Dust to Dust

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Dust to Dust

• Anthrax

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A Possible Case History

• Day 0 74,000 exposed 16,000 infected 4,000
  downwind

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Day 2

• 400 people ill
• Fever, cough, shortness of breath, chest pain
• Over the counter medicine, family doctors,
  hospital
• Flu has been present in city

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Day 3

• City health department notified
• Bacillus isolated resembles soil bacterium
• 1,200 ill, 80 dead

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Day 4

• CDC begins investigation
• Media speculate about Spanish and bird flus
• Mayor learns of threats

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Day 4

• B. anthracis ID confirmed by USAMRIID
• Antibiotic supplies short
• 2,700 ill 300 dead

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Day 5

• Schools become disaster centers
• Rumors of mobs, drugs withheld
• Pilots wont fly into Northeast
• 50,000 receive antibiotics no records
• 3,200 ill 900 dead

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Day 6

• 40 drug distribution centers set up
• Morgues full
• Lawsuits
• 4,000 ill 1,000 dead

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Day 7

• Workers absent
• Emergency responses delayed
• Looting
• 4,800 ill 2,400 dead

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Final Tally

• 20,000 infected 4,000 deaths
• gt250,000 treated
• Dead Zone in city abandoned
• No tourists
• FBI receives threats to 5 more cities

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Northeast
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The Fifth Plague

• Then the Lord said to Moses, Go to Pharaoh and
  say to him, This is what the Lord, the God of
  the Hebrews, says Let My people go, so they may
  worship Me. If you refuse to let them go and
  continue to hold them back, the hand of the Lord
  will bring a terrible plague on your livestock in
  the field - on your horses and donkeys and camels
  and on your cattle and sheep and goats.

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• Then the Lord said to Moses and Aaron, Take
  handfuls of soot from a furnace and have Moses
  toss it into the air in the presence of Pharaoh.
  It will become fine dust over the whole land of
  Egypt, and festering boils will break out on men
  and animals throughout the land.
• So they took soot from a furnace and stood before
  Pharaoh. Moses tossed it into the air, and
  festering boils broke out on men and animals. . .

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Bacillus anthracis

• First bacterium shown to cause disease (Koch,
  1877)
• One of first organisms to which a vaccine was
  developed (Pasteur, 1881)

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Koch

• Studied anthrax in rural Germany
• Grew bacteria in pure culture in the eyeball of a
  cow
• Observed spores
• Injected mice and caused disease

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Kochs Postulates

• Isolate the organisms from a sick person or
  animal and grow it in pure culture
• Inoculate it into another animal
• See the same disease symptoms
• Isolate the same organism from the second animal

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Louis Pasteurs Bet

• Pasteur had discovered attenuation (weakening the
  organism so it no longer caused disease) with
  fowl cholera
• Accepted a bet with veterinarian H. Rossignol of
  Agricultural Society of Melun to demonstrate
  anthrax vaccine

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Anthrax Vaccination 1881
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Anthrax

• Primarily a disease of domesticated and wild
  herbivorous animals
• Human infection arises from contact with diseased
  animals or carcasses

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Anthrax in Herbivores

• May be listless or without appetite
• After death, bleeding from body cavities
• Dark blood, swollen spleens

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North American Anthrax

• 2001
• S. Texas (deer, cattle, horses)
• Minnesota (cattle)
• South Dakota (buffalo)
• Manitoba
• Saskatchewan
• Alberta

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Bacillus anthracis

• A vegetative cell
• B spore

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Endospores

• Formed by some bacteria when environmental
  conditions are not optimal
• Resistant to heat, radiation, drying
• Become growing bacteria when conditions improve

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Endospore Morphology

• Low water content
• SASPs protect DNA

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Spore Formation

• Growth ceases due to nutrient lack
• DNA replicated, condenses
• Spore septum forms
• Dehydration and formation of coat layers, SASPs
• Vegetative cell disintegrates

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Spore Survival

• Documented in lab
• Clostridium aceticum
• 34 years

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Spore Survival

• Thermoactinomyces
• Roman ruins in Britain
• 2,000 years

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Spore Survival

• Thermoactinomyces
• Minnesota lake sediment
• 7,000 years

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Spore Survival

• Thermoactinomyces
• Fly in amber
• 25-40 million years

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Ecology of Animal Infection

• Spores endemic in soil
• Spores eliminated in unsuitable soils
• Acidity
• Biological competition
• Organism ? spore ? organism

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Livestock Infection

• Soil with pH gt 6.0, ambient temp gt 15.5C
• Catastrophic change in soil microenvironment ?
  incubator area
• Water-filled depression
• Dried up wash
• Hillside seep areas

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Livestock Infections

• Dry season
• Skin abrasions and fly bites
• Flies insignificant vectors for livestock, can
  transmit to humans

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1957 Epidemic

• Sedalia Trail
• Rolling prairie, narrow wooded streams, areas of
  wooded hills
• Soils developed from limestone

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1957 Epidemic

• Livestock watered at small ponds wet spring
  after 3 years of drought

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1957 Epidemic

• No cases on hay lands, well-drained fields, over
  shale or sandstone
• Some outbreaks on rock lands
• Contained by selective vaccination

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1959 Epidemic

• Wayne Co. Illinois (July)
• Farm divided by road, all cases on south side of
  road
• Hickory gravelly loam overlaid by fertile Bluford
  yellow-gray silt loam

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1959 Epidemic

• Seven other farms (24 cattle) Hickory and
  Bluford
• Seven other farms (15 cattle) Hickory soils
• Bottomland farm (3 cattle) 20 August
• No cases upstream late soil drying

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Global Anthrax
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Global Anthrax

• Developing countries
• Countries without veterinary public health
  programs
• South and Central America
• Southern and Eastern Europe
• Asia, Africa, Caribbean, Middle East

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Tanning Industry

• Woolsorters Disease
• Mostly imported wool and goat hair
• Waste
• Rivers
• Fertilizers

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Human Routes of Infection

• Enter through breaks in skin ? cutaneous anthrax
• Enter through ingestion ? gastrointestinal
  anthrax
• Enter lungs ? inhalational anthrax (size)

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Cutaneous Anthrax

• North Carolina, 1987
• 42-year-old maintenance worker at NC textile mill
• Sore on forearm ? edema, pain, fever, chills
• Treated with antibiotics
• B. anthracis grown from W. Asian cashmere,
  Australian wool, surface debris from storage area

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Cutaneous Anthrax

• Skin ulcer and vesicle

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Cutaneous Anthrax

• 95 of naturally occurring human cases
• Raised itchy bump, painless black ulcer
• Lymphatic swelling, septicemia
• 20 of untreated cases fatal

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Gastrointestinal Anthrax

• August 2000 Minnesota
• Downer cow vet. approved meat for consumption
• 6 family members consumed meat
• 2 had diarrhea, abdominal pain, fever
• Recovered without treatment

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Gastrointestinal Anthrax

• Eating undercooked meat from infected animals
• Nausea, vomiting, loss of appetite, abdominal
  pain
• Vomiting blood, severe diarrhea
• 25-60 of cases fatal

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Inhalational Anthrax

• Woolsorters disease
• Early symptoms resemble colds or influenza
• High fever, chest pain
• Systemic hemorrhagic pathology
• Often fatal

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Inhalational Anthrax

• X ray showing widened mediastinum

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Inhalational Anthrax

• X ray showing pleural effusion (fluid and cells
  in lungs)

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Anthrax

• B. anthracis in blood of infected patient with
  PMNs (neutrophils)

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Anthrax Disease

• Not spread person-to-person (not contagious)
• Most common in countries without veterinary
  public health programs
• NOW germ warfare threat

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Bacillus genus

• B. subtilis common bacterium in soil,
  non-pathogenic
• B. anthracis - anthrax
• B. cereus food poisoning
• B. thuringiensis insect pathogen toxin gene
  inserted into Bt cotton

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Anthrax WWIIGruinard Is. (Scotland)
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Anthrax Research Cold War
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Sverdlovsk Biowarfare Facility Accident 1979
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Sverdlovsk Outbreak
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Sverdlovsk Timeline
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USA2001
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Index Case AMI, Boca Raton

• AMI photo editor
• Index case first confirmed case of disease
• First fatality in US in 50 years

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US Outbreak 2001

• October 4-November 2 10 confirmed inhalational
  cases (12 cutaneous)
• DC, Florida, New Jersey, New York
• Age range 43-73,70 male
• 9/10 known or believed to have had contact with
  mail containing B. anthracis spores

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Anthrax Envelopes Recovered
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Disinfection
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Anthrax 2001 Timeline
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Anthrax 2001 DC Area
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Anthrax 2001 Geography
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Anthrax in the Mail

• Spores were able to penetrate sealed envelopes
• Still low incidence of disease

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US Outbreak Symptoms
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US Outbreak Symptoms
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US Outbreak Symptoms
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US Outbreak Clinical Findings
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US Outbreak

• Median incubation period 4 days (range 4-6 days)
• With antibiotics and supportive care, survival
  rate 60

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Anthrax 2001 Prophylactic Antibiotic Compliance
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Anthrax Pathogenesis

• Oxygen depletion
• Shock
• Increased vascular permeability
• Respiratory failure
• Cardiac failure

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Virulence Factors

• Capsule protects against bactericidal serum
  components and phagocytic engulfment

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Anthrax Toxin

• Factor I edema factor (EF) adenylate cyclase
• Factor II protective antigen (PA) induces
  protective antitoxin cell binding
• Factor III lethal factor (LF) zinc
  metalloprotease

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Anthrax Toxin

• Protective antigen binds to host cells
• Edema factor (adenylate cyclase) and lethal
  factor enter and damage host cells
• B. anthracis initially grows in lymph nodes, can
  spread to other organs

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Immunity to Anthrax

• Variation in genetic susceptibility among animal
  species
• Permanent immunity requires antibodies to both
  capsule and toxin

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Immunity to Anthrax

• Vaccine protocol three subcutaneous injections
  given two weeks apart
• Three additional subcutaneous injections at 6,
  12, and 18 months
• Annual boosters
• Given routinely to military

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Immunity to Anthrax

• Livestock vaccine nonencapsulated toxigenic
  stain produces sublethal amounts of toxin to
  induce protective antibody formation

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Immunity to Anthrax

• Human vaccine PA from culture filtrate of
  avirulent, nonencapsulated strain

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Anthrax Vaccination

• Vaccine efficacy
• Vaccine safety
• Vaccine availability

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Vaccine Efficacy

• 25 monkeys vaccinated with 2 doses
• Challenged with anthrax aerosol 8-38 weeks later
• All survived

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Vaccine Efficacy

• 10 monkeys vaccinated with 2 doses
• Challenged with anthrax aerosol 2 years later
• 9 survived

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Vaccine Efficacy

• 10 monkeys vaccinated one time
• Challenged with anthrax aerosol 6 weeks later
• all survived

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Vaccine Efficacy

• 20 monkeys vaccinated at 0 and 4 weeks
• Challenged with anthrax aerosol 10-20 weeks later
• 19 survived

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Vaccine Safety

• Mild reactions (30 of men 60 of women)
  redness, swelling, tenderness at injection site

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Vaccine Safety

• Moderate reactions redness, swelling, tenderness
  at injection site as above but larger (1-5)
• Large local reaction (gt5) in less than 1-2 of
  subjects

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Vaccine Safety

• Systemic reactions flu-like symptom - lt0.2 of
  subjects
• 5-35 muscle aches, joint pain, rash, chills,
  fever, loss of appetite, malaise.

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Vaccine Safety

• Symptoms requiring hospitalization in 1/200,000
  cases.
• Severe allergic reactions in 1/100,000 cases
• No long-term side effects

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Anthrax as a Bioterrorist Agent

• Easy to obtain and to grow
• History of Ames strain (IDed in US outbreak)
• First thought to be from US bioweapons program
  Fort Detrick MD
• From cattle outbreak in Texas

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Anthrax as a Bioterrorist Agent

• Spores very stable
• Can be spread by air
• Inhalational anthrax has high mortality rate
• Initial symptoms mimic other more common diseases
  so treatment delayed

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Anthrax as a Bioterrorist Agent

• Spores must be treated to make them small enough
  to enter lungs
• Disease is curable with antibiotics even after
  symptoms appear
• Vaccine is available

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Anthrax as a Bioterrorist Agent

• Other considerations
• Killing spores in mail or water
• Antibiotic use cost and side effects
  ciprofloxacin 204/person vs. doxycycline
  12/person

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Key Concepts

• Discuss the history of human and animal anthrax.
• Discuss the ecology of anthrax spores in the
  environment and its effect on animal infections.

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Key Concepts

• Compare and contrast human anthrax infections by
  the cutaneous, gastrointestinal, and respiratory
  routes.
• Discuss the interaction of B. anthracis with the
  immune system.

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Key Concepts

• Discuss the efficacy and drawbacks of using
  anthrax as a bioterrorist agent.