Final Exam Epi Flashcards
Define epidemiology. What are epi’s two main uses?
The study of the frequency, distribution, and determinants of health- related states in populations, and the application of such knowledge to control health problems.
** Epi serves as an investigative tool and diagnostic tool to support preventive action against disease–> aimed to produce information for action
What is health?
A state of complete well being and not merely the absence of disease
What is One Health?
The collaborative effort of multiple disciplines locally, nationally, and globally to atain optimal health for people, animals, and the environment
How is the approach to epi slightly different than the traditional clinical approach?
The unit of concern is the population, as opposed to the individual. The “well” animals are just as important as the sick animal. The aim is prevention, not just treatment.
What disease has Australia successfully eradicated, making AUS the only major exporter in the world to do so? How?
Bovine Tuberculosis
*Recent history of ruminants on the continent
*Geographical isolation
*Strict biosecurity
* National commitment
* adequate compensation to farms for culled stock
* whole herd test and slaughter program
* database of cattle properties and laboratory test results
* prevention of establishment in potential reservoirs
* ongoing abattoir surveillance to demonstrate disease freedom
What does this indicate? Define the terminology.
Propagating Epidemic. An epidemic is the occurrence of a disease affecting a number of individuals in clear excess of what would be expected for the population in a specific region and period of time. An epidemic is about something changing that favours the spread of the disease.
** That is, the disease is clustered in SPACE AND TIME.
e.g. Ebola- movement of people meeting highly susceptible populations- so you get massive spikes.
When does this pattern occur?
Sporadic. The disease occurs infrequently and without a pattern in a population. E.g. Hendra
** The agent is usually maintained in:
- a reservoir host and only infrequently comes in contact with this host
OR
- carriers (hosts with inapparent infection)
** Clinical disease when factors tip the host-agent-environment balance
Endemic. Predictable pattern (long term trends, seasonal variation, cyclical variation). The disease is constantly present in a population in a given region, it is clustered in SPACE but NOT IN TIME. e.g. Ross River Virus- endemic mossie borne virus in Victoria- transmitted from native wildlife reservoirs to humans
** Stable longterm balance between host, agent, and the environment
** Source of major ongoing losses in animal production systems (parasites, mastitis, abortions)
** Environment important- disease in one region and not in another
Explain the importance of epi in veterinary practice
* Epi is about prevention
* Knowledge of disease transmission: Cat transmitting TB to humans and therefore disease control. Advising clients on how to ensure their family remains healthy, other animals in the home, neighbors/ friends animals are unaffected by their sick animal
* Herd immunity- encouraging vaccination in a non-compliant population therefore cutting down on parvo virus, for example
* Evidence based medicine- integrating the best research evidence with clinical expertise and each patients’ unique circumstances– epidemiology is the science underlying evidence based medicine
* Does a causal relationship exist? Is a key question we will answer everday when diagnosing, deciding on treatment, and of course prevention! Most infections have multiple causal components before the injury or disease can occur
What is an EID?
Emerging Infectious Disease
* newly recognized in a population
* known for some time but is rapidly increasing in incidence or range
* Mutation, mixing, and trafficking of pathogens
* Encroachment on wild animal habitats previously untouched– “spill over”
** 60% of EIDs are zoonoses and 72% of these are from wildlife reservoirs
Point source epidemic. Clustered in SPACE AND TIME. e.g. Cholera- one water point contaminated or food borne outbreak at a birthday party (poor food handling practices)
** steep up-slope and gradual down slope because no further susceptible animals at risk
What are the factors that tip the balance towards disease?
What is infectivity?
Ability of an agent to infect. Says nothing about the severity of disease.
What is pathogenicity?
The ability of an agent to produce disease in an infected host. (Virulence and infectivity).
What is virulence? What is the equation?
The ability of an agent to produce severe disease.
What is an EAD?
Emergency Animal Disease. An animal disease that requires an emergency response. It may be:
* Exotic- has penetrated quarantine barriers (e.g. Rabies)
* Emerging- start within Australia, previously unrecognized (e.g. Hendra)
* Re-emerging- known to occur in Australia, but now spreading more widely than previously (e.g. Bluetongue)
What is biosecurity?
Measures to protect populations of people and animals, plants, and ecological systems from infectious disease and other biological threats.
What is the incubation period?
The interval between effective exposure to an infectious agent and the appearance of the first sign of the disease in question.
What is the latent or prepatent period? What two periods is the animal in when in the “danger period?”
The interval between infection to shedding of the infectious organism.
* In the danger period in incubation period and latent period– shedding disease before clinical signs and symptoms
What is the iceberg effect?
Within a population, subclinical/asymptomatic disease is often the big problem. e.g. persistent carriers shedding disease constantly
What is the host?
Animal capable of being infected. Replication/ development of the agent typically occurs in the host.
What is the vector?
Animate object that transmits infection (insects with vector borne viruses)
What is a vehicle of transmission?
Inanmiate object that transmits infection e.g. fomites
What are carriers?
Infected host without clinical signs, potential source for others. The carrier state may be unapparent throughout infection (healthy or asymptomatic carrier) or may occur during the incubation period (an incubatory carrier in the danger period) or recovery phase for an animal with clinically recognizable disease (convalescent carrier).
What is a reservoir?
Source where agent normally lives (wildlife/soil/water)
What is a TAD? Examples?
Transboundary animal disease. Diseases that cross political or geographical borders.
* Serious socio-economic or public health consequences
* Major importance in trade of animals/animal products
e.g. FMD, Bluetongue, African Swine Fever, Newcastle Disease
What factors cause an epidemic to occur?
* A gross imbalance in favour of the agent:
* new strain (mutation)
* naive host population (viral trafficking)
* environmental shift (climatic change)
What factors shape a propagating epidemic curve? 6 of them!
* Incubation period: delays commencement and prolongs outbreak, waves may correspond to incubation period
* Infectious period: affects number of effective contacts by each infected host
* Herd immunity: > 75% of population resistant to infection, disease won’t propagate, cycling each time susceptible increase
* Density: influences number of contacts, effectiveness of contacts
* Infectivity of the agent
* Surveillance efficiency, reporting practices, and the validity of diagnostic tests
What can be a propagating epidemic that looks like a point source epidemic?
Short incubation period can mimic a point source epidemic
What is an epidemic curve? How is it useful?
A graph of the count of NEW CASES plotted against time on the X axis. It can provide useful info about the nature of causal agents.
Why do diseases often “cycle?” What do you always have to consider that has nothing to do with increase disease incidence?
Initially, the entire population can be susceptible, eventually when >75% of the population is no longer susceptible because they have had the disease, recovered, and are now immune due to vaccination, the disease can no longer propagate. However, eventually the population of susceptible animals MAY increase again and another outbreak can occur. In endemic situations, it is just maintaining itself in the population at a constant but relatively low frequency due to contact with susceptible animals… though there would be levels or resistance to disease present in the population due to antibodies, genetic resistance, etc.
** Always consider surveillance efficiency as it can falsely show an increase in number of cases
Does virulence make sense for an agent? What are two key factors? 2 examples of diseases on opposite ends of the spectrum.
* Over time the relationship between agent and host often moves from parasitic to commensal
* Balance between host and agent, in a given environment
* If illness impairs disease transmission: virulence does not favour the agent
* However, if severe illness or death does not impair transmission e.g. massive increase in shedding- Anthrax and “sit and wait” strategy then it does not impair transmission OR e.g. Adenovirus- causes mild URT infection in dogs- the ability of the host to move is critical because the virus labile in the environment – the dog requires close proximity to other dogs to transmit
** key factor is mode of transmission and resistance in the environment
What allows Influenza to cause pandemics?
Antigenic shift–> 2 different strains infecting the same animal. They can swap parts of their genome to produce a completely new SUBTYPE, therefore the population is now 100% naive.
* Antigenic drift allows the virus to create a new strain and jump species, but not as likely to cause a pandemic as there will be some cross over with immunityin the population from old strains likely
What are the millennium development goals?
- Eradicate extreme poverty and hunger
- Achieve universal primary education
- Promote gender equality and empower women
- Reduce child mortality
- Improve maternal health
- Combat HIV/AIDs, Malaria, and other diseases
- Ensure environmental sustainability
- Global partnership for development
In regards to descriptive studies, why are studies based on prevalence and studies based on incidence not equivalent?
Studies based on prevalent cases are less clear about causation then those based on incidence.
* Prevalence studies consider factors contributing not only to the disease development but also the survival and/or duration of disease.
*While incidence studies examine only factors that contribute to the development and therefore causes of disease.
What is R-naught?
Basic reproductive ratio. R-naught represents the number of new (secondary) infections that arise, on average, from the introduction of one infected individual into an entirely susceptible population (e.g. at the beginning of an epidemic), assuming random (non-preferential) mixing. IT is the MEASURE OF TRANSMISSION POTENTIAL OF AN INFECTION.
** It depends on the number of contacts between individuals in a population (in each time period), the probabily of transmission (per contact), and the duration of infectiousness (infectious period).
** If R-naught> 1 then an outbreak is expected to spread, if R-naught < 1 then, on average, each infected individual infects less than 1 other individual and the epidemic should theoretically die out
What are the drivers of spread?
* Basic reproductive ratio
* Herd immunity and vaccination
What are the measures of disease?
* Case definitions
* Proportions, rates, and ratios
* Prevalence and incidence
* Mortality rates
What is true about R-naught across a population?
It is not uniform across a population, it is influenced by:
What is the effective reproductive ratio? Why do epidemics die out?
Rt represents the average number of secondary infections produced by each infected individual that enters a population that contains non-susceptible individuals or is subject to disease control measures (e.g. as an outbreak progresses).
** Epidemics die out because of decreased effective contact (c x p) AND decreased susceptible proportion (St/N) – Not typically because of a change in virulence of the organism.
What is fcp? How do you determine fcp? What is the fcp of Equine Influenza?
Critical percentage for vaccination to prevent infection. It is the HERD IMMUNITY THRESHOLD. It is the proportion of the population that needs to be immune in order to reduce the incidence of disease.
What is herd immunity?
The resistance of a population to attack by disease to which a large proportion of members are immune, thus lessening the likelihood of an animal with disease coming in contact with a susceptible individual
** you do not need to vaccinate every individual in order to prevent an epidemic… if a population contains less than 25% susceptible animals, it is often not possible for an infectious disease to propagate UNLESS R0> 4. A new wave will only occur when the proportion of susceptible animals builds up again.
When do you use this equation?
If a proportion (f) of the population is vaccinated with a vaccine that is fully protective, then this will calculate the reproductive number (R).
Why do we measure health (disease events)?
To answer questions like: is there an unusual problem with disease? Which animals are at greatest risk?
What is PAR? What is important to keep in mind about PAR? Give an example.
Population at risk. Consider counts of cases in context of the size of the population at risk.
example: “I had 10 calves die of respiratory disease lask week”– if there are 20 calves in the group, that is terrible! If there are 40,000– that’s good!
What two parts does a case definition have?
What is an example of a case definition?
- It specifies the popuation at risk
- It specifies what distinguishes cases from the rest of the population
Proportion equation and example?
a/n
* e.g. 60 of 500 chickens were affected, proportion affected was 0.12 or 12%
Ratio equation and example?
a/ (a+n)
* 8 foetal deaths/ 100 live births= 8/108= 7.4%
What do rates measure? Equation and example?
Why are rates preferred to ratios?
Rates measure the number of occurrences of events in a specified population at risk during a given time period.
The denominator should be based on some form of animal-time units (defined periods of time that one animal is at risk)
* Example: 54 cases of Salmonellosis are reported per 100,000 people per year in Australia.
** Rates are preferred to ratios because they are a measure of risk due to the addition of the time dimension
What is prevalence? Is it a rate or a proportion? What can increase prevalence? What can decrease prevalence? And why can a decrease in prevalence be bad?
The proportion of cases (new and old) in a population at a specific time. It depends on the incidence and duration of infection, so measures of incidence are preferred.
** It is a proportion (no time dependence)
** example of increased prevalence: factors that increase the duration of disease such as an imporvement in a treatment regime for a chronic disease that cannot be cured Diabetes mellitus in dogs
** example of a decrease in prevalence- increase in virulence of a virus, more rapid death (a decrease in prevalence is not always good!)
What is incidence? Is it a proportion or a rate? What are two factors you need to specify? Why is incidence preferred over prevalence?
The frequency of new cases of disease observed in a specified population in a specified time period; must account for both population size and the time that each subject observed.
** a proportion
** Incidence is preferred over prevalence because you need to visit at least twice to determine the animlas that are free from disease and then the second time to assess the number of new cases during the trial period. Prevalence is easier to measure because you only need to visit once to see who appears well and who is sick, but since prevalance is affected by both duration and incidence rate of the disease, DIRECT INTERPRETATION IS OFTEN DIFFICULT.
How do you calculate prevalence? What affects prevalence?
Incidence and duration of disease
When would you use the following equation? Example?
Used for closed populations.
Example: If 20 cats in a cattery housing 100 cats develop respiratory disease with ulcers due to feline calicivirus over a week. Incidence risk after 1 weeks is 20%
- 2nd week (if risk is constant over time): 20% of the remaining 80 cats (16 cats) would have succumbed to infection and the total (cumulative) incidence risk would have risen to 36% (since now 36/100 cats have respiratory disease)
When would you use this equation? How can you be more specific?
In an open population– accounting for those that enter and leave throughout the followup period (births, purchases, sales and deaths)
** you can be more specific by including the mid-point population
When would you use the following equation? When would it be fairly accurate?
In an outbreak situation initial population may be all the data that is available. Attack rate is an approximation of the incidence rate.
* Accurate if the population is stable over the time period which is usually okay since outbreaks are often a short duration of time
How do you calculate the Mortality or Morbidity rate?
Use the incidence rate equation
How do you calculate crude mortality rate? What is it?
Incidence rate in which a case is a DEATH. As deaths occur, the population at risk goes down- you can only die once.
What are you determining when you use this equation?
How many of those that get the disease will die from it? VIRULENCE
When is this equation used? What question does this “rate” NOT answer?
Used when investigator lacks proper denominator data
Does not answer the question: What is the risk of an animal in a population dying of a specific cause?
How do you measure morbidity? Which is the most common measure of morbidity?
Prevalence, Incidence risk, Incidence rate, and attack rate.
* Incidence rate is the most common measure
How do you measure mortality? What is the main measure of mortality?
Mortality rate, Case Fatality Rate, Proportion Mortality Rate.
* Mortality rate is the main measure of mortality
How does epidemiology help distinguish cause from association? (3 main points)
* Provide information to help understand:
- what factors are involved in causal pathways to disease?
- the relative importance of each factor as a determinant of disease
- allows interventions to be targeted at the most important determinants (the most efficient use of resources!)
What are the conditions of a cause?
- Must precede the effect
- Can involve host or environmental factors
- Can be either positive (presence of an exposure causes disease) or negative (protective, e.g. vaccination)
What is confounding? Example?
An alternative explanation for the association between a factor and an outcome
e.g. ice cream consumption and drowning= summer time
Is identification of association quantitative or subjective? What about causality?
What is a component cause? Example?
Pieces of the pie.
A, B, C, or D.
e.g. Factors such as smoking, high cholesterol, lack of exercise, genetics and the presence of concurrent disease are all component causes of coronary heart disease in humans.
What are sufficient causes? Example?
The set of conditions wihtout any one of which disease would not have occurred.
A+B+C or A+ D
Example: Pasteurella spp., respiratory virus and stress are all component caues of respiratory disease in calves. Two of these factors are sufficient to cause disease.
What are necessary causes?
A is present in both (all) causal complexes
* a single component cause may necessary, sufficient, neither or both
* A component cause may be described as THE CAUSE when its removal renders the rest of the component causes insufficient
What does it mean for a cause to precipitate? Reinforce?
* When a cause precipitates: exposure to a specific disease agent tips you over the edge to disease
* When a cause reinforces: repeated exposure may aggravate an established disease state
How can you demonstrate the sufficient and necessary causes of disease?
Causal web diagram. It shows direct and indirect causes.
What are Koch’s postulates?
- the agent has to be present in every case of the disease
- the agent has to be isolated and grown in pure culture
- the agent has to cause disease when inoculated into a susceptible animal
- the agent must then be able to be recovered from that animal and identified
e. g. Anthrax= true, but not true for Leprosy as you cannot culture and grow the bacteria
What are Evan’s unified concepts of causation?
Criteria for judging whether exposures cause disease:
* If association, to determine if it is causal:
- Association exists
- Association is confirmed in PROSPECTIVE STUDIES
- Disease should follow exposure
- Disease should follow exposure sequentially
- Measurable host response: Dose- effect
- The disease should be reproducible experimentally
- Preventing/ modifying the host response should decrease disease
- Elimination of the cause should decrease disease
What is risk?
The likelihood (a probability) of experiencing disease in a defined time period, estimated from previous incidence
What are risk factors? Examples?
Characteristics of some individuals that, on the basis of epidemiological evidence, are associated with increased risk of disease
What happens after you measure the levels of disease in a population? Example?
We ask the question…How do we quantify the association between exposures and outcomes?
e.g. Are cats on dry food diets more likely to get FUS compared with cats on moist food diets.
What are the golden rules with measures of association?
* For a reasonable conclusion to be drawn, the comparison must be “fair” (valid)
* Any observed difference of risk between groups must be considered an “association” that does not necessarily imply causation
How do we measure association?
- Measures of strength: Risk ratios, Odds ratios
- Measures of effect: Attributable risk and Attributable fraction
- Measures of total effect in the population: Population attributable risk and Population attributable fraction
What six things are 2 x 2 tables for association used for?
You can come up with the (1) Risk Ratio or the (2) Odds Ratio which measures HOW MUCH YOUR RISK IS INCREASED IN EXPOSED COMPARED WITH UNEXPOSED.
OR
You can come up with the (3)AR, (4)AF, (5)PAR, and (6)PAF. WE ARE MEASURING THE IMPACT HERE.
OR
You can use it to calculate PPV, NPV, DSe, and DSp to determine when a diagnostic test might be good to use- some tests are good with diseased animals but hopeless with non-diseased animals and the converse can be true.
When would you measure AR and AFexp? What is the questions you are answering?
Measuring effect with both.
AR= attributable risk. How much disease amongst the exposed is due to the risk factor?
AFexp= Attributable fraction. What percent of disease amongst the exposed is due to the risk factor?
When would you measure PAR and PAF? What question are you answering for both?
You are measuring effect with both.
PAR= Population attributable risk. How much disease in the population is due to the risk factor?
PAF= Population attributable fraction. What % of disease in the population is due to the risk factor?
Why would you use these equations?
What does it mean if you have a RR > 1? 1? <1?
State what it means if RR= 10?
You would use Risk Ratio or Relative Risk (RR) when comparing incidence rates. The incidence of the outcome in the exposed group divided by the incidence of the outcome in the unexposed group.
RR>1 indicates an association between exposure and disease
RR= 1 means no association between exposure and disease has been demonstrated
RR<1 indicates a negative association (protection) between the factor and the disease
** If RR = 10 then there is 10 times as much risk of disease in the exposed group than in the unexposed group. A high risk ratio by itself does not mean that exposure is the cause of disease, only that an association has been demonstrated.
Why would you use these equations?
If your odds ratio was 3.5 what does that mean in terms of cows having ketosis?
Odds ratio- comparing odds- an approximation of risk
If only prevalence estimates are available, then we cannot compare incidence rates, but can compare odds of disease in groups with different exposures.
** The odds of fat cows having ketosis were 3.5 times higher than those of normal cows, over the period of observation. This may be interpreted backwards as the odds of cows with ketosis being fat were 3.5 times higher than those of cows that did not have ketosis over the period of observation.
If your OR and RR are very different, why could this happen in certain studies? When would it be okay to use OR instead of RR?
Odds ratios can be a poor estimator of risk ratio due to the fact that prevalence is affected by incidence and duration of disease, therefore direct interpretation is not always accurate. The OR is a reliable estimator of the RR in such studies where incidence risk is <10%.
If you calculated the AR and PAR, how would you state your answer? Example: 1. AR= 0.29 in the fat cows/ ketosis study
- PAR= 0.05
- (AR) Amongst the fat cows studied, 29 cases of ketosis per 100 animals (over the period of observation), was attributable to their exposure (i.e. being fat).
- (PAR) In the population, 5 cases of ketosis per 100 animals (over the period of observation) were attributable to cows being fat.
If you calculated the AFexp and PAF, how would you state your answer? Example: 1. AFexp=49% in the fat cows/ ketosis study
- PAF = 14%
- (AFexp) Amongst the fat cows studied, 49% of the cases of ketosis were attributable to their exposure (i.e. being fat).
- (PAF) In the population, 14% of ketosis is attributable to cows being fat.
What does the PAF for a given exposure depend on? Logical explanation?
- The prevalence of exposure
- The strength of association between the exposure and the outcome
e. g. Even if we have an exposure that is strongly associated with an outcome, removing it will have little effect on disease risk in the population if the prevalence is very low
Surveillance vs. Monitoring
Monitoring: Regularly observing the health of a population to observe trends in disease
Surveillance: Observing the health/ disease status of a population and taking action when disease reaches a specified threshold
Why is surveillance important?
* ID what diseases exist in the population
* Estimate prevalence and therefore set priorities for resources
* Plan, implement, and evaluate control programs
* Detect emerging diseases
* Meet international reporting requirements
* Demonstrate disease freedom to trading partners
Components of a surveillance system
* Clearly defined objectives
* The hazard or health state under surveillance
* Case definition
* Target population(s)- region, species, farms, animals
* Timing of sampling intervals
* Data management- capture, collation, and cleaning
* Methods for data analysis and triggers for action
* Feedback and dissemination of results
What are 3 examples of inputs and 3 examples of outputs of surveillance in Australia?
Inputs: National Arbovirus Monitoring Program (NAMP), Australia Wildlife Health Network, Australian Milk Residue Analysis Survey
Outputs: Animal Health Surveillance Quarterly Report, Animal Health in Australia annual report, NAMP annual report
What are the main two main bodies that collect data in Australia?
- DAFF (Dept of Agriculture, Forestry, and Fisheries)- Australian Chief Veterinary Officer (ACVO)
- Animal Health Australia (AHA)- National Animal Health Information System (NAHIS)
What is a key factor in influencing the chance of controlling disease and reducing economic and social impacts?
Early detection of notifiable diseases
How quickly do you have to legally report:
- Exotic animal diseases and anthrax?
- Serious but not exotic diseases?
- Less serious notifiable diseases?
* Who do you call?
- Immediately
- Within 12 hours
- Within 7 days
* Chief Veterinary Officer- DEPI
What are OIE notifiable diseases?
* TADs
* zoonotic potential
* significant spread in naive populations
* emerging diseases
* significant potential for trade impacts
What are some examples of active surveillance?
What is passive surveillance?
Surveys, meat inspection, diagnostic laboratory reporting
* Passive surveillance makes use of secondary data (data collected for other purposes e.g. export certification)
What is the National TSE Surveillance Program? Objective? Who is tested?
Targeted surveillance for Transmissible Spongiform Encephalopathy
*Objective: to demonstrate AUS freedom and early detection
* Downer cows are tested that are showing neurological signs or reluctance to walk
What are the two meanings of “risk based surveillance?” Example?
* Preferential surveillance for hazards with more serious consequences
* preferential testing in sub-populations that have a higher risk of having disease
e.g. HPAI (highly pathogenic avian influenza) surveillance in Bhutan- smaller country with 45 vets
What is syndromic surveillance? Example?
*automated data acquisition and statistical alerts to monitor in real time
* tracks disease trends by syndromes based on clinical features rather then specific diagnoses
* allows you to detect outbreaks of disease earlier (theoretically)
e.g. using google searches to ID flu trends
What is participatory surveillance? Examples?
A form of active surveillance relying on community consultation. Resource intensive but does provide a qualitative understanding of contect and disease/ impacts/ response at community level
e.g. community interviews and mapping. HPAI surveillance in Indonesia.
What are good questions to ask yourself when interpreting surveillance data? Surveillance cases are often an indicator of what??
Are these results likely to reflect the pattern of disease in the target population?
Has there been any change in the tendency to report the disease?
Has there been any change in disease diagnostics?
** Surveillance cases are often the tip of the iceberg, so likely there is a bigger problem e.g. for each notified case of salmonellosis there were a further 6 community cases not notified
What are some attributes of an effective surveillance system?
Clear objectives, ownership by stakeholders, simplicity (to encourage reporting), flexibility, sensitivity (high detection rate), specificity (low number of false positives), representativeness (reflect true occurrence and distro in all communities), timeliness
What is the 10 step process to outbreak investigation?
- Prepare for fieldwork (let govt. agencies know)
- Verify the outbreak (are there changes in reporting procedures? changes in number of reported cases?)
- Verify the diagnosis (clinical exams, necropsies, ddx list)
- Define, ID, and count cases (case definition for consistency of diagnoses, enhance surveillance)
- Describe the outbreak according to individual, place and time (INDIV: compare unaffected and affected animals, attack rate, risk ratio, attributable fraction, PLACE AND TIME– helps determine transmission, and clustering will help find “ point source” or continuous source)
- Develop hypotheses (need quantitative information first!)
- Evaluate and test hypotheses (predict what you should find in other animals such as test results or production effects and then test your predictions)
- Follow-up investigations (clinical, pathological, microbiological, toxicological examination of tissues, feeds, etc… clinical trials, epi follow up– looking for additional cases, diagrams of movement of animals)
- Implement controls (what can I do today to decrease the impact of this problem? e.g. administer 2 litres of thawed colostrum via stomach tube)
- Communicate your findings
What are the key questions during an outbreak?
* What is the problem?
* Can something be done to control it?
* Can future occurrences be prevented?
What does it mean for outbreaks to be multithreaded and recursive?
* Multithreaded- a number of problems may be occurring at once
* Recursive- new information causes a previous step to be revisited
What is Stevenson’s First Law of Veterinary Science?
Multiple clinical signs in an individual animal tend to arise from a single aetiology (i.e. single cause) but single syndromes in a population (e.g. suboptimal production, infertility) tend to have multiple aetiologies
What are examples of the following types of problems: acute? Additive (or cyclic)? Chronic?
* acute: management or husbandry error
* additive of cyclic: combo of management or husbandry errors over time
* Chronic: long action of management or husbandry errors that required the passage of time before the consequences became of sufficient magnitude to be recognized
Making a diagnosis involves SOAP
* History taking (Subjective)
* Clinical examination (Objective)- measurement & samples for testing
* Assessment- DDxs, tests to rule in or rule out, interpreting the results
* Plan
Factors affecting diagnostic accuracy
* ability to elicit relevant information/ ask appropriate questions
* accuracy, objectivity, and completeness of relevant memories
* psychological attributes (tolerance for uncertainty, willingness to engage in constructive self criticism)
* external and personal factors (difficult clients and cases, fatigue)
* ability to gain client’s confidence and evaluate accurately both verbal and nonverbal responses
* TESTS THEMSELVES
* Test availability and cost
* Constant attention as a diagnostician, maintenance of skills, sensitive interpersonal skills
What is a test?
Any procedure that reduces uncertainty about the state of disease
* questions posed during history taking
* Clinical signs (exams and measurements)
* lab findings (haematology, serology, biochem, histopath)
* post mortem findings
Diagnostic windows for FMD
If it is past 4 days testing for serum antibodies would be okay, but the best test is really virus in oral/pharyngeal fluid because it starts the day before clinical signs and lasts for at least 24 days
How do you define the limits of normality? What do measurements outside of the range indicate? Example?
*Statistically: the range of values which capture 95% of all values observed in the population of healthy animals
* Measurements outside the range indicates UNUSUALNESS but is not a definitive sign of disease
* e.g. In 100 healthy dogs: 95 will have a White cell count within reference range but 5 HEALTHY dogs will have a value outside the interval
What is the standard deviation in a normal distribution- two-tailed?
95% of observations lie within 2 standard deviations of the mean.
Dog mean Temperature = 38.6 +/- 1.96
Ref range= 38.0-39.2
* if skewed use percentiles 2.5%
What happens with the standard deviation if enzymes are only abnormal if elevated, so one-tailed distribution?
* Within 5% (> mean +1.65)
e.g. Lipase, Amylase, AST, CK
What does it mean if an animal falls outside of the reference range? What percentage do we expect to fall outside the reference range?
* Measurements outside the reference range indicate unusualness
* Reference ranges are an arbitrary statistical definition
- NOT a definitive sign of disease
- we expect 5% of healthy dogs to fall outside the range (FALSE POSITIVES)
What is the probability of a false positive?
= 1 - (0.95)^n
n= the number of tests
* this means that the more you test, the more likely you are to get a false positive
What would make up the perfect diagnostic test?
* Would allow us to differentiate between disease positive and disease negative individuals without error
* Does not exist- the test that we use are imperfect
* To understand how good they are we need to evaluate them against a reference
What does it mean if a test is fit for intended purpose?
- Accurate
- Precise (repeatability- measures closeness of repeated test results performed with same conditions, assuming a normal distribution. Repeatability= 1.96 x SD (SD= standard deviation of the observed differences))
What does it mean for a test to be optimised?
Efficient protocol
What does it mean for a test to be standardised?
* Calibrated “best” practice “standard” results
What does it mean for a test to be robust?
* Reliable, unaffected by small changes in test situation
Repeatable v.s Reproducible
Repeatable = Precise (repeatability- measures closeness of repeated test results performed with same conditions, assuming a normal distribution. Repeatability= 1.96 x SD (SD= standard deviation of the observed differences))
Reproducible- test results are repeatable between replicated runs in DIFFERENT LABS
Analytic Sensitivity vs. Diagnostic Sensitivity
Analytic Sensitivity- Limit of detection
Diganostic Sensitivity- Few false negatives (when tested in animals of known status from the target population)
Analytic Specificity vs. Diagnostic Specificity
Analytic Specificity- Distinguishes target from other compounds
Diagnostic Specificity- Few false positives (when tested in animals of known infection status from the target population)
What does it mean for a test to be valid?
The results are unbiased with respect to the true values
Diagnostic Sensitivity
Low number of false Negatives
* The probability of correctly detecting infected animals (should include early/subclinical cases, not just experimentally infected animals tested late in disease)
Diagnostic Specificity
Low number of false Positives
* The probability of correctly detecting uninfected animals
Pathognomic tests
Those which the detection of a sign, substance, reponse, or tissue change is an abosulte predictor of the presence of the disease or disease agent
Surrogate tests
Detect secondary changes, which it is hoped will predict the presence or absence of disease or the disease agent. For example, a positive culture of Brucella abortus from a cow’s milk sample is pathognomic for Brucella infection. However, testing for antibodies to Brucella, is a surrogate test since it is not measuring the presence of Brucella abortus per se but rather the body’s reaction to Brucella or cross- reacting antigens.
What does high sensitivity imply?
High specificity?
High sensitivity implies a low number of false negatives
High specificity implies a low number of false positives
When is high sensitivity important? 2 examples?
There is a high cost from calling a diseased animal negative.
ruling out: SNout
** testing for a high prevalence condition
e.g. Quarantine/ testing new stock entering a herd
When is high specificity important?
There is a high cost from calling a non-diseased animal positive
e.g. culling or depopulating based on test results, or trade impacts when you get false positives
* ruling-in: SPin
* Testing for a low prevalence condition (Sn is still important)
How do you improve diagnostic accuracy? What two ways?
- Use a battery of (several) tests instead of a single test. It can be done in two ways:
* Parallel testing (OR)- the animal is considered infected if it is positive to ANY test. Improves seNsitivity. Use if worried about false Negatives. e.g. Liver disease tests- any of the enzymes off, the animal has liver disease
* Serial testing (AND)- the animal must be positive to ALL tests in order to be considered infected. Improves SPecificity. Use if worried about false Positives. e.g. Liver disease- an animal has to have all enzyme values off in order for the liver to be considered diseased
- Use a different cut-off point for the context. But always a trade off. Improving sensitivity will reduce specificity and vice versa.
What happens if you move the cut off by increase sensitivity?
Specificity will decrease. Therefore, more diseased animals are classed as positive but more non-diseased animals are also classed as positive (FALSE POSITIVES).
** BUT increasing sensitivity means that those animals identified as negative are VERY LIKELY TO BE TRULY NEGATIVE
What happens if you move the cut off to decrease sensitivity?
Specificity will increase which means that less diseased animals are classed as positive. BUT less non-diseased animals are classed as positive.
* Therefore, increasing specificity means that those animals identified as positive are very likely to be TRULY DISEASED.
What question does Positive Predictive Value (PPV) answer?
Given that an animal has tested positive to a particular condition, what is the probability of the animal really having the condition?
What question does Negative Predictive Value (NPV) answer?
Given that an animal has tested negative, what is the probability that the animal is really free from the condition.
What do predictive values do for a test? What causes them to be variable? What 3 estimates do you need to calculate predictive values?
Evaluate a test’s ability to correctly identify the condition of interest. However, predictive values vary with probability (prevalence) of the condition!!
** To calculate them you need:
- DSe
- DSp
- the probability of the animal having the condition PRIOR to testing (prevalence can be used)
What does control mean?
*Implies that you are doing something to:
- reduce the morbidity due to disease
- reduce the mortality due to disease
What does eradication imply?
* Implies that you are doing something to:
- completely remove the disease from the population
- reduce the prevalance of disease to such a level that transmission cannot occur
- reduce prevalence so that the disease is no longer a major problem, but transmission may occur
- cause a disease to become extinct in a region or zone within a country (elimination)
What are strategies to control disease?
- Movement restriction- people, equipment and animals (EI, FMD)
- Quarantine- length of time proportional to incubation period, import and export restrictions
- Biosecurity- cleaning and disinfection entry protocols, isolate incoming animals or only those sourced from a tested clean population
- Outbreak investigation and surveillance- identify infected premises
- Vaccination- pre-emptive (blanket)- all animals vaccinated for a time period OR strategic- ring vaccinating in an outbreak
- Treatment and improved husbandry- reduce clinical phase and shedding
- Treatment and improved husbandry- reduce clinical phase and shedding
- Vector and reservoir control- rabies, tuberculosis (UK, NZ), insects, feral and wild animals
- Slaughter and disposal- blanket culling (highly pathogenic avian influenza), test and remove (bovine TB), pre-emptive culling of exposed animals
- Do nothing
Criteria for eradication
- Biological and technical feasibility- absence of a reservoir, low probability of spread, ease of diagnosis, effective practical intervention available (e.g. vaccination)
- precedent set elsewhere - Political will and popular support
- Preconditions: sound epi understanding of dx, clear evidence of community benefit, vaccine, appropriate control options, availability of resources, understanding of ecological consequences, appropriate legislation
- Must compensate herd manager otherwise they won’t contact you
- Biosecurity has to be cost effective and practical
Common reasons for eradication failure
* wildlife reservoir
* survival of agent in the environment
* poor diagnostics
* expense of test and either poor DSp or DSe
** Diagnostic difficulties arise towards the end of eradication programs when prevalence is very low
Eradication of Rinderpest vs. Johne’s Disease
Eradication vs. Elimination
Eradication- no disease globally as a result of deliberate efforts
Elimination- no disease in a defined geographic area as a result of deliberate efforts
What are the main efforts to contain and control disease intending to do? What are the 3 main ways?
They aim to break the transmission cycle
- Preventing contact between the agent and susceptible animals
- Stopping the production of the agent by infected or exposed animals
- Increasing disease resistance of susceptible animals to the agent
What are the four main areas that should be considered when appraising scientific literature?
- Describing the evidence- type of study, outcome measured, population investigated, results.
- Assessing the internal validity of the study
- non-causal explanations: bias, confounding, chance
- causal explanations: temporal relationship, strength of relationship, dose-response, consistency, specificity - Assessing the external validity of the study- can the results be applied to the eligible population, source population, and other relevant populations?
- Comparing the results with other available evidence-
- are the results consistent with other evidence?
- are the results biologically plausible?
- is there coherency with the distribution of the exposure and the outcome?
If there is severe observation bias, what does it mean for the study?
No analytical manipulation of the data will overcome the problem. The study is fundamentally flawed.
Define confounding. What does it mean if there is confounding for a study?
An alternative explanation for the association between a factor and an outcome
e.g. many smokers are also drinkers– so how do we know that laryngeal cancer is due to smoking and not drinking?
* Appropriate analysis, in most cases, will overcome the problem.
What are the two parts to internal validity?
Non-causal explanations that might have influenced the internal validity- bias, confounding, and chance
Causal explanations- once the non-causal explanations have been ruled out- attention turns to considering the features of the study that support the claim that there is a relationship between exposure and outcome–
- Is there a temporal relationship?
- Is the relationship strong?
- Is there a dose-response relationship?
- Consistency?
- Specificity? Exposure produces a specific outcome e.g. asbestos and mesothelioma.
What does plausability refer to?
Observed association being biologically understandable on the basis of current knowledge concerning its likely mechanisms. But keeping in mind that John Snow prevented cholera in London 25 years before the isolation of cholera bacillus.
What does coherency refer to?
An association is regarded as coherent if it fits the general features of the distribution of both the exposure and the outcome under assessment. e.g. If lung cancer is due to smoking, the frequency in different populations and in different time periods should relate to the frequency of smoking in those populations at earlier relevant time periods.
What is evidence based medicine?
A form of medicine that aims to optimize decision making by emphasizing the use of evidence from well designed and conducted research.
What is external validity?
- Can the results be applied to the eligible population?
- Can the results be applied to the source population?
- Can the results be applied other relevants populations?
** If the internal validity is poor- then no!
What is the difference between a descriptive and analytical epidemiological study? Give examples of each. What are the three main types of studies?
* Descriptive studies do not have a hypothesis– earliest studies done on a new disease in order to characterize it, quantify its frequency, and determine how it varies in relation to individual, place, and time
e.g. Looking at injuries in a ER in Philadelphia- authors found a high incidence of intentional interpersonal injury in that part of the city
* Analytical studies are undertaken to identify and test hypotheses about the association between an exposure of interest and a particular outcome. (the major difference is that in experimental studies the investigator has direct control over study conditions)
e.g. does cigarette smoking cause lung cancer?
* Three main types: Descriptive, Analytical, and Experimental
Major features of Case reports. Example?
A “newsworthy” clinical occurrence, such as an unusual combinabtion of clinical signs, experience with a novel treatment, or sequence of events that may suggest previously unsuspected causal relationships.
e.g. fatal aplastic anaemia in an 88 yo man on a new drug that inhibits platelet aggregation.
** good because it raises awareness, increases surveillance
Major features of case series
A case report shows something can happen once, a case series shows it can happen repeatedly.
e.g. If the aplastic anaemia that killed the 88 yo man also killed other patients on the same platelet inhibiting drug
** good because it raises awareness, increases surveillance
Major features of descriptive studies
Based on rates quantify the burden of disease in a population using incidence, prevalence, morality, or other measures of disease frequency. Most use data from existing sources (birth and death certificates, disease registries or surveillance systems).
** can be a rich source of hypotheses that lead later to analytic studies
e.g. Looking at injuries in a ER in Philadelphia- authors found a high incidence of intentional interpersonal injury in that part of the city
Major features of ecological studies. Advantages and disadvantages?
A type of analytical study. Unit of analysis is a group– looking at a group to determine if inferences made at an individual level might be valid.
e.g. examining association between chlorinated drinking water and cancer in Taiwan comparing different municipalities
** The biggest problem is cross-level inferences! Making inferences at the individual level rather than the group level!! e.g. women with breast cancer eating more calories makes them at higher risk… probably not true! Though it may be true more breast cancer in the US and the US also consumes the most calories out of any country.
* Advantages: quick and cheap & data (often collected for other purposes) readily available
* Disadvantages: ecological fallacy- an association observed between variables at the aggregate level may not necessarily represent the association that exists at the individual level
Major features of cross sectional studies. Strengths and weaknesses.
A sample is taken at a signle or a short period of time. Individuals are examined for the presence of disease and their status with regard to the PRESENCE OR ABSENCES of specified exposures.
Often use surveys!!
e.g. mask wearing vs. smoking off of a snap shot of an airport
* Advantages: Quick and relatively cheap
* Disadvantages: Cannot provide info on the incidence of disease– only prevalence. NOT suited for diseases of short duration.
Major features of cohort studies. Strengths and weaknesses.
Comparing disease incidence over time between groups (cohorts) that are found to differ on their exposure to the factor of interest. Can be either PROSPECTIVE (followed over time- think of british study) or RETROSPECTIVE (disease cases have been identified)
* Advantages: estimates of absolute incidence of disease in exposed and non-exposed individuals. Helps demonstrate whether exposure preceded disease. GOOD for RARE exposures.
* Disadvantages: Require a long follow up period. Large groups are necessary for rare diseases. And losses to follow up can be a problem (disappear, move away,etc.). Often very expensive.
e.g. studying carcinogenic effects of cell phones in exposed group who were clients of a cell phone company vs. non-exposed group who were not part of the cell phone client list.
Major features of case control studies.
What is the achilles heel of case control studies?
Intended to provide the same answer in a much simpler way by studying all of the dogs who got bladder cancer and sample of dogs who did not.
e.g. 117 dogs with bladder cancer and 117 dogs who remained free of disease. We can work out the odds of cancer in the exposed vs. unexposed groups and compare them. Is Benzidene associated? We can use Odds Ratio because the outcome of interest (bladder cancer) was relatively rare.
** the key is to make sure the cases and controls are similar in every way except for the exposure factors hypothesised to be associated with disease of interest
*** The CONTROL group is the achilles heel because you first have to select appropriately. And then you have to break them up into positive and negative groups based on the exposure.
** As well as RECALL BIAS
Major features of clinical trials (randomized and community too). Strengths and weaknesses.
Advantages and disadvantages of case control studies
Advantages: case control studies are an efficient method for studying rare diseases. Quick to run and cheap.
Disadvantages: Cannot provide info on the disease incidence in the studied population. The study is reliant on the quality of past records or recollection of study participants. It can also be difficult to ensure an unbiased selection of the control group and therefore the representativeness of the sample selection process is difficult to guarantee.
Cohort vs. Case control study
* Cohort study- exposure status comes first (postive or negative). Subjects are then followed over time to determine their outcome status (disease positive or disease negative)
* Case-control study- outcome status is defined first (disease positive or disease negative). The history provided by each subject provides info about exposure status (positive or negative)
** STARTING AT OPPOSITE ENDS OF THE SPECTRUM
When are experimental studies used? What are some important concepts in the design?
* Designed to test hypotheses between specific exposures and outcomes
* Investigator has direct control over study conditions
* Important concepts in the design:
- Use of a control group (due to placebo, natural healing over time, and hawthorne effect)
- Randomisation (groups must not differ with respect to relevant characteristics other than the exposure being studied)
- Admission criteria
- Outcome ascertainment
- Ethics (you cannot knowingly expose a participant to known harm, you cannot knowingly withold a known benefit, equipoise must exist (balanced doubt) must exist for a clinical trial to take place
Why do we need a control group in experimental studies?
Use of a control group helps to neutralize the following effects:
* Placebo- positive effects because of an inert intervention
* Hawthorne effect- positive effects because of observation
* Natural improvements in condition over time
What are the major concepts surrounding randomisation of clinical trials?
* Groups being compared must not differ with respect to relevant characteristics (e.g. characteristics that determine the outcome) other than the exposure being studied
* otherwise, results will be confounded
* The most reliable way to encourage comparability is by assigning the treatment according to chance mechanisms (randomisation)
What is meant by admission criteria in experimental studies?
* Restriction of study subjects to those with uniform characteristics
* types of admissibility criteria:
- person, place, time
- demographic (age, sex, race)
- prior condition (having or lacking a particular disease)
- risk factor restriction (non-smokers)
What is meant by outcome ascertainment in experimental studies? what are the three types?
* outcome ascertainment must be reproducible and valid
* blinding may be applied to balance inaccuracies
* single blinding= blind study subjects so they don’t know which treatment they are receiving
* double blinding= blind subjects and evaluators
* triple blind= blind subject, evaluators, and statisticians
When comparing evidence. What are the four aspects of comparison that should be considered?
- Are the results consistent with other evidence?
- Are the results plausible biologically? (think cholera and John Snow but also think ice cream and drowning)
- Is there coherency with the distribution of the exposure and the outcome? (e.g. if lung cancer is due to smoking, the frequency of lung cancer in different populations and in different time periods should relate to the frequency of smoking in those populations)
What are randomized clinical trials?
* resembles a laboratory experiment
* objective is to test the possible effect of a therapeutic or preventive intervention
* the design’s key feature is that a formal chance mechanism is used to assign participants to either the treatment or control group
* subjects then followed over time to measure one or more outcomes, such as occurrence of disease
What are advantages and disadvantages of randomized clinical trials?
* Advantages: randomization generally provides excellent control over extraneous variables (confounders), even factors that may be hard to meausre or that may be unknown to the investigator
* Disadvantages: expensive, many exposures may not be ethical or feasible to conduct a clinical trial (e.g. exposure to pollution), impractical if long periods of follow-up required
What are community trials?
* Instead of randomly assigning individuals to treatment or control groups, community trials assign interventions to entire groups of individuals
* In the simplest situation one group (community) receives the treatment and another serves as a control
Problem: Polioencephalomalacia (PE) in calves- became most common disease in NZ- does not appear to be linked to the text book explanation of diet change from fibrous to lush.
- What are the questions that need to be answered?
* What is the unit of interest- animal or farm?
* One this is answered, what is the incidence of PE?
* Does the incidence of PE vary with the animal, temporal, or spatial factors?
* What factors are associated with an increased incidence of PE?
* Once risks for PE have been identified, can they be managed?
Problem: Polioencephalomalacia (PE) in calves- became most common disease in NZ- does not appear to be linked to the text book explanation of diet change from fibrous to lush.
- If you’re involving a number of practioners in an investigation, what do you need to do?
* Be very clear about case definition
* Good idea to develop this case definition by consensus (e.g. hold a meeting of practioners participating in your study and develop a suitable case definition collectively)
Problem: Polioencephalomalacia (PE) in calves- became most common disease in NZ- does not appear to be linked to the text book explanation of diet change from fibrous to lush.
- How would you go about calculating the incidence of PE?
* When a case is identified, get the practitioners to encourage the client to keep a record of date of onset of subsequent cases and outcome (survived or died)
* Define your study period “e.g. the 2009 milking season”
* Incidence risk:
- numerator= number of PE cases
- denominator= (#calves born+ (0.5x #purchased))- (0.5 x # sold, died, other reasons))
Problem: Polioencephalomalacia (PE) in calves- became most common disease in NZ- does not appear to be linked to the text book explanation of diet change from fibrous to lush.
- What study design would you use to identify risk factors for PE?
* If low numbers of cases per herd (i.e. 1 or 2) then use farm as the unit of interest and use a case control approach
* advantages: quick and relatively cheap
* disadvantages: recall bias in terms of identifying exposures, selection bias or controls (need to ensure control farms were truly disease negative)
OR
* if large numbers of PE are seen within affected herds then either a prospective or retrospective cohort study would be useful
- advantages: easier to ID cause-effect relationships
- disadvantages: length of time to conduct the study, expensive
Problem: Polioencephalomalacia (PE) in calves- became most common disease in NZ- does not appear to be linked to the text book explanation of diet change from fibrous to lush.
- Once you have identified factors that were associated with the presence of PE, what would be your next step?
* set about managing the identified risk factors with the aim of reducing the impact of the problem
- if exposure to lush pastures was a risk factor, then careful grazing management e.g. limiting exposure to lush pasture should provide a useful start
- a randomized intervention trial might also be useful (particularly if your proposed control measures were expensive or difficult to implement)
When are analytical studies conducted? What are the three ways in which information can be analyzed? What are the 4 main types of analytical studies?
to test a hypothesis
* the hypothesis usually involves working out whether a certain exposure is associated with (or casues) a certain outcome
* prospective, retrospective, and non-directional
- Cross-sectional
- Cohort studies
- Case control studies
- Ecological studies
What is a time varying exposure?
What is a time invariant?
** why is this relevant to epi?
Time varying exposure- diet (healthy kick)
Time invariant exposure- gender (something that can’t change)
** Cohort studies- prospective and retrospective studies– you can assess things that change, it is not a snap shot, it is over time
