Epidemiology and vax wk 4

• source of disease agent, transmission and host
• can break at any level.

various methods, used with objective of preventing occurrence, limiting spread or working towards elimination/eradication

• control infectious host: test and removal (cull), mass therapy
• control fomites and vectors

• quaratine, isolation, population density reduction
• reduce probability of exposure of susceptible hosts.

increase resistance of susceptible: improve nutrition, reduce stress, chemoprophylaxis, vaccination, maximize maternal antibodies

• 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).

• 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)

reduction of the frequency of disease in a population to an acceptable level

larger scale project to control/eradicate a disease (compulsory or voluntary)

total elimination of a disease due to removal of its cause.  Requires a definition of an area.  Time-limited process.

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)

• ID infectious agents
• acquire information
• evaluate host-pathogen-environment interactions
• adapt strategies
• monitor strategies
• develop surveillance system

remove vectors - destroy habitat or destory vector via insecticides etc

• 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

• 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

• 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.

drug or chemical administrated to prevent disease (malaria meds)

• 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

• 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)

• FeLV and Rabies vaccines
• specific to cats
• very low risk
• possibly linked to adjuvent
• vaccinate low on limbs

• 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)

• mucosal immunity required for pathogens that invade mucosa (IgA)
• systemic immunity required for paraenteral and disseminated infections

• 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

• 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.

• 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)

non-pathogenic, but live.  Can carry killed and subunits, but induce cytotoxic lymphocytes, memory and possibly mucosal responses

• Plasmid-encoded antigens expressed in cytosol.  
• Taken up by dendritic cells = cytotoxic lymphocyte responses
• taken up by other cells, cause antibody response

• 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

• 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

• made of soap, cholesterol, phospholipid
• surround antigen in nanoparticle, fuse with membrane to deliver to cytosol, presented by MHC class I to stimulate CD8+

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

• 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.

number of cases (no info about study population size!)

• Probability
• ratio
• (sick/total = attack rate)
• we care most about this one.

• denomenator is time-units (cow-month)
• 40 cows in 100 herd over 2 months 
• 40/(100 x 2) = 0.2 cases/cow-month

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.

• animals susceptible to condition of interest in defined place and time.
• Need to know unit of counting and case definition.

• 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)

• 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.

• 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.

• 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

• 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

• new cases since onset / total at risk at onset x 100
• measure of RISK (used where risk period is limited)

• describes infectiousness/ease of spread of infectious agents
• = (new cases since onset - initial) / (total at risk at onset) x 100
• measure of RISK

• proportion of animals WITH a disease that die from it
•  = animals dying/cases of disease
• measure of risk

• when appropriate denominator is unknown
• mortality = dying of disease / total deaths (regardless of cause)
• morbidity = cases of disease / total sick (regardless of cause)