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Measuring the Transmissibility of

Infections (EC03)
Module: EPM301 Epidemiology of Communicable Diseases
Course: PG Diploma/ MSc Epidemiology

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These study materials have been prepared by the London School of Hygiene & Tropical Medicine as part of
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London School of Hygiene & Tropical Medicine September 2013 v2.0

Section 1: EC03 Measuring the Transmissibility of Infections


Aims
To understand how to measure the transmissibility of infections.
Objectives
By the end of this session you should be able to:

explain the historical origins of the secondary attack rate


define, calculate and interpret a secondary attack rate
explain the practical applications of the secondary attack rate
define, calculate and interpret a net reproduction number and a basic
reproduction number
explain the practical applications of reproduction numbers
This session should take you between 2.5 and 4 hours to complete.

Section 2: Introduction
A fundamental property of most infections/infectious agents is their transmissibility.
Infectious agents are transmitted from one host to another either directly or
indirectly in a wide variety of ways. The efficiency of transmission of an infection
determines population patterns of the infection and disease and has important
implications for disease control.
Several measures have been developed for evaluating the transmission probability of
infectious diseases. In this session we will discuss the history, strengths and
weaknesses of two of the most common measures used: the secondary attack
rate and the reproduction number.

Section 3: Secondary attack rate


History
From the early 19th century onward, epidemiologists have collected data on the
clustering of cases of infectious diseases within households. Households have been a
popular unit of study because they represent small, relatively stable communities
where people live in close contact with each other.

3.1: Secondary attack rate


During the 19th century, epidemiologists collected a large number of observations
of the following types:
Number of households in which more
than one case occurred
Proportion of households in which more

than one case occurred


Proportion of all cases in the
community that occurred in households
with more than one case
The following hypothetical data is expressed in the form used by these early
epidemiologists.

3.2: Secondary attack rate


(RHS remains static - chart)
Exercise
Can you use these data to calculate which of these diseases has the highest
transmission probability? Click on the answer below:
Interaction: Hotspot: Yes (appears in new window)
In fact, the data presented cannot be used to calculate or compare the
transmission probability of the diseases.
These early measures give no indication of the number of susceptible people exposed
to infection or the number of resultant cases.
Interaction: Hotspot: No (appears in new window)
That's correct. The data presented cannot be used to calculate or compare the
transmission probability of the diseases.
These early measures give no indication of the number of susceptible people exposed
to infection or the number of resultant cases.

3.3: Secondary attack rate


A few 19th century epidemiologists expressed their observations in terms of the
number of families having one, two, three or more cases.

Interaction: Hotspot: Yes (appears in new window)


Exercise
Would you be able to use this data to compare the transmission probability of
different diseases?
In fact, these measures are also inadequate. They give no indication of the size of
the families in which the cases occurred, so they still do not provide data on the
number of susceptible people exposed to infection.
Interaction: Hotspot: No (appears in new window)
That's correct. These measures are also inadequate. They give no indication of the
size of the families in which the cases occurred, so they still do not provide data on
the number of susceptible people exposed to infection.

3.4: Secondary attack rate


From 1884 to 1905, Dr. Charles Chapin, the Superintendent of Health of the City
of Providence, Rhode Island compiled a series of annual reports on various
aspects of the epidemiology of scarlet fever and diphtheria.
He was interested in measuring the frequency of spread of scarlet fever to other
members of the same family. To answer this question, he collected a large
number of observations on different aspects of the occurrence of cases of scarlet
fever in households.
The following table (Frost 1938) contains some of the data that Chapin collected
on cases of scarlet fever in 1888.

Interaction: Hyperlink: inunction: output (appears in new window)


Inunction
The application of an ointment to the skin.

3.5: Secondary attack rate


(RHS remains static)
Exercise
Using these data, is it possible to compare the transmission probability of scarlet
fever in families where inunction was practised with the transmission probability in
all families?
Interaction: Hotspot: Yes (appears in new window)
That's correct. Charles Chapin collected data on the number of susceptible children
exposed and the number of these children who were 'attacked' (became cases of
scarlet fever).
You can use these data to calculate the proportion of exposed susceptible children
who became cases in families where inunction was practised, and the proportion of
exposed susceptible children who became cases in all families. This proportion is
called the 'secondary attack rate (SAR)'.
SAR in all families
= 511 / 827 = 62%
SAR in families in which inunction was practised
= 319 / 496 = 64%
Interaction: Hotspot: No (appears in new window)
In fact you can use these data to compare transmission probabilities. Charles
Chapin collected data on the number of susceptible children exposed and the
number of these children who were 'attacked' (became cases of scarlet fever).
You can use these data to calculate the proportion of exposed susceptible children
who became cases in families where inunction was practised, and the proportion of
exposed susceptible children who became cases in all families. This proportion is
called the 'secondary attack rate (SAR)'.
SAR in all families
= 511 / 827 = 62%
SAR in families in which inunction was practised
= 319 / 496 = 64%

Section 4: How to calculate a secondary attack rate: direct


method

The secondary attack rate is used to calculate the probability that an infectious
disease will be transmitted in a small community such as a household or a school
class.
The secondary attack rate is the proportion of susceptible individuals who have
contact with the primary case and go on to develop the disease as a consequence of
this contact. Note that the secondary attack rate is actually a proportion (risk), not a
true rate.

Number of exposed persons who


develop the disease
(secondary cases)
SAR = ___________________
total number of susceptible persons
exposed to a primary case
Interaction: Hyperlink: secondary cases: output (appears in new window)
Secondary case
A case arising directly from a primary case.
Interaction: Hyperlink: primary cases: output (appears in new window)
Primary case
The first case of a disease in the community.

4.1: How to calculate a secondary attack rate: direct method


Interaction: Tabs: 1 : output
To calculate a secondary attack rate, we need to know the time periods of infection
and the time periods of disease for the infectious agent that we are studying.
We need this information to help define which individuals have been exposed to a
potentially infective contact, and which of these individuals may have developed the
disease as a result of the contact.

Interaction: Tabs: 2 : output


First we need to define the time period during which secondary cases could have
occurred due to contact with the primary case. To define this, we must first identify
the beginning of the period of infectiousness of the primary case. This is time (0).
We then add to this the minimum incubation period for the disease (E1). Any
secondary cases must occur after this time.
Interaction: Button: show: output (changes table on RHS)

Interaction: Tabs: 3 : output


If we add the maximum infectious period (I) of the primary case to the maximum
incubation period of any secondary cases (E2), then we also know that any
secondary cases must occur before this time.
Interaction: Button: show: output (changes table on RHS)

So, the period from the end of E1 to the end of the combined period (I + E2) is the
period during which any cases occurring amongst the contacts can be attributed to
contact with the primary case.
Interaction: Button: show: output (changes table on RHS)

Interaction: Tabs: 4 : output


So, for a hypothetical disease with:
a minimum incubation period (E1)
of 4 days,
a maximum incubation period (E2)
of 5 days, and
a maximum infectious period (I)
of 5 days,
if a primary case becomes infectious at time 0, any cases appearing between days 4
and 10 will be considered secondary cases.
Interaction: Button: show: output (changes table on RHS)

Interaction: Tabs: 5 : output


Any cases occurring before this time could not have been infected by the primary
case, and are called co-primary cases.
The co-primary cases should not be included in either the denominator or the
numerator of the SAR equation, as they are not susceptible to infection from the
primary case.
Interaction: Button: show: output (changes table on RHS)
Interaction: Button: show: output (changes table on RHS)

Interaction: Tabs: 6 : output

Similarly, any cases occurring after this time could not have been infected by the
primary case. These are called tertiary cases.
The tertiary cases are excluded from the numerator, as they do not become infected
due to contact with the primary case. However, they should be included as the
denominator as they were susceptible to infection from the primary case.
Interaction: Button: show: output (changes table on RHS)

4.2: How to calculate a secondary attack rate: direct method


As you can see, to calculate a SAR you require the following information:
Exact time of onset of each case
Number of susceptibles exposed to the
primary case
Estimate of the maximum infectious
period and the minimum and maximum
incubation periods of the disease
(Review this from FE07).
On the following cards, you will look at some of the practical issues involved in
obtaining and using these pieces of information.

4.3: How to calculate a secondary attack rate: direct method


Practical issues 1:
Identifying time of onset of each case

You must clearly identify the time of onset of each case if you are to distinguish
between primary cases, secondary cases and tertiary cases. It is important to use
a standard manifestation of the disease to identify the date of onset of each case.
In 1948, Hope-Simpson developed the following guidelines for choosing the most
suitable manifestation for measurement:
Interaction: Hyperlink: 1. Obtrusiveness and memorability: output (appears
on RHS)
1. Obtrusiveness and memorability
The manifestation should be
clearly noticeable and be likely
to be remembered to reduce extraneous variability
Interaction: Hyperlink: extraneous variability: output (appears in new
window)
Extraneous variability
Variability not attributable to the biology of the disease, e.g. variability in memory,
reporting, observation etc.
Interaction: Hyperlink: 2. Constancy of presence: output (appears on RHS)
2. Constancy of presence
The manifestation should be present in
the majority of cases of the disease to
reduce the number of false negatives.
(Back to LHS page)
Interaction: Hyperlink: 3. Stability in the cycle of the disease: output (appears
on RHS)
3. Stability in the cycle of the disease
The manifestation should appear at
a stable point in the cycle of the
illness to reduce internal variability.
Interaction: Hyperlink: internal variability: output (appears in new window)
Internal variability
Variability attributable to the biology of the disease.
For example, the onset of jaundice in hepatitis A may appear between 21 and 35
days after infection.

4.4: How to calculate a secondary attack rate: direct method


Exercise

The table below (Hope-Simpson 1948) shows the range of onset times for
different manifestations of measles. Assume that all of these manifestations are
present in a large proportion of cases (guideline 2).
Click on the manifestation below that you would choose in order to measure the time
of onset in a secondary attack rate study.

Interaction: Hotspot: Onset of illness (hotspot 1) (appears in new window)


Onset of illness
The onset of the illness is a rather vague manifestation that is probably not very
memorable (guideline 1). Also, there is a wide range of variation in the appearance
of the onset of the illness within the cycle of illness (guideline 3). This probably
would not be the best manifestation to choose.
Interaction: Hotspot: Onset of illness (hotspot 2) (appears in new window)
Onset of rash
The onset of the rash appears at a relatively stable point in the cycle of the illness
(guideline 3). Whether you choose to use this manifestation or the time of the
fullest rash will depend on which sign you expect to be most noticeable and
memorable within the context of the study (guideline 1).
Hope Simpson himself argued that the time of the fullest rash was the most
noticeable and memorable and used this manifestation in his secondary attack rate
studies.
Interaction: Hotspot: Onset of illness (hotspot 3) (appears in new window)
Fullest rash
The time of the fullest rash is slightly less variable in the cycle of the illness than
the onset of the rash (guideline 3). Whether you choose to use this manifestation
or the onset of the rash will depend on which sign you expect to be most noticeable
and memorable within the context of the study (guideline ).

Hope Simpson himself argued that the time of the fullest rash was the most
noticeable and memorable and used this manifestation in his secondary attack rate
studies.
1. Obtrusiveness and memorability
The manifestation should be
clearly noticeable and be likely
to be remembered to reduce
extraneous variability.
Interaction: Hyperlink: extraneous variability.: output (appears in new window)
Extraneous variability
Variability not attributable to the biology of the disease, e.g. variability in memory,
reporting, observation etc.
2. Constancy of presence
The manifestation should be present in
the majority of cases of the disease to
reduce the number of false negatives.
3. Stability in the cycle of the disease
The manifestation should appear at
a stable point in the cycle of the
illness to reduce internal variability.
Interaction: Hyperlink: internal variability: output (appears in new window)
Internal variability
Variability attributable to the biology of the disease.
For example, the onset of jaundice in hepatitis A may appear between 21 and 35
days after infection.

4.5: How to calculate a secondary attack rate: direct method


Practical issues 2:
Identifying the number of exposed susceptibles
The denominator of the secondary rate is composed of all the susceptible
individuals in the community under study that make contact with the primary
case.
To calculate this figure, you need to know how many susceptibles there are in the
community under study, and how many of them were exposed to the primary
case.

4.6: How to calculate a secondary attack rate: direct method

Identifying the number of exposed susceptibles:


a) Identifying the number of
susceptibles in the community
The means of identifying susceptible individuals varies according to the disease
being studied and the time and resources available. Sometimes researchers carry
out immunological tests to identify susceptible individuals.
Click below for an example.
Interaction: Button: Example: output (appears on RHS)
Example
In a study of secondary attack rates in household contacts of a primary case with
acute hepatitis B infection, the researchers tested all household contacts for
hepatitis B surface antigen (HBsAG) or antibodies to hepatitis B surface antigen
(anti-HBs) (Koff et al 1977).
Only contacts who were negative for both HBsAG and anti-HBs were considered to
be susceptible. http://www.cdc.gov/hepatitis/HBV/index.htm for details of the
clinical presentation and epidemiology of hepatitis B infection.

4.7: How to calculate a secondary attack rate: direct method


Often however, researchers define as susceptible all persons who have no past
history of the illness or vaccination against the illness.
For rare diseases where no vaccination has been carried out in the community, or
for diseases that do not confer life-long immunity, some researchers assume that
all members of the community are susceptible.
Obviously, the method of identifying or defining susceptibles will affect the
calculation of the secondary attack rate.
Exercise
If you count as susceptible some individuals who are actually immune to the
disease, what effect would this have on the calculated SAR? Click on one of the
following options.
Interaction: Hotspot: The calculated SAR would be an overestimate of the
true transmission probability. (appears in new window)
Remember that SAR = (no. of secondary cases / total no. of exposed susceptibles).
So, including individuals who are not actually susceptible to the disease would
artificially raise the denominator. In these circumstances the calculated SAR would
be an underestimate of the true transmission probability.

Interaction: Hotspot: The calculated SAR would be an underestimate of the


true transmission probability. (appears in new window)
That's correct. Including individuals who are not actually susceptible to the disease
would artificially raise the denominator. In these circumstances the calculated SAR
would be an underestimate of the true transmission probability.

4.8: How to calculate a secondary attack rate: direct method


Identifying the number of exposed susceptibles:
b) Definition of exposure to a
primary case
The definition of exposure to a primary case will vary from study to study and
should always be clearly expressed.
Interaction: Button: Examples: output (appears in new window)
Examples
In a household secondary attack rate study, you could define exposure to a primary
case as 'eating and sleeping in the same house as a primary case during a specific
period of time.'
In a secondary attack rate study in a school class, you could define exposure to a
primary case as 'attendance in the same class as a primary case during a specific
period of time'.
The mode of transmission of the infectious agent will determine which types of
contact lead to a potentially infectious exposure.
Interaction: Button: Examples: output (appears in new window)
Examples
For an infectious agent transmitted by droplet spread (such as measles) you could
define exposure as living in the same house as the primary case during the period
of infectiousness of that case.
For a sexually transmitted agent (such as gonorrhoea), you could define exposure
as having sexual intercourse with the primary case during the period of
infectiousness of that case.
As the definition of exposure will vary from study to study, the value of the
secondary attack rate is not constant for each disease. The value of the SAR depends
on the definition of exposure used.

4.9: How to calculate a secondary attack rate: direct method


Exercise

The measles virus is transmitted by droplet spread. The three SAR studies listed
below all calculated a SAR for measles in susceptible children under the age of
14.
School SAR study
Classroom SAR study
Household SAR study
Which study would you expect to have found the highest SAR? Which would you
expect to have found the lowest SAR?
Click and drag boxes from each of the studies in the orange boxes opposite to the
results you would expect.
Interaction: Hyperlink: School SAR study: output (appears in new window)
School secondary attack rate study
Exposure was defined as attending the same school as a primary case.
Interaction: Hyperlink: Classroom SAR study: output (appears in new window)
Classroom secondary attack rate study
Exposure was defined as attending the same school class as a primary case.
Interaction: Hyperlink: Household SAR study: output (appears in new window)
Household secondary attack rate study
Exposure was defined as eating and sleeping in the same house as a primary case.

School secondary
attack rate study

Highest
SAR

Classroom secondary
attack rate study

Intermediate
SAR

Household secondary
attack rate study

Lowest
SAR

Interaction: Drag and Drop: School secondary attack rate study

Correct response: (drag to Lowest SAR button)


That's correct. In a whole school, a lower proportion of children are likely to
have had close enough contact with a primary case to result in transmission
than in a household or classroom. This is likely to result in a lower SAR.
Incorrect response: (drag to Intermediate SAR or Highest SAR button)
In fact, in a whole school, a lower proportion of children are likely to have
had close enough contact with a primary case to result in transmission than
in a household or classroom. This is likely to result in a lower SAR.
Interaction: Drag and Drop: Classroom secondary attack rate study
Correct response: (drag to Intermediate SAR button)
That's correct. In a classroom, a smaller proportion of children are likely to
have had close enough contact with a primary case to result in transmission
than in a household. However, a higher proportion of children are likely to
have had close enough contact with a primary case to lead to transmission
than in a whole school. This is likely to result in an intermediate SAR.
Incorrect response: (drag to Highest SAR or Lowest SAR button)
In fact, in a classroom, a smaller proportion of children are likely to have
had close enough contact with a primary case to result in transmission than
in a household. However, a higher proportion of children are likely to have
had close enough contact with a primary case to lead to transmission than
in a whole school. This is likely to result in a Intermediate SAR.
Interaction: Drag and Drop: Household secondary attack rate study
Correct response: (drag to Highest SAR button)
That's correct. In a small unit like a household, all children are likely to have
had closer contact with the primary case than in larger units such as a
classroom or whole school. This is likely to result in a higher SAR.
Incorrect response: (drag to Lowest SAR or Intermediate SAR button)
In fact, in a small unit like a household, all children are likely to have had
closer contact with the primary case than in larger units such as a
classroom or whole school. This is likely to result in a higher SAR
(Once all tasks have been completed correctly text below appears)
Well Done, You have completed this task successfully

4.10: How to calculate a secondary attack rate: direct method


Exercise
Now turn to the following article in your reader:
"The Meningococcal Disease Surveillance Group. Meningococcal Disease.
Secondary Attack Rate and Chemoprophylaxis in the United States, 1974. JAMA
1976, 235: 261-265."

This is an example of a study that used the direct method to calculate the
secondary attack rate of meningococcal disease.
Read through the article. While you are reading, answer the questions opposite.
What criteria were used to establish
the onset of each case? Think about
your answer then click below.
Interaction: Button: cloud: output (appears in new window)
In the article, the criterion used to establish the onset of each case is not explicitly
described. As the definition of a secondary case is "...meningococcal disease in a
household member with onset more than 24 hours but less than 31 days after
hospitalisation of the index patient" (p.262), it appears that the time of
hospitalisation was used to date the primary case.
The criterion used to establish the onset of the secondary case appears to be onset
of symptoms (see p262, subheading 'Secondary Attack Rate' paragraph 2). As we
only have detailed information on the time course of onset of symptoms for one
household, it is impossible to judge whether this apparent inconsistency may have
led to an underestimate of the number of co-primary cases and a subsequent
overestimate of secondary cases.
(back to main text)
What estimate of the maximum
infectious period and the minimum and
maximum incubation periods of
meningococcal disease were used in
this study?
Interaction: Button: cloud: output (appears in new window)
The definition of a secondary case used in this study is "meningococcal disease in a
household member with onset more than 24 hours but less than 31 days after
hospitalisation of the index patient" (p.26).
From this, we can assume that the minimum incubation period used in this study
was 24 hours after hospitalisation of the primary case and the combined
maximum infectious period and maximum incubation period was 31days after
hospitalisation of the primary case. The source of these estimates is not given.
(back to main text)
How was the number of exposed
susceptibles determined?
Interaction: Button: cloud: output (appears in new window)
All people who "lived in the same house (or dormitory room) with a patient in the
week prior to the onset of the patient's illness" (p.262) were counted as exposed
susceptibles.

Section 5: How to calculate a secondary attack rate: indirect


method
To calculate a direct SAR you need detailed information on the number of
secondary cases among susceptibles exposed to a primary case in each small
community under study. Often, this type of detailed information is not available.
However, it is possible to estimate an SAR using routine surveillance data that
distinguishes between primary and secondary cases.
To do this, you need to take the information about primary and secondary cases
from the routine data source. You then estimate the number of exposed
susceptible persons using data on the mean size of the communities under study.

Estimated household SAR =

N
_____________
h x (m-1)

where:

h = number of households with a primary case


m = mean number of people per household
N = total number of secondary cases

5.1: How to calculate a secondary attack rate: indirect method


Exercise
Turn to the following article in your reader:
De Wals P, Hertoghe L, Borlee-Grimee I et al. Meningococcal disease in Belgium.
Secondary attack rate among household, day-nursery and pre-elementary school
contacts. Journal of Infection 1981; 3, Supplement 1: 53-61

This article is an example of a study in which routine surveillance data was used to
estimate the secondary attack rate of meningococcal disease. Read through the
article. While you are reading, answer the questions on the following cards.
1. What was the case definition of meningococcal disease used in this study?
Think about your answer and then click on the button here.
Interaction: Button: cloud: output (appears in new window)
The case definitions used are presented on p. 54 of the article.
Possible case: An illness reported as meningococcal disease by a local physician.
Confirmed case: An illness reported as meningococcal disease by a local physician
in which N. meningitidus was isolated from cerebrospinal fluid, blood or petechial
skin lesions.
(back to main text)
2. What was the definition of a secondary case used in this study?
Think about your answer and then click on the button here.
Interaction: Button: cloud: output (appears in new window)
The secondary case definition is also presented on p. 54 of the article.
Secondary case: ' A case of meningococcal disease in a patient's contact with onset
less than 60 days after the onset of the primary case'.

5.2: How to calculate a secondary attack rate: indirect method


Exercise (continued)
3. What was the definition of a co-primary case used in this study?
Think about your answer and then click on the button here.
Interaction: Button: cloud: output (appears in new window)
Co-primary cases were not distinguished from secondary cases in this study. Any
case occurring 0 _60 days after the onset of the primary case was considered to
be a secondary case.
(back to main text)
4. How did the researchers estimate the number of exposed susceptibles in
households?
Think about your answer and then click on the button here.
Interaction: Button: cloud: output (appears in new window)
The number of exposed susceptibles in households was estimated by taking the
number of primary cases less than 15 years old (1665) and multiplying this by (the
average size of households with children of this age 1):

Number of exposed susceptibles


= 1665 x (4.07 1)
= 5112
(see p 56 and table III p 57).
5. How did the researchers estimate the number of exposed susceptibles in daycare nurseries?
Think about your answer and then click on the button here.
Interaction: Button: cloud: output (appears in new window)
The number of exposed susceptibles in day-nurseries was estimated by taking the
number of primary cases in children less than 3 years old attending day nursery
(28) and multiplying this by (the mean number of children in these nurseries,
multiplied by the occupancy rate 1):
Number of exposed susceptibles
= 28 x 35.4
= 991
(see p 56 and table III p 57).
(back to main text)
6. How did the researchers estimate the number of exposed susceptibles in preelementary schools?
Think about your answer and then click on the button here.
Interaction: Button: cloud: output (appears in new window)
The number of exposed susceptibles in pre-elementary schools was estimated by
taking the number of primary cases in children attending pre-elementary school
(302), multiplied by the likelihood that these cases occurred during effective school
time (9/12): (302 x 9/12 = 227).
This was then multiplied by (the mean number of children per pre-elementary
school 1) (80):
Number of exposed susceptibles = 227 x 80 = 18,160
(see p.57 and table III).

5.3: How to calculate a secondary attack rate: indirect method


Exercise (continued)
The estimated household secondary attack rate in this study is more than double
the household SAR calculated using the direct method in the study by the
Meningococcal Surveillance Group (MSG). Think back at the article by the MSG (in
your reader) and answer the following question:

Which of the reasons shown opposite could explain this difference in the
household secondary attack rate for meningococcal disease obtained in the two
studies?
Click 'true' or 'false' for each reason. The tabs will change colour accordingly green
for true, red for false.
Interaction: Tabs: 1 : output (appears in new window)
The secondary attack rate of meningococcal disease in Belgium from 1971 to 1976
may have been genuinely higher than the secondary attack rate in the United States
from November 1973 to March 1974.
Interaction: Button: true: output (appears in new window)
That's correct. The secondary attack rate is not fixed for a specific disease, but varies
according to a number of different circumstances. The secondary attack rate of
meningococcal disease is known to be much higher in epidemic periods than in nonepidemic periods. The US study was deliberately carried out during a non-epidemic
period. The Belgium study was carried out over a much longer time period (4 years)
and may have included epidemic periods. Other factors that can influence the
secondary attack rate are the age and sex of exposed individuals, and factors that
influence how often cases and susceptibles make contact, such as crowding and
social structure.
Interaction: Button: false: output (appears in new window)
In fact this is true. The secondary attack rate is not fixed for a specific disease, but
varies according to a number of different circumstances. The secondary attack rate
of meningococcal disease is known to be much higher in epidemic periods than in
non-epidemic periods. The US study was deliberately carried out during a nonepidemic period. The Belgium study was carried out over a much longer time period
(4 years) and may have included epidemic periods. Other factors that can influence
the secondary attack rate are the age and sex of exposed individuals, and factors
that influence how often cases and susceptibles make contact, such as crowding and
social structure.
(back to main text)
Interaction: Tabs: 2 : output (appears in new window)
The possible classification of co-primary cases as secondary cases in the De Wals
study may have led to an overestimation of the household secondary attack rate in
this study.
Interaction: Button: true: output (appears in new window)
That's correct. Table II on p.56 of the De Wals article shows that 30% of the
secondary cases for whom time interval data was available occurred ~< day after
the primary case. These cases would probably have been considered to be coprimary cases by the Meningococcal Study Group. However, the lack of a clear
statement about which manifestation was used to date the onset of the cases in both
studies makes it difficult to judge the exact impact of this difference.
Interaction: Button: false: output (appears in new window)

In fact this is true. Table II on p.56 of the De Wals article shows that 30% of the
secondary cases for whom time interval data was available occurred ~< day after
the primary case. These cases would probably have been considered to be coprimary cases by the Meningococcal Study Group. However, the lack of a clear
statement about which manifestation was used to date the onset of the cases in
both studies makes it difficult to judge the exact impact of this difference.
(back to main text)
Interaction: Tabs: 3 : output (appears in new window)
The method used to estimate the number of susceptible household contacts in the
study by De Wals may have led to an overestimation of the household secondary
attack rate in this study.

Interaction: Button: true: output (appears in new window)


That's correct. The estimate of the number of susceptible household contacts in the
De Wals study is based on the national average size of households with children less
than 15 years old. The households in which primary cases actually occurred may
have been significantly larger (or smaller) than this, leading to either an
overestimation or an underestimation of the secondary attack rate.
Interaction: Button: false: output (appears in new window)
In fact this is true. The estimate of the number of susceptible household contacts in
the De Wals study is based on the national average size of households with children
less than 15 years old. The households in which primary cases actually occurred may
have been significantly larger (or smaller) than this, leading to either an
overestimation or an underestimation of the secondary attack rate.
(back to main text)
Interaction: Tabs: 4 : output (appears in new window)
The case definition of meningococcal disease in the De Wals study may have led to
the inclusion of more cases than the case definition used in the Meningococcal Study
Group study.
Interaction: Button: true: output (appears in new window)
In fact, the case definition for meningococcal disease used by both studies was
almost identical, so this is unlikely to be responsible for the different results obtained
by the two studies.
Interaction: Button: false: output (appears in new window)
Yes, the case definition for meningococcal disease used by both studies was almost
identical, so this is unlikely to be responsible for the different results obtained by the
two studies.
(back to main text)

Interaction: Tabs: 5 : output (appears in new window)


Reporting of secondary cases in Belgium between 1971 and 1976 may have been
more complete than reporting of secondary cases in the United States between
November 1973 and March 1974.
Interaction: Button: true: output (appears in new window)
That's correct. As you are comparing data derived from different surveillance
systems, you should be aware that there may be differences in the completeness of
reporting in the two studies.

Interaction: Button: false: output (appears in new window)


In fact this is true. As you are comparing data derived from different surveillance
systems, you should be aware that there may be differences in the completeness of
reporting in the two studies.

Section 6: Why calculate a SAR


As the secondary attack rate is a standard measure, you can use it to compare the
transmission potential of an infectious disease according to various characteristics
of both the primary case and those exposed.
For example, you could calculate a secondary attack rate according to
characteristics such as the sex, age, type of contact, and management of the
primary case or those exposed.
This information can help elucidate the transmission routes of the infectious agent
and help determine which control measures may reduce transmission. You can also
use the SAR to help measure post-licensure vaccine efficacy by comparing the SAR
in vaccinated and unvaccinated contacts.
In the following pages, you will look in more detail at the practical applications of the
SAR.

6.1: Why calculate a SAR


Using the SAR to investigate possible transmission routes
You can calculate the secondary attack rate for a specific disease in different
groups of exposed persons according to the type of contact they have had with a
primary case. This can help us to understand the transmission routes of an
infectious agent.
Interaction: Button: name: output (appears on RHS)
Example
Before the transmission routes of hepatitis B virus were well established, an
epidemiological study (Koff et al 1977) estimated the SAR for different kinds of
household contacts of a primary case of acute hepatitis B infection.

The study found a secondary attack rate of 0% in parents, siblings and other
domestic contacts and 23% in sexual contacts. This study, along with other
evidence, suggests that the sexual route is the most important route for the
transmission of hepatitis B virus from an acute primary case within the household.

6.2: Why calculate a SAR


Exercise
In a study of an outbreak of an acute illness in an elementary school, the
following data was collected:
No. of susceptible children in the same
class as the primary case = 27
No. of susceptible children who used the
same toilet facilities as the primary
case = 75
No. of secondary cases in the same class
No. of secondary cases who used the
same toilet facilities as the primary
case = 33

as the primary case = 4

On the basis of these data, which of the following transmission routes is likely to
have been the most important?
Interaction: Button: Hint: output (appears in new window)
Hint
Calculate the SAR for children in the same class as the primary case and children
who share the same toilet facilities as the primary case.
(back to main text)
Interaction: Hotspot: droplet spread: output (appears in new window)
SAR among children in the same class as a primary case = 4 / 27 = 15%
SAR among children who used the same toilet facilities as a primary case = 33 / 75
= 44%
If droplet spread were the most important transmission route, we would expect the
SAR among children in the same class as a primary case to be higher than the SAR
in children who used the same toilet facilities as a primary case. Please try again.
Interaction: Hotspot: faecal oral spread: output (appears in new window)
Correct
SAR among children in the same class as a primary case = 4 / 27 = 15%
SAR among children who used the same toilet facilities as a primary case = 33 / 75
= 44%
As the SAR in children who used the same toilet facilities as a primary case was
higher than the SAR among children in the same class as a primary case, faecal-oral
spread was probably the most important transmission route.

Interaction: Hotspot: skin to skin contact: output (appears in new window)


SAR among children in the same class as a primary case = 4 / 27 = 15%
SAR among children who used the same toilet facilities as a primary case = 33 / 75
= 44%
If skin-to-skin contact were the most important transmission route, we would expect
the SAR among children in the same class as a primary case to be higher than the
SAR in children who used the same toilet facilities as a primary case. In this
example, faecal-oral spread was probably the most important transmission route.

6.3: Why calculate a SAR


Using the SAR to help determine control measures
You can use secondary attack rate data to help decide what action to take after
contact with a primary case.
Example
The American Public Health Association recommends the prophylactic
administration of an effective chemotherapeutic agent to the following contacts of a
primary case of meningococcal disease:
Household contacts
Military personnel sharing the same
living space
People socially close enough to have
shared the same eating utensils (e.g.
close friends at school but not the
whole class)
Younger children in day care centres
These recommendations are based on data on secondary attack rates, which show a
greatly increased risk of infection among these specific types of contacts.

6.4: Why calculate a SAR


Using the SAR to measure post licensure vaccine efficacy
Before a vaccine is licensed for use its efficacy must be demonstrated, usually in a
randomised double-blind trial. After licensure, the effectiveness of both the vaccine
and the vaccination programme must continue to be monitored. One way to do this
is to compare the secondary attack rates in vaccinated and unvaccinated persons in
households with a primary case of the disease under study.

Vaccine Efficacy (VE) = 1 SARv


_______
SARu
where:

SARv = secondary attack rate in vaccinated persons


SARu = secondary attack rate in unvaccinated persons

This is dealt with in more detail in session EC07

Section 7: Assumptions underlying the calculation of a SAR


The calculation of a SAR is based on a number of important assumptions. If these
assumptions are not met, the SAR may be subject to considerable error. On the
following cards you will examine the assumptions underlying the SAR and their
implications.
1. The SAR assumes that each secondary case is derived from a single
primary case within the household.
Can you think of two circumstances in which apparent secondary cases may not
have derived from a single primary case within the household?
Write down your answers then click on the think button below.
Interaction: Button: cloud: output (appears on RHS)
Interaction: Tabs: circumstances 1 : output
If there is more than one primary case in the household
In this case, any secondary cases may result from transmission from any of the
primary cases. Most secondary attack rate studies deal with co-primary cases by
excluding them from both the denominator and the numerator of the secondary
attack rate calculation. This ignores their potential influence on transmission. If the
data are available, it may be possible to stratify by the number of primary cases.
Interaction: Tabs: circumstances 2 : output
If there is extra-household transmission
Apparent secondary cases may be attributable to infection acquired outside the
household. Failure to separate community-acquired infection from true secondary
household infection can lead to serious inaccuracies in the calculation of the SAR.
Methods to correct for extra-household transmission have been developed by

Kemper (1980) and Longini et al (1982). These methods are beyond the scope of
this course.

7.1: Assumptions underlying the calculation of a SAR


1. The SAR assumes that each secondary case is derived from a single
primary case within the household.
Exercise i
What effect may ignoring transmission from co-primary cases or extra-household
cases have on the calculated SAR?
Click on one of the options opposite.
Interaction: Hotspot: The calculated SAR may be an overestimation of the true
transmission probability. output (appears in new window)
That's correct. SAR = no. secondary cases/total no. exposed susceptibles. So, if you
overestimate the number of secondary cases due to transmission from a single
primary case within the household you will overestimate the transmission probability.
Interaction: Hotspot: The calculated SAR may be an underestimation of the true
transmission probability. output (appears in new window)
Remember that SAR= no. secondary cases/ total no. exposed susceptibles. So, if you
overestimate the number of secondary cases due to transmission from a single
primary case within the household you will overestimate the transmission probability.

7.2: Assumptions underlying the calculation of a SAR


2. Most SAR studies assume that all cases of successful transmission of
infection are symptomatic. The presence of asymptomatic infections can lead to
substantial errors in the calculation of a SAR.
Exercise ii
Imagine that you are carrying out a SAR study of an infection that produces life-long
immunity. You decide to use a past history of the disease to distinguish between the
exposed persons who are susceptible and those who are immune. What would
happen to the SAR if a large proportion of the infections that occurred before the
onset of the study were asymptomatic?
Click on one of the options below.
Interaction: Hotspot: This would lead to an overestimation of the SAR. output
(appears in new window)
A large proportion of asymptomatic infections before the onset of the study would
lead to an overestimation of the number of persons who are susceptible. SAR = no.

secondary cases / total no. exposed susceptibles. So, this would in fact lead to an
overestimation of the denominator and an *underestimation* of the SAR
Interaction: Hotspot: This would lead to an underestimation of the SAR. output
(appears in new window)
That's correct. A large proportion of asymptomatic infections before the onset of the
study would lead to an overestimation of the number of persons who are susceptible.
SAR = no. secondary cases/total no. exposed susceptibles. So, this would lead to an
overestimation of the denominator and an underestimation if the SAR.

7.3: Assumptions underlying the calculation of a SAR


2. Most SAR studies assume that all cases of successful transmission of
infection are symptomatic. The presence of asymptomatic infections can lead to
substantial errors in the calculation of a SAR.
Exercise iii
In the same study, what would happen to the SAR if a large proportion of
secondary infections were asymptomatic?
Again, click on the correct answer opposite.
Interaction: Hotspot: This would lead to an overestimation of the SAR. output
(appears in new window)
Remember that SAR = no. secondary cases / total no. exposed susceptibles. As
asymptomatic secondary infections would not be included in the numerator of the
SAR calculation, this would lea to an *underestimation* of the secondary attack rate.
Interaction: Hotspot: This would lead to an underestimation of the SAR. output
(appears in new window)
That's correct. SAR = no. secondary cases/total no.exposed susceptibles. As
asymptomatic secondary infections would not be included in the numerator of the
SAR calculation, this would lead to an underestimation of the secondary attack rate.

7.4: Assumptions underlying the calculation of a SAR


2. Most SAR studies assume that all cases of successful transmission of
infection are symptomatic. The presence of asymptomatic infections can lead to
substantial errors in the calculation of a SAR.
Exercise iv
In the same study, what would happen to the SAR if a large proportion of coprimary infections were asymptomatic?
Once again, click on the correct option opposite.
Interaction: Hotspot: This would lead to an overestimation of the SAR. output
(appears in new window)

Persons with asymptomatic co-primary infection would be falsely classified as


susceptible and included in the denominator of the SAR calculation. This would lead
to an underestimation of the SAR. However, you should also remember that coprimary infections can also transmit infection. If you ignore the transmission
potential of asymptomatic co-primary cases, you may overestimate the number of
secondary cases due to the transmission from a single case within the household.
This could lead to an overestimation of the SAR. As you can see, it is extremely
difficult to predict the overall impact of asymptomatic cases on the calculated SAR!
Interaction: Hotspot: This would lead to an underestimation of the SAR. output
(appears in new window)
Persons with asymptomatic co-primary infection would be falsely classified as
susceptible and included in the denominator of the SAR calculation. This would lead
to an underestimation of the SAR. However, you should also remember that coprimary infections can also transmit infection. If you ignore the transmission
potential of asymptomatic co-primary cases, you may overestimate the number of
secondary cases due to the transmission from a single case within the household.
This could lead to an overestimation of the SAR. As you can see, it is extremely
difficult to predict the overall impact of asymptomatic cases on the calculated SAR!

7.5: Assumptions underlying the calculation of a SAR


3. Most SAR studies assume that all individuals in the denominator are
equally susceptible.
However, susceptibility to infection may vary according to a number of
characteristics of the exposed persons, such as age and sex. Ideally secondary
attack rates should be stratified by age and sex and any other variables that are
likely to be relevant.

Section 8: Modifications to the SAR


The SAR only takes into account the potentially infective contact that a susceptible
makes with a primary case. It ignores the fact that susceptibles who escape infection
during this primary contact may go on to make further potentially infective contacts
because of exposure to secondary and subsequent generation cases.
In 1952, Hope Simpson developed the susceptible-exposure attack rate to take
into account all the exposures that may occur as an infection is transmitted
through a community (see Hope Simpson 1952).
The susceptible-exposure attack rate is the proportion of exposures of susceptibles
leading to transmission.

8.1: Modifications to the SAR


Example
Interaction: Tabs: 1 : output

Suppose there is a household containing 5 individuals susceptible to chickenpox.


Interaction: Button: show: output (appears on RHS)

Interaction: Tabs: 2 : output


A is a primary case who has potentially infective contact with B,C,D and E.
Interaction: Button: show: output (appears on RHS)

Interaction: Tabs: 3 : output


B becomes infected, but C, D and E escape infection.

Interaction: Button: show: output (appears on RHS)

Interaction: Tabs: 4 : output


Then B has potentially infective contact with C, D and E who all become infected.
Show Button
In this household there are 7 exposures and 4 transmissions, so the susceptibleexposure attack rate
= 4 / 7 = 57%.
Interaction: Button: show: output (appears on RHS)

8.2: Modifications to the SAR


Exercise
Suppose there is a household containing 5 individuals susceptible to measles.
A is a primary case.
A infects B, but C, D and E escape
infection.
B then infects C, but D and E again
escape.
Then C infects D, but E again escapes.
E also escapes the infective stage of D,
so escaping infection altogether.
Can you answer the questions on the tabs opposite?
Interaction: Tabs: Question 1 : output
Question 1
What is the secondary attack rate in this household? Give your answer to the
nearest whole percent.
Interaction: Calculation: SAR = % output (appears in new window)
Incorrect response:
Sorry, that's not right. Remember that the secondary attack rate is the number of
secondary cases divided by total number of exposed susceptibles, so:
SAR = 1 / 4 = 25%
Correct response:
That's correct. The secondary attack rate is the number of secondary cases divided
by total number of exposed susceptibles:

SAR = 1 / 4 = 25%
Interaction: Tabs: Question 2 : output
Question 2
What is the susceptible-exposure attack rate in this household? Give your answer
as a percentage.
Susceptible-exposure
Interaction: Calculation: attack rate = % output (appears in new window)
Correct response:
That's correct. In this household there were 3 transmissions as a result of 10
exposures, so the susceptible-exposure attack rate is 30%.
Incorrect response:
Sorry, that's not right. In this household there were 3 transmissions as a result of 10
exposures, so the susceptible-exposure attack rate is 30%.
Interaction: Tabs: Question 3 : output
Suppose that E is actually immune to infection, and has been misclassified as
susceptible. Will this error have a greater impact on the SAR or the susceptibleexposure attack rate?
Interaction: Hotspot: Greater impact on SAR output (appears in new window)
In fact, if E is actually immune the true SAR would be 1/3 = 33% and the true
susceptible-exposure attack rate would be 3/6 = 50%. Overestimation of
susceptibles has a greater impact on the susceptible-exposure attack rate because
the 'false susceptibles' are repeatedly counted in denominator.

Interaction: Hotspot: Greater impact on susceptible-exposure attack rate output


(appears in new window)
That's correct. if E is actually immune the true SAR would be 1/3 = 33% and the
true susceptible-exposure attack rate would be 3/6 = 50%. Overestimation of
susceptibles has a greater impact on the susceptible-exposure attack rate because
the 'false susceptibles' are repeatedly counted in denominator.

8.3: Modifications to the SAR


The assumption that susceptibles are repeatedly exposed to infection by each
"generation" of cases is the underlying principle behind more sophisticated "chain
binomial models".
Statistical methods are available, based on these models, for estimating an average
generation attack rate from the distribution of proportions of members affected per
household. These methods are beyond the scope of this course.

Section 9: Reproduction numbers


History
An alternative way of measuring the transmission of an infectious disease in a
population is based on the demographic concept of the 'net reproduction rate'. This
concept has been used in demography since the late nineteenth century. It refers to
the average number of female children born to a woman subject to current agespecific mortality and fertility rates throughout her lifetime.
In 1952, Macdonald adapted this concept for epidemiological use. He used the term
'basic reproduction rate' in the context of malaria to refer to 'the number of
infections distributed in a community as the direct result of the presence of a single
primary non-immune case'. See MacDonald (1952).
More recently, the term introduced by Macdonald is often replaced by the phrase
basic reproduction number to reflect the fact that it is not a true rate.

9.1: Reproduction numbers


The basic reproduction number, R0, for microparasitic diseases is the expected
number of secondary cases (successful transmissions) produced when a single
primary case is introduced into a totally susceptible population.
Click below for an example.
Interaction: Button: cloud: output (appears in new window)
Example
In Maryland, USA, between 1908-17, the basic reproduction number for diphtheria
was estimated to be between 4 and 5. This means that, on average, each primary
case produced between 4 and 5 secondary cases when introduced into a totally
susceptible population.
(Data quoted in Anderson and May 1992.)
Interaction: Hyperlink: microparasitic: output (appears in new window)
Microparasite
A microparasite is an infectious agent which reproduces directly within the host, e.g.
bacteria, virus.
The basic reproduction number
For directly-transmitted microparasitic infections, the basic reproduction number is a
product of the number of contacts per unit time (c), the transmission probability per
contact (p) and the duration of infectiousness (d):

As R0 is influenced by the number of contacts made by the infectious case during


the infectious period it is not a constant for a specific infectious agent.
Rather, R0 reflects the transmission potential of a specific infectious agent within a
specific host population at a particular point in time.

9.2: Reproduction numbers


Exercise 1
How would you expect R0 for measles in an urban area to compare with R0 for
measles in a rural area?

Click on the correct answer below.


Interaction: Hotspot: The R0 for measles would probably be higher in an urban
area output (appears in new window)
That's correct. An infective case is likely to make more contacts in an urban area
than in a rural area, so R0 is likely to be higher. Studies in the USA have estimated
a R0 of 12.2 in urban Baltimore and a R0 of 5.4 in rural Kansas.

Interaction: Hotspot: The R0 for measles would probably be higher in a rural area
output (appears in new window)
In fact, an infective case is likely to make more contacts in an urban area than in a
rural area, so R0 is likely to be higher. Studies in the USA have estimated a R0 of
12.2 in urban Baltimore and a R0 of 5.4 in rural Kansas.

Interaction: Hotspot: The R0 for measles would probably be the same in both
areas output (appears in new window)
In fact, an infective case is likely to make more contacts in an urban area than in a
rural area, so R0 is likely to be higher. Studies in the USA have estimated a R0 of

12.2 in urban Baltimore and a R0 of 5.4 in rural Kansas.

9.3: Reproduction numbers


Exercise 2
Gonorrhoea is a sexually transmitted bacterial disease. The infectious period for a
case of gonorrhoea may extend for several months in untreated individuals.
Effective antimicrobial therapy ends communicability within hours.
What effect would you expect active tracing and treatment of contacts to have on
the R0 of gonorrhoea in a population?
Click on the correct answer opposite

Interaction: Hotspot: The R0 for gonorrhoea would probably increase output


(appears in new window)
In fact, active tracing and treatment of contacts is likely to reduce the average
length of the infectious period. If other factors remain unchanged, this would
decrease R0.
Interaction: Hotspot: The R0 for gonorrhoea would probably decrease output

(appears in new window)


That's correct. Active tracing and treatment of contacts is likely to reduce the
average length of the infectious period. If other factors remain unchanged, this
would decrease R0.
Interaction: Hotspot: The R0 for gonorrhoea would probably stay the same output
(appears in new window)
In fact, active tracing and treatment of contacts is likely to reduce the average
length of the infectious period. If other factors remain unchanged, this would
decrease R0.

9.4: Reproduction numbers


For microparasites transmitted by vectors, the basic reproduction number is a
product of the vectorial capacity (v) and the duration of the host infectiousness (d):

R0 = v d
The vectorial capacity is defined as the average number of potentially infective
bites that will ultimately be delivered by all the vectors feeding on a single host in
one day. It is a function of the density of the vector population, its propensity to
feed on the host species in question and its life expectancy.
Interaction: Hyperlink: vectors: output (appears in new window)
Vector
A living carrier, such as an insect, that transports an infectious agent from an
infected individual to a susceptible individual.

9.5: Reproduction numbers


Exercise 3
Malaria is a disease caused by sporozoan plasmodium parasites, which are
transmitted by the female Anopheles mosquito. See
http://www.cdc.gov/malaria/about/index.html
for details on the clinical presentation and epidemiology of malaria. In many
countries the density of Anopheles mosquitoes varies seasonally.

If all other factors were unchanged, how would you expect the R0 to change during
the season of low mosquito density?
Choose from one of the answers opposite.
Interaction: Hotspot: The R0 of malaria would probably increase output (appears in
new window)
In fact, if the mosquito density were to decrease the vectorial capacity would
decrease and R0 would decrease.
Interaction: Hotspot: The R0 of malaria would probably decrease output (appears
in new window)
That's correct, if the mosquito density were to decrease the vectorial capacity would
decrease and R0 would decrease.
Interaction: Hotspot: The R0 of malaria would probably stay the same output
(appears in new window)
In fact, if the mosquito density were to decrease the vectorial capacity would
decrease and R0 would decrease.

9.6: Reproduction numbers


The net reproduction number
The R0 assumes that all contacts are with susceptible persons (see EC03p9c2LHS).
However, a situation where a whole population is susceptible is very unusual.
More commonly, some individuals within a population will be immune or already
infected. In these circumstances, the expected number of secondary cases produced
by a single primary case will be less than R0.
In a situation where some of the population is not susceptible, you can calculate
the net reproduction number, R (sometimes called the effective reproduction
number). R is the average number of secondary infective cases produced by each
primary case in a population where some of the individuals are not susceptible.
If all the individuals in a population mix together at random, so that infectious
cases are as likely to make contact with susceptibles as with immunes, then R is
the product of R0 times the proportion of the population that are susceptible (x).

R = R0 x
NB: Note that to generate this formula, we assume that all individuals in the
population mix at random. However, this assumption is not always true. The
estimation of R for population in which individuals do not mix at random is discussed

in details in the module Introduction to the Mathematical Modelling of Infectious


Diseases.

9.7: Reproduction numbers


Example
Suppose we have a population where 60% of individuals are susceptible to
measles.
Interaction: Button: show: output (appears in new window)

(back to main text)


If R0 for measles in this population is 10, then the net reproductive rate will be:
R = 10 x 0.6 = 6.
So, each case of measles will produce, on average, 6 new secondary cases in this
population.
Interaction: Button: show: output (appears in new window)

9.8: Reproduction numbers


Exercise 4
If each infective case of mumps produces an average of 7 secondary infective
cases in a population in which all individuals are susceptible, what is the average
number of new cases that would be produced by each primary case in a population
in which 30% of the population is susceptible?
Enter your answer to one decimal place.
Interaction: Calculation: Number of new cases = output (appears in new window)
Correct response:
That's right, in this case R0 = 7 and x = 0.3, so:
R = 2.1
Incorrect response:
No, remember that R = R0 x .
In this case R0 = 7 and x = 0.3.
Therefore R = 2.1
Interaction: Hyperlink: mumps: output (appears in new window)
Mumps
For more information about this disease see
http://www.cdc.gov/mumps/index.html.

Section 10: How to calculate a basic reproductive number


Direct estimation
Method 1
In theory, it should be possible to measure R0 directly by counting the number of
infective secondary cases that are produced after a primary case of infection is
introduced into a totally susceptible population.
Click below for an example.
Interaction: Button: Example: output (appears in new window)
Example
If a case of measles were introduced into an isolated tribe that has not had contact
with the infection for several generations, it would be theoretically possible to count
the number of infective secondary cases.
However, this scenario only occurs very rarely and it is not usually possible to carry
out an epidemiological study in these circumstances.

10.1: How to calculate a basic reproductive number


Direct estimation
Method 2
Remember that for directly transmitted microparasitic infections, the basic
reproduction number is a product of the number of contacts per unit time (c), the
transmission probability per contact (p) and the duration of infectiousness (d):
So, if you have data on c, p and d, you will be able to calculate R0. However, it can
be very difficult to obtain reliable estimates of these parameters and it is only
possible for diseases (such as STDs) where contacts can be clearly defined and
counted.
Despite these difficulties, this type of calculation is the basis of many models of the
potential spread of a disease in a population. Click below for an example.
Interaction: Button: example: output (appears in new window)
Blower, Anderson and Wallace (1990) collected data on the average rate of sex
partner change for a group of 780 heterosexuals in England and Wales. They then
obtained estimates of the average transmission probability of HIV infection during a
sexual contact and the average duration of infectiousness of HIV during the
incubation period from the published literature. They used these data to estimate a
R0 for HIV infection in this population of between 0.8 and 1.6.

10.2: How to calculate a basic reproductive number


Indirect estimation
Note that in equilibrium conditions, where the average incidence and prevalence of
the disease is stable, R = 1.
As R = R0 x , in these circumstances R0 will be equal to the reciprocal of the
proportion susceptible to the disease.
So, in equilibrium conditions, if you have serological data on the proportion of the
population that is susceptible to the disease (x), you can estimate R0.

R0 = 1 / x
Interaction: Button: example: output (appears in new window)
Example
In 1950, a study collected data on the age-specific prevalence of antibodies to type 2
poliovirus in an unimmunised urban population in Miami. Fine and Carneiro (1999)
used this data, along with data on the age-demographic structure of Miami from
1950 1955, to estimate that 25% of this population were susceptible to poliovirus
type 2. They used this figure to estimate a R0 of 4 for poliovirus type 2 in this
population.

10.3: How to calculate a basic reproductive number


Indirect estimation
When it is not possible to carry out a seroprevalence survey, you can estimate the
proportion of the population that is susceptible.
For diseases that result in life-long immunity, if the population is stable (with births
exactly balancing deaths) and no one has been vaccinated against the disease, you
can estimate the proportion susceptible from the life expectancy (L) and the
average age of infection (a) using the following formula:

x=a/L
NB: This formula works for populations with a rectangular age distribution, i.e. in
which the mortality rate is low and fairly homogeneous across age groups, and the
life expectancy is high. This is observed mostly in several high-income countries.

For population with an exponential age distribution like many low and middle-income
countries (i.e. shorter life expectancy, high mortality rates, hence high proportions of
young age groups, and low proportions of older age groups), the following formula
can be used:
X = 1/(1+L/A)1 + a/L

10.4: How to calculate a basic reproductive number


Indirect estimation
Example
Suppose we have a stable population where no one has been vaccinated against
measles. The average life expectancy in this population is 60 and the average age
of contracting measles is 7 years.
The estimated proportion susceptible to measles will be:
x = a / L = 7 / 60 = 0.12

So, we would estimate that approximately 12% of this population would be


susceptible to measles.

10.5: How to calculate a basic reproductive number


Indirect estimation
Consider the same population, where the average life expectancy in this population
is 60, and the average age of contracting measles is 7 years.

Suppose that this is a stable population in which births exactly balance deaths. No
one in this population has been vaccinated against measles.
If the incidence and prevalence of measles in this population is stable, what is the
R0 for measles to one decimal place?
R0 = calc 1
It is important to be aware that this method can only be used if the population mixes
together homogeneously and there are no age-related differences in the
transmission rate.
Interaction: Calculation: R0 = calc 1 output (appears in new window)
Correct response:
That's correct. If the incidence and prevalence of measles in this population is
stable, then
R = 1, and
R0 = L / a = 60 / 7 = 8.6
Incorrect response:
Remember that if the incidence and prevalence of measles in this population is
stable, then
R = 1, and R0 = 1/ x.
If x = a / L, then
R0 = L / a = 60 / 7 = 8.6

Section 11: Use of the reproduction number


The reproduction number is a central concept for understanding the population
biology of an infectious agent in a host population. If you know the reproduction
number of an agent in a specific population, you can predict how the agent will
extend in that population.
You can use the information provided by the reproduction number to help predict
the effects of public health interventions on the transmission of an infectious agent
in a population.

11.1: Uses of the reproduction number


Interaction: Tabs: R=1 : output
If R = 1, then, on average, each case of the disease will produce one infective
secondary case.
Show Button
In these circumstances, the incidence of the disease in the population will be static.

Interaction: Button: show: output (appears on RHS)

(back to main text)


If R ~> 1, then, on average, each case will produce more than one infective
secondary case.
Show Button
In this case, the incidence of the disease in the population will increase.
Interaction: Button: cloud: output (appears in new window)

(back to main text)

If R ~< 1, then, on average, each case will produce less than one infective
secondary case.
Show Button
In this case, the incidence of the disease will decrease, and the disease will
eventually be eliminated from the population.
Interaction: Button: cloud: output (appears in new window)

11.2: Uses of the reproduction number

Vaccination programmes
Vaccination can reduce transmission of infection by reducing the proportion of
susceptibles in a population (x) and increasing the proportion immune (1 x).
The proportion of the population immune to infection is called the herd immunity
(HI).
The higher the herd immunity, the less likely an infected case is to make contact
with a susceptible and transmit the infection. At a certain threshold, called the
herd immunity threshold, each case will only be able to transmit the infection to
one other case.
The herd immunity threshold (HIT) is thus the proportion of the population that
need to be immune (1 x) for the disease to become stable (R = 1).

11.3: Uses of the reproduction number


You can therefore use knowledge of R0 to estimate the proportion of the population
that will have to be immune to ensure that the disease becomes stable.
Given that R = R0 x , and HI = 1 x , when R = 1 (at the herd immunity

threshold):

HIT

= 1 (1 / R0)
= (R0 1) / R0

Example
If R0 for measles is 9, then you can calculate the proportion of the population that
would have to be immune to measles if any major outbreaks are to be avoided, as
follows:
HIT = (R0 1) / R0 = 8 / 9 = 0.89
So more than 89% of the population would have to be immune to measles if major
outbreaks are to be avoided.

11.4: Uses of the reproduction number


If vaccination confers complete and lifelong immunity to all those vaccinated, then
the HIT tells us the proportion of the population that would have to be vaccinated
to reduce transmission of an infectious disease to a level where it will eventually
die out.
Interaction: Button: example: output (appears in new window)
Example

Assume again that R0 for measles is 9. If you had a vaccine that provided
complete and lifelong immunity, you would have to immunise at least 89% of the
population to prevent any major measles outbreaks. This ignores any immunity in
the population from previous infection.
The proportion of the population that would have to be vaccinated to make R0 ~<
1 increases if the vaccine does not provide full immunity to all those vaccinated.

11.5: Uses of the reproduction number


Exercise
Rabies is an acute viral disease caused by a rhabdovirus. Transmission to humans
occurs mainly following a bite from an infected animal, most commonly a dog.
See http://www.cdc.gov/rabies/ for details of the clinical presentation and
epidemiology of this disease.
A study using data from dog rabies epidemics in rural Indonesia estimated a
R0 of 1.79 with a 95% confidence interval from 0.91 to 2.67 (Coleman & Dye 1996).
Use these data to calculate the proportion of dogs that would have to be
immunised to prevent a major outbreak of dog rabies in at least 97.5% of
occasions in this setting.
Assume that vaccination confers complete and lifelong immunity.
Give your answer to the nearest whole percentage.
More than

calc 1 % of dogs would have to be immunised.

Interaction: Calculation: calc 1 output (appears in new window)


Correct response:
Yes, if the 95% upper confidence interval for R0 is 2.67, we would expect R0 to be
less than 2.67 on 97.5% of occasions.
The 95% upper confidence interval for R0 is 2.67, so the HIT for this value of R0 is:
HIT = 1 _(1 / 2.67) = 1 0.37 = 63%.

The WHO recommends that 70% of dogs in a population should be immunised to


eliminate or prevent outbreaks of rabies, which is consistent with this data and data
from other studies that have estimated a slightly higher R0.
Incorrect response:
Sorry, that's not correct. There is a 5% chance of R0 being outside the 95%
confidence interval, which could mean
R0 ~> 2.67 or R0 ~< 0.91. Therefore, focussing on one side of this interval, there

is a 2.5% chance that R0 ~> 2.67, and so we would expect R0 to be less than 2.67
on 97.5% of occasions.

Therefore we calculate the HIT at the 95% upper confidence limit in order to
answer the question. When R0 is 2.67, the HIT is:
HIT = 1 (1 / 2.67) = 1 0.37 = 63%.

The WHO recommends that 70% of dogs in a population should be immunised to


eliminate or prevent outbreaks of rabies, which is consistent with this data and data
from other studies that have estimated a slightly higher R0

11.6: Uses of the reproduction number


Public health strategies to reduce the duration of infectiousness, the
transmission probability per contact or the contact rate.
Remember that R0 is a function of the number of contacts per unit time (c), the

transmission probability per contact (p) and the duration of infectiousness (d).

R0 = c p d
It follows that you can use data on the effects of a public health intervention on
any one of these factors to help predict the impact the intervention will have on R0
and thus the potential for transmission in a population.

Click below for an example.


Interaction: Button: example: output (appears in new window)
Example
Pertussis (or whooping cough) is an acute respiratory tract disease caused by the
pertussis bacillus. See http://www.cdc.gov/pertussis/ for details of this disease. A
study in urban Baltimore estimated an R0 for pertussis of 16. Suppose that the
average period of infectiousness for pertussis is 22 days without treatment. If the
average period of infectiousness is reduced to 11 days by the use of effective
antibacterial therapy, the R0 would be reduced to 16 / 2 = 8.

11.7: Uses of the reproduction number


Exercise
Tuberculosis is a chronic mycobacterial disease that is a major cause of death and
disability in the world. http://www.cdc.gov/tb/ for more details of this disease.
Suppose that before intervention an average case of tuberculosis in a population is
infective for a year and produces six other cases. The local public health department
has proposed combining active case-finding and antimicrobial therapy to reduce the
average period of infectiousness.

How short would the average infectious period have to be to eventually eliminate
tuberculosis from this population? Enter your answer to the nearest number of
whole weeks.
An average case of TB would have to be infectious for less than Calc 1 weeks.
Interaction: Calculation: Calc 1 output (appears in new window)
Correct response:
That's correct. If R0 = 6 then the period of infectiousness would have to reduce more
than sixfold, from 52 weeks to 8 weeks, to produce R ~< 1.

Incorrect response:
In fact, if R0 = 6 then the period of infectiousness would have to reduce more than

sixfold to produce R ~< 1. If the average duration of infectiousness before


intervention is 52 weeks, then this would have to be reduced to less than 52 / 6 = 8
weeks.

11.8: Uses of the reproduction number


Exercise
Suppose that an average case of HIV in a population produces 12 new infective
cases. Suppose that condoms reduce the transmission probability per contact by
90%.
If all HIV cases in this population used condoms, would the transmission of HIV be
eventually eliminated?
Interaction: Hotspot: Yes output (appears in new window)
In fact, if the transmission probability were reduced by 90% then R0 would be
reduced to 1.2. As the reproduction number would still be greater than 1, the
transmission of HIV infection would still continue in this population.
Interaction: Hotspot: No output (appears in new window)
That's correct. If the transmission probability is reduced by 90% then R0 would be
reduced to 1.2. As the reproduction number would still be greater than 1, the
transmission of HIV infection would still continue in this population.

Section 12: Reproduction numbers for macroparasitic diseases


For macroparasitic diseases, the basic reproduction number is defined in a
different way than for microparasitic diseases.
In macroparasitic diseases, some hosts may be infected with a large number of
parasites, while others may be infected with only a few. The total number of
parasites in each host is often more important in determining morbidity and
transmission than the prevalence of infection per se.
Interaction: Hyperlink: macroparasitic: output (appears in new window)
Macroparasite

An infectious agent that does not reproduce directly within the definitive host, e.g.
most parasitic helminths and arthropods.
To reflect this, the basic reproduction number is defined as the expected number of
mature female offspring that one female parasite will produce in her lifetime. This
is similar to the initial demographic concept of the net reproduction rate.

12.1: Reproduction numbers for macroparasitic diseases


Example
Onchocerciasis is a disease caused by onchocerca worms located in the
subcutaneous tissues of the human host. See
http://www.cdc.gov/parasites/onchocerciasis/index.html for details of the clinical
presentation and epidemiology of onchocerciasis.
A study in Cameroon estimated the R0 for onchocerca to be 50. This means that a
single female worm produces an average of 50 mature female offspring in her
lifetime.

12.2: Reproduction numbers for macroparasitic diseases


Exercise
The disease ascariasis is caused by the large intestinal roundworm ascaris
lumbricoides. According to Heymann [2008] the maximum lifespan of adult worms
is 24 months in the large intestine of the human host and the female worm can
produce up to 200,000 eggs a day.
A study in Iran calculated a R0 of between 4 and 5 for ascariasis (Croll et al 1982,
cited in Anderson & May 1985).
Use this information to decide whether each of the following statements is true or
false:
A female worm could infect up to 146
million secondary hosts in her lifetime.
Interaction: Hotspot: True output (appears in new window)
Although a female worm could produce up to 146 million eggs in her lifetime, this
does not mean that this will lead to the same number of secondary infections. In
fact the R0 tells us that only a tiny proportion of these eggs develop into a
mature female worm.

Interaction: Hotspot: False output (appears in new window)


That's correct. Although a female worm could produce up to 146 million eggs in
her lifetime, this does not mean that this will lead to the same number of
secondary infections. In fact the R0 tells us that only a tiny proportion of these
eggs develop into a mature female worm.

(back to main text)


A female worm infects an average of
4 secondary hosts in her lifetime.
Interaction: Hotspot: True output (appears in new window)
In fact, the R0 tells us how many mature female worms are produced by an

average female worm in her lifetime. As these worms could be in one host or in
several, this does not tell us how many secondary hosts are infected.

Interaction: Hotspot: False output (appears in new window)


That's correct. The R0 tells us how many mature female worms an average

female worm produces in her lifetime. As these worms could be in one host or in
several, this does not tell us how many secondary hosts are infected.
(back to main text)
A female worm produces an average of
4 mature female worms in her
lifetime.

Interaction: Hotspot: True output (appears in new window)


That's correct.
Interaction: Hotspot: False output (appears in new window)
In fact, a R0 of 4-5 shows that a female worm does produce an average of 4-5
mature female worms in her lifetime.

Section 13: Assumptions underlying the use of RO and R


There are two important assumptions that you should be aware of when
calculating or interpreting data on reproduction numbers:
1. Assumption of average transmissibility
2. Assumption of homogeneous mixing
Click on each of these to obtain more
details.
Interaction: Hyperlink: 1. Assumption of average transmissibility: output
(appears on RHS)
Assumption of average transmissibility
The R0 and R provide estimates of the average number of infective secondary
cases produced by a single primary infective case.

However, you should not always assume that transmissibility is constant for all
individuals within a population. There are many examples of particular individuals
who are exceptionally efficient transmitters of infection. Such individuals are
sometimes called 'superspreaders'. Superspreaders may arise for biological or social
reasons.
Interaction: Button: example: output (appears in new window)

Example
Typhoid fever is a disease caused by the bacterium Salmonella typhi. See
http://www.cdc.gov/nczved/divisions/dfbmd/diseases/typhoid_fever / for details on
the clinical presentation and epidemiology of typhoid fever. Chronic typhoid carriers
excrete S.typhi in the stools over a period of many years. The chronic carrier state is
often acquired in middle age. There are important examples of food handlers who
have been chronic typhoid carriers and have been exceptionally efficient transmitters
of S.typhi.
(back to main text)
Interaction: Hyperlink: 2. Assumption of homogeneous mixing: output
(appears in new window)
Assumption of homogeneous mixing
The R depends on the assumption that there is random mixing within the
population and that there is an equal chance of an infective case making contact
with a susceptible person or an immune person.
However, most human populations do not mix randomly. People tend to form
groups who mix more with their own members than with other groups.
Non-homogenous mixing patterns can have a significant impact on transmission
within a population.

Section 14: Summary


This is the end of EC03. When you are happy with the material covered here please
move on to session EC04.
The main points of this session will appear below as you click on the relevant title.
Secondary attack rate
The secondary attack rate (SAR) is used to calculate the transmission probability of
an infectious disease in a small community such as a household or a school class.
The SAR is the proportion of susceptible individuals who have contact with the
primary case and go on to develop the disease as a consequence of this contact.

Interaction: Hyperlink: secondary cases: output (appears in new window)


Secondary case
A case arising directly from a primary case.
Calculating a SAR: direct estimation

To calculate a direct SAR you require the following information:


Exact time of onset of each case
Number of susceptibles exposed to
each primary case
Estimate of the maximum infectious
period and the minimum and maximum
incubation periods of the disease
(Review this from FE07).
Calculating a SAR: indirect estimation
You can use routine data sources to estimate the SAR using the following formula:

Estimated household SAR =

N
_______

h x (m 1)
where:
h = number of households with a primary case
m = mean number of people per household
N = total number of secondary cases
Why calculate a SAR?
The SAR can be used to:
help elucidate the transmission routes
of an infectious agent
help determine which control measures
may reduce transmission
help measure post-licensure vaccine
efficacy.
Assumptions in calculating a SAR
1. The SAR assumes that each secondary
case is derived from a single primary
case within the household.
2. Most SAR studies assume that all
cases of successful transmission of
infection are symptomatic.
3. Most SAR studies assume that all
individuals in the denominator are
equally susceptible.

Basic reproduction number


The basic reproduction number, R0, for microparasitic diseases is the expected
number of secondary cases (successful transmissions) produced when a single
primary case is introduced into a totally susceptible population.
For directly-transmitted microparasitic infections, the basic reproduction number
is a product of the number of contacts per unit time (c), the transmission
probability per contact (p) and the duration of infectiousness (d) :

R0 = c p d
The net reproduction number
The net reproduction number (sometimes called the effective reproduction number)
R is the average number of secondary infective cases produced by each primary
case in a population where not all the individuals are susceptible.
If all the individuals in a population mix together at random, so that infectious cases
are as likely to make contact with susceptibles as with immunes, then R is the
product of R0 times the proportion of the population that are susceptible (x):
R = R0 x
How to calculate R0: direct estimation
Method 1
In theory, it should be possible to measure R0 directly by counting the number of
infective secondary cases that are produced after a primary case of infection is
introduced into a totally susceptible population.
Method 2

R0 = c p d
So, if you have data on c, p and d, you can calculate R0.
How to calculate R0: indirect estimation
In equilibrium conditions where the average incidence and prevalence of the
disease is stable,

R0 = 1 / x
If, in addition, all of these are true:
The disease results in life-long immunity
The population is stable (with births
exactly balancing deaths)
No one has been vaccinated against the
disease, then:

R0 = L / a
L = average life-expectancy in the population
a = average age of infection
NB: As discussed in EC03, this formula applies to populations with a rectangular
age distribution.
Uses of the reproduction number
The reproduction number is a central concept for understanding the population
biology of an infectious agent in a host population. You can use the reproduction
number to help predict the effects of public health interventions on the
transmission of an infectious agent in a population.

Assumption in the use of R0 and R


Assumption of average transmissibility
R0 and R provide estimates of the average number of infective secondary cases

produced by a single primary infective case. However, you should not always
assume that transmissibility is constant for all individuals within a population.

Assumption of homogeneous mixing


R depends on the assumption that there is random mixing within the population and
that there is an equal chance of an infective case making contact with a susceptible
person or an immune person. Non-homogenous mixing patterns can have a
significant impact on transmission within a population.

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