MEASURES OF DISEASE FREQUENCY

Introduction

Animal Health Practitioners routinely use population-based information to support clinical decisions
about the diagnosis, treatment and prognosis of individual animals. Comparison of the history and
clinical signs of an individual animal with knowledge about the frequency and pattern of disease in
the general population is an essential step in the clinical work-up of a case

A necessary part of the investigation of disease in a population is the counting of affected animals so
that the amount of disease can be described. Furthermore, it is usually desirable to describe when
and where disease occurs, and to relate the number of diseased animals to the size of the population
at risk of developing disease so that a disease's importance can be assessed. A report of 10 cases of
ECF in a farm, for example, does not indicate the true extent of the problem unless the report is
considered in terms of the number of cattle in the farm: there may be only 10 cattle present, in
which case all of the cattle are affected, or there may be 100 cattle, in which case only a small
proportion of the cattle are affected.

The amount of disease is the morbidity (Latin: morbus = disease); the number of deaths is the
mortality. The times of occurrence of cases of a disease constitute its temporal distribution,
whereas places of occurrence comprise its spatial distribution. The measurement and description of
the size of populations and their characteristics constitute demography (Greek: demo= people; -
graphia = writing, description).

Measures of disease frequency are essentially a proportion where the numerator is the number of
animals experiencing an event and the denominator is the total number of animals at risk because
they are biologically capable of experiencing the same event.

Measures of morbidity

One of the most fundamental tasks in epidemiological research is to quantify the occurrence of
disease. This can be done by counting the number of affected individuals however, to compare levels
of disease among groups of individuals, time frames and locations, we need to consider counts of
cases in context of the size of the population from which those cases arose.

A ratio defines the relative size of two quantities expressed by dividing one (numerator) by the other
(denominator). Proportions, odds, and rates are ratios. Say we have a herd of 100 cattle and 58 are
found to be diseased. The odds of disease in this herd are: 58:42 or 1.4 to 1.

A proportion is a fraction in which the numerator is included in the denominator. Say we have a herd
of 100 cattle and 58 are found to be diseased. The proportion of diseased animals in this herd is 58 ÷
100 = 0.58 = 58%.

A rate is derived from three pieces of information: (1) a numerator: the number of individuals
diseased or dead, (2) a denominator: the total number of animals (or animal time) in the study group
and/or period; and (3) a specified time period. To continue the above example, we might say that
the rate of disease in our herd over a 12-month period was 58 cases per 100 cattle.

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The term morbidity is used to refer to the extent of disease or disease frequency within a defined
population. Two important measures of morbidity are prevalence and incidence.

Prevalence

Prevalence refers to the number of cases of a given disease or attribute that exists in a population
at a specified time.

Prevalence = Number of existing disease cases

Size of population

Or

Prevalence = number of individuals having a disease at a particular point in time

number of individuals in the population at risk at that point in time

Prevalence can be interpreted as the probability of an individual from a population having a disease
at a specified point in time.

If 20 cows in a herd of 200 cows were lame on a particular day, then the prevalence of lameness in
the herd on that day would be 20/200, that is, 0.1. This is a proportion that represents the
probability of an animal having a specified disease at a given time. Sometimes, it is expressed as a
percentage.Thus, a prevalence of 0.1 = 10%.

Incidence

Incidence measures how frequently initially susceptible individuals become disease cases as they
are observed over time. An incident case occurs when an individual changes from being susceptible
to being diseased. The count of incident cases is the number of such events that occur in a defined
population during a specified time period. There are two ways to express incidence: incidence risk
and incidence rate.

Incidence risk

Incidence is the number of new cases that occur in a known population over a specified period of
time. The two essential components of an incidence value are:

1. the number of new cases;

2. the period of time over which the new cases occur.

Incidence risk (also known as cumulative incidence, or risk) is the proportion of initially susceptible
individuals in a population who become new cases during a defined time period.

Incidence, like prevalence, can be defined simply in terms of the number of affected animals, but
again is usually expressed in relation to the population at risk.

Incidence risk = Number of incident cases

Number of individuals initially at risk
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The defined time period may be arbitrarily fixed (e.g. 5-year incidence risk of mastitis) or it may vary
among individuals (e.g. the lifetime incidence risk of mastitis). In an investigation of a localised
epidemic the defined time period may be simply defined as the duration of the epidemic.

• Individuals have to be disease-free at the beginning of the observation period to be

included in the numerator or denominator of this calculation.

• The time period to which the risk applies must be specified.

• The quantity is dimensionless and ranges from 0 to 1.

Example: Last year a herd of 121 cattle were tested for tuberculosis using the tuberculin test and all
tested negative. This year the same 121 cattle were tested and 25 tested positive. The incidence risk
would then be 21 cases per 100 cattle for the 12-month period. We can also say that the risk of an
animal becoming positive to the tuberculin test for the 12-month period was 21%. This is an
expression of average risk applied to an individual (but estimated from the population).

Incidence rate

Incidence rate, measures the rapidity with which new cases of disease develop over time. Incidence
rate (also known as incidence density) is the number of new cases of disease that occur per unit of
individual time at risk, during a defined time period. The denominator of incidence rate is measured
in units of animal (or person) time.

Incidence rate =Number of incident cases

Amount of at-risk experience

Because the denominator is expressed in units of animal- or person-time at risk those individuals
that are withdrawn or are lost to follow up are easily accounted-for. The denominator is measured as
'animal-years at risk'. This is the sum of the periods of observation for each animal during which the
latter is free from the disease (i.e., is at risk). As soon as an animal becomes diseased, it no longer
contributes to this value. For example, six cows, free from disease, observed for 1 year would
constitute '6 animal-years at risk; equally, one cow observed for 6 years would constitute '6 animal-
years at risk'. Note that incidence rate has a dimension, time-I; incidence rate is calculated per
animal-week, per animal-year, and so on.

EXAMPLE

In a village which has a total 100 cows at the beginning of the study.

• 5 cows die after 2 months which means they were 5* 2 = 10 animal months at risk

• 2 cows die after 5 months which means they were 2 * 5 = 10 animal months at risk

• 3 cows die after 8 months which means they were 3 * 8 = 24 animal months at risk

This means a total of 10 cows die, and these experienced 44 animal months at risk based on the
calculation (5* 2 + 2*5 + 3*8).

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• 90 cows survive past the study period which means they were 90*12 months = 1080 animal
months at risk. The total animal months at risk = 44+1080 = 1124

Therefore, the incidence density of cow mortality in this village is calculated as 10 /1124 = 0.009
deaths per animal month.

How is prevalence and incidence used in clinical practice?

1. Assigning probability that an animal has a particular condition: Prevalence - guides diagnosis
& treatment

2. Predicting the clinical course of a patient: Incidence rate = predicts the probability of future
occurrence

3. Making comparisons: Prevalence & incidence - compare the frequency of a disease between
groups of animals with and without exposure to a risk factor

THE RELATIONSHIP BETWEEN PREVALENCE AND INCIDENCE

Table below compares the main features of the three measures of disease frequency that we have
described.

Table: Comparison of the measures of morbidity

Item Prevalence Incidence risk (I ) Incidence rate (R)

Numerator All cases counted New cases occurring New cases occurring
during a single survey during a time period during a time period
of a group among a group initially among a group initially
free of disease free of disease

Denominator All animals examined – Number of susceptible Sum of time periods

cases and noncases animals present during during which animals
the time period could have developed
disease

Approximation - Initial number at risk over time period (Start

ofdenominator minus half of the # + End #)/2
withdrawals
Time Single point or Duration of period For each animal from
period start of observation
until disease develops
Study type Cross‐sectional Cohort study Cohort study
study

Interpretation Probability of having Risk of developing Rate at new cases

disease at a particular disease over given time develop over given
point in time period time period

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Figure below provides a worked example for calculating the various measures of disease frequency.
The example is based on a herd of 10 animals which are all disease-free at the beginning of the
observation period and followed for a 12-month period. Disease status is assessed at monthly
intervals.

Application to animal health practice

Animal health Practitioners can use prevalence and incidence information in three different ways:

1. To assign a probability that an animal has a particular condition. Prevalence is useful in

guiding diagnosis and treatment because it provides information about the probability of an
animal with particular demographic and clinical characteristics having a condition.

2. To predict the clinical course of a patient. Incidence as a rate measure can be used to predict
the probability that an animal with a similar presentation will develop the disease condition
in the future.

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 3. To make comparisons. Both prevalence and incidence measures can be used to compare the
frequency of a disease between groups of animals with and without exposure to a risk factor.

MEASURES OF MORTALITY

Mortality measures are analogous to incidence measures where the relevant outcome is death
associated with, rather than new cases of, a specific disease. Often in veterinary work, measures of
mortality or deaths are useful for understanding the outcomes of disease and associated economic
impact. Two common measures are the crude mortality rate and the case-fatality rate.

Crude mortality rate is calculated as:

Total number of deaths in a time period

Average number of animals at risk

Mortality rate

Mortality rate (mortality density), M, is calculated similarly to incidence rate. The numerator
comprises the number of deaths. However, since an animal is at risk of dying after onset of disease,
animals that develop disease continue to be included in the denominator until they die. Formula =

number of deaths due to a disease that occur ina population during a particular period of time
the sum, over all individuals, of the length of time at risk of dying

Case fatality
The tendency for a condition to cause the death of affected animals in a specified time is the case
fatality, CF. Case-fatality rate, CFR, (or risk) is defined as the incidence of death among individuals
who develop the disease. Case fatality risk reflects the prognosis of disease among cases, while
mortality reflects the burden of deaths from the disease in the population as a whole. CFR is
calculated as:
Total number of deaths from disease X
Total number of animals developing disease X

To calculate cause-specific mortality or morbidity rates limit the numerator to the specific cause of
interest. Thus, Proportional mortality implies the proportion of all deaths that are due to a particular
cause for a specified population and time period:

Proportional mortality = Number of deaths from the disease

Number of deaths from all causes

To calculate age-specific mortality or morbidity rates limit both the numerator and denominator to
the specific age of interest.

Examples of calculations

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Suppose a veterinarian investigates a disease that runs a clinical course ending in either recovery or
death, in a herd of cattle. On 1 July 2003 the herd is investigated when the disease is already present.
The herd is then observed for the following year, during which period the herd size remains the same
and all animals are followed up (i.e., there are no censored observations).

Total herd size on 1 July 2003: 600

Total number clinically ill on 1 July 2003: 20

Total number developing clinical disease between 1 July 2003 and 1 July 2004: 80

Total number dying from the disease from 1 July 2003-1 July 2004: 30

Prevalence on 1 July 2003 = 20/600 = 0.03

Cumulative incidence 1 July 2003-1 July 2004 = 80/580 = 0.14

Incidence rate = 80/1 (580 + 500)/2) = 0.15 per animal-year at risk

Cumulative mortality 1 July 2003-1 July 2004 = 30/600= 0.05

Mortality rate = 30/{(600 + 570)12}= 0.05 per animal-year at risk

Case fatality 1 July 2003-1 July 2004 = 30/100 = 0.30

OTHER COMMONLY USED FORMULAS

MEASURES OF ASSOCIATION

Risk is the probability that an event will happen. A characteristic or factor that influences whether or
not an event occurs, is called a risk factor.

• Worn-out tyres are a risk factor for motor vehicle accidents.

• High blood pressure is a risk factor for coronary heart disease.

• Vaccination is a protective risk factor in that it usually reduces the risk of disease.

If we identify those risk factors that are causally associated with an increased likelihood of disease
and those causally associated with a decreased likelihood of disease, then we are in a good position
to make recommendations about health management. Much of epidemiological research is
concerned with estimating and quantifying risk factors for disease.

Associations between putative risk factors (exposures) and an outcome (usually a disease) can be
investigated using analytical observational studies. Consider a study where animals are disease free
at the start of the study and all are monitored for disease occurrence for a specified time period. If
both exposure and outcome are binary variables (yes or no), the results can be presented as a 2 × 2
table.

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FOR PREVALENCE – The measure of association is called the ODDS RATIO.

TO CALCULATE – First construct a 2 × 2 Contingency Table

Then use the data in the table to calculate the odds ratio.

The odds ratio measures the odds (or chance) of disease being present when a risk factor is present
compared to the odds of disease being present when the risk factor is absent.

For an OR greater than 1, the higher the odds ratio, the greater the association between the risk
factor and the occurrence of disease. An OR of 1 indicates no association, whereas an OR of less
than 1 indicates a sparing or protective effect.

Example: If we compare 100 people who have one copy of gene variant "X" to 100 SHEEP who do not have
any copies gene variant "X":
# of SHEEP with disease # of SHEEP without disease Total
One copy of gene variant "X" 50 50 100
No copies of gene variant "X" 2 98 100

The odds of having the disease with one copy of the gene variant are 50/50 or 1.0. The odds of
having the disease with no copies of the gene variant are 2/98 or 0.02. Therefore, the odds ratio of
having the disease when one copy of the gene variant is present versus when no copies of the gene
variant are present: 1.0/0.02 = 50.

FOR INCIDENCE – The measure of association is the RELATIVE RISK.

TO CALCULATE – Again the first step is to construct a 2 × 2 Contingency Table

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Then use the data in the table to calculate the relative risk.

The relative risk indicates the chance of a disease event occurring in the exposed group relative to
the chance of a disease event occurring in the unexposed group. The relative risk, RR, is the ratio of
the incidence of disease in exposed animals to the incidence in unexposed animals. You can use
either incidence risk or incidence rate to calculate RR, as long as you use the same form of incidence
in the numerator and denominator.

Example for RR:

In the table below, the term “two-by-two” refers to the two variables (sex and disease status), each
with two categories. The outcome (ECF or not) is shown at the top of the table and exposure or risk
factor is shown along the left side (male or female). Note the letters assigned to each cell of the table
(A-D). They are important in calculating the risk in each group.

East Coast Fever

No Yes Total

Female A 46 B 1438 (A+B) 1484

Male C 18 D 1401 (C+D) 1419

Using the data in the table above, we can calculate the relative risk of ECF for females versus males.
First, we must calculate the risk of ECF among females and among males:

Risk among females (incidence) = a/a+b = 46/1484 = 0.031 x 100 = 3.1%

Risk among males (incidence) = c/c+d = 18/1419 = .013 x 100 = 1.3%

To calculate the RR for females vs. males, females are considered the group of primary interest and
males are the comparison group. The formula is:

Relative ratio = 3.1%/1.3% = 2.4

So we can say that the risk of ECF in females appears to be 2.4 times higher than the risk in males. If
the RR is 1.0, that means the risk of disease is equal in the two groups. If the RR is greater than 1.0,
then the group of interest has a higher risk of disease. If the RR is less than 1.0, then the group of
interest has a lower risk of disease. However, before we can interpret RR figures, they must be
subjected to a test of statistical significance such as the Chi square or some variation of it.