Feldmand. Module 1 – Intro to Epidemiology & Measures of Disease

Question 1

Definition of epidemiology

Answer 1

• From Greek

• – Epi (among, upon)
• – Demos (the people)
• – Logos (knowledge, doctrine)

• The study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to the control of health problems (Dictionary of Epidemiology)

Question 2

Goals of Epidemiology

Answer 2

• Elaboration of causes that explain patterns of disease occurrence
• Determine extent of disease
• Study natural history of disease
• To promote, protect and restore health
• Provide foundation for developing public policy and regulatory decisions

Question 3

Typical Epidemiologic Approach

Answer 3

• Determine existence and magnitude of problem
• Describe WHO has the problem (animal/person, place, time)
• Develop hypotheses about WHY problem is happening
• Test the hypotheses using appropriate study designs and statistical tests
• Develop interventions based on findings
• Evaluate effectiveness of interventions

Question 4

Basic Tenet of Epidemiology

Answer 4

• Disease does not occur randomly in a population

• – Disease occurrence is related to environment of species being studied
• – Environment includes physical, biological, sociological, meteorological, & management characteristics

• Epidemiology triad

Question 5

Epidemiologic Triad

Answer 5

• Disease is result of forces within a dynamic interaction between

– Agent

– Host

– Environment

Question 6

Measures of Disease: Ratios

Answer 6

• An expression of the relationship of 2 quantities
• Numerator is not in the denominator
• With a dimension – # of dogs owned / 100,000 population
• Without a dimension – # 2nd year vet students / # 3rd yr vet students

Question 7

Measures of Disease: Proportions

Answer 7

• Ratio in which numerator is contained in the denominator
• Dimensionless
• Ranges from 0 – 1
• Tells us what fraction of population is affected

vets sitting ACVPM exam / Total # vets

Question 8

Rates

Answer 8

• Ratio in which there is a relationship between the numerator and the denominator
• A true rate is instantaneous change in one quantity per unit change in another quantity (usually time).
• Tells us how fast disease occurs in a population

tests taken in vet curriculum / person-years in vet curriculum

Question 9

Measures of Morbidity: Prevalence

Answer 9

• Prevalence (point prevalence, prevalence rate) – Proportion of pop’n with disease at a specific time

of subjects with disease at a point in time / Population at the same point in time

• Period prevalence – Frequency of disease for a given time interval

of subjects with disease for given time interval / Population at mid-interval

Question 10

Interpretation of prevalence

Answer 10

Probability of having disease at a particular point in time.

Question 11

Measures of Morbidity: Cumulative incidence, incidence proportion

Answer 11

– Proportion of subjects who develop disease during a certain time period

– Unitless, interpret in the context of time period

– Measure of average risk for a population

events during a period of time / Population without disease at beginning of period

Question 12

Measures of Morbidity: Incidence • Incidence rate, incidence density

Answer 12

– Occurrence of new event per unit time

– The numerical value has no interpretability because it depends on the arbitrary selection of the time unit

new events / Total person-time at risk in population

Question 13

Measures of Morbidity: Incidence • Attack rate

Answer 13

– Cumulative incidence used for particular populations observed for limited periods of time, as in an outbreak

– Usually expressed as a percent

events of dz during epidemic time period / Population at risk at start of period

Question 14

Interpretation of cumulative incidence

Answer 14

Risk of developing disease over given time period

Question 15

Interpretation of incidence density

Answer 15

Rapidity with which new new cases develop over given time period

Question 16

Relation between Prevalence, Incidence & Duration

Answer 16

• Prevalence is not a measure of risk: Does not take into account the duration of the disease
• If prevalence (P) is small and incidence rate (I) and duration (D) are constant over time then P ≈ IxD

Question 17

Measures of Mortality

Answer 17

• Mortality rate: Total # deaths from all causes in 1 year / Population at mid-year
• Disease-specific mortality rate: Total # deaths from specific dz in 1 year / Population at mid-year
• Case-Fatality Rate (CFR) # deaths after dz onset or diagnosis / # individuals with the dz
• Proportionate Mortality # deaths from specific dz in time period / Total # deaths in that time period

Question 18

Mortality: when can it be a good index of the risk of disease?

Answer 18

• Can indicate severity of disease and also be an index of the risk of disease

• – If a disease is not typically fatal, mortality is not a good index of incidence • E.g., West Nile virus
• – When the case fatality rate is high and duration of disease is short, mortality is good reflection of risk • E.g., Rabies

Question 19

Risk

Answer 19

• The probability of a disease-free individual developing a given disease over a specified period, conditional on that individual not dying from any other disease during the period
• Risk is without units, ranges from 0 to 1
• Risk=Attack rate in outbreak settings: # events of disease during time period / Population at risk at start of period

Question 20

Odds

Answer 20

• The probability of an event occurring compared to the probability of that event not occurring

Probability event occurs / Probability event does NOT occur

Question 21

2-by-2 tables

Answer 21

Disease Present Absent

Exposure +

Exposure -

Note that the disease status is across the top and the exposure status is on the left

Question 22

(use of) Ratio Measures of Association

Answer 22

• Assess the strength or magnitude of the statistical association between the exposure and disease of interest
• In cohort studies, use relative risk
• In case-control studies, use odds ratio

Question 23

Identification of Risk Factors

Answer 23

Epidemiological studies are conducted to identify risk factors through the comparison of incidence or prevalence between groups exposed and not exposed to a risk factor.

Probabilities of disease occurrence can be compared using:

• measures of strength of association: RR, OR
• measures of potential impact: attributable risk, attributable fraction.

Question 24

Measures of strength of association and information provided

Answer 24

Involves calculation of ratios such as relative risk and odds ratio which measure the magnitude of a statistically significant association between risk factor and disease.

They are used to identify risk factors, but do not provide information on absolute risk.

Question 25

Relative Risk (RR)

Answer 25

* The relative risk is the excess risk in the exposed group, compared to the unexposed (background, expected group) * Expressed as a ratio * RR = Riskexposed / Riskunexposed * Riskexposed = # events of dz in exposed group / pop’n at risk in exposed group = a / (a + b) = a / h1 * Riskunexposed = # events of dz in unexposed group / pop’n at risk in unexposed group = c / (c + c + d) = c/h2 * RR = Riskexposed / Riskunexposed = (a/h1) / (c / h2) * The RR will be **\> 1.0 when risk is greater in the exposed** group than in the unexposed group – i.e., when exposure is risk factor for disease * The relative risk will be **\<1.0** when risk in the exposed group is less than risk in the unexposed group – i.e., when exposure is **protective** * When **no association between exposure and disease, RR = 1**

Question 26

Odds Ratio (OR) - (type of studies to use, why)

Answer 26

* In case-control studies, you cannot directly calculate the risk of disease because you do not have a denominator population * You can calculate the odds of exposure among cases and controls * The OR compares the odds of exposure in cases to the odds of exposure in controls

Question 27

Measures of Potential Impact: what are those and why are important

Answer 27

* Reflect the **apparent contribution** of an **exposure** to the **frequency** of disease in a population * Important for policy makers and funding sources to understand impact a prevention program might have

Question 28

Measures of potential impact and information provided

Answer 28

Measures of potential impact include differences such as the _attributable risk_ or fractions such as the _attributable fraction_. These allow **quantifying the consequences from exposure** to a risk factor, and are used to **predict**, **quantify** the effect of **prevention** and to **plan control** programs

Question 29

Risk Difference

Answer 29

Measure of potential impact. • Also called excess risk, attributable risk: Risk Difference = Riskexposed – Riskunexposed • Excess risk in those exposed

Question 30

Attributable Risk Percent

Answer 30

* Only appropriate if RR \> 1 * **Proportion of cases in the exposed group attributable to exposure** * The most that we can hope to accomplish in reducing risk of disease if we completely eliminate the exposure **(Riskexposed – Riskunexposed) / Riskexposed** = (RR – 1) / RR

Question 31

Population Attributable Risk Percent

Answer 31

• Proportion of cases in the entire population (exposed and unexposed) attributable to exposure (Riskoverall – Riskunexposed) / Riskoverall

Question 32

Prevented Fraction in the Exposed - Vaccine Efficacy

Answer 32

* Comparable measure to attributable risk percent for a protective factor, such as vaccination * Only appropriate if the RR\<1.0 * Proportion of potential new cases which would have occurred had the exposure been absent (the **proportion of potential cases prevented by the exposure**) * Prevented fraction in the exposed = (Riskunexposed - Riskexposed) / Riskunexposed = 1 - RR

Question 33

Formula for True Prevalence (from Apparent Prevalence)

Answer 33

TP = (AP + Sp - 1) / (Specificity + (Sensitivity - 1)

Question 34

Formulas to calculate PPV

Answer 34

PPV = a / (a + b) PPV = TP / (TP + FP)

Question 35

Formulas to calculate NPV

Answer 35

NPV = d / (c + d) NPV = TN / (TN + FN)

Question 36

Definition of infectivity

Answer 36

**Ability** of an agent **to establish itself in a host** (ID50 = numbers of agents required to infecto 50% of exposed susceptible animals under controlled conditions)

Question 37

Definition of pathogenicity

Answer 37

Ability of an agent to **produce disease** in a range of hosts under a range of environmental conditions

Question 38

Definition of virulence

Answer 38

**Measure of the severity of disease** caused by a specific agent. It is commonly quantified using the LD50 (= numbers of agents required to kill 50% of exposed susceptible population under controlled conditions)

Question 39

Definition of carrier state

Answer 39

A *true carrier state* is characterised by an infected host who is **capable of dissemination of the agent**, but typically does **not** show evidence of clinical **disease**.

Question 40

Definition of incubatory carrier

Answer 40

Incubatory carriers are **infected**, **disseminate** the agent but are in the **pre-clinical stage**.

Question 41

Definition of convalescent carriers

Answer 41

Convalescent carriers are **infected**, **disseminate** the agent and are in the **post-clinical stage**.

Question 42

Definition of antigenic variation

Answer 42

Refers to biological situations where an agent evades the host defence by changing its antigenic characteristics.

Question 43

Definition of incubation period

Answer 43

Defined as the **time between infection** and the first appeareance of **clinical signs**.

Question 44

Definition of period of communicability

Answer 44

Time during which the infected host is capable of **transmitting** the agent

Question 45

What is a natural reservoir of infection

Answer 45

A species is considered a natural reservoir of infection if **infection** can be **maintained** within the species population without requiring periodic re-introduction.

Question 46

Unified concept of causation criteria:

Answer 46

Developed by Evan, is accepted for identifying cause-effect relationships. * The proportion of **individuals with the disease** should be **higher** in those **exposed** to the cause than in those not exposed. * **exposure** to the cause should be more **common** in **cases** than in those without the disease * number of **new cases** should be higher in those **exposed** to the case than in those not exposed (as shown in prospective studies) * temporally, the **disease** should **follow exposure** to the cause * There should be a **measurable** biological spectrum of host **responses** * The host **response** should be **repeatable following exposure** to the cause * The disease should be **reproducible experimentally** * **preventing** or modifying the host **response** should **decrease** or eliminate the expression of **disease** * **elimination of the cause** shoud result in a **lower incidence** of the disease * the **relationship** should be **biologically and epidemiologically plausible**

Question 47

What are necessary and sufficient causes of disease?

Answer 47

Cause of disease can be categorised into: * necessary causes: must be present for a disease to occur (e.g. distemper virus in canine distemper) * sufficient causes: set of minimal conditions and events inevitably producing disease.

Question 48

False Negative Rate (β)

Answer 48

beta = type II error beta = 1 - Se beta = False Neg / (True Pos + False Neg)

Question 49

False Positive Rate (alpha)

Answer 49

alpha = type I error alpha = 1 - Sp alpha = False Pos / (False Pos + True Neg)

Question 50

Positive likelihood ratio calculation

Answer 50

Positive likelihood ratio (LR+) = Se / (1 - Sp) [LR+ = True Pos Rate / False Pos Rate] Interpretation: likelihood ratio for a positive test = 3 this means that a positive test (in this case PFL\>=4) is 3 times more likely to come from an animal with disease (e.g. SL) than from an animal with NSL.

Question 51

Negative likelihood ratio calculation

Answer 51

Negative likelihood ratio (LR-) = (1 - Se) / Sp [LR- = False Neg Rate / True Neg Rate]

Question 52

Accuracy calculation

Answer 52

ACC = (True Pos + True Neg) / Population

Question 53

Diagnostic Odds ratio (DOR)

Answer 53

DOR = LR+ / LR- (positive likelihood ratio / negative likelihood ratio)

Question 54

calculation of True Positives (a) with prev and test parameters

Answer 54

True Pos = True Prev \* Se

Question 55

calculation of False Positives (b) (with prev)

Answer 55

False Pos = (1 - True Prev) (1 - Sp)

Question 56

calculation of True Negatives (d) with prev and test parameters

Answer 56

True Neg = (1 - True Prev) \* Sp

Question 57

calculation of False Negatives (c) with prev and test parameters

Answer 57

False Neg = True Prev \* (1 - Se)

Question 58

Strategies for selection of an appropriate test to rule out disease and to find evidence of disease

Answer 58

* If the objective of diagnostic testing is to _rule out_ disease, it means that a _reliable negative result_ is required and therefore the test should generate few false negatives (=**high sensitivity**). * In contrast, in order to _find evidence_ (=rule in) of true disease and minimise false positive results, a _reliable positive result_ is required with few false positives (=**high specificity**).

Question 59

Methods for choosing normal / abnormal criteria (i.e. criteria for deriving cut-off values)

Answer 59

* Gaussian distribution method * percentile * therapeutic * risk factor * dianostic or predictive value * culturally desirable