vaccines epidemiology wk2

transfer of pustular material to shallow cuts in the skin

• Edward Jenner - cow pox/smallpox ("vacca" = cow)
• (Louis Pasteur in 1800s, Fowl Cholera, Anthrax and Rabies)

vaccines > bacteria > parasites

• attenuated/modified-live: genetically engineered to be avirulent
• Heterotypic: different organism with similarities (cowpox vs smallpox, etc)
• vectored: made using recombinants, put gene from another pathogen into a vector to kick off immune

• live
• killed
• subunit

whole killed bacteria used as a killed vaccine

• protein fixatives: cross-linking agents like formalin, organic solvents like phenol/alcohol/acetone
• alkylating agents: iodoacetate, beta-propriolactone
• aziridine compounds: binary ethyleneimine
• lipid solvents: "split vaccines" against enveloped virus, takes the envelope off with a detergent like either, or non-ionic detergents like Triton X-100

• made to stimulate immune against a PART of a microbe
• bacterial virulence determinants: adhesions (fimbrae), toxoids (inactivated toxins), agglutinins, polysaccharide capsular material
• surface proteins on viruses and parasites: viral envelope proteins (Hep B), protozoan surface antigens

inactivated toxins, used in subunit vaccines

• genetic engineering to create better vaccines
• subunit antigens, live recombinant vaccines (rationally attenuate vs vectored), genetic/DNA vaccines

recombinant proteins made in cultured cells, stimulates immune against microbe based on one part

rationally attenuated

live pathogens with the genetic material altered to reduce virulence

• live attenuated viruses or bacteria (vectors) carrying genes for protective antigens from pathogenic microbes
• canarypox/avipox often used as a vector--causes very mild disease in mammals (our rabies and distemper are canarypox based)

• inject naked DNA into animal, taken up and made.  
• Plasmid DNA vectors carrying genes for protective antigens from pathogenic microbes
• West Nile Virus in horses

Hyper-immunize mom in last trimester to increase immunoglobulins in colostrum, make sure progeny get enough colostrum

vaccines that target multiple pathogens or multiple strains of the same pathogen in a single formulation or dose

• made from pathogens found in an individual, herd or geographical location and can only be used in that particular herd/flock
• custom for one farm

vaccines where antigen is covalently linked to a substance that enhances immunogenicity (double antigens for more potent vaccine)

effect on vaccinated animals have in protecting unvaccinated animals in a herd/population (lost when vaccinations are low)

vaccine that blocks transmission (provides little benefit to vaccinated individual

• a substance that boosts immunogenicity to co-administered antigens
• typically contain a carrier substance (like alum), an immunomodulary substance, or both.

• associated with eradication programs
• mass vaccinations in a circle around infected person or location

• high enough benefit and low enough risk to be used in most patients
• used for diseases that are: endemic to a region, of public heath significance, required by law, virulent/highly infectious, pose a risk of severe disease

study of disease in populations and factors that determine occurrence

individual that has met with an infectious agent in a way we know from experience may cause disease

• aka outbreak
• sudden, usually unpredictable increase in numbers of cases of infectious disease in a population.  Frequency greater than expected

disease occurs at expected frequency (often predictable).  Always present in population, usually at a stable low level

epidemic over multiple countries

disease occurring irregularly and halfhazardly; appropriate circumstances have occurred locally that produced small localized outbreaks

infections transmitted from one generation to the next by infection of embryo or fetus while in utero (mammals) or in ovo (birds, reptiles, amphibians, fish, arthropods)

• infections transmitted from any segment of a population to another (one puppy to another, zoonoses, etc)
• Direct is when a susceptible host contracts through physical contact with infected host
• indirect involves intermediate (living = vector or inanimate = fomite)

vectors are living, fomites are inanimate

any animal species, insect, soil or combination of these in which the infectious agent normally lives and multiplies so that it can be transmitted to a susceptible animal

all of body's defenses against infection (relative for most diseases--enough will overcome almost anything)

• resistance associated with cells or antibodies of the immune system.  Can be active or passive.
• active: immunity acquired by previous exposure to antigens of agent (previous infection or vaccination).  Can be life-long or just a few years.  
• passive: acquired through transfer of antibodies like colostrum, transplacental transfer or administration of hyperimmune serum (generally short)

• duration of contagious period
• amount of infectious agent an animal can transmit

time lapse between infection and ability to transmit

individual who harbors the organism but without clinical symptoms (subclinical)

• period of time between infection and development of CLINICAL SIGNS (not infectiousness).  
• Subclinical infections have latent period but not incubation period (because never have clinical signs

able to transmit virus but don't have clinical signs (ever, not a stage but an endpoint).  Have latent period but not incubation period.

• simplified version of a complex phenomenon
• animal models
• mathematical models

susceptible to infectious (rabies in Foxes)

• susceptible to infectious back to susceptible (e. coli in cattle, common cold)
• No immune/recovered period, straight back to susceptible

• susceptible, infectious, recovered.  Never susceptible again
• Malaria in humans, H1N1 in pigs

• susceptible, infectious, recovered, susceptible
• salmonellosis in cattle, seasonal flu.  Immune for a minute, then can get again

• susceptible, infEcted, infectious, recovered
• measles, chicken pox, FMD
• infected period before being infectious, lifelong immunity

• susceptible infEcted, infectious, recovered, susceptible
• infected period before becoming infectious, short immunity then back to susceptible (seasonal flu, ebola, equine influenza)

deterministic vs stochastic

• difference equations (discrete time steps like weeks, etc)
• vs
• differential equations (continuous time)

• rate of change of y (like number of infectious individuals) with respect to x (time)
• rate of change in number of individuals in a given category (infectious individuals) is given by 
• + the number who enter it
• - the number who exit it

• beta = cp (rate of susceptible to infectious)
• c is probability of contact between susceptible and infectious during the time interval and
• p is the probability of transmitting infection when contact occurs (required infectious dose and attack rate = cases/exposed)
• we rarely know C, so we just try to make beta fit.

rate of leaving the infectious state to enter recovered state = inverse of duration of infectious state (10 days of illness = 1/10)

• duration of infection
• x
• number of new infections produced per unit time
• = 
• number of new infections per infectious host during whole infection period (does not include time specifically)

• expected number of secondary cases produced by typical infected individual during entire infectious period in completely susceptible population (only applies at the beginning)
• Later, use R0*x where x is fraction of host population that is susceptible)
• R0 = (betaN/a) = cnN/a
• betaN is number of new infections each infectious host produces per unit time
• 1/alpha = duration of infection
• only applies to early stage of the outbreak

• R0>1 = exponential growth, epidemic
• R0=1 = stable growth, endemic
• R0<1 = incidence decreases over time, transmission eventually eliminated

• decrease alpha (duration of infection) by treatment or culling, vaccination
• decrease beta by decreasing contacts (quarantine, isolation, decreased stocking density) Or decrease probability of susceptible catching infection by vaccination

• 1/R0 
• If R0 = 10, infection will persist is susceptible is >10%
• What proportion vaccinated for herd immunity?  H=1-1/R0

• H = 1-1/R0
• minimum number we need to vaccinate to keep infection from spreading
• (if R0 is 2, we end up with 0.5, must vaccinate at least 50% of pigs)

modeling two populations (vector and susceptibles)

H=1-(1/R0)

R0*x where x is fraction of host population that is susceptible