23. Smallpox Flashcards
what causes smallpox?
dsDNA virus called variola
what was the first disease controlled by vaccination?
smallpox
what was the mortality of smallpox?
30%
what is the only disease to be completely removed from the environment?
smallpox
how is smallpox spread?
it is spread by secretions from the nose and mouth
close contact with person or their clothes is enough
how was smallpox used as the first bioweapon?
when colonising the americas the indigenous people were given blankets from small pox patients to remove them from the land
they were an immune naive population so it was deadly
how does small pox disease progress?
develop symptoms ~2weeks after exposure
feel sick and get a fever and aches
2-4 days later you develop a rash which develops into the small pox
- often confused with chickenpox
what is an identifying characteristic of smallpox?
the pox occuring on the hands and feet and the majority of pox on the arms and legs
why were photos taken of infected smallpox patients?
to educate people in what smallpox looks like
helped people identify cases and report them especially in places with less medical infrastructure
what is the Variola virus?
part of Poxviridae family of viruses
dsDNA virus
virus structure is complex and poorly understood
what other viruses are in the Poxviridae family?
vaccinia
monkeypox
Camelpox
cowpox
penguinpox
myxoma
what is the structure of the variola virus?
brick shaped with multiple envelopes
linear dsDNA about 180,000bp (very big)
over 150 genes identified
what does variola’s size mean?
it can be seen with a good light microscope
what is unique about variola’s replication cycle?
It replicates in the cytoplasm when most DNA viruses replicate in the nucleus to make use of host proteins
what enables variola to replicate in the cytoplasm?
it encoded its own RNA polymerase and DNA polymerase
what is the variola replication cycle?
- attachment
- entry and uncoating and the initation of transcription and translation of early genes like polymerases
- replication of DNA
- late mRNA and protein production
- Assembly of viral particle
- Maturation - passing through the cell membrane
- final release of the viral particle
what is the genome of variola?
linear dsDNA
what is unusual about the ends of the variola viral genome?
instead of free ends they are covalently closed in hairpin loops made from inverted terminal repeats
what are the places where the virus replicates in the cytoplasm called?
virus factories
where does most of our knowledge of variola come from?
studying the vaccina virus used to make the smallpox vaccine
what is the history of the smallpox vaccine - variolation?
Chinese/indian/persian cultures used variolation for a long time
lady montague brought it to the uk
still dangerous but had 2% mortality opposed to 30%
possibely safer due to route of infection
what is the history of the smallpox vaccine - Jenner?
jenner wasn’t the first to figure out the connection between smallpox and cowpox but was the one who proved it worked and promoted and published it.
started thinking about vaccines for other diseases
what is the immune response to smallpox?
Vigorous
cell mediated immunity = clearance and survival
humoral immunity = long term protection and prevent reinfection
cannot improve our understanding as we cannot research it
what is the criteria for a virus to be a good candidate for eradication?
- humans are the only host
- no sub clinical or latent form
- virus only 1 stable serotype
- easy clinical diagnosis
- only infectious when symptomatic
- very effective vaccine with protection lasting for at least 5 years
why was smallpox a good candidate for eradication?
- only infected humans
- no sub clinical form
- virus only 1 stable serotype
- easy clinical diagnosis
- only infectious when symptomatic
- very effective vaccine with protection for 5 to 15 years
why was smallpox a good candidate for eradication - easy diagnosis?
very obvious and unique symptoms
why was smallpox a good candidate for eradication - infectious when symptomatic?
can only transmit small pox when you have active and visible pox
How effective is the smallpox vaccine?
provides protection for 5-15 years
cannot be infected once vaccinated so you cannot transmit smallpox
Why is covid not a good candidate for eradication?
- zoonotic
- has latent forms
- multiple strains
- non distinctive symptoms
- asymptomatic transmission
- vaccine doesn’t prevent infection
what was the twofold strategy use to eradicate smallpox?
- mass vaccination
- rapid identification of cases and contact tracing
when was the last natural case of smallpox?
1977
when was the world declared smallpox free?
1980
why wouldn’t a vaccine like the smallpox one be used today?
the complication rate of the vaccine was very high and in the absence of smallpox this would be unacceptable
how did smallpox escape from a lab?
containment labs are not perfect due to human error
why was all the smallpox destroyed?
it was deemed to dangerous to keep in containment labs as it kept escaping and the population immunity was waning
what is the virus used in the smallpox vaccine?
vaccinia
(not variola or cowpox)
why was vaccinia used for the vaccine?
it is related to variola but rarely causes fatal infections
why are we still studying the smallpox vaccine virus?
it makes a large number of genes that can modulate the immune response by preventing interferon signalling or complement function.
it can be genetically modified to express foreign genes
what is controversial about still using vaccinia virus in vaccines?
there are conflicting reports of safety with some strain reverting back to more pathogenic phenotypes
what happened with the M8 vaccinia vaccine strain?
normally is slow growing and less dangerous producing a small plaque phenotype
a small number of colonies reverted back to more pathogenic large plaque phenotypes
they idenified the gene and so they could completely delete it rather then rely on mutations
what is a problem with the vaccinia vaccine?
the vaccine was only deployed when smallpox was mostly eradicted so we don’t know the full effects of it
what does the BR5 vaccinia gene do?
helps the virus acquire lipid envelopes during maturation
where is variola currently held?
CDC in atlanta
koltsovo in russian federation
only a few labs in the world are equipped to work with it
why do we still need live variola?
to develop better vaccines
to develop antiviral drugs
should we destory all the stocks of variola?
yes and no
Pathogenesis is still not understood and we could gain useful knowledge
further study could lead to escape and terror threats
smallpox and bioterrorism
there is s possibility it could be used to terrorism
most populations are unvaccinated now
countries have started stockpiling vaccines
why is the emergence of monkeypox a concern?
shows the need for more research into this group of viruses
current effect vaccine but still high hospitalisation rates
