ANSC 375 Final study 1

  1. Emerging Diseases
    = diseases of infectious origin whose incidence in humans has increased in the last 2 decades or threatens to increase in the near future
  2. zooanthroponosis
    transmission is from animal (or invertebrate) to people
  3. anthrozooponosis
    transmission is from human to animal (ie CMV in monkeys)
  4. Emerging Disease agents (3 broad groups)
    • 1) previously ID agent in a new geographic location (= bad news ie would be like AB Ontario getting FMD)
    • 2) previously ID agent presenting in a previously unsusceptible species (naïve species) (ie paramixovirus can move species)
    • 3) Previously unknown agent detected for the first time (ie always was present just never ID)
  5. Determinants of emerging diseases (6)
    • Human demographics and behavior ie growing population
    • technology and industry ie globalization
    • economic land use and industry
    • international (local) travel and commerce
    • microbial adaptation and change
    • disruption (changes) of public health measures
  6. Disease:
    • Maintenance: each host has to be a source of infection for at least 1 other host to maintain the disease in a population
    • Propagation: each new host has to be a source of infection for more than 1 other host to propagate the diseases in a population
  7. Influenza
  8. 3 Types of Influenza
    • Type A: multiple species (most virulent)
    • -avian is the natural host
    • -Hemagglutinin (H or HA) -these antigens bind the virus to the cell
    • -neuraminidase (N or NA)- these antigens cleave neuraminic acid from mucin allowing viral release from the cells
    • -H1N1, H1N2m H3N2 are among ppl
    • Type B: affects humans
    • -less severe symptoms
    • -can vaccinate seasonal (2 strains A and 1 of B - cross protect because no accurate prediction of strain type)
    • Type C: human and swine
    • -rare occurrence
    • -mild symptoms
  9. Fowl Plague
    • Swollen feet- congestion and edema
    • Lung- congestions, hemorrhage and edema
    • ****:
    • Epicardial petechial hemorrhage
    • Intestinal hemorrhage
    • Proventricular hemorrhage

    • so basically just drown in fluid and blood
    • sudden death
    • drop in egg production
    • CNS signs
    • swollen combs cyanotic (blue)
    • resp signs
  10. Swine Flu
    • WW1 soldier Id with H1N1
    • swine- have glycoside linkages on tracheal epithelium--> avian influenza binds to these (pigs generate a poor antibody response)--> incorporates changes--> and give to people
    • *** Humans and pigs have similar internal protein genes and so their influenzas affect
    • each other (marked genome arrangement)
    • depression
    • anorexia
    • pyrexia
    • cough
    • muscular wearkness
    • mucus discharge from conjunctiva and nose
  11. Spanish Flu
    • Swine
    • "ring around a rosey"
    • more deaths than ww1 itself
    • intersitual pneumonia
    • treathments: supportive, antiviral, vaccinations, quarantine, slaughter
  12. Common theme in "terrorism"
    involves violence or the threat of violence
  13. Bioterrorism
    Biological agents targeting humans, animals, plants
  14. Agroterrorism
    • biological, chemical, and radioactive agents targeting mainly agriculture products, animals, and crops
    • can also have impact on workers and other industries involved in the food supply
  15. What is the goal of agroterrorism?
    • To cause economic crisis in the agriculture and food industries, social unrest, and loss of confidence in government (this is what they want to topple gov and cause civil unrest so they leave their country alone)
    • killing animals and plants is just the means to an end and not the direct goal
  16. Why are agro and bio terrorism not used often?
    Can not control infectious diseases and so they could turn around and get back to the terrorists' country
  17. Agent agroterrorism means Introduction
    • obvious accidental by travelers vs secretive (weapon)
    • simultananeous into multiple areas
    • natural vs intentional
    • real vs hox (doesn't even have to be real if media misinterprets then there is loss of consumer confidence as well as costs)
  18. Identification of agro terrorism
    • If 2 or more of these are present it may be suspected:
    • odd presentations of animal deaths
    • suspicious history of incidence
    • many areas across region or country hit simultaneously
    • odd presentation of the disease (ie unusual signs)  
    • exotic disease causing morbidity and mortality
    • common disease with increased levels of morbidity and mortality
  19. Why is there less chance of retaliation in agro terrorism ?
    • attack on crops or animals is not as emotional as an attack on people
    • it is difficult to trace back to plausible deniability!-could go undetected for a while
  20. History of Agro terrorism
    • -pseudomonas mallei
    • -WW1-infected Russian horses (therefore supplies and transportation)
    • -WW2-Japanese and germans experimented
    • -post WW2- soviets experimented and so did the US
  21. Why did the use of bioweapons stop?
    • military reasons- could not guarantee success OR control!
    • more effective weapons (ie nuclear)
    • banning of chem and bioweapons
  22. Desired outcomes of bioweapons
    • Potential for mass disruption: weaken workforce, destabilize gov (weaken political govs, and possibly more extreme policies)
    • shocking public images
    • loss of freedoms (movement of ppl and products)
    • would increase food costs and could lead to trade embargos and food shortages (3rd world countries)
    • loss of consumer confidence- in product safety
  23. Costs of agroterrorism attacks?
    • local, regional, and national economies are damaged (ie trade embargos that could affect many products)
    • direct costs of control and eradication: diagnosis, surveillance, disinfection, salaries, welfare slaughter extension: other industries: restaurants,  suppliers, vacationing and tourism
  24. What affects livestock vulnerability
    • Density of animals
    • mixing of animals in auction markets, transport, feedlots, slaughter plants
    • no previous immunity of exotic disease and few vaccines to stop outbreak
    • centralised feed supply and distribution (ie if contaminate food it would affect many animals in many locations)
    • poor records of animals
    • expanded trade and travel along with the ever expanding danger of exotic diseases from trading countries
    • poor monitoring at international borders
    • movement of wildlife uncontrolled over borders
    • inadequate on farm biosecurity
    • lack of foreign animal disease awareness
  25. Prevention... against agroterrorism attack effects
    • Excellent: biosecurity, surveillance (rapid monitoring) and reporting. Along with effective responses
    • On farm: good sanitation, restricted movement and entry
    • Local: control of auction markets and other forms of animal mixing, animal ID tracing, control movement
    • Regional: control movement, notify local gov agencies, quarantine imports
    • National: same as regional and also notify OIE of outbreaks
    • Agencies involved: CFIA, Public health agency of CN, law enforcement, military
  26. Other names for Anthrax
    • Malignant pustule
    • malignant edema
    • Woolsorters disease
    • raypickers disease
    • maladi charbon
    • splenic fever
    • black bane
  27. What is Anthrax (scientific name) ?
    • Bacillus anthracis
    • a disease of warm blooded animals (mainly livestock- humans as well)
    • Bacteria: gram +, non-motile, spore forming
    • vegetative form: multiplies and hills  and spores form 'box cars' in rows --> survive environment
  28. Anthrax spores
    • the predominant form in environment-> need nutrient poor environment and presence of O2 to sporulate
    • spores germinate in environments rich in aa, nucleosides, glucose (blood and tissue)
    • very resistant to: temp extremes, pH, dessication, and chemicals (disinfectants), UV light--> lives 50-250 years as spore form
    • spore inactivation 5% hypochlorate (strong bleach), paraformaldehyde vapor, phenol or autoclaving
    • LD 50!
  29. What are the three forms of human anthrax?
    • cutaneous
    • gastrointestinal
    • inhalational
    • (some less common other ones: meningitis, sepsis, renal, opthamalic)
  30. Cutaneous anthrax (humans)
    • most common kind- 95% of cases
    • enters through cuts or abrasions (ie through handling contaminated animals, products, or ppl)
    • incubation 1-12 days
    • Infection:begins as small pupule to vesicles to eschar (eschar- necrotic black ulcer) and sometimes to secondary vesicle
    • Other symptoms: swollen lymph nodes, fever, malaise, and headache
    • dead septicemia or toxemia
    • 5-20% mortality without antibiotics
    • <1% with antibiotics
  31. Define: septicemia vs bacteremia vs toxemia
    • septicemia: actively dividing bacteria in blood
    • bacteremia: bacteria in blood
    • toxemia: bacteria that release a lot of toxins
  32. Differential diagnosis for cutaneous anthrax
    • spider bite
    • ecthyma gangrenosum
    • ulceroglandular tularemia
    • plague
    • staphylococcal or streptococcal cellulitis
    • herpes simplex virus
  33. Gastrointestinal Anthrax
    • usually appears in livestock ingesting spores and then the people eat the contaminated meat
    • 1-7 day incubation
    • Oropharynx: base of tongue, tonsils, sore throat, dysphagia, lymphadenopathy
    • Lower GIT- acute necrosis and inflammation of the gut, nausea, vomiting (+/- blood), dysentery (bloody diarrhea), fever, and malasia
    • no treatment= ~25% death
    • Death: septicemia, toxemia, and shock
  34. Differential diagnosis for GIT anthrax
    • acute appendicitis
    • ruptured viscus
    • diverticulus
    • diseases that cause actue cervical lymphaditis or acute gastritis
    • dysentery (bloody diarrhea)
  35. Inhalational Anthrax
    • Originally known as "woolsorters disease"
    • incubation 1-43 days
    • bioterrorism uses this type
    • highly lethal
    • case fatality= 85-97% without antibiotics
    • **75% die even with antibiotics
    • 45% mortality with intense therapy (death can occur within hours of symptoms)
    • get mediastinal widening
  36. Differential diagnosis for inhalation anthrax
    • mycoplasmal pneumonia
    • viral pneumonia
    • legionhaires disease
    • histoplasmosis (fibrous mediastinitis)
    • psiffacosis
    • tuleremia
    • q fever
    • coccidiomycosis
    • malignancy
  37. Other types of anthrax
    meningitis = 50% of ppl with inhalation anthrax goes to brain
  38. Pathogenesis pathway of anthrax***KNOW
    • lung-->
    • macrophage engulfs the spore-->
    • spore germinates in macrophage in lymph nodes and releases from dead macrophage-->
    • vegetative bacteria divides extracellularly (septicemia) and release toxins (endotoxemia)-->
    • Mild illness of fulminating disease and rapid death (shock, hemorrhage, dyspnea (difficult or labored breathing))
  39. The 2 plasmids that promote the anthrax toxins
    • pOX1- carries protective antigen (PA), lethal factor (LF), and edema factor (EF)
    • pOX2 -encoded for proteins that synthesis polyglutamic acid capsule (helps to protect dividing bacteria to evade engulfment and phagocytosis)
  40. What is the function of PA (protective antigen) carried by pox1 in anthrax? **************
    • PA + LF = lethal toxin (LT)
    • PA + EF = Edema toxin (ET)
    • mediates entry into the cytosol
    • (PA = pore in membrane that allows LT and ET inside the cell)
  41. LT (Lethal Toxin) of Anthrax
    • *is a zinc dependant metalloproteinase
    • the catalytic domain of LT exclusively cleaves mitogen-activated protein kinase kinase kinases (MKKK)
    • (MKK is a middle component of phosphorylation cascade -involved stimuli include growth factors, stress responses and cytokines)
    • consequences: shut down of ERK JNL and p38 pathways
    • common affect: impairment of host defenses and immunity. Virtually all cells involved in immune functions require MAPK pathways for proper function
    • alters the innate immunity (macrophages and dendritic cells) and adaptive immunity (lymphocytes)
  42. How does LT affect Neutrophils?
    • inhibition of chemotaxis (movement) - loss of filamentous actin assembly
    • decrease production of superoxide anions- drop in puss production -augmented if pre exposed to TNF-alpha
    • cripples innate immunity
  43. How does LT affect macrophages?
    • macrophages are important mediators of inflammatory responses and produce proinflammatory cytokines -->which are important for the activation, direction and magnitude of inflammatory and immune responses----LT impairs MAPK activity
    • inflammatory cytokines are immune system messengers and anthrax kills the macrophages that produce the cytokines 
    • *LT causes reduced chemotaxis and
    • phagocytosis (similar to neutrophils)
    • LT kills macrophages by inducing their swelling and and lysis
    • initially there is an influx of ions (k+) followed by ATP depletion, loss of mitochondrial function, shutdown of protein synthesis and eventual loss of membrane integrity
    • Know step by LT death of macrophages (on another card)
  44. *** 4 steps to macrophage death by LT
    • 1.  Activates inflammazones so the macrophages will digest internally: NalplB gene codes for NLB proteins (part of inlammazones)--> LT activates caspase 1 and inflammasomes induce and inflammatory cascade and macrophage death
    • 2. Modulation of Wnt target genes: inactivation of GSK-3B (kinase) = see increased macrophage necrosis
    • 3. LRP6 (LDL protein Receptor on macrophage) an a co-receptor wnt target genes: assist in protective antigen uptake into macrophages
    • 4. LT blocks survival pathways of activated macrophages: LT indirectly inactivates NF-KB (cell activation and cell survival) allowing TNF-alpha to induce apoptosis (so blocks survival of genes = apoptosis)
  45. Lethal Toxin affect on adaptive immunity
    • Important cognitive interactions between dendritic cells and T lymphocytes disturbed
    • decrease in up-regulation of co-stimulatory molecules ie "loss of 2nd signale" --- so therefore acquires anergy (body fails to tolerate) and apoptosis occurs
    • inflammatory cytokines
  46. What other cells does anthrax LT affect?
    • Melanin producing cells (ie melanoma cells)
    • FOLLOWING treatment of LT melanin is produced: characteristic black pigment in skin lesions (cutaneous anthrax)
  47. Anthrax Edema Factor (EF)
    • a calcium and calmodium dependant adenlyate cyclase
    • increases cellular cAMP which activates protein kinases which makes protein action
    • elevated cAMP affects cAMP levels in other compartments within the cell - thus loss of intracellular cAMP homeostasis
    • so have over stimulation and activation within the cell and it cant deal with it
    • impairs phagocytosis and superoxide anion production
    • increased cAMP blocks pathways and this necreases neutrophil, macrophage and T lymphocyte proliferation
  48. LT and ET TOGETHER
    • *cooperate synergistically (not additive)
    • together are more harmful to host
    • more potent effect because they target a similar spectrum of cell types but operate with different mechanisms (more toxic)
  49. 3 forms of Anthrax in Animals
    • 1) Peracute (sudden death)-ruminants
    • 2) Acute (24-48 hrs after appear ill)- ruminants and equine
    • 3) Subacute-chronic (<48hours) -swine, dogs, cats
  50. Anthrax in Ruminants
    • peracute and acute infection
    • sudden death
    • **bloody discharge from body orifices
    • incomplete rigor mortis
    • RAPID bloat
  51. Anthrax in Swine
    • sudden death - usually from localised swelling in throat - obstructive swelling
    • death by lack of O2
    • ingestion of spores: anorexia, vomiting, enteritis (GI anthrax)
  52. Anthrax in Equine
    • very prone to intestinal and enteritis forms
    • Ingestion: enteritis, severe colic, high fever, weakness, death
    • Insect bite/ vector: hot painful swelling, spread to throat, sternum, abdomen, external genitalia, death
  53. Anthrax in Dogs and Cats
    • Quite resistant- get if eat contaminated meat
    • clinical signs- fever, enteritis, edema of neck
    • death from aspiration, toxemia, septicemia
  54. Anthrax: Diagnosis and Treatments
    • Never open a carcass!
    • Sample blood: from a closed system and cover with disinfectant gause
    • treat with penicillin, ciproflaxin, slaughter, decontaminate, vaccinate
  55. Anthrax: Vaccinations
    • do a ring treatment to prevent spread
    • vaccinate in endemic areas
    • sterne strain- an attenuated spore vaccine licensced for use in livestock only
    • immunity within 10 days after injection
    • off label for pets- used in working dogs
  56. Anthrax: control
    • MUST report to authorities
    • quarantine area
    • don't open carcass
    • minimize contact
    • wear protective clothing
    • vaccination of susceptible animals
    • destroy carcasses: burn and bury
    • decontaminate soil: 50% lye or quicklime, hydrogen peroxide, peracute acid or gluteraldehyde
    • no high pressure cleaners!!!!!!
    • (they don't depopulate entire herd instead they vaccinate and watch)
    • surfaces: 1:10 household bleach
    • preliminary infection: 10% formaldehyde
    • cleaning: hot water, scrubbing, protective clothing
    • Final disinfection with: 10% formaldehyde & 3% peroxide, or 4% gluteraldehyde and 1% peracute acid
  57. ANTHRAX as a bioweapon
    • transmission by respiration, stability in spore form
    • mortality LARGE
    • need treatment right away: but don't have infrastructure and material to do it
  58. Anthrax: Livestock economics
    • National level problems: potential for exports to be closed but it hasn't happened- most places have anthrax so borders aren't shut
    • Regional level: not too many animals are affected, CFIA cant cover entire costs
    • PROBLEM: not as much an issue in livestock economics but huge human and public health impact
Card Set
ANSC 375 Final study 1
Some of the 375 terms and concepts