Lecture 29

Question 1

Biological Warfare:

1. What is an example of accidental use of pathogens?
2. Intentional use:
   
   1. What happened in 1763?
   2. What happened in 1775?
   3. What happened in 1917-18?
   4. What happened in 1932-45?
   5. What happened in 1944-45?
   6. What happened in 1943-68?

Answer 1

1. 1500’s Spanish invasion of the New World, smallpox, influenza, measles. 56 million native people were killed, no immunity to pathogens presented by Europeans.
2. Intentional use:
   
   1. Smallpox spread through blankets given to Native Americans by British military. Spread to the North and West inflicting the Sioux and Plains Indians, crossed the Rockies and infected California Natives.
   2. British military forced people sick with smallpox tointeract with soldiers of the Continental Army. The illness and deaths weakened the US undeoendence movement and lead George Washington to institute a vaccination program.
   3. Anthraz and other agents used by German military in Russia.
   4. Smallpox, plague, anthrax and other agents used by Japanese military in China.
   5. Various agents used by German military.
   6. Development by U.S. of offensive weapons based on various agents; not used.

Question 2

Intentional use continued:

1. What happened in 1940s-2000?
2. What happened in 1979?
3. What happened in 1984?
4. What happened in 1995?
5. What happened in 2001?

Answer 2

1. Development of offensice weapons based on various agents, including enhanced and bi-engineered agents, by Soviet government.
2. 1 gram of anthrax spores was accidentally released from a biological weapons facility in Sverdlovsk, Russia; dispite quick immunizations and antibiotic therapy, 77 cases of “pulmonary anthrax” with 66 deaths.
3. Oregon “cultists” sprayed salad bars with Salmonella, 751 cases of food poisoning.
4. Tokyo, Japan, radical political group release sarin gas into the subway system, many injuries and several deaths.
5. Anthrax in the U.S.; unknown individuals sent weaponized anthrax spores through the U.S. mail.

Question 3

1. What are catagory A agents?
2. What are three important characteristics of a biowarfare agent?

Answer 3

1. Those with the highest potential to be effective biological weapons. Anthrax, Botulism, Plague, Smallpox, Tularemia, Viral hemorrhagic fevers.
2. Important Characteristics:
   
   1. Easy to produce and deliver
   2. Safe for use by the offensive forces/individuals.
   3. Able to kill or incapacitate effectively.

Question 4

1. Why is it called smallpox?
2. What impact has it had on the world?
3. What is its mortality rate?

Answer 4

1. Latin “pox” for “spotted” and refers to the raised bumps that appear on the face and body of an infected individual.
2. Feared for many centuries in all parts of the world, with good reason, as one of the most highly communicable and devastating disease known to humanity.
3. 30% mortality, and 65-80% of survivors are marked with deep pitted facial scars. In the 1700’s, smallpox killed 400,000 people each year in Europe and accounted for one-third of all instances of blindness. 300-500 million deaths in the 20th century.

Question 5

1. What is the causative agent of smallpox?
2. What are they pathogens of?
3. What are the two clinical forms of smallpox?

Answer 5

1. Variola virus, an enveloped DNA virus, a member of the genus Orthopoxvirus, of the family Poxviridae.
2. The Poxviridae are pathogens of cattle, humans and many other vertebrates. Vaccinia virus (vacca, cows, rodents; disease, cowpox) and variola virus (humans; disease, smallpox)
3. Variola major: 10-30% mortality in unvaccinated individuals; Variola minor: 1% mortality in unvaccinated individuals.

Question 6

1. Describe the morphology of the smallpox virus.
2. What kind of DNA does it have?
3. How many nucleotides does its genome contain?
4. Where does the virus replicate?

Answer 6

1. Brick-shaped, 200 nm in diameter, 250-300 nm long, 250 nm high. Core is biconcave with two lateral bodies.
2. One molecule of linear double stranded DNA.
3. Genome of vaccinia, a related virus, length is 185,000 nucleotides; virions contain 4% lipid.
4. Variola replicates in the host cell cytoplasm; virus particles carries into host cell viral DNA and several viral-encoded proteins, and all proteins expressed once infection has begun are viral-encoded. Shuts off cell’s genes.

Question 7

1. What is the incubation period of smallpox?
2. When do its initial symptoms occur?
3. When does the early rash form?

Answer 7

1. 7 to 17 days following exposure - not contagious may not have any symptoms and may feel well.
2. 2 to 4 days - sometimes contagious (prodrome stage). First symptoms appear: fever, tiredness, head and body aches, and sometimes vomiting. Fever is usually high (101-104 degrees F), usually too sick to be active.
3. About 4 days - most contagious.
   
   1. First as small red spots on the tongue and in the mouth that develop into sores that break open and spread large amounts of the virus into the mouth and throat, highly contagious.
   2. Then, a rash appears on the skin, starting on the face and spreading to the arms and legs and then to the hands and feet, spreading to all parts of the body usually withing 24 hours.
   3. By the third day of the rash, the rash becomes raised bumps that by the fourth day, fill with thick, opaque fluid and often have a depression in the center that looks like a bellybutton, a mjor distinguishing characteristics of smallpox.

Question 8

1. How long does the Pustular Rash of smallpox form?
2. Pustules and Scabs?
3. Resolving scabs?
4. Scabs resolved?

Answer 8

1. About 5 days - contagious. The bumps become pustules: sharply raised, usually round and firm.
2. About 5 days - contagious. The pustules begin to form a crust and then scab; most of the sores have scabbed over by the end of the second week.
3. About 6 days - contagious. Scabs begin to fall off, leaving marks on the skin that become pitted scars, most scabs fall off by three weeks after the rash appears, contagious until all the scabs have fallen off.
4. Non contagious! Many smallpox survivors have permanent scars over large areas of their body, especially the face. Some are left blind. The outcome is either death or recovery with immunity. The virus does not persist in the body after recovery.

Question 9

1. Is smallpox highly contagious to some other viral disease?
2. What is the usual rate at which it is spread?
3. Why does it not spread to as many people?

Answer 9

1. No it is not. Measles and influenza are more contagious.
2. In past smallpox outbreaks, each infectious person is thought to have infected 5 to 6 susceptible close or household contacts, but not casual or brief contacts. At this rate, approx. 3000 people would be infected by the fifth generation of infection.
3. The long asymptomatic (and non-contagious) incubation period gives substantial time for public health workers to contain and stop an outbreak.

Question 10

1. Are humans the only natural hosts of the variola virus?
2. How is the disease transmitted?

Answer 10

1. Yes!
2. Transmission:
   
   1. Direct (within 6-7 feet) and fairly prolonged (approximately 3 hours) face-to face contact with someone who has smallpox (usually someone who already has a smallpox rash). Most people become infected with smallpox in the past through close, intimate, or household contact with symptomatic (with rash) smallpox patients. S person can be exposed to someone who has smallpox and not become infected.
   2. Direct contact with infected bodily fluids or contaminated objects. e.g., bedding, clothing containing the virus.
   3. Exposure to an aerosol release of smallpox. Rare. Smallpox can be spread by virus carried in the air in enclosed places such as buildings, buses, and trains. However, the smallpox virus is fragile and is killed by UV radiation and heat. Lab test show that 90% of aerosolized smallpox virus dies within 24 hours; in the presence of sunlight, killing would be faster.

Question 11

1. Is there treatment available for smallpox?

Answer 11

1. No proven treatment is currently available. However, new antiviral agents, such as cidofovir, which may be effective against the smallpox virus, are being tested. Also, supportive therapy, i.e., intravenous fluids, medicine to control fever or pain, and antibiotics against secondary bacterial infections, may be helpful.

Question 12

1. How can smallpox be prevented?
2. How effective is vaccination within 3 days of exposure? What about 4 days?
3. What is the origin of the vaccination?

Answer 12

1. Infection by live vaccinia virus (cowpox virus) confers cross-immunity; used for vaccination. Vaccinia vaccine can be completely protective if given before exposure to smallpox.
2. Will prevent or greatly lessen the severity of smallpox in most people.
   
   1. Offers some protection or can decrease severity. Once rash is evident, vaccination does not help.
3. Variolation
   
   1. Edward Jenner - Physician, 1796
   2. Benjamin Jesty - farmer, 1774
   3. Cowpox, milkmaids immune to smallpox, vacca = cow. Cross immunity in poxviridae.

Question 13

1. Why were vaccination strategies made?
2. What is the first strategy?

Answer 13

1. To eradicate smallpox globally, WHO carried out a program from 1966-1977. Close monitoring of incidence of the disease, quarantining of infected person, and an aggressive vaccination effort.
2. Mass vaccination (1966) - The smallpox vaccine was given to large numbers of people who had not been exposed to smallpox. Helped protect people from smallpox, but it did not completely stop the disease. Not every got vaccinated, and those who did not were able to catch and spread the disease.

Question 14

1. What is the second vaccination strategy?

Answer 14

1. Ring vaccination (started in 1967):
   
   1. This strategy involved finding people who were exposed to an infected person and giving the vaccine to the exposed person and those people he or she had been in contact with.
   2. To create a “ring” of vaccinated people around the people who were infected with smallpox. Ring vaccination strategy proved to be a highly effective vaccination strategy; it worked to completely get rid of the disease. Last naturally occuring Variola major was in 1975, last Variola minor was in 1977.

Question 15

1. What does the vaccine contain?
2. How was the vaccine derived?

Answer 15

1. It contains live vaccinia virus, a “pox”-type virus related to smallpox. So, the smallpox vaccine cannot give you smallpox. Standard potency vaccine (Dryvax) contains a relatively low pathogenicity vaccinia virus.
2. Derived from calf lymph, and currently licensed in the U.S., is a lyophilized, live-virus preparation of infectious vaccinia virus.

Question 16

1. What are the four features that made smallpox an easier eradication than other viruses?

Answer 16

1. Four features:
   
   1. Variola virus infects humans only; there are no animal reservoirs.
   2. The characteristic rash identifies an infected person.
   3. Infected individuals are not infectious during the fairly long incubation period, giving time for quarantine procedures to be implemented.
   4. Vaccine mode from cowpox (vaccinia) virus is very effective in conferring immunity (cross immunity) against variola.

Question 17

1. Why not vaccinate everyone, the why it was done in the past?

Answer 17

1. Expense - manufacture of the bifurcated needles, preparation of the vaccine, testing, distribution, vaccination programs, etc., are expensive.
2. Significant Risk - mild adverse reactions to vaccination in many people, not recommended for people with skin conditions, heart disease, or are pregnant, or those with reduced immune competence; and 1/1000 develop severe complications, with 1 or 2/1,000,000 deaths.
3. Virus no longer found in nature, so risks and expense outweigh possible benefits of vaccinating the entire population.
4. More than 2.4 million people have been vaccinated with smallpox vaccine since December, 2002.

Question 18

Are there any stocks of the virus left?

Answer 18

Yes, there are currently two known stocks in highly secured biomedical research labs, one in Russia, the other in the United State. They are kept for research. People fear that they will be stolen for biowarfare or terrorism. However, the WHO has decided to not destroy these stocks.