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factors in disease transmission
- source of disease agent, transmission and host
- can break at any level.
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disease control
various methods, used with objective of preventing occurrence, limiting spread or working towards elimination/eradication
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eliminate source of disease
- control infectious host: test and removal (cull), mass therapy
- control fomites and vectors
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prevent transmission of infection
- quaratine, isolation, population density reduction
- reduce probability of exposure of susceptible hosts.
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reduce host transmission
increase resistance of susceptible: improve nutrition, reduce stress, chemoprophylaxis, vaccination, maximize maternal antibodies
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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).
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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)
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disease control
reduction of the frequency of disease in a population to an acceptable level
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disease control program
larger scale project to control/eradicate a disease (compulsory or voluntary)
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eradication
total elimination of a disease due to removal of its cause. Requires a definition of an area. Time-limited process.
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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)
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steps in disease control/eradication
- ID infectious agents
- acquire information
- evaluate host-pathogen-environment interactions
- adapt strategies
- monitor strategies
- develop surveillance system
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vector control
remove vectors - destroy habitat or destory vector via insecticides etc
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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
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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
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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.
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therapeutic or prophylactic chemotherapy
drug or chemical administrated to prevent disease (malaria meds)
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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
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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)
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fibrosarcomas in cats
- FeLV and Rabies vaccines
- specific to cats
- very low risk
- possibly linked to adjuvent
- vaccinate low on limbs
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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)
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vaccines and mucosal, systemic immunity
- mucosal immunity required for pathogens that invade mucosa (IgA)
- systemic immunity required for paraenteral and disseminated infections
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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
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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.
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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)
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Vectored vaccines advantages
non-pathogenic, but live. Can carry killed and subunits, but induce cytotoxic lymphocytes, memory and possibly mucosal responses
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DNA vaccines
- Plasmid-encoded antigens expressed in cytosol.
- Taken up by dendritic cells = cytotoxic lymphocyte responses
- taken up by other cells, cause antibody response
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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
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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
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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+
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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
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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.
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Count in epidemiology
number of cases (no info about study population size!)
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proportion in epidemiology
- Probability
- ratio
- (sick/total = attack rate)
- we care most about this one.
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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
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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.
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population at risk (PAR)
- animals susceptible to condition of interest in defined place and time.
- Need to know unit of counting and case definition.
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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)
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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.
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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.
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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
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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
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attack rate (in outbreak)
- new cases since onset / total at risk at onset x 100
- measure of RISK (used where risk period is limited)
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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
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case fatality
- proportion of animals WITH a disease that die from it
- = animals dying/cases of disease
- measure of risk
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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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