(Updated 28 January 2015)

Anthrax (Bacillus anthracis)

An aside on antibiotic prophylaxis and treatment

Antibiotics: Prophylaxis or Treatment?

Antibiotic Resistant Bacteria

• Analogy of the armor-piercing shells and the tanks
  • Moral: beware of the single exception
• Analogy of the Hannibal and the elephants
  • Moral: it only works once

Vaccines: Prophylaxis or Treatment?

• Timing and vaccination
  • Takes time for vaccines to “take”
    • Differs for different vaccines
    • Sometimes partial protection
• Need to know the enemy in advance
  • Partial resistance usually defends against vaccine resistance
  • But smallpox vs. HIV

Bacillus anthracis

• Cause of anthrax
• Found in soil
• Pathogenic for grazing animals
• Humans get if from animals (or from intentional inoculation)
• B. anthracis makes spores that are very hardy survivors

Spores

• Designed for survival
• Non-growing (dormant) state
• Very little water
• Hard outer shell
• Smaller than growing cells
• If a cell is a cocktail sausage, a spore is a marble

Spores are very resistant

• British germ warfare experiment 1942
• Gruinard Island (Coast of Scotland)
• Spores active for decades
• Decontaminated by spraying 280 tons of formaldehyde diluted in 2000 tons of seawater (1986 — declared “safe” in 1990)
• Spores are known to be active even 100 years later! (medieval hospital site)

Pathology of Anthrax

• Three routes of infection
  • Skin contact (scratches)
  • Ingestion (eating) — rare in developed world
    • Eating undercooked meat from infected animals
  • Inhalation (breathing)
• Inhalation and ingestion are the worst

Human Anthrax (historical)

• Skin anthrax from handling infected animals and wool
• “Woolsorters disease” from breathing dust form wool
• Both were bad

Conquest of Anthrax

• Robert Koch (started as country doctor)
  • Identified bacillus — first one ever
  • Basic science approach
• Louis Pasteur (started as a chemist)
  • Made vaccine
    • “attenuated strain”
  • Not a physician

Robert Koch

• Koch’s postulates
  • Germ present in all with disease and none without
  • Germ grown in culture causes disease
  • Germ isolated from inoculated (and diseased) causes disease in another
• Father of microbiology

Human Anthrax (modern)

• Before 2002
  • Antibiotic treatment effective 90% for skin anthrax
  • But only 10% for inhalation anthrax
• After 2002
  • Almost 100% effective for skin anthrax
  • About 50% for inhalation anthrax

Effective weapons

• Large spores (or clumps) ineffective
  • Filtered by nose and throat
  • Expelled by mucus escalator and ciliary sweeping
• Small spores
  • Trapped in small sacs in lungs
  • Grow and develop

How anthrax works

• Spores break out of dormancy and start growing
• If outside of cells (e.g. in lungs) grow and make a capsule and two toxins

Capsule

• “Capsule” is a fancy name for “slime coat”
• Make it hard for phagocyte to capture cells
• Genes for capsule are on an extra piece of DNA called a plasmid
• If no slime, cells are eaten before they can cause damage

Toxins

• LF or Lethal Factor (kills mice)
• EF or Edema Factor (causes fluid accumulation)
• PA or “Protective antigen” (Definite misnomer!)
  • Delivers the other two toxins to the cells
  • Really the Trojan horse of the system

PA: The “Trojan Horse”

• PA, LF, and EF excreted by cells, but diluted
• If in phagocyte, all are concentrated
• “PA” makes a hole in the membrane

Corrupting the Defenses

• LF and EF sit on top of the hole
• When lysosome fuses, something happens and LF and EF are transported through the hole
• That kills the cell and lets the germs grow and thrive
• Cell ruptures and more are released

Cause of Death

• Needs lots of cells — often enough to “clog the plumbing”
• But death caused by too much toxin, not clogging.
• After death, bacteria thrive on rotting flesh until none left
• Then they convert to dormant spores to wait for next victim

Anthrax as bioterrorism

• Well publicized attacks via US Mail in 2001 (after 9/11)
  • 23 cases, 12 cutaneous, 11 inhalation, 5 deaths
• Sporadic scares of white powder sent to people
  • Most are something harmless

What makes bioterror effective? Bio or Terror?

• What do we fear?
• Define risk
  • Probability of occurrence
  • Probability of death
• Longterm effects (e.e. 9/11/2001)

Ebola Hemorrhagic Fever

• Ebola is an RNA virus
• Attacks cells lining the blood vessels (sepsis)
• Blood vessels leak out, heart cannot pump blood to organs
• Organs die (septic shock)

Clinical features of Ebola

• Start with flu-like symptoms
• Then stomach and chest pain
• Then blindness or bleeding from orfices
• Very lethal (70-90% in Africa but still 50% in the best western hospitals)

Subtypes of Ebola differ by region

• First seen in 1970
• Four subtypes cause human disease (so far)
• One subtype (Ebola Reston) causes disease in non-human primates
  • Book: Hot Zone
  • Transmission to humans, but no disease
• Marburg virus is related to Ebola virus

Transmission

• Non-infectious until first symptoms
  • Fever is first (before infectious)
• Direct contact with blood, secretions, organs, or semen
  • Even after death
  • Funeral practices are one source of contagion
• Infectivity persists for days after recovery, but even 7 weeks in semen

Prevention and treatment

• No treatment available (supportive therapy only)
• Prevention by isolation and barrier precautions

Natural reservoir (where does it come from?)

• Somewhere in the rain forests of Africa
• Non-human primates can cause some outbreaks
  • But not likely a reservoir — they also die quickly
• Recent theory: bats
  • They are infected but don’t die
  • Good candidate for maintaining the virus

Ebola Reston Virus

• 1989 discovery in macaques imported from Phillipines to a facility in Reston Virginia
• Other outbreaks in the 1990’s
• Ebola-like symptoms in monkeys
• At least 12 humans infected (US and Phillipines)
  • No clinical symptoms, but antibodies present
• Scariest news: Ebola Reston is transmitted airborne
  • Human Ebola is not (so far)
• Newest twist: Ebola Reston found in pigs
  • Pigs are a lot like humans in terms of infectious disease
  • Again, human infection (antibodies) but no disease

Bioterror(ism)

What makes a good bioweapon?

• Highly infectious
• Cause death or incapacitation
• Easily dispersed
• Easily grown in large quantities
• Stable in storage
• Resistant to environment (till infection)
• Resistant to treatment (by enemy)
• Cure or vaccine available (for self — so affect only the enemy)

Yes, the vaccine is the real weapon

• USSR and smallpox eradication story
• USSR produced nearly all the vaccine — huge capacity for smallpox vaccine
• Vaccine production limited in western countries

Would Ebola or Anthrax make a good bioweapon?

• What about other candidates in this course?