reference virus if smallpox reappears (monkeypox?)
•Complete virus is needed for studying in detail its pathogenesis at molecular level
•Do not have the right to destroy a life-form and cause extinction of the smallpox virus

Bioterrorism

•Several areas of the large smallpox virus genome can be used for introduction of foreign genetic material

•Genetic material of Venezuelan equine encephalitis has been spliced into smallpox genome
>Venezuelan equine encephalitis virus invades the brain → severe headache/coma but not lethal

•Genetic material of Ebola virus has been spliced into smallpox genome to produce Ebolapox virus
>Stable chimera virus that replicates in culture and in animals
>Hemorrhagic smallpox (blackpox) without skin vesicles but severe internal hemorrhage invariably fatal as skin darkens