lectures 20-23 Flashcards

1
Q

define what is meant by biological warfare

A

the use of infectious agents or biological toxins with intent to kill or incapacitate people, animals, or plants as an act of war

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2
Q

define what is meant by bioterrorism

A

terrorism involving the release or dissemination of biological agents

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3
Q

briefly outline what happened in the 1340s siege of Kaffa

A

1343 - Genoese in Kaffa, Tatars began invading
1346 - reinforcements brought the plague which spread through Tatars, plague-ridden dead catapulted over walls, Genoese surrender
- plague spread through europe - in london by 1348

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4
Q

what happened in 1925?

A

the first multilateral agreement was signed that extended the prohibition of chemical agents to biological agents as well
NOT SIGNED BY JAPAN

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5
Q

how did the Japanese army use biological warfare 1930-1945?

A

1930s - Japan invaded Manchuria and field tested biological weapons on Chinese soldiers and civilians (plague, anthrax, cholera)
1940 - plague infected fleas were dropped by Japanese planes in Ningbo

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6
Q

how did the UK test BWs in Gruinard Island?

A
  • they experimented by dropping anthrax
  • 1986 bombed with formaldehyde to inhibit anthrax effects
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7
Q

what occurred in the 1966 subway experiment?

A

a lightbulb containing Bacillus globigii (non harmful bacteria) was dropped in the NYC subway and circulation was monitored

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8
Q

what non-governmental use of BWs has been observed?

A

1984 - contaminated salad bars with salmonella in Oregon
1995 - anthrax, botulinum toxin, and ebola virus to use against population of Japan (never successful)

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9
Q

where was an anthrax attack recorded in 2001?

A
  • spores were sent to several locations via the US postal service
  • 22 cases recorded?
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10
Q

which US president was sent a letter which may have contain ricin?

A

Donald Trump

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11
Q

what features of bioterror agents need to be present for a category A classification?

A
  • easily disseminated or transmitted from person to person
  • high mortality rates, potential for major public health impact
  • may cause public panic and social disruption
  • require special action for public health preparedness
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12
Q

which bacterial bioterror agents feature in category A?

A
  • anthrax
  • botulism
  • plague
  • tularemia
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13
Q

which viral diseases feature in category A?

A
  • smallpox
  • viral hemorrhagic fevers (Ebola, Marbug)
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14
Q

what features are found in category B classifications?

A
  • the agent is moderately easy to disseminate
  • moderate morbidity rates, or low morbidity rates
  • they require enhanced disease surveillance
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15
Q

what diseases are under class B?

A
  • food safety threats: Salmonella, E. coli, Shigella
  • systemic cell death: ricin toxin
  • water safety threats: Vibrio Cholerae, Cryptosporidium Parvum
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16
Q

what are the features of category C?

A
  • they are emerging pathogens
  • could be engineered due to availability
  • ease of production and dissemination
  • potential for high morbidity rates and major health impacts
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17
Q

what agents are categorised under class C?

A
  • Nipah virus
  • hantavirus
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18
Q

what are the main features of the Yersinia pestis bacteria?

A
  • Gram negative
  • intracellular rod
  • facultatively anaerobic
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19
Q

what animal group is Yersinia pestis endemic to?

A

rodents

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20
Q

how is Yersinia pestis transmitted?

A

through the bite of an infected flea

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21
Q

how many people died in the second plague pandemic?

A

100 mil worldwide

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22
Q

is bubonic plague infectious?

A

nope

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23
Q

how does Yersinia pestis reach the lymph nodes to cause swelling?

A

1 - Y. pestis is phagocytosed by a macrophage
2 - the bacteria are transported to a lymph node
3 - the bacteria replicate in the phagosome
4 - bacteria escape from the phagosome and convert to phagocytosis-resistant encapsulated forms that cause systemic bacteraemia

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24
Q

what are the symptoms of septicaemic plague?

A
  • fever & chills
  • necrosis of tissues
  • possible bleeding into the skin and other organs
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25
Q

what is the incubation period of pneumonic plague?

A

2-3 days

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26
Q

is there a vaccine for plague?

A

no

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27
Q

which antibiotic is used to treat plague and lower mortality?

A

streptomycin

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28
Q

what is the only form of plague that can be spread from person to person?

A

pneumonic plague

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29
Q

can Y. pestis be aerosolized?

A

yes

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30
Q

why is yersinia pestis a candidate for bioterrorism?

A
  • high mortality rate
  • easy human to human transmissibility
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31
Q

what are the main features of Bacillus anthracis?

A
  • Gram positive
  • facultatively aerobic
  • spore forming
  • rod shaped
32
Q

how do humans become infected with Bacillus anthracis?

A
  • coming into contact with infected animals or their by-products
33
Q

how does Bacillus anthracis evade the immune system?

A
  • it has a capsule which protects the bacterium from complement opsonization and prevents phagocytosis by macrophages
34
Q

what is the most common form of anthrax?

A

cutaneous anthrax

35
Q

which form of anthrax has the highest mortality rate?

A

inhalation - mortality in 95% to 100% of cases

36
Q

why is anthrax considered an agent of bioterrorism?

A
  • longevity of spores
  • ease of weaponization
  • proof of prior use as a BW
37
Q

what are the main features of Francisella tularensis?

A
  • small
  • Gram negative
  • coccobacillus
38
Q

how can Francisella tularensis enter the body?

A
  • inhalation
  • ingestion
  • through skin lesions
39
Q

what organelle does Francisella tularensis replicate within?

A
  • macrophages and neutrophils
40
Q

what are the routes of infection of Francisella tularensis?

A
  • direct contact with infected animal
  • direct contact with products from infected animal
  • contact/ingestion of contaminated water or soil
  • direct inhalation of bacteria via aerosols
41
Q

what is the incubation period of tularaemia?

A

2-5 days

42
Q

what are the symptoms of tularaemia?

A
  • high fever
  • headaches
  • chills
  • septicaemia
43
Q

what is the chance of being infected with tularaemia after inhaling a single bacterium?

A

40%

44
Q

is there a vaccine available for tularaemia?

A

no

45
Q

what is the mortality rate of tularaemia?

A

> 30%

46
Q

what is the standard treatment for tularaemia?

A

administration of doxycycline or ciprofloxacin

47
Q

which countries developed biological weapons containing tularaemia in the late 1960s?

A

Japan
Germany
USA

48
Q

why is tularaemia considered a bioterror agent?

A

it is the most infectious pathogen known

49
Q

what are the general features of Clostridium botulinum?

A
  • Gram positive
  • spore forming
  • anaerobic
  • rod shaped
50
Q

what is the most potent toxin known?

A

botulinum toxin

51
Q

how does botulinum toxin act?

A
  • each toxin molecule is made up of a heavy chain and a light chain connected by a disulphide bond
  • the light chain penetrates the lipid bilayer in synapses and destroys SNARE proteins proteolytically
  • this causes paralysis as Ach can no longer be released as a neurotransmitter
52
Q

what can be used to reduce the severity of symptoms caused by botulinum toxin?

A

antitoxin

53
Q

what is the mortality rate of botulism?

A

10-20%

54
Q

why has botulinum toxin received attention as a possible agent of bioterrorism?

A

it has a very high toxicity

55
Q

what are the TOPOFF exercises and what have been the result?

A
  • designed to simulate actual WMD threats by fictionalised international terrorist organisations
  • UK joined in 2005
  • 1st exercise showed that regions with adequate bioterrorism response plans can respond to even a sizeable attack
56
Q

how is anthrax detected?

A

1 - detection of capsule and cell wall antigens by fluorescent antibody/immunohistochemical techniques
2 - B. anthracis specific PCR
3 - detection of antibodies in infected people

57
Q

can Ebola be transmitted between people?

A

yes

58
Q

is ebola a DNA or RNA virus?

A

RNA

59
Q

what is the natural host of Ebola?

A

the fruit bat

60
Q

how is Ebola spread?

A

human to human transmission via contact with bodily fluids

61
Q

what is the fatality rate?

A

60%

62
Q

what is the treatment for Ebola?

A
  • currently it is rehydration treatment
  • current trials underway on using combinations of monoclonal antibodies and developing a vaccine
  • a vaccine used in ring vaccination trials showed efficacy
63
Q

describe the mechanisms of cellular entry by Ebola virus

A
  • it primarily targets the macrophages
  • cathepsins activate Ebola virus inside endosomes
  • it is then uncoated in the endosome and then enters the cytosol of the cell
64
Q

what is the fatality of the smallpox virus?

A

30%

65
Q

what is the causative agent of smallpox?

A

Variola major

66
Q

how is smallpox transmitted?

A

via direct and prolonged face to face contact

67
Q

how was smallpox eradicated?

A

by a very successful vaccine programme

68
Q

how many lab retain variola virus for ‘bioterrorism defence purposes’?

A

2 - one in Russia and one in the USA

69
Q

what toxin does ricin produce?

A

AB toxin

70
Q

what toxin does E. coli produce?

A

Shiga like toxin 1 (SLTx1) - same as Shiga toxin

71
Q

which toxins have identical active sites?

A

AB toxin and SLTx1

72
Q

how do AB toxin and SLTx1 cause cell death?

A

1 - the cell surface receptor binds and endocytosis occurs
2 - both toxins are retrograde trafficked through the lumen (shiga like toxin is faster)
3 - protein disulphide isomerase separates the A and B chain of ricin, SLTx1 is also separated (mechanism by which is not yet known)
4 - the A chain dislocates from the ER lumen to the cytosol
5 - the A chain regains its original structure (this requires chaperones in ricin)
6 - the toxins prevent protein synthesis occurring so the cell dies

73
Q

how are AB toxin and SLTx1 toxin treated for?

A
  • there is no cure for either toxin
  • antibodies can be used but have to be administered within 15 minutes from exposure
  • chemical inhibitors of trafficking can be used but are harmful if used for a long period of time
74
Q

what virus is influenza caused by?

A

Orthomyxoviridae RNA viruses

75
Q

what are the 2 different serotype antigens found on influenza viruses

A
  • haemagglutinin
  • neuraminidase
76
Q

why was the H5N1 influenza strain considered to be a bioterror agent?

A

it was found that H5N1 could be engineered to be more transmissible in ferrets - so some argued it could provide a blueprint for the creation of a bioweapon
- it was not found to spread between person to person

77
Q

what is the mortality rate of H5N1 influenza?

A

50%