Epidemiology and vax wk 4

  1. factors in disease transmission
    • source of disease agent, transmission and host
    • can break at any level.
  2. disease control
    various methods, used with objective of preventing occurrence, limiting spread or working towards elimination/eradication
  3. eliminate source of disease
    • control infectious host: test and removal (cull), mass therapy
    • control fomites and vectors
  4. prevent transmission of infection
    • quaratine, isolation, population density reduction
    • reduce probability of exposure of susceptible hosts.
  5. reduce host transmission
    increase resistance of susceptible: improve nutrition, reduce stress, chemoprophylaxis, vaccination, maximize maternal antibodies
  6. strategies of control/eradication
    • selective slaughter/euthanasia: remove diseased or + for protection of majority (Johne's Disease or rabies)
    • depopulation: One + animal = entire population destroyed.  Only okay in severe epidemics (foot and mouth, newcastle disease, highly pathogenic avian influenza).
  7. criterion for culling
    • permanent infection
    • treatment not effective as in viral or long, expensive and not effective treatment as in brucellosis or tuberculosis
    • potential for spread high
    • major zoonosis
    • exotic or rare disease
    • absence of reservoir (wildlife or soil)
  8. disease control
    reduction of the frequency of disease in a population to an acceptable level
  9. disease control program
    larger scale project to control/eradicate a disease (compulsory or voluntary)
  10. eradication
    total elimination of a disease due to removal of its cause.  Requires a definition of an area.  Time-limited process.
  11. Mass therapy
    restricted to local situation where all POTENTIALLY infected animals are treated without testing.  Due to emergencies, high-risk segments of population, target clusters (treat intermediate host like echinococcosis in sheep by treating dogs), impossible to treat individually (fish)
  12. steps in disease control/eradication
    • ID infectious agents
    • acquire information
    • evaluate host-pathogen-environment interactions
    • adapt strategies
    • monitor strategies
    • develop surveillance system
  13. vector control
    remove vectors - destroy habitat or destory vector via insecticides etc
  14. reservoir control
    • reduce/prevent contact with wildlife
    • reduce/control populations (poison rats, trap, forbid sale of dangerous (too small pet turtles for salmonellosis)
    • free mass rabies vaccination
    • control of cat/dog reproduction
    • stray cat/dog euthanasia
  15. Quarantine
    • isolation of animals suspected of being infected/exposed (NOT SICK, that's isolation)
    • for imported animals
    • duration depends on incubation period (before clinical signs) or on time before confirmation of disease or time to become non-infectious
  16. isolation
    • separate SICK (not like quarantine) during infectious period.  Most useful if subclinical carriers are not as important in spreading disease
    • Trace back infection to source
    • follow up if chance of spread to another farm.
  17. therapeutic or prophylactic chemotherapy
    drug or chemical administrated to prevent disease (malaria meds)
  18. core vax for cats and dogs
    • feline panleukopenia
    • feline rhinotracheitis (herpesvirus-1)
    • feline calicivirus
    • rabies
    • feline leukemia virus (only when warranted)
    • canine distemper
    • canine parvovirus
    • hepatitis (canine adenovirus type 1 with cross-reactive CAV-2 vaccine)
    • rabies
  19. reasons vaccines fail
    • improper shipping/storage (need to be kept cold), particularly live vaccines
    • improper administration (incorrect route or failure to boost)
    • improper manufacture
    • appearance of new pathogenic strains (surveillance programs and autogenous vaccines)
    • immune status of host (responses diminish with age. Sex, breed, concurrent infections, immunodeficiencies)
    • interference by maternal antibodies
    • some vaccines just suck (esp for latent infections or those that don't confer immunity)
  20. fibrosarcomas in cats
    • FeLV and Rabies vaccines
    • specific to cats
    • very low risk
    • possibly linked to adjuvent
    • vaccinate low on limbs
  21. humoral/antibody responses vs cell-mediated responses for clearance of which?
    • humoral (antibody) responses required for clearance of extracellular pathogens, requires CD4+ and production of both Th1 and Th2 cytokines
    • cell-mediated responses and CD8+ required for clearance of intracellular pathogens, but intracellular often need BOTH (live vaccines)
  22. vaccines and mucosal, systemic immunity
    • mucosal immunity required for pathogens that invade mucosa (IgA)
    • systemic immunity required for paraenteral and disseminated infections
  23. Live vaccines stimulates which kinds of immunity?
    • humoral and cell-mediated immune responses
    • provide antigens and PAMPs to both MHC class I and II pathways
    • If you want CD8, you need live
    • Can breach epithelial barrier and induce local (IgA) responses
    • Persistence may restimulate T cells, induce LONG-TERM memory
  24. vaccines in the gut
    • killed and subunit degraded in stomach and small intestine, sampled as food, result in oral tolerance (prevents reaction to antigen)
    • Live INFECTS, so can breach epithelial barrier and stimulate local as well as humoral and cell mediated responses.
  25. disadvantages of modified-live
    • residual pathogenicity = side effects (fever, pain, swelling, malaise, abortion, encephalitis
    • reversion to virulence (back mutation, recombination vs emergence of new strains) (most rationally attenuated)
    • pathogenic in non-host species (da2pp deadly in ferret and fox)
    • iatrogenic disease in target species
    • immunosuppression of host
    • biological instability
    • contamination (oncogenic viruses, prions)
  26. Vectored vaccines advantages
    non-pathogenic, but live.  Can carry killed and subunits, but induce cytotoxic lymphocytes, memory and possibly mucosal responses
  27. DNA vaccines
    • Plasmid-encoded antigens expressed in cytosol.  
    • Taken up by dendritic cells = cytotoxic lymphocyte responses
    • taken up by other cells, cause antibody response
  28. adjuvents
    • boost immunogenicity of co-administered antigens
    • contain carrier (alum) and/or immunomodulatory substance (bacterial cell wall components)
    • Directly stimulates immune responses to co-administered antigens via PRR - ramp up expression of costimulation on APC and cytokines
  29. carrier substances
    • vehicles for delivery of antigen (alum, oil, lipid, detergent, latex beads, biodegradable polymers, large proteins)
    • are more readily taken up by APCs (particulate, phagocytosed)
    • depots for slow release (increase memory?)
    • stimulate cytotoxic lymphocytes by delivering antigen to cytosol
    • can provide additional epitopes for t-cells
  30. Protein carriers (liposomes, ISCOMS)
    • made of soap, cholesterol, phospholipid
    • surround antigen in nanoparticle, fuse with membrane to deliver to cytosol, presented by MHC class I to stimulate CD8+
  31. Hapten/carrier effect
    Hapten: small molecule antigen (sugar, nucleotide, etc) lacking T-cell epitopes but can be recognized by B cell.  Don't stimulate immune response alone, but are paired with protein carrier.  T cell reacts to protein, but that causes B cell to recognize hapten and make antibody
  32. Protein carriers (conjugate vaccines)
    • provide additional epitopes to stimulate T cells. Can boost immune response to T-independent antigens that may not stimulate immune alone.
    • Hapten/carrier effect
    • Paired with a protein (can be a toxin like tetanus or just a protein).  Protein stimulates T, so B gets the signal to respond to the hapten.
  33. Count in epidemiology
    number of cases (no info about study population size!)
  34. proportion in epidemiology
    • Probability
    • ratio
    • (sick/total = attack rate)
    • we care most about this one.
  35. rate in epidemiology
    • denomenator is time-units (cow-month)
    • 40 cows in 100 herd over 2 months 
    • 40/(100 x 2) = 0.2 cases/cow-month
  36. Odds
    ratio where the numerator is NOT part of the denomenator (40 out of a hundred cows are sick, then 40/(100-40) are the odds of being sick (or 4/6 = 2/3 = 2:3, so the odds are 2 to 3 of getting sick.
  37. population at risk (PAR)
    • animals susceptible to condition of interest in defined place and time.
    • Need to know unit of counting and case definition.
  38. Prevalence
    • proportion of existing cases of disease present in population at a given point of time
    • P = number of cases / population at risk (susceptible regardless of new or existing case)
    • number of infected farms/total number of cattle farms.  
    • Could be POINT prevalence or PERIOD prevalence (over a longer period of time)
  39. Incidence
    • number of NEW cases over a period of time (make sure you have a definition of NEW case, esp for reinfected)
    • Can be cumulative incidence (incidence risk), incidence density (incidence rate) or inceidence count.
  40. incidence risk (Cumulative incidence) = R
    • probability (proportion) than an animal will contract or develop a disease in defined time period 
    • Answer can be 0-1.  Good for individual predictions (likelyhood a dog will develop a disease in the next year)
    • R = (NEW cases over a period) / (PAR and disease free at start of the period)  PAR = animals WITHOUT disease.
    • If animals withdraw in the middle (slaughter) - just few?  Take the average. A lot?  use incidence rate.
  41. difference between prevalence and incidence risk
    • Prevalence: (existing cases at a point) / (all examined) at a POINT in time = risk of having disease at any point
    • incidence risk: (new cases among initially uninfected) / (initially uninfected) over DURATION = risk of getting disease in a time period
  42. mortality rate (+ cause specific and age specific)
    • mortality rate = deaths over a period / animals at risk at the start
    • cause-specific mortality rate = deaths due to disease of interest / animals at risk
    • age-specific = deaths over a period of an age / animals at risk among that age
  43. attack rate (in outbreak)
    • new cases since onset / total at risk at onset x 100
    • measure of RISK (used where risk period is limited)
  44. secondary attack rate
    • describes infectiousness/ease of spread of infectious agents
    • = (new cases since onset - initial) / (total at risk at onset) x 100
    • measure of RISK
  45. case fatality
    • proportion of animals WITH a disease that die from it
    •  = animals dying/cases of disease
    • measure of risk
  46. proportional morbidity/mortality rate
    • when appropriate denominator is unknown
    • mortality = dying of disease / total deaths (regardless of cause)
    • morbidity = cases of disease / total sick (regardless of cause)
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Epidemiology and vax wk 4
epidemiology vax 4