Lecture 21. Biowarfare - Four Key Bacteria Flashcards
What are the three bioterror agent classifications?
Category A, B & C
What are category A bioterror agents?
High priority agents
Easily disseminated or transmitted from person to person
High mortality rates, potential for major public health impact
Might cause public panic and social disruption
Require special action for public health preparedness
What are examples of bacterial category A agents?
Anthrax
Botulism
Plague
Tularemia
What are examples of viral category A agents?
Smallpox
Viral haemorrhagic fevers
What are category B bioterror agents?
Second highest priority agents
Moderately easy to disseminate
Moderate morbidity rates, low mortality rates
Require enhanced disease surveillance
What are examples of bacterial category B agents that are food safety threats?
Salmonella, Escherichia coli O157:H7, Shigella
What is an example of a bacterial category B agent that causes systematic cell death?
Ricin toxin from Ricinus communis (castor beans)
What are examples of bacterial category B agents that are water safety threats?
Vibrio cholerae, Cryptosporidium parvum
What are category C bioterror agents?
Emerging pathogens that could be engineered because of:
Availability
Ease of production and dissemination
And potential for high morbidity/mortality rates and major health impact
What is Yersinia pestis?
Gram-negative, facultatively anaerobic, facultatively intracellular rod discovered by Yersin in 1894 during the Third Pandemic
What is Yersinia pestis endemic to and how is it transmitted?
Y. pestis is endemic to rodents and is transmitted through the bite of infected fleas
Humans are susceptible and may contract the disease in this manner
What was the first Plague pandemic?
Justinian Plague AD 541-544
It arose in Central Asia and ~25 million people died
What was the second Plague pandemic?
Black Death, 14th Century, started in Central Asia
~100 million people died worldwide
China: ~58 million, Europe: ~25 million, Africa: ~10 million
There were five further outbreaks in the 14th Century
What was the third (modern) Plague pandemic?
Started in Yunnan, China 1855
Spread to Hong Kong in 1884
Then to Bombay in 1896
And then to several major ports including San Fransisco
~26 million deaths
What was the last major Plague outbreak and where?
Surat, India, 1994 100 cases and 50 deaths
What happens to Y. pestis in a sylvatic (rural) cycle?
Relatively resistant host rodents maintain a low-profile, stable rodent - flea infection cycle, resulting in endemic enzootic plague
What happens to Y. pestis in an urban cycle?
Relatively sensitive host rodents e.g. urban rats, die rapidly resulting in epizootic plague
What does Y. pestis transmission result in?
Non-infectious bubonic plague
What are the symptoms of bubonic plague?
Sudden onset of fever, headache, chills, and weakness. Painful buboes (swelling of the lymph nodes) develops within 2 to 7 days after the flea bite, usually in the groin or axillary areas
How does Y. pestis get to the lymph nodes?
- Y. pestis is phagocytosed by a macrophage
- The bacteria are transported to a lymph node
- The bacteria replicate in the phagosome
- 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, extreme weakness, abdominal pain, shock, and possibly bleeding into the skin and other organs Skin and other tissues may turn black and die, especially on fingers, toes, and the nose (the Black Death)
What did the Smithfield tests conclude?
The Black Death was caused by Yersinia pestis
Without treatment, what is the probability of bacteraemia and death in bubonic/septicaemic plague?
50-75%
What is the chance of death if you contract pneumonic plague?
100%
Is there a vaccine for pneumonic plague?
No
What lowers the mortality rate of pneumonic plague to 10-20%?
Streptomycin
What causes pneumonic plague?
Aerosolisation of Y. pestis
Develop from inhaling infectious droplets
What is the causative agent of anthrax?
Bacillus anthracis, a Gram-positive, facultatively aerobic, spore-forming rod
Where is anthrax commonly found?
Common disease of livestock such as cows and sheep
How do humans become susceptible to B. anthracis?
After coming in contact with infected animals or their by-products
What comprises the exotoxin that B. anthracis releases?
Protective antigen (PA), edema factor (EF), lethal factor (LF)
Together they produce the systemic effects of anthrax
Mechanism of action of anthrax
- Anthrax toxin binds cell receptors
- Anthrax toxin is endocytosed into early endosomes (EE)
- Protective antigen forms a pore in the late endosomal (LE) membrane
- Lethal factor and edema factor enter the cytosol
What are the three forms of anthrax?
Cutaneous, gastrointestinal, inhalational
What is cutaneous anthrax?
Cutaneous anthrax is the most common form of the disease. The exotoxin causes a painless round black lesion on the skin 2 to 5 days after exposure, the result of localised tissue necrosis. Without antibiotic therapy, the bacteria will continue to proliferate and enter the bloodstream, possibly causing death
What is gastrointestinal anthrax?
A rare form of the disease, is caused by ingestion of spores from improperly cooked, contaminated meat. B. anthracis matures and replicates within the intestine, causing a necrotic lesion
Symptoms include vomiting, abdominal pain, and bloody diarrhoea. Mortality rates are high (25% to 60%) if untreated
What is inhalational anthrax (Woolsorter’s disease)?
Occurs when the spores are inhaled. The bacteria mature and replicate in the lungs, where the exotoxin is released. Symptoms, which include fever, cough, malaise, fatigue, and body aches, generally develop within 7 days of exposure.
Respiratory distress and death quickly follow in 95% to 100% of untreated cases.
What is the causative agent of Tularemia?
Francisella tularensis
What is Francisella tularensis?
A small Gram negative coccobacillus. Difficult to isolate (requires cysteine). Slow growing
What are the three main subspecies of Francisella tularensis?
F. tularensis subsp tularensis
F. tularensis subsp holoartica
F. tularensis subsp mediasiatica
What is a very closely related species to F. tularensis?
F. novocida
How can a F. tularensis enter the body?
By inhalation, ingestion or through skin lesions
How does F. tularensis enter macrophages?
F. tularensis uses type IV pili to bind to the exterior of host macrophages and thus become phagocytosed
Mutant strains lacking pili show severely attenuated pathogenicity
How does F. tularensis enter neutrophils?
Requires opsonisation by antibodies or complement
The intracellular replication of F. tularensis
- F. tularensis is phagocytosed by a macrophage
- The phagosomal membrane is degraded
- The bacteria replicate in the cytosol
- Cell death releases bacteria
- Re-infection
What are the typical routes of infection of F. tularensis?
Direct contact with infected animals
Direct contact with products from infected animals
Contact/ingestion of contaminated water/soil
And worst of all: direct inhalation of bacteria via aerosols
What is the most acute form of F. tularensis?
Respiratory tularaemia
Is there a vaccine for F. tularensis?
No
What is the mortality of F. tularensis subsp. tularensis?
> 30%
What is Clostridium botulinum?
The causative agent of botulism, is a Gram-positive, spore-forming, anaerobic rod
What does C. botulinum release?
A potent neurotoxin (botulinum toxin); the lethal
dose for humans is less than 1 μg, making it the most potent toxin know
What is the most common source of botulism?
Home-canned vegetables and home-preserved fish
What is Botox?
Botulimum toxin injected to reduce the appearance of facial wrinkles
What does botulinum toxin act on after being absorbed in the small intestine?
Neuromuscular junctions causing muscle paralysis
What are the symptoms of botulism?
Difficulty in swallowing and breathing, then
Without administration of the appropriate antitoxin, respiratory paralysis
Death follows in 10% -20% of cases
What is effective in reducing the severity of symptoms if administered early?
Antitoxin
