lectures 20-23 Flashcards
define what is meant by biological warfare
the use of infectious agents or biological toxins with intent to kill or incapacitate people, animals, or plants as an act of war
define what is meant by bioterrorism
terrorism involving the release or dissemination of biological agents
briefly outline what happened in the 1340s siege of Kaffa
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
what happened in 1925?
the first multilateral agreement was signed that extended the prohibition of chemical agents to biological agents as well
NOT SIGNED BY JAPAN
how did the Japanese army use biological warfare 1930-1945?
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
how did the UK test BWs in Gruinard Island?
- they experimented by dropping anthrax
- 1986 bombed with formaldehyde to inhibit anthrax effects
what occurred in the 1966 subway experiment?
a lightbulb containing Bacillus globigii (non harmful bacteria) was dropped in the NYC subway and circulation was monitored
what non-governmental use of BWs has been observed?
1984 - contaminated salad bars with salmonella in Oregon
1995 - anthrax, botulinum toxin, and ebola virus to use against population of Japan (never successful)
where was an anthrax attack recorded in 2001?
- spores were sent to several locations via the US postal service
- 22 cases recorded?
which US president was sent a letter which may have contain ricin?
Donald Trump
what features of bioterror agents need to be present for a category A classification?
- 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
which bacterial bioterror agents feature in category A?
- anthrax
- botulism
- plague
- tularemia
which viral diseases feature in category A?
- smallpox
- viral hemorrhagic fevers (Ebola, Marbug)
what features are found in category B classifications?
- the agent is moderately easy to disseminate
- moderate morbidity rates, or low morbidity rates
- they require enhanced disease surveillance
what diseases are under class B?
- food safety threats: Salmonella, E. coli, Shigella
- systemic cell death: ricin toxin
- water safety threats: Vibrio Cholerae, Cryptosporidium Parvum
what are the features of category C?
- they are emerging pathogens
- could be engineered due to availability
- ease of production and dissemination
- potential for high morbidity rates and major health impacts
what agents are categorised under class C?
- Nipah virus
- hantavirus
what are the main features of the Yersinia pestis bacteria?
- Gram negative
- intracellular rod
- facultatively anaerobic
what animal group is Yersinia pestis endemic to?
rodents
how is Yersinia pestis transmitted?
through the bite of an infected flea
how many people died in the second plague pandemic?
100 mil worldwide
is bubonic plague infectious?
nope
how does Yersinia pestis reach the lymph nodes to cause swelling?
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
what are the symptoms of septicaemic plague?
- fever & chills
- necrosis of tissues
- possible bleeding into the skin and other organs
what is the incubation period of pneumonic plague?
2-3 days
is there a vaccine for plague?
no
which antibiotic is used to treat plague and lower mortality?
streptomycin
what is the only form of plague that can be spread from person to person?
pneumonic plague
can Y. pestis be aerosolized?
yes
why is yersinia pestis a candidate for bioterrorism?
- high mortality rate
- easy human to human transmissibility
what are the main features of Bacillus anthracis?
- Gram positive
- facultatively aerobic
- spore forming
- rod shaped
how do humans become infected with Bacillus anthracis?
- coming into contact with infected animals or their by-products
how does Bacillus anthracis evade the immune system?
- it has a capsule which protects the bacterium from complement opsonization and prevents phagocytosis by macrophages
what is the most common form of anthrax?
cutaneous anthrax
which form of anthrax has the highest mortality rate?
inhalation - mortality in 95% to 100% of cases
why is anthrax considered an agent of bioterrorism?
- longevity of spores
- ease of weaponization
- proof of prior use as a BW
what are the main features of Francisella tularensis?
- small
- Gram negative
- coccobacillus
how can Francisella tularensis enter the body?
- inhalation
- ingestion
- through skin lesions
what organelle does Francisella tularensis replicate within?
- macrophages and neutrophils
what are the routes of infection of Francisella tularensis?
- 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
what is the incubation period of tularaemia?
2-5 days
what are the symptoms of tularaemia?
- high fever
- headaches
- chills
- septicaemia
what is the chance of being infected with tularaemia after inhaling a single bacterium?
40%
is there a vaccine available for tularaemia?
no
what is the mortality rate of tularaemia?
> 30%
what is the standard treatment for tularaemia?
administration of doxycycline or ciprofloxacin
which countries developed biological weapons containing tularaemia in the late 1960s?
Japan
Germany
USA
why is tularaemia considered a bioterror agent?
it is the most infectious pathogen known
what are the general features of Clostridium botulinum?
- Gram positive
- spore forming
- anaerobic
- rod shaped
what is the most potent toxin known?
botulinum toxin
how does botulinum toxin act?
- 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
what can be used to reduce the severity of symptoms caused by botulinum toxin?
antitoxin
what is the mortality rate of botulism?
10-20%
why has botulinum toxin received attention as a possible agent of bioterrorism?
it has a very high toxicity
what are the TOPOFF exercises and what have been the result?
- 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
how is anthrax detected?
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
can Ebola be transmitted between people?
yes
is ebola a DNA or RNA virus?
RNA
what is the natural host of Ebola?
the fruit bat
how is Ebola spread?
human to human transmission via contact with bodily fluids
what is the fatality rate?
60%
what is the treatment for Ebola?
- 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
describe the mechanisms of cellular entry by Ebola virus
- 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
what is the fatality of the smallpox virus?
30%
what is the causative agent of smallpox?
Variola major
how is smallpox transmitted?
via direct and prolonged face to face contact
how was smallpox eradicated?
by a very successful vaccine programme
how many lab retain variola virus for ‘bioterrorism defence purposes’?
2 - one in Russia and one in the USA
what toxin does ricin produce?
AB toxin
what toxin does E. coli produce?
Shiga like toxin 1 (SLTx1) - same as Shiga toxin
which toxins have identical active sites?
AB toxin and SLTx1
how do AB toxin and SLTx1 cause cell death?
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
how are AB toxin and SLTx1 toxin treated for?
- 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
what virus is influenza caused by?
Orthomyxoviridae RNA viruses
what are the 2 different serotype antigens found on influenza viruses
- haemagglutinin
- neuraminidase
why was the H5N1 influenza strain considered to be a bioterror agent?
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
what is the mortality rate of H5N1 influenza?
50%
