Studied by 1 personWhich virus family is variola in?
Poxviridae
What are some other members of the poxviridae family?
Vaccinia virus, cowpox, mpox
What type of virus is chickenpox?
Herpes
What is the genome of variola?
Single linear double-stranded DNA
Approximately how many genes does the variola genome encode?
200
Where does variola replicate?
Cytoplasm
Which forms of variola are infectious?
Enveloped and non-enveloped
Variola Minor
Fewer systemic symptoms
Variola Major
More severe symptoms
What are the two strains of variola?
Variola minor and variola major
Who are the only natural hosts of variola?
Humans
How does variola virus most commonly spread?
Direct contact
What is a less common way variola spreads between people?
Aerosol route
How long after exposure do symptoms of smallpox develop?
12-14 days
What are the initial symptoms of smallpox?
High fever, malaise, headache, and backache
When do the infamous small bumps start to occur and how and when do they change?
Become pus filled within 1-2 days
Crust over after 8-9 days
Contagious for 2+ weeks
What are some complications of smallpox?
Disfiguring marks on skin, bacterial superinfection of skin and organs, pneumonia, sepsis, arthritis
How do lesions of smallpox spread?
Trunk → limbs → head
What are the five types of variola major?
Ordinary, modified, malignant/flat, hemorrhagic, variola sine eruption
What are the characteristics of ordinary variola major?
90% of cases in unvaccinated people
What is the fatality rate with ordinary variola major
30%
What are the characteristics of modified variola major?
Produces fewer, smaller, and more superficial lesions
2% of unvaccinated people, 25% of vaccinated people
What is the fatality rate of modified variola major?
Rare
What are the characteristics of malignant/flat variola major?
Flatter lesions, evolved slower, coalesced
7% of cases in unvaccinated people
What is the fatality rate of malignant/flat variola major?
97%
What are the characteristics of hemorrhagic variola major?
Rash accompanied by bleeding into mucous membranes and skin
Less than 3% of cases
What is the fatality rate of hemorrhagic variola major?
100%
What are the characteristics of variola sine eruptione?
Occurs in previously vaccinated contacts or infants with maternal antibodies
Asymptomatic or had short-lived fever, headache, and flu-like symptoms
No documented transmission
What is the fatality rate of variola sine eruptione?
No data
What is cowpox?
An infectious cattle disease
How does cowpox present in cows and horses?
Production of smallpox-like skin lesions and swollen lymph nodes
Who can contract cowpox?
People in close contact with cows (ex. milkmaids, farmers)
When transferred to humans, how did cowpox present?
Created painful skin lesions, but not fatal disease
Which disease did cowpox provide immunity against?
Smallpox
Edward Jenner (1796)
Tested cowpox as a vaccine for smallpox
What did the steps Edward Jenner took to infect a child with cowpox?
Took a lesion from a milkmaid and used it to infect 8 year old James Phipps, who developed mild cowpox
6 weeks later, Jenner exposed James to smallpox
James did not develop smallpox and a vaccine was created
Why does Jenner get all the credit?
He was the first to publicize his finding
Why was smallpox so easy to eradicate?
It only infects humans, no animal reservoir
What type of infection does variola not cause?
Latent or persistent
What was the benefit of smallpox being so recognizable?
Once, it is identified, contacts can be treated
Why was the smallpox vaccine so effective?
Easily delivered by minimally-trained personnel, highly effective at low doses
How does a single dose of smallpox vaccine do for protection?
Leads to long-term protection
How easily can the smallpox vaccine be mass produced?
Very, does not need to be refrigerated, transported dried
When did parts of Europe eradicate smallpox?
By 1900
When was the smallpox vaccine created?
1950
How did the vaccine lead to quick eradication of smallpox?
It was heat stable and freeze dried
When did the World Health Assembly call for the eradication of smallpox?
1958
How was smallpox controlled prior to 1967?
Mass vaccination
Why was mass vaccination not the ideal way to eradicate smallpox?
It was inefficient and logistically complex
Within how many days can smallpox vaccination prevent smallpox?
1-3
Vaccination makes the disease severity of smallpox shorter by how many days?
4-7
What other public health measures can be taken to contain smallpox?
Isolation, containment, targeted vaccination
What is Dryvax? (availability, company, main ingredient)
Commercially available
Made by Wyeth Pharmaceuticals
Vaccinia grown on the skin of calves
How is the smallpox vaccine delivered?
Via 15 pokes with a bifurcated needle to the upper arm
When was the Dryvax vaccine discontinued?
2008
What did the World Health Assembly do in 1948 (smallpox)?
Formed a study group
What did the World Health Assembly do in 1958 (smallpox)?
Called for global eradication
What did the World Health Organization do in 1959 (smallpox)?
Launched the Smallpox Eradication Program
How did the progression of smallpox become eradicated around the globe?
Europe, South America, West and Central Africa, Asia, East Africa
When and where was the last case of smallpox diagnosed and treated?
1977, Somalia
When did the WHO declare smallpox to be eradicated?
1980
What is the only human disease to be eradicated?
Smallpox
What attributes of smallpox make it an attractive agent for biological warfare?
Highly contagious via person to person transmission
No widely available treatment or cure
High fatality rate
Low levels of immunity in the present day population
Stable as an aerosol
Low infectious dose
Where are the last known stick of variola virus stored?
Atlanta and Moscow
Lab accident involving smallpox
Happened in 1978 UK, lab worker died, PI died by suicide, hundreds of people were put under quarantine
ACAM2000/Imvamune/Imvanex and APSV (Aventus Pasteur Smallpox Vaccine)
Replication competent smallpox vaccines
Live attenuated viruses set up a limited infection
Produces immunity with one dose
Cannot be used in immunocompromised patients
Vaccination site needs to be covered
Jynneos
Replication deficient smallpox vaccine
Can be used in immunocompromised individuals
Delivered as two doses, separated by four weeks
Where does malaria come from?
Mosquitoes
How many people died from malaria in 2022?
627,000
What types of people are more susceptible to malaria?
Pregnant women and children
What type of parasites cause malaria?
Protozoan
What is the genus of the protozoan parasites?
Plasmodium
What are the five species of plasmodium which cause malaria in humans?
P. falciparum
P. vivax
P. ovale
P. malariae
P. knowlesi
P. flaciparum
Causes the most severe forms of malaria
P. vivax
Mild to moderate malaria symptoms
P. ovale
Mild to moderate malaria symptoms
P. malariae
Mild malaria
P. knowlesi
Most commonly affects NHP’s, but can cause severe disease inhumans when transferred
How is immunity created with malaria?
Over time
How does plasmodium stay hidden from the immune system?
Susceptibility to drugs is reduced, parasites are amplified with each host, cycles between mosquito and vertebrate hots
What are the symptoms of malaria?
Profuse sweating
Vomiting
Diarrhea
Anemia
Convulsions
Bloody stools
Muscle pain
How long is the incubation period for blood stage parasites
7-30 days
“Uncomplicated” malaria
Attacks last 6-10 hours
Flu-like symptoms
Weakness and mild jaundice
“Complicated” malaria
Cerebral malaria - CNS symptoms
Severe anemia and hemoglobinuria
Coagulation disorder
Low blood pressure
Kidney injury
Acute respiratory distress syndrome (ARDS)
Disease is severe in pregnant women and preterm birth
Why are adults less susceptible to malaria than children?
Repeated exposures to Plasmodium leads to immunity
Where is malaria most severe?
South America, Africa, and Southeast Asia
How much of the world’s population lives in malaria endemic regions?
50%
Where does the earliest evidence of human malaria come from?
Clay tablets in Mesopotamia and Egyptian mummies
What do Indian writings refer to malaria as?
“King of disease”
How did Chinese mythology explain malaria?
Three demons:
One with a hammer - headaches
One with a pail of water - chills/sweating
One with a stove - fever
Which two Greek philosophers mentioned malaria in their works?
Homer and Hippocrates
Why did malaria become more severe in Rome’s classical era
Ecological changes - increased deforestation, agriculture, introduction of non native mosquitoes
Before Germ Theory, what was malaria associated with?
Swamps and marshes
What is the entomology of malaria?
Mal - bad
aria - air
How did the pre Germ Theory world deal with malaria?
Drained swamps and wetlands
Who discovered Plasmodium as the cause of malaria?
Charles Lavern
How can malaria be prevented?
Appropriate clothing
Bed nets, especially insecticide treated nets
Limiting activity when mosquitoes are biting (night)
How were adult mosquitoes killed post germ theory?
DDT, whcih left lots of ecological damage
What was the first antimalarial compound to be isolated as a treatment?
Quninine
What is the current main-line antimalarial used today?
Artemisinin
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