Anthrax

What is Anthrax?

Bacillus anthracis

A disease of warm-blooded animals Mainly affects livestock and humans disease bacteria

Which animals are susceptible to Anthrax?

Herbivores (ruminants and equidae): acute form animals susceptibility

Which animals are relatively resistant to Anthrax?

Carnivores (canine and swine) Reptiles: less acute form animals resistance

Who identified the microbial origin of Anthrax?

Robert Koch in 1876 history microbiology

Who created the first animal vaccine for Anthrax?

Louis Pasteur in 1881 history vaccines

What type of bacteria is Bacillus anthracis?

Gram positive Non-motile Spore forming bacteria classification

What does the vegetative form of Bacillus anthracis do?

Multiplies and kills the host Forms 'box cars' in rows bacteria pathogenicity

How many strains of Bacillus anthracis are there?

Over 1200 strains bacteria diversity

What is the predominant form of spores in nutrient-poor environments?

Spores are the predominant form in nutrient-poor environments with aerobic conditions. biology spores

What conditions lead to spore germination?

Rich in amino acids, nucleosides, glucose (e.g., blood or tissue). biology spores

How long can spores survive?

Spores can survive for 50-250 years under extreme conditions. biology spores

What are methods for spore inactivation?

5% hypochlorite (bleach) Paraformaldehyde vapour Phenol Autoclaving biology spores

What is the lethal dose (LD 50) for humans regarding spores?

2500-55000 spores or one deep breath at time of release. biology spores

What was the cause of alarm in the USA regarding anthrax?

Surprising ease of anthrax contamination in areas. history anthrax

What happened in Sverdlosk, Russia in 1979?

94 people ill; 64 succumbed to inhalational anthrax. history anthrax

What did the Russian government claim about the 1979 outbreak?

Indicated meat contamination as the cause. history anthrax

What did the USA argue regarding the 1979 outbreak?

Violation of Bioweapons Convention of 1972. history anthrax

What was revealed in 1992 about the Sverdlosk outbreak?

Outbreak at weapons facility due to a faulty exhaust filter. history anthrax

What was the outcome of the Sverdlosk outbreak?

Deaths of animals and people along wind's downward movement from facility. history anthrax

What was the impact of anthrax in Rhodesia during the late 1970s?

104,738 contacted anthrax 182 died Reduced cattle population Food shortages history disease

What was the outcome of the anthrax release by Aum Shinrikyo?

No human injuries, used vaccine form history terrorism

What are the three main forms of human anthrax?

- Cutaneous - Gastrointestinal - Inhalational

What is the most common form of anthrax?

Cutaneous Anthrax (95% of cases)

How does cutaneous anthrax enter the body?

Through cuts or abrasions

What are the initial symptoms of cutaneous anthrax?

- Small papule - Vesicle - Eschar

What is the fatality rate of cutaneous anthrax without antibiotics?

5-20% fatality

What is the fatality rate of cutaneous anthrax with antibiotic treatment?

What are potential differential diagnoses for Cutaneous Anthrax (6)?

- Spider bite - Ecthyma gangrenosum - Ulceroglandular tularemia - Plague - Staphylococcal or streptococcal cellulitis - Herpes simplex virus

What is the main cause of Gastrointestinal Anthrax in humans?

Eating contaminated meat or drink

What are symptoms of Gastrointestinal Anthrax (3)?

- Sore throat Dysphagia - Fever Nausea Vomiting (+/- blood) - Dysentery (bloody diarrhea)

What is the case fatality rate of Gastrointestinal Anthrax without treatment?

25-65%

What are potential differential diagnoses for Gastrointestinal Anthrax?

- Acute appendicitis - Ruptured viscus - Diverticulitis Acute cervical lymphadenitis - Acute gastritis - Dysentery anthrax

What is another name for Inhalational Anthrax?

Woolsorter's disease What is the lethal dose of spores for Inhalational Anthrax?

What is the incubation period for Inhalational Anthrax?

1-43 days (median 10 days)

What are typical symptoms of Inhalational Anthrax (6)?

- Non-productive cough - Fatigue Myalgia - Fever Dyspnea - Cyanosis - Shock

What is the case fatality rate of Inhalation Anthrax without antibiotics?

85-97%

What is the case fatality rate of Inhalation Anthrax with antibiotic treatment?

75%

What is the case fatality rate of Inhalation Anthrax with intensive therapy?

45%

What are some differential diagnoses for Inhalational Anthrax?

- Mycoplasma pneumonia - Legionnaires’ disease - Psittacosis - Tularemia - Q fever - Viral pneumonia - Histoplasmosis - Coccidioidomycosis - Malignancy

What is the “other” (Not the ones mentioned previously) anthrax associated with?

Septicemia and localized injury

What are the two important plasmids in pathogenesis?? pOX1 pOX2

What does pOX2 encode?? Proteins that synthesize polyglutamic acid capsule

What does pOX1 encode?? Protective antigen (PA) Lethal factor (LF) Edema factor (EF)

What is formed when PA combines with LF?? Lethal toxin (LT)

What is formed when PA combines with EF?? Edema toxin (ET)

What does 7 x PA form?? Heptamer that creates a pore in the cell membrane

What are the effects of intravenous LT in mice (4)?? Shock, vascular collapse, generalized hypoxia

What are the effects of intravenous ET in mice (4)?? Tissue damage, organ failure, hemorrhage

What happens when both toxins are administered?? Increased severity, onset of symptoms, and mortality

What type of enzyme is Lethal Factor?? Zinc dependent metalloproteinase

What does LT cleave in the MAPK pathway?? MKKK (mitogen-activated protein kinase kinases)

What is the consequence of LT activity on MAPK pathways?? Shut down of ERK, JNK, and p38 pathways

How does LT affect immune functions?? Impairment of host defense and immunity

What immune cells are affected by LT?? - Macrophages - Neutrophils - Dendritic cells - Lymphocytes

What is inhibited in neutrophils by LT?? Chemotaxis and filamentous actin assembly

What is decreased in neutrophils due to LT?? Production of superoxide anions

What are macrophages important for?? Mediators of inflammatory responses Produce pro-inflammatory cytokines (e.g. TNF-α, IL-6, IL-1β, IL-10) Impaired MAPK activity

What do cytokines do in inflammation?? - Activate immune responses - Direct inflammatory responses - Determine magnitude of responses

What is the effect of lethal toxin on macrophages (3)?? - Induces swelling and lysis (necrosis) - Increases cation permeability - Causes ATP depletion and mitochondrial dysfunction

What is Nalp1B gene's role in macrophage death?? Codes for NLR proteins which activates inflammasomes and caspase 1 and induces inflammatory cascade leading to macrophage death

How does lethal toxin affect Wnt target genes?? Inactivates GSK-3B kinase Increases macrophage necrosis

What role does LRP6 play in macrophages?? Assists in protective antigen uptake Impaired by lethal toxin

How does lethal toxin block macrophage survival?? Inactivates NF-κB Allows TNF-α to induce apoptosis

What is the effect of lethal toxin on dendritic cells and T lymphocytes?? Impairs cognitive interactions and decreases up-regulation of co-stimulatory molecules. Can cause anergy (tolerance) and apoptosis

What does edema factor do in cells?? Increases cellular cAMP levels which activates Protein Kinase A

How does edema factor affect intracellular cAMP?? Causes loss of intracellular cAMP homeostasis

What are the effects of elevated cAMP due to edema factor?? Impairs phagocytosis Decreases neutrophil and macrophage function Inhibits T lymphocyte proliferation

How do lethal and edema toxins work together?? Cooperate synergistically Target similar cell types Operate through different mechanisms, increasing toxicity

What is produced by melanoma cell lines following treatment of lethal toxin?? Melanin Characteristic black pigment in skin lesion (cutaneous anthrax)

What are the two microenvironments mentioned in ecology?? 1) Low-lying depressions with standing water 2) Rock lands with dry courses of water

Why is anthrax common in dry weather?? Forces grazing animals to feed closer to the ground

How do infected animals shed microbes?? In urine In feces

What transfers organisms from animal to animal?? Mosquitoes Biting flies

What are the three forms of anthrax illness in animals?? 1) Peracute (sudden death) 2) Acute (24-48 hours ill) 3) Subacute-chronic (< 48 hours)

What are signs of peracute infection in ruminants (4)?? - Sudden death - Bloody discharge from body orifices - Incomplete rigor mortis - Rapid bloat

What are the symptoms of anthrax in equines (6)?? - Ingestion - Enteritis - Severe colic - High fever - Weakness - Death (48-96 hours)

What causes swine death from anthrax (6)?? - Laryngeal edema - Asphyxiation - Ingestion of spores - Anorexia - Vomiting Enteritis

What are the clinical signs in dogs and cats for anthrax?? - Resistant to contaminated raw meat - Fever Enteritis Edema of neck Death

What is the diagnosis protocol for anthrax (3)?? - Never open carcass - No necropsies - Sample blood from closed system

What is the treatment for anthrax?? Penicillin Ciprofloxacin Doxycycline

What is the preferred disposal method for anthrax carcasses?? Incineration Burn to ash Decontaminate ashes

What is the vaccination recommendation for anthrax?? Vaccinate in endemic areas Use Sterne strain vaccine

When does immunity occur after vaccination?? Within 10 days following injections

Is the vaccine approved for pets?? Yes, but it's 'off label' and can cause reactions

What should be done if there is a control situation?? - Report to authorities - Quarantine the area - Do not open carcass

How should carcasses be destroyed?? Burn (best-slow and hot) or bury with decontamination

What is a recommended method for decontaminating soil?? Use hydrogen peroxide, peracetic acid, or 10% formalin

What is the recommended bleach solution for surfaces?? Household bleach for preliminary disinfection

What are the bioweapon risks associated with Bacillus anthracis?? Transmission by respiration, stability in spore form, and high mortality

What is the mortality trend for treatment after multiple days of exposure?? Similar to no treatment

Is Anthrax a problem at the national level?? Potential for exports to be closed.

What is the main public health problem associated with anthrax?? Bioterrorism

How does anthrax impact livestock?? Not an economic problem compared to public health issues

What do all bioterrorism pathogens have in common?? Significant public health concerns and economic costs