Exam 2 Info 2/2-2/21

Which 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

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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