Class 8A: Biological agents of terrorism and warfare

Question 1

What is bioterrorism?

Answer 1

Bioterrorism is the malevolent use of bacteria, viruses or toxins against
humans and animals in an attempt to cause harm and fear.

Question 2

Why use biological weapons?

Answer 2

• cheap and easy to make compared to nuclear and chemical weapons
• point of release is typically unknown = “silent” (escape easy)
• very contagious = spreads very effectively
• causes significant and widespread panic

Question 3

What are the characteristics of an ideal bioterrorism agent? (3)

Answer 3

Accessibility,
Durability, and
Infectiousness

Question 4

How are bioterrorism agents ranked?

Answer 4

Agents are ranked on a scale of A-C by Centre for Disease Control

Based on perceived threat

Question 5

Name two examples of A category agents.

Answer 5

Anthrax and Smallpox

Question 6

Bioterrorism in History:

Plague example

Answer 6

1346: Tatars catapulted plague victims over walls of the black sea city of Kaffa
- Black Death almost wiped out half of Europe!

WWII: Japanese attempted to infect
Chinese by dropping plague-infected
fleas onto them
-inefficient & unpredictable!

Question 7

Bioterrorism in History:

Smallpox example

Answer 7

1763: Sir Jeffery Amherst commissioned the use of smallpox-infected
blankets to wipe out the Native Americans

Question 8

Bioterrorism in History:

Anthrax example

Answer 8

• Germans infected cattle destined to be consumed by allied forces with
  anthrax

-The Russian bioweapons program, Biopreparat, produced aerosolized forms of
anthrax
-50kg was estimated to be able to kill 36,000 and infect about 100,000
people!
-an “accident” in the facility in 1970s led to ~100 deaths downstream of the
facility

Question 9

Describe Bacillus anthracis.

Answer 9

-gram-positive bacterium

-forms stable endospores when
nutrients are limited

• long-lived
• resistant to destruction/environment
• ability to cause lethal infections

Question 10

In Bacillus anthracis, what is the infectious particle?

Answer 10

The spore is the infectious particle.

Question 11

Bacillus anthracis spores:

Name 3 main clinical forms of disease caused by anthrax.

Answer 11

Cutaneous anthrax

Gastrointestinal anthrax

Inhalational anthrax

Question 12

Describe cutaneous anthrax.

Answer 12

One of the 3 main clinical forms of disease caused by anthrax

Cutaneous anthrax
-most common

• contact with spores or infected animals – entry through cuts in hands
• ulceration of skin that clears without scarring – antibiotics recommended

Question 13

Describe Gastrointestinal anthrax.

Answer 13

One of the 3 main clinical forms of disease caused by anthrax

Gastrointestinal anthrax
-ingestion of spore-contaminated meat

• bloody stools, massive edema and abdominal pain
• mortality is very high = shock and blood/fluid loss

Question 14

Describe Inhalational anthrax.

Answer 14

One of the 3 main clinical forms of disease caused by anthrax

Inhalational anthrax
-rare

-aerosolized spores are inhaled

-spores reaching the alveoli are engulfed by macrophages and transported
to lymph nodes where replication occurs

• flu-like symptoms, extensive internal hemorrhage, meningitis
• very high mortality = fatal unless treated very early on

Question 15

What is the most common clinical disease caused by anthrax?

Answer 15

Cutaneous anthrax

Question 16

What is the clinical disease caused by anthrax that results in bloody stools, massive edema, and abdominal pain?

Answer 16

Gastrointestinal anthrax

Question 17

An individual is showing flu-like symptoms, extensive internal hemorrhage and meningitis. What clinical form of disease caused by anthrax does this patient have?

Answer 17

Inhalational anthrax

Question 18

What category is anthrax in?

Answer 18

Category A of the list of Priority Biological Agents of the CDC

= highest priority research

Question 19

What is involved in the process of “weaponization” of anthrax?

Answer 19

“weaponization” of anthrax: drying and milling the spores to a size that reaches deep into the lungs and remains airborne longer

-anthrax does not spread from person to person

-rapid progression to death means that antibiotics and vaccine
supplies critical

Question 20

Does anthrax spread from person to person?

Answer 20

No, anthrax does not spread from person to person

Question 21

What is the top choice for germ warfare? Why?

Answer 21

Anthrax

top choice for germ warfare!

• concern due to the ease of manufacture and dissemination
• dissemination could be as high tech as missiles, aerial bombs or as low tech as the mail! –> 2001 in the USA

Question 22

What does the virulence of f B. anthracis depend on?

Answer 22

the presence of its 2 large plasmids

1. Plasmid pXO2 –> genes for the capsule
2. Plasmid pXO1 –> toxins

Question 23

Bacillus anthracis virulence:

What does Plasmid pXO2 contain?

Answer 23

genes for the capsule

Question 24

Bacillus anthracis virulence:

What does Plasmid pXO1 contain?

Answer 24

toxins

1. Edema toxin –contains edema factor (EF) which is a calmodulindependent
   adenylate cyclase –> increases cAMP levels –> upsets cellular water balance
2. Lethal toxin –contains lethal factor (LF) , a zinc metalloprotease which inactivates many cytosolic enzymes including MAPK.
3. Protective antigen (PA) – mediates cell entry of LF & EF

Question 25

An Anthrax attack

Answer 25

Soon after 9/11, anthrax-laced mail was sent to various recipients in the US -17 were sickened and 5 people died - The FBI investigation involved: - more than 10,000 witness interviews on six different continents - recovery of more than 6,000 items of potential evidence - in the process, new scientific breakthroughs occurred which have changed the way such investigations will happen in the future

Question 26

How is Anthrax treated?

Answer 26

Antibiotics = penicillin, tetracycline, erythromycin, and ciprofloxacin (Cipro). -Inhalational anthrax requires infusion of antibiotics continuously! Military Vaccine Agency of the US has an FDA approved effective vaccine -only available to the military and “at risk” individuals (until now) -still used in conjunction with antibiotics if an “attack” were to occur -has been linked to “Gulf war syndrome” -multi-symptom rheumatic disorder in veterans of the 1990-1991 war -The August 2002 article is entitled "Antibodies to Squalene in Recipients of Anthrax Vaccine" (Exp. Mol. Pathol. 73,19-27 (2002)).

Question 27

Plague Throughout history...

Answer 27

–Multiple plague pandemics in history -The Black Death; in ~1346; killed 30 million in Europe! –Controlled through the use of antibiotics and rodent transmission - ~2000 cases/year worldwide (WHO, 2016)

Question 28

What is plague caused by?

Answer 28

Caused by a bacterium: Yersinia pestis - gram negative bacterium (Coccobacillus) - many virulence factors that are anti-phagocytic and anti-inflammatory - also a lipopolysaccharide endotoxin

Question 29

How do humans become infected by plague?

Answer 29

A zoonotic infection of rodents -rats are the animal reservoir and is transmitted between them by the bite of their fleas -humans become infected when fleas bite them after biting an infected rodent

Question 30

Plague: Within the body

Answer 30

–Bacteria migrate to the lymph nodes –Associate with mononuclear cells and multiply -swelling = bubo =bubonic plague –fever, chills, bubos –migration to the lungs = pneumonic plague - Can also get primary pneumonic plague by direct inhalation of bacteria - symptoms similar to pneumonia –disseminate to the bloodstream = septicemic plague -black lesions on fingers and toes = Black death

Question 31

Plague as a bioterror agent

Answer 31

–Contagious =pneumonic form; spreads easily from human to human –Stable -up to 1 hour in aerosolized form –Highly infective - 100-500 organisms can cause significant infection –High mortality =100% for pneumonic form –Public panic –Difficult to diagnose quickly; e.g. pneumomic plague would manifest as pneumonia -if treatment is not started within 24 hours of infection, mortality =100%

Question 32

A more recent example of plague

Answer 32

13th April 2010 -6.9 magnitude earthquake in Qinghai province -plague endemic in this region spread by marmots = a burrowing rodent -marmots could spread Y. pestis to humans huddled in shelters -through flea bites -marmot hunting for pelts is prevalent -Researchers cordoned off marmot burrows that were found to be Y. pestis infested

Question 33

Plague: treatment

Answer 33

–Treated with antibiotics such as streptomycin, gentamicin, tetracyclines -must be administered early in infection or prophylactically -Quarantine

Question 34

What is smallpox caused by?

Answer 34

–Smallpox is caused by an orthopox (DNA) virus = variola virus

Question 35

When was the last naturally occurring case of Smallpox?

Answer 35

-last naturally occurring case was in 1977 in Somalia - WHO declared the disease eradicated in 1980 - vaccination discontinued since then - original vaccine was live vaccinia (related virus) - the world is no longer immune to the virus

Question 36

What is smallpox disease characterized by?

Answer 36

–Disease is characterized by disfiguring skin eruptions, fever and a high rate of mortality -antivirals are not all that effective -vaccination is the best protective measure -rapid isolation would be required of infected individuals

Question 37

Where are the last remaining repositories of the smallpox virus?

Answer 37

–The last remaining repositories of the virus are at the CDC in the US and the Institute of Virus Preparations in Russia. -some stocks may be available to countries split off from Russia -WHO controls the reserves of freeze-dried vaccine

Question 38

Smallpox: Why would bioterror attacks using aerosolized variola be very detrimental?

Answer 38

–Bioterror attacks using aerosolized variola could be very detrimental - 30% mortality associated with disease - very rapid person-to-person transmission - difficult to tell apart from chicken pox in early (contagious) stages

Question 39

How is smallpox transmitted?

Answer 39

Person-to-person

Question 40

In a case of a smallpox attack, what would be necessary?

Answer 40

–In case of an attack, rapid isolation, contact tracing of individuals and rapid vaccination of health care providers and the general population would be necessary -Are governments really prepared for such a scale of action?

Question 41

Viral Hemorrhagic fevers How can hemorrhagic fever viruses be contracted?

Answer 41

bite of a mosquito, animal excrement or contact with infected animals or humans

Question 42

What are some examples of Viral Hemorrhagic fevers?

Answer 42

Examples are Ebola, Marburg, Lassa, Junin and Machupo –All these HF viruses were developed as bioweapons in Russia and US until the mid-1990s -would have been used in an aerosolized attack - Lack of humoral response in those infected - require good antivirals = seriously lacking!

Question 43

What is Botulinum toxin?

Answer 43

Most potent toxin known to man! Made by the spore-forming microbe, Clostridium botulinnum

Question 44

How does Botulinum toxin function?

Answer 44

Acts at neuromuscular junctions to prevent release of acetylcholine - a neurotransmitter that stimulates muscle contraction - leads to paralysis, eventually respiratory paralysis

Question 45

What is the common name for Botulinum toxin?

Answer 45

BoTox! | BoTox only contains about 0.3% of the lethal inhalational dose

Question 46

Where is the spore-forming microbe, Clostridium botulinnum, found?

Answer 46

–C. botulinnum is ubiquitous in soil and very easy to culture - easy to purify toxin - 0.7 to 0.9μg inhaled is sufficient to kill a 70Kg human!