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Microbiology: Bioterrorism (Jackson)
BACKGROUND:
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Category A Diseases/Agents: high-priority agents pose a risk to national security because they
Can be easily disseminated or transmitted from person to person
Result in high mortality rates and have the potential for major public health impact
Might cause public panic and social disruption (require special action for public healthy preparedness)
o Anthrax (Bacillus anthracis)
o Botulism (Clostridium botulinum toxin)
o Plague (Yersinia pestis)
o Smallpox (variola major)
o Tularemia (Francisella tularensis)
o Viral hemorrhagic fevers
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Filoviruses: Ebola, Marburg
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Arenaviruses: Lassa, Machupo
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Category B Diseases/Agents: second highest priority
Moderately easy to disseminate
Result in moderate morbidity rates and low mortality rates
Require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance
o Brucellosis (Brucella species)
o Epsilon toxin of Clostridium perfringens
o Food safety threats
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Salmonella spp.
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EHEC
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Shigella
o Glanders (Burkholderia mallei)
o Melioidosis (Bukholderia pseudomallei)
o Psittacosis (Chlamydia psittaci)
o Q fever (Coxiella burnetii)
o Ricin toxin from Ricinus communis (castor beans)
o Staphylococcal enterotoxin B
o Typhus fever (Rickettsia prowazekii)
o Viral encephalitis
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Alphaviruses: VEE, EEE, WEE
o Water safety threats:
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Vibrio cholera
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Cryptosporidium parvum
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Category C Diseases/Agents: third highest priority agents
Include emerging pathogens that could be engineered for mass dissemination in the future because of availability
Ease of production and dissemination
Potential for high morbidity and mortality rates and major health impact
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Reasons for Concern:
Plague: US and Soviet Union developed techniques to aerosolize plague bacillus; intentional dissemination via
aerosol would result in pneumonic plague
Anthrax: 2001 contamination of letters with anthrax spores
Tularemia: one of the most infectious pathogenic bacteria we know
o US military has stockpiles of weapons that would disseminate aerosols
o Soviet Union engineered resistant strains
AGENTS OF BIOTERRORISM:
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Bacillus anthracis (Anthrax):
Virulence Factors: encoded on 2 separate plasmids
o Polypeptide capsule made of D-glutamic acid: antiphagocytic
o Anthrax Toxin: made of 3 elements
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Protective Antigen (PA): binding subunit; used for vaccine
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Edema Toxin: PA + edema factor (EF)
 EF is an adenylate cyclase (increases cAMP)
 Disrupts cell metabolism
 Requires calmodulin as a co-factor
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Lethal Toxin: PA + lethal factor (LF)
 LF is a metalloprotease that cleaves MAP kinases 1 and 2
 Short circuits major signal transduction pathway in monocytes
Etiology:
o Primarily a disease of herbivores: sheep, cattle etc. (humans rarely infected)
o Endemic areas: Asia, Africa, Middle East
o Ideal biological weapon: due to formation of endospores
Pathogenesis:
o Infection follows entry of endospores through injured skin/mucosa:
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Spores in soil or contaminated animal products (hide, wool, bone)
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Spores highly resistant to disinfectants, heat, desiccation and UV radiation
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Remain viable for >50 years in the soil
o Cutaneous Anthrax: spores contaminate scratch/abrasion and germinate in the tissue
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Toxins cause development of papule 12-36 hours later
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Development of painless ulcer with coal-black necrotic center
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Bacilli can spread to lymphatics, and untreated cases can spread to the blood (causing
septicemia and death)
o Inhalation Anthrax (Woolsorter’s Disease): spores germinate in the lungs after inhalation
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Initial symptoms are non-specific (low grade fever, dry hacking cough, malaise)
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Respiratory distress with shock and sudden death
 RD: due to massive pulmonary edema and mediastinal hemorrhage
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Antibiotic therapy may not even save patient
o GI Anthrax: ingestion of spores through contaminate meat (rare)
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Abdominal pain, vomiting and bloody diarrhea
Clinical ID:
o Collect fluid from local lesion, blood or sputum
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Large Gram (+) bacilli
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Non-motile
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Non-hemolytic on BAP
Prevention: a vaccination is available for high risk groups
Yersinia pestis (The Plague):
Virulence Factors:
o Invasins: induce actin RAR in epithelial cells and facilitates uptake of bacteria into nonprofessional
phagocytes (expressed at 20 degrees C)
o Type III Secretion: toxic products directly injected into mammalian cell cytoplasm
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Yops (Yersinia outer membrane protein): effector Yops are kinase and phosphatase (disrupt
actin and cytokine production  disruption of macrophage and PMN function)
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Low calcium response (Lcr): released by type III secretion but NOT injected into cells (low
Ca++ signal opens the pore formed by the Yops)
o Plasminogen Activator: activates plasminogen to dissolve fibrin clots and prevents chemotaxis of PMNs
(may facilitate spread)
Etiology:
o Arthropod Vector: rat flea regurgitates Yersinia upon blood meal
o Animal Reservoir: rats, ground squirrels, mice, antelope, domestic cats
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Rats die in large number due to infection, precipitates movement of fleas from rat to human
o Person to person transmission: only with pneumonic plague
Pathogenesis:
o Bubonic Plague: most people infected by flea bite develop this
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Symptoms: appear 2-7 days after flea bite
 Fever, lymphadenitis, vasculitis, bubonic purpura, gangrenous necrosis
 Formation of buboes (large, grossly swollen LNs)
 Gangrene of acral regions (peripheral parts of the body- “black death”)
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Sepsis with no bubo (primary septicemic plague): develops in small minority of patients
 Hemorrhagic and necrotic lesions on all organs
 Meningitis
 Septic shock
 High mortality rate (50-75%)
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Pneumonic Plague: occurs in a small number of patients with bubonic or septicemic plague
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Hematogenous spread
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Bronchopneumonia (person to person droplet spread)
 Aerosol transmitted organisms are more virulent (adaptation to human host)
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Higher mortality rate than bubonic plague
Clinical ID:
o Specimen collection from blood, aspiration from buboes, sputum (pneumonic)
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Gram (-) rod (safety pin appearance)
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Immunofluorescence staining
Prevention: vaccination available for high risk groups
Francisella tularensis (Tularemia or Rabbit Fever):
Etiology:
o Reservoirs: carried by many species of wild rodents, rabbits, beavers and muskrats
o Human Infection:
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Bitten by infected tick, deerfly or other insect
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Handling infected animal carcasses
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Eating or drinking contaminated food or water
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Inhalation of the bacteria
Pathogenesis:
o Highly infectious: ID 10-50 bacteria
o Different types of infection:
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Ulceroglandular (most common; cutaneous ulcer and lymphadenopathy)
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Oculoglandular (conjunctivitis and lymphadenopathy)
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Oropharyngeal
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Pneumonic tularemia
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Systemic tularemia (highest mortality- acute illness with septicemia)
Clinical ID:
o Gram (-) pleiomorphic rod
o Can be grown in lab, but risk of lab-acquired infection is high
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Brucella abortus (Brucellosis):
Etiology:
o Causes spontaneous abortions in animals (cows)
o Rare disease in humans living in developed nations
o Contracted by:
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Drinking unpasteurized milk
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Direct contact with infected animal (skin abrasions, aerosol)
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No person to person spread
Pathogenesis:
o Relapsing fever
o Enlarged LNs
o Hepatitis
Clinical ID:
o Gram (-) coccobacilli (can be isolated from blood and urine)
o Rising titers to infection are diagnostic
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Rickettsia prowazekii (Epidemic Typhus):
Virulence Factors: similar to R. rickettsii
Etiology:
o Vectors: human head and body lice (bites and defecates simultaneously, bacteria rubbed into wound)
o Reservoirs: flying squirrels
o Predisposing factors: poverty, overcrowding, poor sanitation
Pathogenesis:
o Course of Disease: similar to RMSF (involves multiple organ systems and has higher mortality rate)
o Brill Zinsser (BZ) Disease: recrudescence of old typhus infection (can survive in LN for 50 years with no
symptoms; source of new typhus epidemic)
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Clinical ID:
o Gram (-) coccobacillii
o Complement fixation and immunofluorescence tests
Treatment: control lice with insecticide
Coxiella burnetti (Q fever):
Etiology: relative of Rickettsia but NOT transmitted by arthropod vector
o Infection of livestock that is transmitted by aerosols (vets and handlers at risk)
Pathogenesis:
o Q fever: respiratory infection accompanied by atypical pneumonia, headache and fever
Clinical ID:
o Gram (-) coccobaccili
o Indirect immunofluorescence assay
o 4 fold rise in complement fixing Ab titer
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