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BIOD29 > Class 8A: Biological agents of terrorism and warfare > Flashcards

Class 8A: Biological agents of terrorism and warfare Flashcards

1
Q

What is bioterrorism?

A

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

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2
Q

Why use biological weapons?

A
  • 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
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3
Q

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

A

Accessibility,
Durability, and
Infectiousness

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4
Q

How are bioterrorism agents ranked?

A

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

Based on perceived threat

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5
Q

Name two examples of A category agents.

A

Anthrax and Smallpox

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6
Q

Bioterrorism in History:

Plague example

A

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!

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7
Q

Bioterrorism in History:

Smallpox example

A

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

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8
Q

Bioterrorism in History:

Anthrax example

A
  • 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

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9
Q

Describe Bacillus anthracis.

A

-gram-positive bacterium

-forms stable endospores when
nutrients are limited

  • long-lived
  • resistant to destruction/environment
  • ability to cause lethal infections
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10
Q

In Bacillus anthracis, what is the infectious particle?

A

The spore is the infectious particle.

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11
Q

Bacillus anthracis spores:

Name 3 main clinical forms of disease caused by anthrax.

A

Cutaneous anthrax

Gastrointestinal anthrax

Inhalational anthrax

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12
Q

Describe cutaneous anthrax.

A

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
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13
Q

Describe Gastrointestinal anthrax.

A

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
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14
Q

Describe Inhalational anthrax.

A

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
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15
Q

What is the most common clinical disease caused by anthrax?

A

Cutaneous anthrax

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16
Q

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

A

Gastrointestinal anthrax

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17
Q

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

A

Inhalational anthrax

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18
Q

What category is anthrax in?

A

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

= highest priority research

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19
Q

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

A

“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

20
Q

Does anthrax spread from person to person?

A

No, anthrax does not spread from person to person

21
Q

What is the top choice for germ warfare? Why?

A

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
22
Q

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

A

the presence of its 2 large plasmids

  1. Plasmid pXO2 –> genes for the capsule
  2. Plasmid pXO1 –> toxins
23
Q

Bacillus anthracis virulence:

What does Plasmid pXO2 contain?

A

genes for the capsule

24
Q

Bacillus anthracis virulence:

What does Plasmid pXO1 contain?

A

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
25
Q

An Anthrax attack

A

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
26
Q

How is Anthrax treated?

A

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)).

27
Q

Plague

Throughout history…

A

–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)

28
Q

What is plague caused by?

A

Caused by a bacterium: Yersinia pestis

  • gram negative bacterium (Coccobacillus)
  • many virulence factors that are anti-phagocytic and anti-inflammatory
  • also a lipopolysaccharide endotoxin
29
Q

How do humans become infected by plague?

A

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

30
Q

Plague: Within the body

A

–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

31
Q

Plague as a bioterror agent

A

–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%

32
Q

A more recent example of plague

A

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

33
Q

Plague: treatment

A

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

-Quarantine

34
Q

What is smallpox caused by?

A

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

35
Q

When was the last naturally occurring case of Smallpox?

A

-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
36
Q

What is smallpox disease characterized by?

A

–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

37
Q

Where are the last remaining repositories of the smallpox virus?

A

–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

38
Q

Smallpox:

Why would bioterror attacks using aerosolized variola be very detrimental?

A

–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
39
Q

How is smallpox transmitted?

A

Person-to-person

40
Q

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

A

–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?

41
Q

Viral Hemorrhagic fevers

How can hemorrhagic fever viruses be contracted?

A

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

42
Q

What are some examples of Viral Hemorrhagic fevers?

A

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!
43
Q

What is Botulinum toxin?

A

Most potent toxin known to man!

Made by the spore-forming microbe, Clostridium botulinnum

44
Q

How does Botulinum toxin function?

A

Acts at neuromuscular junctions to prevent release of acetylcholine

  • a neurotransmitter that stimulates muscle contraction
  • leads to paralysis, eventually respiratory paralysis
45
Q

What is the common name for Botulinum toxin?

A

BoTox!

BoTox only contains about 0.3% of the lethal inhalational dose

46
Q

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

A

–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!

BIOD29 (4 decks)

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