Ec 02

Is the disease infectious?
(EC01)
Module: EPM301 Epidemiology of Communicable Diseases
Course: PG Diploma/ MSc Epidemiology
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London School of Hygiene & Tropical Medicine September 2013 v2.0
Section 1: EC02 Is the disease infectious?

Aim
To determine whether a disease is caused by an infectious agent or not.
Objectives
By the end of this session, you should be able to:
identify the factors that suggest that a disease has an infectious cause
use these factors to determine whether a disease of unknown cause is likely to
be infectious.
This session should take you about 2 to 3 hours to complete.
Section 2: Introduction
How can you know whether a disease is caused by an infection or by exposure to
some other factor?
You may remember that Koch's postulates list a number of criteria that can be
used to decide whether an infectious agent is responsible for a disease. Review
these criteria and think about what their limitations are.
(You might want to refer back to session FE13 to fully review the subject of
causality.)
Koch's postulates (1892)
The agent must be consistently
demonstrable in diseased individuals
The agent must be isolated from a
diseased individual and grown in pure
culture
Inoculation of the agent must induce
the disease experimentally
2.1: Introduction
Often it is not possible to fulfil Koch's postulates because no infectious agent has
yet been identified, or it is not possible to culture a suspected agent, or there are
no experimental hosts.
In these cases, there are a number of epidemiological characteristics that might
indicate an infectious aetiology.
In this session you will learn about some common features of infectious diseases
that can help you assess whether a disease is infectious or not.
When might this be necessary?
Interaction: Hyperlink: aetiology: output (appears in new window)
Aetiology
Aetiology is often used in epidemiology to refer to "cause".
The search for an infectious cause may begin when:
a new disease syndrome emerges
Example button
new knowledge about old diseases
raises questions about possible
infectious causes
Example button
new technology opens-up new areas of
investigation
Example button
Interaction: Button: Example: output (appears in new window)
The search for the causative agent of AIDS began when the syndrome was
recognised and became increasingly prevalent in the early 1980s.
A variety of infectious agents have now been associated with diseases that were
previously considered to be chronic conditions:
human papillomavirus and
cervical cancer see
http://www.who.int/vaccine_research/diseases/viral_cancers/en/index3.html)
Helicobacter pylori and
gastritis
parvovirus (see http://www.cdc.gov/parvovirusB19/about-parvovirus.html) and
arthritis.
Example 1: Since the advent of molecular biological tools such as the Polymerase
Chain Reaction (PCR), it is possible to identify pathogens from smaller quantities of
tissue. New techniques like Genome Wide Sequencing, Single Nucleotide
Polymorphisms (SNP) genotyping are now available for further studies of genetic
variability in various pathogens.
Example 2: New agents are continually being recognised through advanced
virological techniques (e.g. hepatitis C virus, hepatitis E virus).
Section 3: Epidemiological characteristics of infectious disease

What characteristics might suggest that a disease has an infectious cause?
We can consider the characteristics of infectious aetiology under the following
headings:
Time when the disease occurs
Place where the disease is
distributed
b Person who develops the disease
On the next few pages each of these categories are considered in turn.
Section 4: Time when the disease occurs

How can time be used to indicate an infectious aetiology?
There are 4 main patterns, which are described on this page:
1. Do disease cases occur close together
in time? (Temporal clustering)
2. Does disease occurrence change with
the climate during the year?
(Seasonality)
3. Are there periodic changes in disease
occurrence? (Cyclical patterns)
4. Is there a change in disease
occurrence over long time periods
(more than one year)? (Long-term
trends)
4.1: Time when the disease occurs

1. Temporal Clustering:
Do disease cases occur close together in time?
Temporal clustering is more easily recognised for rare diseases or when there are
few sources of infection. It is especially important in identifying the causes of
epidemics.
Epidemiologists have developed a 'moving window' test to distinguish between
random temporal clustering of cases and clustering due to an exposure.
This assesses the statistical probability of whether more cases occur within a
specified time interval than would be expected by chance. By 'moving' the window
continuously across the period of observation you can sum the number of cases
occurring during the interval at different times.

The 'moving window' test
By sliding the 28-day 'window' along the time-line opposite, you can see that the
number of cases in the window changes.
Use the buttons beneath the graph to move the window left and right.
(buttons moves green line left or right)


Knox and Lancashire (1982) used this method to show that pityriasis rosea a
mild skin disease occurred in temporal clusters.
They found a maximum of 16 cases within a 28-day window. This was significantly
higher than the average of 4.8 cases expected in any 28-day interval from the
overall data. This supported the hypothesis of an infectious aetiology.

2. Seasonality :
Does disease occurrence change with the climate during the year?
The reasons for seasonality of cases are unclear. Seasonality may be associated
with changes in temperature and humidity that determine the survival and
transmissibility of the infectious agent, or the prevalence of vectors.
Behaviour can also vary with season, affecting the amount of contact with potential
sources of infection.
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.
Examples
Interaction: Tabs: Meningitis : output
For meningococcal meningitis, in which season would more cases generally occur,
and why might this be? Choose one of the seasons below:
Interaction: Button: temperate summer/tropical wet season: output (appears in
new window)
In fact, the incidence of droplet- or aerosol-transmitted diseases such as
meningococcal meningitis tends to peak in the temperate winter or tropical dry
season for a number of reasons. In temperate climates, there tends to be more
crowding and less ventilation in winter. This leads to increased contact, recirculation of air and dry nasal mucosa, providing a better environment for
transmission. In the tropics, the free bacterial particles in droplets survive better at
lower temperatures, and dry nasal mucosa provides a better environment for
transmission.
Click the 'graph' button below to see an example.
Interaction: Button: temperate winter/tropical dry season: output (appears in new
window)
That's correct. The incidence of droplet- or aerosol-transmitted diseases such as
meningococcal meningitis tends to peak in the temperate winter or tropical dry
season for a number of reasons. In temperate climates, there tends to be more

crowding and less ventilation in winter. This leads to increased contact, recirculation of air and dry nasal mucosa, providing a better environment for
transmission. In the tropics, the free bacterial particles in droplets survive better at
lower temperatures, and dry nasal mucosa provides a better environment for
transmission.
Click the 'graph' button below to see an example.
Interaction: Button: graph: output (appears in new window)
This graph shows that the epidemic of meningococcal meningitis started towards the
end of the dry season when the weather was hot, with the dry and dusty Harmattan
wind blowing from the Sahara. The incidence of the disease declined as the absolute
humidity rose and the epidemic stopped shortly after the wind stopped and the rains
began.
Interaction: Tabs: Malaria : output
For malaria, in which season would more cases generally occur, and why might this
be? Choose one of the seasons below:
Interaction: Button: temperate summer/tropical wet season: output (appears in
new window)
That's correct, the incidence of vector-borne diseases such as malaria tends to peak
in the temperate summer/tropical wet season because the mosquito vector
abundance is dependent on warm temperatures and water pools for breeding.
Interaction: Button: temperate winter/tropical dry season: output (appears in new
window)
In fact, incidence of vector-borne diseases such as malaria tends to peak in the

temperate summer/tropical wet season because the mosquito vector abundance
is dependent on warm temperatures and water pools for breeding.
(back to main card)

Interaction: Tabs: Shigella : output
For shigella (bacterial dysentery), in which season would more cases generally occur,
and why might this be? Choose one of the seasons below:
Interaction: Button: tropical wet season: output (appears in new window)
That's correct. The incidence of faecal-oral diseases such as shigella tends to peak in
the tropical wet season for a number of reasons. Higher temperatures lead to
increased multiplication of bacteria in contaminated food, and there are likely to be
more flies contaminating food. There is an increased possibility of water
contamination, due to flooding, for example.
Interaction: Button: tropical dry season: output (appears in new window)
In fact, the incidence of faecal-oral diseases such as shigella tends to peak in the
tropical wet season for a number of reasons. Higher temperatures lead to
increased multiplication of bacteria in contaminated food, and there are likely to be
more flies contaminating food. There is an increased possibility of water
contamination, due to flooding, for example.

2. Seasonality :
Some infections do not strictly follow these patterns. Rotavirus is transmitted by
the faecal-oral route, yet it is frequent in the winter in temperate climates, but is
detected all year round in the tropics. This characteristic might support the
hypothesis that it is also spread by aerosol transmission (Cook et al 1990).
Interaction: Hyperlink: Rotavirus: output (appears in new window)
Rotavirus
For more information about this infection, see
http://www.cdc.gov/vaccines/pubs/pinkbook/rota.html
However, it is likely that factors other than mode of transmission are also
involved in determining seasonality.
Click below to see graphs that show how different strains of the same virus can
have different seasonal patterns. The incidence of parainfluenza virus type 3
peaks in summer, while types 1 and 2 peak in winter (Noah 1989).
Interaction: Hyperlink: parainfluenza virus: output (appears in new window)
Parainfluenza virus
For more information about this infection see

http://www.cdc.gov/vaccines/pubs/pinkbook/rota.html.
Interaction: Button: Graph: output

2. Seasonality :
When looking for seasonality it is important to take into account changes in
population size.
For example, seasonal population migration or seasonal variation in birth rates (for
a disease of infants) could falsely indicate a seasonally-transmitted disease because
the number of cases might increase as the population size increases.
Even if seasonality of the disease exists, there are a number of alternative
aetiological explanations. Can you think of non-infectious exposures that might also
vary seasonally?
Interaction: Button: Cloud: output (appears in new window)
Nutritional status varies seasonally, especially in poorer countries or communities
(e.g. Kigutha et al 1995). Exposure to toxins has also been shown to be
associated with season, for example aflatoxin in West Africa (e.g. Wild et al
2000). You may have thought of other examples.
Interaction: Hyperlink: aflatoxin: output (appears in new window)
Aflatoxin
A metabolic product of fungi of the Aspergillus spp. that grow on cereals and grains.
It has been identified as a risk factor for liver cancer.

3. Cyclical patterns:
Are there periodic changes in disease occurrence?
What other periodic events might influence the temporal pattern of a disease?
Interaction: Tabs: Example 1 : output
Periodic visits to the market to sell goods may increase the potential for contact
with infected individuals at particular times.
Seasonal movements from the highlands to the malaria-endemic lowlands for
farming can expose non-immune individuals to malaria resulting in a peak of
malaria cases at harvest time.
Interaction: Hyperlink: malaria: output (appears in new window)
Malaria
For more information about this disease see http://www.cdc.gov/malaria/.
(back to main card)
Annual increases in measles transmission have been shown to coincide with the
start of school terms, which provide an ideal opportunity for contact between
infected and susceptible children (e.g. Fine & Clarkson 1982).
Interaction: Hyperlink: measles: output (appears in new window)
Measles
For more information about this disease, see
http://www.cdc.gov/measles/index.html.

In addition to the annual cycles, larger peaks of measles cases occurred at regular
2-year intervals in England and Wales before the national immunisation programme
was introduced.
Click the 'plot' button below to see a plot that illustrates this.
Interaction: Button: Plot: output (appears in new window)
Can you think of a reason for this 2-year cycle? Bear in mind that measles infection
confers lifelong immunity.
Interaction: Button: Cloud: output
For infections that confer lifelong immunity, it may take a number of years until
there are sufficient numbers of susceptible individuals born into the population to
enable the infection to circulate widely.
This "critical threshold of susceptibles" will be discussed in session EC06.

Changes in climate may occur over longer periods of time. These can also cause
variations in disease occurrence.
The El Nio_ Southern Oscillation affects weather patterns in certain parts of the
world at approximate intervals of 4 to 6 years.
It shows a close association with the between-year variation in malaria incidence in

South America and the Indian subcontinent. This association is due to periods of
intense drought or rainfall affecting the density of malaria mosquito vectors
Interaction: Hyperlink: El Nio: output (appears in new window)
El Nio
The El Nio Southern Oscillation is a periodic climatic phenomenon associated with a
warmer than average sea surface temperature in the eastern equatorial Pacific
Ocean.

4. Long-term trends
Is there a change in disease occurrence over long time periods (more than one
year)?
Long-term trends in a disease are useful if they can be associated with changes in
the proposed mode of transmission.
For example, the trend in mortality from cervical cancer in England and Wales was
correlated with the trend in gonorrhoea incidence at the age of 20 for the same
birth cohorts of women. Click below to see a graph of this trend.
This provided strong evidence that cervical cancer was a sexually transmitted
disease. It has subsequently been associated with human papilloma virus infection
(Beral 1974).
Interaction: Hyperlink: gonorrhoea: output (appears in new window)
Gonorrhoea
For more information about this disease, see http://www.cdc.gov/std/Gonorrhea/
Interaction: Hyperlink: birth cohorts: output (appears in new window)

Birth cohorts
Cases were grouped by year of birth, not year of onset.
Section 5: Place where the disease occurs

What spatial distributions can be characteristic of infectious diseases?
1. Do cases occur close together within a
specified area? (Spatial Clustering)
2. Does the disease tend to occur only in
specific geographical locations?
(Geographical Restriction)
5.1: Place where the disease occurs

1. Spatial Clustering:
Do cases occur close together within a specified area?
Spatial clustering is useful to identify a common source of infection.
Can you remember an example of this from the epidemiological work of John
Snow?
Interaction: Button: cloud: output (appears in new window)
John Snow plotted the residence of fatal cases of cholera

http://www.cdc.gov/cholera/index.html on a map to identify the water pump
responsible for the cholera epidemic in Soho, London in 1854. Review this from
FE01.
(appears on RHS)
More recently, the cases of new variant Creutzfeld-Jacob disease were
analysed to assess whether more cases lived near to meat rendering plants than
would be expected by chance. There was no evidence that the distance from
residence to the nearest rendering plant was a risk factor for the disease (Cousens
et al 1999).
Click below to see the map from this study.
Show Button
Interaction: Hyperlink: new variant: output (appears in new window)
New variant Creutzfeld-Jacob disease
For more information about this disease see
http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/CreutzfeldtJakobDis
ease/
Interaction: Hyperlink: Creutzfeld-Jacob disease: output (appears in new
window)
New variant Creutzfeld-Jacob disease
http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/CreutzfeldtJakobDise
ase
Interaction: Hyperlink: rendering plants: output (appears in new window)
Rendering plants are factories involved in the production of meat and bone meal
from animal carcasses.
Interaction: Button: Show: output (appears in new window)

It is important to remember that spatial clustering of cases can also indicate an
environmental (non-infectious) cause.
A point-source exposure, such as a toxic contaminated water source, would also
produce a geographical cluster of cases.

Household clustering of cases can be a good indicator of infectious aetiology.
Think about which non-infectious causes could also explain household clustering.
Individuals from the same family and household are likely to be exposed to the
same genetic and environmental factors, such as socio-economic conditions, diet,
and air pollution. Any of these could provide an alternative, non-infectious
explanation for the disease.
Measures of household spread of infection will be discussed in EC03.

2. Geographical restriction:
Does the disease tend to occur only in specific geographical locations?
Climatic and ecological conditions are responsible for the geographical
restriction of infectious diseases.
Certain conditions favour the development of the infective agent, transmission of
the infection, and breeding of vectors.
Examples
Interaction: Tabs: 1 : output
Schistosomiasis is distributed in tropical and sub-tropical areas, because optimal
survival of the parasite in water, infectivity to the intermediate snail host, and
development in the snail occurs at 25_. Click below to see a map of the world
distribution of this disease. http://www.cdc.gov/parasites/schistosomiasis/.
Map Button
Interaction: Hyperlink: Schistosomiasis: output (appears in new window)
Schistosomiasis
For more information about this disease see .
(Back to main card)
Interaction: Button: Map: output (appears in new window)

Sandflies, and therefore the Leishmania parasitic infection that they transmit, are
distributed in the tropics and subtropics, and are extending into southern European
climates.
Click below to see a map of the world distribution of this disease.
Map Button
Interaction: Hyperlink: Leishmania: output (appears in new window)
Leishmania
For more information about this infection see
http://www.cdc.gov/parasites/leishmaniasis/index.html
(Back to main card)

Burkitt's lymphoma is geographically restricted to the lowlands of Africa, despite a
wider distribution of Epstein-Barr virus, which is implicated in the disease. The
association with areas of high rainfall and warm temperatures suggests that malaria
might play a role in the aetiology of the disease (de Th 1979).
Map Button
Interaction: Hyperlink: Leishmania: output (appears in new window)
Burkitt's lymphoma
For more information about this disease.
Burkitt's lymphoma and climate in Africa
The red overlay on this map shows the distribution of Burkitt's lymphoma. The
unshaded areas of the map beneath represent regions of high rainfall and high mean
temperature (in the coolest month).

2. Geographical restriction:
Does the disease tend to occur only in specific geographical locations?
There are a number of characteristics that can help to associate a disease with a
particular place. They are listed opposite.
1. The disease is equally common in all
ethnic groups that live in the area;
2. the disease is much less common
among people from similar groups
that live elsewhere;
3. individuals migrating into the area

become ill with the same or a greater
frequency;
4. individuals migrating out of the area
do not become ill with the same
frequency.
Section 6: Person who develops the disease

How might particular groups of individuals be at greater risk of infection and
disease?
Some characteristics of particular groups may increase their exposure to infection
or facilitate the onset of the disease. Groups to consider are:
1. Occupational
2. Behavioural
3. Socio-economic
4. Immunological status
6.1: Person who develops the disease

1. Occupational:
A number of infections are associated with occupational exposure.
Occupation often acts to bring a specific group of individuals in contact with
infection as a direct result of the activity.
For example, butchers are more likely to develop warts. (Keefe et al 1994).
Interaction: Hyperlink: warts: output (appears in new window)
Warts
For more information about this disease see www.cdc.gov/hpv.
In the same way, it might be expected that cattle farmers in the UK should be more
likely to develop new-variant Creutzfeld-Jakob disease because of their
increased contact with cattle that have Bovine Spongiform Encephalitis. So far there
have been too few cases to assess this risk.
Interaction: Hyperlink: warts: output (appears in new window)
New-variant Creutzfeld-Jakob disease
http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/CreutzfeldtJakobDise
ase/.
1. Occupational:
Occupational groups can also be at greater risk of disease because of associated
behaviours. In the tropics, illegal night-time fishing and logging activities increase
outdoor exposure to mosquito bites and therefore increase the risk of malaria
infection.
Long-distance truck drivers tend to have a more promiscuous sexual behaviour,
leading to an increased risk of HIV infection (Bwayo et al 1994).

2. Behavioural:
Certain lifestyle or cultural behaviours may increase the risk of an infectious
disease by increasing the likelihood or amount of exposure to the infectious
agent.
This aspect may be less easy to investigate, for reasons of cultural sensitivity or
privacy, for example sexual behaviours.
Examples
1. Pneumocystis pneumonia and
Kaposi sarcoma in homosexuals
2. Kuru and cannibalism
Interaction: Hyperlink: Pneumocystis pneumonia: output (appears in new
window)
Pneumocystis pneumonia
http://www.cdc.gov/fungal/pneumocystis-pneumonia/.
Interaction: Hyperlink: Kaposi sarcoma: output (appears in new window)
Kaposi sarcoma
http://www.cancer.gov/cancertopics/pdq/treatment/kaposis/HealthProfessional
Interaction: Hyperlink: Kuru: output (appears in new window)
Kuru
For more information about this disease see Collinge et at (2006)
http://dx.doi.org/10.1016/S0140-6736(06)68930-7

3. Socio-economic:
Many infectious diseases are related to socio-economic status.
This is often related to living-conditions that can affect transmission, such as levels
of crowding, poor-sanitation, dampness and house-structure.
For example, tuberculosis is frequently associated with overcrowded and lowincome households (Mangtani et al 1995).
Interaction: Hyperlink: tuberculosis: output (appears in new window)
Tuberculosis
For more information about this disease see http://www.cdc.gov/tb/.
Can you think of non-infectious causes of disease that might also be associated with
socio-economic status?
Malnutrition and toxic exposure could both cause disease and are also likely to be
related to socio-economic status. You might have thought of other exposures.

4. Immunological status:
High incidence of a disease among people lacking immunity or with an impaired
immunological system is highly suggestive of an infectious cause.
Individuals undergoing therapy with immunosuppressive drugs or suffering from an
immunodeficiency are more susceptible to infectious agents.
Diseases among these groups are likely to be of an infectious aetiology, e.g. the
increased incidence of lymphomas in transplant patients.

4. Immunological status:
Migrants moving from an area of low to high endemicity will be at greater risk of
being infected and developing the disease, as they have not developed a protective
immunological response.
Example
Studies of migrants have shown that there is a critical age at exposure for multiple
sclerosis, after which an individual is less likely to develop the disease (for example,
see Gale & Martin 1995).
Interaction: Hyperlink: multiple sclerosis: output (appears in new window)
Multiple sclerosis
Multiple sclerosis (also called disseminated sclerosis) is a chronic, often disabling
disease of the central nervous system, characterised by impairment of transmission
of nerve impulses, particularly those involved with vision, sensation, and the use of
limbs. There appear to be multiple causes, possibly including viruses and
environmental, genetic, and immune system factors.
Section 7: Interactions
Often, identifying the cause of a disease is not straightforward. Interactions can
occur between any of the factors already mentioned.
The main areas to consider are:
Are cases clustered in both space and
time? (Spatial-temporal clustering)
Does the incidence vary by
geographical region? (Regional
variation)
Are there other factors that are
necessary or seem to pre-dispose an
individual to disease? (Co-factors)
7.1: Interactions
1. Spatial-temporal clustering:
Are cases clustered in both space and time?
Spatial-temporal clustering occurs because of person-to-person transmission,
and can be investigated in a number of ways.
One way is to pair each individual with every other individual who has the disease.
Distance in time and geographical distance between each possible pair can be plotted
against each other to look for any correlation.
By considering particular intervals of time and distance, a chi-squared test can be
used to test for any association (Messenger et al 1982).
This method has been adapted to study diseases with long latent periods.
Another adaptation involves recording all significant contacts between cases of a
disease, and between appropriate controls - a difficult task! (Pike & Smith 1974)
7.2: Interactions
2. Regional variation:
Does the incidence vary by geographical region?
Regional variations in infectious diseases are likely to be due to an interaction
between geographical, socio-economic, immunological, dietary and cultural
factors.
Genetics and other environmental exposures also vary by place and it is important
to exclude these as possible causes before specifying an infectious aetiology.
Some infections are limited to particular countries. In the case of political
boundaries, these variations in disease incidence are usually due to socioeconomic factors such as the degree of financial investment in infrastructure (e.g.
sanitation systems) and public health measures (e.g. immunisation programmes).
7.3: Interactions
3. Co-factors:
Are there other factors that are necessary or seem to pre-dispose an individual to
disease?
In the case of a number of malignant diseases, the infective agent may not be a
sufficient cause of disease. There might be a sequence of epidemiological,
immunological and molecular events that are additionally required to cause the
disease.
Often, external (environmental) and/or internal (genetic and physiological) factors
also play a necessary role. The involvement of these 'co-factors' makes the search
for an infectious aetiology more difficult.
Interaction: Hyperlink: sufficient cause: output (appears in new window)
Sufficient cause refers to a particular exposure providing the full explanation for an
outcome. In this case, infection alone is not enough to cause disease.
It is suspected that Hodgkin's disease occurs in only a proportion of individuals
infected with Epstein-Barr virus because of some genetic or environmental co-factor
(Stiller 1998).
Interaction: Hyperlink: Hodgkin's disease: output (appears in new window)
Hodgkin's disease
http://www.who.int/vaccine_research/diseases/viral_cancers/en/index1.html
(Back to main page)

Burkitt's lymphoma (BL) is a tumour whose epidemiological characteristics
strongly suggested Epstein-Barr virus (EBV) as the cause. However, EBV is
widespread and the restricted geographical distribution of BL suggested that malaria
might be involved. A higher incidence of BL was found among migrants with lower
immunity to malaria. This was consistent with malaria being the major co-factor
necessary for the disease (de-Th_1979).
Interaction: Hyperlink: Burkitt's lymphoma: output (appears in new window)
Burkitt's lymphoma
http://www.who.int/vaccine_research/diseases/viral_cancers/en/index1.html
7.4: Interactions
Over the next few pages you will complete an exercise to determine whether or
not a disease of unknown aetiology is infectious.
You may like to take a break at this point, before going on to complete the
exercise.
Section 8: Exercise: A disease of unknown aetiology

This exercise demonstrates how the epidemiological pattern of a disease can be
defined by morbidity surveys.
Using the information you have covered earlier in this session, interpret the data
provided to decide whether the disease under investigation is infectious or not.
Clinical information is not given, to show you that the answer can be reached by
epidemiological assessment alone.
On the following pages, you will be shown a number of tables. Examine each
table and summarise the epidemiological features that you think are most
important.
Consider the information from each table separately, and then evaluate all the
information together to determine the aetiology of this disease.
8.1: Exercise: A disease of unknown aetiology

Background
The disease was recognised in the early 1900s and could be diagnosed with
reasonable accuracy by experienced physicians. It was thought to be associated
with poor and unsanitary living conditions.
Cases appeared to be localised in their geographical distribution. Multiple cases

were frequently observed in the same family and recurrent attacks were common.
A number of hypotheses were proposed for the aetiology of the disease. These
included infection, genetic susceptibility, toxicity, etc.
8.2: Exercise: A disease of unknown aetiology

To collect data on this disease in a defined population, a responsible agency
undertook an extended survey. This was done in an area in the Northern
Hemisphere where there had been a high incidence of the disease over a period
of years.
The data presented in this exercise were collected from 24 villages during a oneyear period.
The name, age, sex and marital status of each family member were recorded for
all individuals in the villages surveyed. Each household was visited every two
weeks.
Reported symptoms and a clinical examination were used to determine the
occurrence of 'the disease'. Questionable cases were referred to a more
experienced physician who was directing the study.
Note: The number of cases is the same in the first three tables but the
population size is inconsistent, leading to different estimates of disease risk. The
reason for this is unclear, but may be due to missing data on age and sex.
Section 9: Exercise: Table 1

Table 1 opposite shows the total number of cases and risk of 'the disease' in
each village during the survey year.
Summarise the data in Table 1:
The village population size ranges from
Calc 1
to
Calc 2.
The minimum number of cases in one village is Calc 3. The maximum number
of cases in one village is Calc 4
The lowest risk of disease is Calc 5 per 1000, and the highest risk of disease is
Calc 6 per 1000.
Interaction: Calculation:
Correct response:
Correct
Calc 1
That's right, the smallest population size is 284 individuals in village 'Fn'.
Incorrect response:
Sorry, that's not right. The smallest population size is 284 individuals in village 'Fn'.
Correct response:
Correct
Calc 2
That's right, the largest population size is 1569 individuals in village 'Ola'.
Incorrect response:
Sorry, that's not right. The largest population size is 1569 individuals in village 'Ola'.
Correct response:
Correct
Calc 3
That's right, the minimum number of cases is 13, in village 'Gr'.

Incorrect response:
Sorry, that's not right. The minimum number of cases is 13, in village 'Gr'.
Calc 4
Correct response:
That's right, the maximum number of cases is 119, in village 'Rc'. in village 'Rc'.
Incorrect response:
Sorry, that's not right. The maximum number of cases is 119, in village 'Rc'.
Correct response:
Correct
Calc 5
That's right, the lowest risk of disease is 19.6 per 1000, in village 'Gr'.
Incorrect response:
Sorry, that's not right. The lowest risk of disease is 19.6 per 1000, in village 'Gr'.
Correct response:
Correct
Calc 6
The highest risk of disease is 100.8 per 1000, in village 'In'.

Incorrect response:
Sorry, that's not right. The highest risk of disease is 100.8 per 1000, in village 'In'.
9.1: Exercise: Table 1
RHS remains static (chart)

Which epidemiological feature of 'the disease' can we assess from these data? Click
on the answer from the options below:
Interaction: Hotspot: Clustering in ethnic groups (appears in new window)
No, the table does not give us any information on whether there is any ethnic
variation by village - there is insufficient data presented to assess this feature.
Interaction: Hotspot: Geographical variations (appears in new window)
Yes, we can assess whether the cases are distributed randomly between the villages
or whether they are clustered in particular villages
Interaction: Hotspot: Temporal trends (appears in new window)
No, there is no information in this table about how 'the disease' was distributed over
time - the table shows the total number of cases diagnosed in a one-year period.

(RHS remains static)
Is there spatial clustering of cases? Look at the data and write down your answer
without doing any formal tests.
A number of villages have a risk of disease considerably higher or lower than the
overall risk of 50.6 per 1000 (see final row of Table 1). This indicates that there
might be clustering of cases.
(appears on main card below original text)
How can you tell if there is significant geographical variation? Think carefully about
what statistical test you could use and then click on the box below.
A chi-squared test of the observed population size and number of cases would show
whether the cases are distributed randomly between all the villages. The results of
a chi-squared test are:
_ = 186.8, 23 degrees of freedom, P ~< 0.001.

How are cases distributed?
Interaction: Hotspot: Randomly (appears in new window)
In fact, the significant chi squared value indicates that cases are *not* randomly
distributed among villages.
Interaction: Hotspot: Randomly (appears in new window)
That's right. The chi-squared value indicates that there is a significant association
between villages and cases. Some villages have more cases and some villages have
fewer cases than would be expected if cases were randomly distributed.

Another approach to the distribution of cases is to consider population size as a risk
factor for 'the disease'.
The best way to visualise this is to plot a graph of the data. Drag and drop the
variables in the boxes below into the blue bays next to the appropriate axes
opposite.
Reset
Button
Interaction: Drag and Drop: Risk of disease
Correct response: (drag to top box on RHS)
That's right, the number of cases observed will be a function of the number
of individuals in the village. We need to use risk of disease as our outcome
variable to adjust for differences in the denominator population being
observed.
Incorrect response: (drag to bottom box on RHS)
In fact it is more conventional to put the dependant or outcome variable on
the Y-axis.
Interaction: Drag and Drop: Number of cases
Incorrect response: (drag to either box on RHS)
Thats not quite right. The number of cases observed will be a function of
the population size. For villages with the same risk, those with more
individuals will have more cases. We need to use risk of disease to adjust
for differences in the denominator population.
Interaction: Drag and Drop: Population sizes
Correct response: (drag to bottom box on RHS)
That's correct, it is better to put the independent or 'exposure' variable on
the x-axis.
Incorrect response: (drag to top box on RHS)
Actually it is more conventional to put the independent or exposure variable
on the x-axis.
In fact it is more conventional to put the dependent or outcome variable on

the y-axis.

Is there an association between population size and risk of 'the disease'?
Interaction: Hotspot:
yes
In fact the data are scattered randomly, implying that there is *no* association
between population size and risk of 'the disease'.
no
That's correct - if there had been an association between population size and risk
of 'the disease', the points would have formed more of an ellipse.
(back to main text)
Does this mean that over-crowding is a risk factor for 'the disease'?
yes
In fact, population size is not the same as population density (number of people in a
specified area), so we have no information on whether crowding might be a risk
factor.
no
That's correct, population size is not the same as population density (number of
people in a specified area), so we have no information on whether crowding might be
a risk factor.

Exercise: Table 2
Table 2 opposite shows the risk of 'the disease' by age and gender. The data for
males are shown first; click 'swap' to see the data for females. Notice that the
age groups that have been used are not even.
Complete Table 2 by calculating the missing risk value for males to one decimal
place. Next click 'swap' and complete the corresponding table for females.
Then, look at the data in Table 2 and try to identify the main epidemiological
features of 'the disease'. Think about how this data can be better visualised.
By plotting a graph of risk of 'the disease' by age group for each gender, the
distribution of 'the disease' by age and the comparative trends for each gender will
be clearer.
Calc 1
Correct response:
That's right, the risk for males aged 5 to 9 years is (193 / 1574) x 1000 = 122.6.
Remember to also calculate the empty cells in the table for females.
Incorrect response:
Sorry, that's not correct. The risk for males aged 5 to 9 years is given by the
number of cases divided by the population in that age group:
Risk per 1000 = (193 / 1574) x 1000 = 122.6.
Try again with the empty cells in the table for females.
(Back to main page)
Interaction: Button: Swap: output (changes table on RHS)
Calc 1
Correct response:
That's right, the risk for females aged 2 years is (16 / 365) x 1000 = 43.8.
Incorrect response:
Sorry, that's not correct. The risk for females aged 2 years is given by the number
of cases divided by the population in that age group:
Risk per 1000 = (16 / 365) x 1000 = 43.8
Calc 2
Correct response:
That's right, the risk for females aged 25 to 29 years is (75 / 997) x 1000 = 75.2.
Incorrect response:
Sorry, that's not correct. The risk for females aged 25 to 29 years is given by the
number of cases divided by the population in that age group:
Risk per 1000 = (75 / 997) x 1000 = 75.2.

(RHS remains static - chart)
The button below will show a graph of the data in Table 2.
Look at the graph and identify the main characteristics of 'the disease'. Think
about epidemiological inferences that are consistent with each of the
characteristics.
Write down your answer before continuing.

The points listed opposite summarise the data shown in the graph. We can
potentially make inferences from some of these points.
Click below if you would like to see the graph again.
1. There are no cases during the first

year of life.
Interaction: Button: Inferences: output
Inferences
This feature is consistent with a number of potential inferences:
The disease is caused by an
infection with a long incubation
period.
Infants are protected from a
nutritional deficiency by a
breast milk diet.
Infants are protected from an
infection by passive immunity
from the mother
Infants are not exposed to the
causal factor because of some
behavioural difference.
(back to main text)
2. There is a rapid rise in risk to a peak
at age 5-9 that is similar for both
genders.

Inferences
A peak of disease among school-aged children is consistent with transmission of
an aerosol infection, such as measles, chickenpox, etc.
(back to main text)
3. The risk falls to a very low level
among adolescents (15-19).
4. In adulthood there is a difference
between the genders with males
having a lower risk from 20-50 years,
and then having excess risk above 60
years.
Inferences
Women aged 20 50 years old are of childbearing age and may have a lower
immunity to infection or a greater nutritional requirement.
Men above 60 years could have some behavioural difference in exposure but this is
difficult to assess without sociological information.

Table 3 opposite shows the distribution of cases by month of onset, adjusted to a
31-day month.
How would you describe the distribution of the cases? How do you interpret this?
There is a dramatic peak of cases in May and June. The majority of cases occur
between April and July. Over 50% of cases occur in May and June alone. This disease
exhibits marked seasonality, which is likely to relate to warmer temperatures and
increased sunlight hours in the Northern Hemisphere.

Table 4 opposite shows the relationship between risk of 'the disease' with sanitary
rating at the village level.
These ratings are developed by sanitary engineers and are based on composite
indices of general cleanliness, excreta disposal and water supply. The ratings are
given on a scale of 000 where less than 40 is to be poor sanitation, and 70 and
above is good sanitation.
Relationship between risk of the disease and sanitary ratings
Unknown disease
Describe the data in Table 4 by selecting the correct words from the drop-down
menus below:
The highest risk of 'the disease' is in villages with the
pulldown 1 sanitation.
The lowest risk of 'the disease' is in villages with the

sanitary rating.
pulldown 2
The risk of 'the disease' pulldown 3

decrease with increasing sanitary rating.
Interaction: Pulldown: pulldown 1 (appears in new window)
Correct response: best
Yes, the risk is highest in the village with the highest sanitary rating.
Incorrect response: intermediate
No, the village with the intermediate sanitation (a rating of 40 69) does not have
the highest risk of disease. Try again.
Incorrect response: worst
No, the village with the worst sanitation (a rating of less than 40) does not have the
highest risk of disease. Try again.
Correct response: intermediate
Yes, the risk is lowest in the village with the intermediate sanitary rating (40 69).
Incorrect response: best
No, the village with the highest sanitary rating in fact has the highest risk of disease.
Try again.
Incorrect response: worst
No, the village with the worst sanitation (a rating of less than 40) does not have the
lowest risk of disease. Try again.

Correct response: does not
That's right, there is no evidence here that the risk of 'the disease' decreases with
increasing sanitary rating.
Incorrect response: does
In fact the risk does not decrease with increasing sanitary rating, since the risk is
higher in the village with the best sanitation than it is in the village with the worst
sanitation.

(RHS remains static chart)
Sanitation is a risk factor for the spread of a faecal-oral transmitted disease. Is the
sanitary rating used here a good measure of the quality of sanitation? Think about
how the investigators might have validated this rating score during their study.
To validate whether the rating used here is useful, you could compare it with a
disease known to be spread by faecal-oral transmission. Information was collected
on the risk of typhoid fever, which is an intestinal infection transmitted by the faecaloral route.
(appears below main text on LHS card)
By looking at the data you can see that the risk of typhoid fever decreases as the
quality of sanitation improves. This suggests that this sanitary rating is a good
indicator of the quality of sanitation, which is related to the spread of faecal-oral
transmitted infections.
(appears on RHS card)
Typhoid fever

Now think about how you would interpret the data from Table 4.
Interaction: Button: cloud: output (appears below main text on LHS)
There does not appear to be any association between sanitation and risk of 'the
disease' of unknown aetiology.
This is surprising as sanitation levels are usually correlated with standards of living,
hygiene, nutrition, etc., which are linked to many kinds of diseases. However, these
ratings are allocated at the village level and may hide variations at the household
level.

Table 5 opposite shows the risk of disease by economic status. The measure
used is weekly family income per Adult Male Index (AMMAIN).
By studying a large number of families in the survey area, the consumption of all
types of goods, services and food was estimated for each family member. Males
aged 25 years were found to consume the most. Adult females, children and older
adults consumed less. The amount of consumption of a 25-year-old male was
arbitrarily chosen as one unit, and other individuals were weighted according to
this. In this way, family income was adjusted for family consumption.
Interaction: Hyperlink: AMMAIN: output (appears in new window)
AMMAIN measures variation in the gross demand for articles of consumption
among individuals of different ages and gender.

(RHS remains static - chart)
Is there an association between adjusted family income and risk of 'the disease'?
Think about how you would describe the epidemiological interpretation of these data.
Write down your answer before continuing.
Interaction: Hyperlink: cloud: output (appears in new window)
There is a clear and dramatic inverse association between risk of 'the disease' and
adjusted weekly income. Risk declines as family income per AMMAIN increases.
(appears on LHS card below main text)
Is this contradictory to the relationship with sanitary rating?
Interaction: Hyperlink: cloud: output (appears in new window)
At first glance it seems that this is contradictory, because sanitation is likely to be
positively associated with income. However, the sanitation ratings used here were
at the village-level, while the income analysis was at the family level.
The mistaken assumption that differences between groups reflect differences
between individuals is sometimes called the 'ecological fallacy'.
Section 13: Exercise: Overall evaluation

Consider all the data together and decide what you think the aetiology of 'the
disease' is. Write it down, together with any supporting evidence from the
information given so far.
Now review what each data table tells you about the epidemiology of 'the disease'.
13.1: Exercise: Overall evaluation

For each data source listed on the next page, select whether there is evidence in
favour of or against the hypotheses listed on the chart opposite.
For each data source listed below, select whether there is evidence for or against the
hypotheses listed opposite. Note that for some hypotheses there is no evidence
either for or against.
Interaction: Button: Geographic village distribution: output
(appears on RHS)
Data source: Geographic-village distribution
Hereditary
Infectious :
aerosol
Infectious :
faecal oral
Infectious :
vector
borne
Infectious :
contact
Nutritional
For
Against
? (hotspot
1)
? (hotspot
2)
? (hotspot
3)
? (hotspot
4)
? (hotspot
7)
? (hotspot
8)
? (hotspot
9)
? (hotspot
10)
Insufficien
t evidence
? (hotspot
13)
? (hotspot
14)
? (hotspot
15)
? (hotspot
16)
? (hotspot
5)
? (hotspot
6)
? (hotspot
11)
? (hotspot
12)
? (hotspot
17)
? (hotspot
18)
Interaction: Hotspot: ? (hotspot 1) (from above table)

Incorrect response: (appears in new window)
In fact, a potentially fatal disease is unlikely to have such a high annual risk if it is
hereditary.
No, in fact there is insufficient evidence or information to support this.

Correct response: (appears in new window)
That's right, a potentially fatal disease is unlikely to have such a high annual risk if it
is hereditary.
In fact there is sufficient evidence in this case. Please try again.

That's right, there is insufficient evidence to support or refute this.
Table is as follows after all hotspots have been clicked on:
Interaction: Button: Age-sex distribution: output

(table changes on RHS)
Data source: Age-sex distribution

For
Against
Hereditary
Infectious :
aerosol
Infectious :
faecal oral
Infectious :
vector
borne
Infectious :
contact
Nutritional
? (hotspot
1)
? (hotspot
2)
? (hotspot
3)
? (hotspot
4)
? (hotspot
7)
? (hotspot
8)
? (hotspot
9)
? (hotspot
10)
Insufficien
t evidence
? (hotspot
13)
? (hotspot
14)
? (hotspot
15)
? (hotspot
16)
? (hotspot
5)
? (hotspot
6)
? (hotspot
11)
? (hotspot
12)
? (hotspot
17)
? (hotspot
18)

That's right. The peak risk among school-aged children is consistent with an infection
spread by aerosol-contact, such as measles, chickenpox, etc.
In this case the evidence is inconsistent.
The decline in risk among older children is consistent with reduced transmission of
faecal-oral transmitted diseases in the older age groups. Younger children tend to
have less hygienic behaviours and therefore have a higher risk of faecal-oral
transmitted diseases. However the increase with age in adulthood is not consistent
with risk of faecal-oral transmitted diseases.
That's right. The high risk among women of child-bearing age is consistent with a
nutritional factor as they have greater nutritional requirements during pregnancy
and lactation. The absence of cases among infants could be because they are
provided with sufficient nutrition from breast-milk. In this case the peak risk among
young children could be explained by patterns of food distribution in the household
or a higher nutritional requirement in this age group.
In fact, the evidence of peak risk among school-aged children is consistent with an
infection spread by aerosol-contact, such as measles, chickenpox, etc.
In fact, the high risk among women of child-bearing age is consistent with a
nutritional factor as they have greater nutritional requirements during pregnancy and
lactation. The absence of cases among infants could be because they are provided
with sufficient nutrition from breast-milk. In this case the peak risk among young
children could be explained by patterns of food distribution in the household or a
higher nutritional requirement in this age group.

In fact, there is insufficient evidence in this case. Please try again.
Interaction: Button: Seasonal distribution: output

Data source: Seasonal distribution
For
Against
Hereditary
Infectious :
aerosol
Infectious :
faecal oral
Infectious :
vector
borne
Infectious :
contact
Nutritional
? (hotspot
1)
? (hotspot
2)
? (hotspot
3)
? (hotspot
4)
? (hotspot
7)
? (hotspot
8)
? (hotspot
9)
? (hotspot
10)
Insufficien
t evidence
? (hotspot
13)
? (hotspot
14)
? (hotspot
15)
? (hotspot
16)
? (hotspot
5)
? (hotspot
6)
? (hotspot
11)
? (hotspot
12)
? (hotspot
17)
? (hotspot
18)

In fact, seasonality of cases is not consistent with a hereditary disease.
Yes, the peak of cases in summer is consistent with a faecal-oral transmitted
infection.
Yes, the peak of cases prior to the harvesting of crops in July and August is
consistent with a nutritional deficiency.

That's right, seasonality of cases is inconsistent with a hereditary disease.
Correct, the peak of cases in summer is not consistent with an aerosol-transmitted
infection.
In fact, the peak of cases in summer is consistent with a faecal-oral transmitted
infection.
In fact, the peak of cases prior to the harvesting of crops in July and August is
consistent with a nutritional deficiency.
In fact, there is insufficient evidence in this case. Please try again

(back to LHS card)

Interaction: Button: Relationship with sanitary ratings: output
Data source: Relationship with sanitary ratings
For
Against
Insufficien
t evidence
Hereditary
? (hotspot
? (hotspot
? (hotspot
1)
7)
13)
Infectious :
? (hotspot
? (hotspot
? (hotspot
aerosol
2)
8)
14)
Infectious :
? (hotspot
? (hotspot
? (hotspot
faecal oral
3)
9)
15)
Infectious :
? (hotspot
? (hotspot
? (hotspot
vector
4)
10)
16)
borne
Infectious :
? (hotspot
? (hotspot
? (hotspot
contact
5)
11)
17)
Nutritional
? (hotspot
? (hotspot
? (hotspot
6)
12)
18)

correct response: (appears in new window)
Thats right, there is sufficient evidence to support or refute this.
In fact, the lack of any association with village sanitary ratings suggests that this is
not a faecal-oral transmitted infection.
That's right, the lack of any association with village sanitary ratings suggests that
this is not a faecal-oral transmitted infection.

Interaction: Button: Relationship with sanitary ratings: output

Data source: Relationship with economic status
Hereditary
Infectious :
aerosol
Infectious :
faecal oral
Infectious :
vector
borne
Infectious :
contact
Nutritional
For
Against
? (hotspot
1)
? (hotspot
2)
? (hotspot
3)
? (hotspot
4)
? (hotspot
7)
? (hotspot
8)
? (hotspot
9)
? (hotspot
10)
Insufficien
t evidence
? (hotspot
13)
? (hotspot
14)
? (hotspot
15)
? (hotspot
16)
? (hotspot
5)
? (hotspot
6)
? (hotspot
11)
? (hotspot
12)
? (hotspot
17)
? (hotspot
18)


An inverse correlation with socio-economic status could indicate an inverse
correlation with household-level sanitation. This would be consistent with a faecaloral transmitted infection. However there is insufficient information from the
economic data to support this.
The inverse correlation with socio-economic status could indicate an inverse
correlation with consumption, and this would be consistent with a disease due to a
nutritional deficiency.
An inverse correlation with socio-economic status would indicate an inverse
correlation with household-level sanitation, and this would be consistent with a
faecal-oral transmitted infection. However there is insufficient information from the
economic data to support this.

In fact, the inverse correlation with socio-economic status could indicate an inverse
correlation with consumption, and this would be consistent with a disease due to a
nutritional deficiency.

What do you consider the aetiology of 'the disease' to be now? Write down your
answer, then look at the hints given below.
Interaction: Button: Hint 1: output (appears in new window)
Hint 1
The disease is highly seasonal, and starts to decline at the time of crop harvest in
July and August.
Hint 2
Income is linked to consumption. There is a strong association between income and
risk of 'the disease'.
Hint 3
Men aged 25 years old have the highest consumption of goods and food. They also
have the lowest risk of 'the disease'.
Has your opinion changed after seeing the hints? Check whether you were correct by
clicking on the button below.
Interaction: Button: Show: output (appears on RHS)
Despite having many epidemiological characteristics of an infectious disease, 'the

disease' is in fact due to a nutritional deficiency.
It is called pellagra, from Italian pelle (skin) and agro (rough) because of the
distinctive photosensitive dermatitis.
The clinical presentations are:
diarrhoea
dermatitis
dementia.
Interaction: Hyperlink: photosensitive dermatitis: output (appears in new
window)
On parts of the body exposed to sunlight, the skin develops a rash that later
develops into the characteristic pellagrous lesions. This may be another reason why
more cases were diagnosed at the height of the summer in May and June.

Pellagra is caused by a deficiency of tryptophan and/or nicotinic acid.
Maize contains nicotinic acid but in an unavailable form, so that a maize-rich diet can
be associated with pellagra. Good sources of nicotinic acid include meat, wheatgerm
and yeast.
The data presented here are from surveys conducted in the Southern USA under
the supervision of J. Goldberger.
See his essay "Considerations on Pellagra", for information on the debate
surrounding the aetiology of the disease prior to these studies.
Interaction: Hyperlink: Considerations on Pellagra: output (appears in new
window)
This is on pages 99-102 of one of the course books: "The Challenge of
Epidemiology: Issues and Selected Readings" Eds. Buck et al. (1989).

This exercise enabled you to use the information learned in the session to
investigate whether or not the case data supplied were due to an infectious
aetiology.
In this case the disease was not infectious despite sharing many epidemiological
characteristics of infectious diseases.
By contrast, Beral's comparison of mortality patterns for cancer of the cervix, with
trends in incidence of sexually transmitted diseases, showed associations between
the temporal, social class, occupational, and geographic distributions for these
diseases (Beral, 1974).
She proposed that the cause of cervical cancer was a sexually transmitted
infection, when many considered it to be a non-infectious disease. Human
papilloma virus has since been associated with cases of the disease.
See Beral (1974) in your workbooks, for the evidence of an infectious aetiology for
cervical cancer.

There are a number of diseases for which the aetiology is still not fully understood.
In many cases the evidence points to the need for a number of co-factors to be
present together before an individual develops the disease.
The cause of multiple sclerosis still remains unknown, but it appears to involve a
complex interaction of genetic and environmental factors. There is also some
evidence that a viral infection may be involved in triggering the disease in
genetically susceptible individuals.
For more information on this topic read the first two pages of the review by
Noseworthy (1999) in your reader.

The aetiology of childhood leukaemia is also still under debate. It has been
associated with exposure to X-rays in utero and to ionising radiation. In a few
cases a link has been found with genetic abnormalities such as Down's syndrome.
Over 80% of cases are still unexplained, and an infectious aetiology has been
proposed for this.
For further information on this topic read the review by Kinlen (1996) on the
evidence supporting the hypothesis of an infectious aetiology of leukaemia in your
reader.
Section 14: Summary

This is the end of EC02. When you are happy with the material covered here please
move on to session EC03.
The main points of this session will appear below as you click on the relevant title.
Characteristics of infectious aetiology
(link returns RHS to relevant page)
During this session we identified a number of epidemiological features that are

associated with, but not exclusive to, infectious diseases. These fall into three
distinct categories:
Time
Place
Person
Time
The temporal distribution of cases can be divided into the following patterns:
(i)
Temporal clustering associated with

a common source or sources of
infection.
(ii)
Seasonality regulated by climatic

changes that restrict transmission of
the infection.
(iii) Cyclical patterns associated with

recurrent social events, periodic
climatic phenomena, or the interval
to reach the critical threshold of
susceptibles.
(iv)
Long-term trends that may indicate
associations with an exposure.
Place
The spatial distribution of cases can occur on two levels:
(i)
Spatial clustering associated with a

common source or sources of
infection.
(ii)
Geographical restriction regulated

by ecological and climatic conditions
that restrict transmission of the
infection.
Person
The disease may be exclusive to, or more common among, a particular group of
individuals:
(i) Occupational groups tend to have
special behaviours and known

exposures that can be associated with
the infection.
(ii) Behaviours may increase exposure
to the infection and can be an
important area
for focusing public
health interventions.
(iii) Socio-economic status is associated
with many infectious diseases, as
poor living conditions often provide
favourable environments for
transmission of infection.
(iv) Immunological status can provide a
clear indication of an infectious
aetiology.
Final tips
When faced with epidemiological data about a disease, think about what each piece
of information might be telling you about the cause.
Remember that some epidemiological features may indicate different aetiologies.
Spatial clustering may be due to an infectious or environmental cause, and at the
family level it can even be genetic.
Also consider that lack of conclusive evidence for a proposed cause does not
necessarily mean that it is not involved. It could suggest that it is only one of a
number of factors required to cause the disease.
Other potential co-factors may need to be investigated to fully understand the
aetiology of the disease and the role, if any, of infectious agents.

Ec 02

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Ec 02

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Is the disease infectious?

Section 1: EC02 Is the disease infectious?

To determine whether a disease is caused by an infectious agent or not.

This session should take you about 2 to 3 hours to complete.

Section 3: Epidemiological characteristics of infectious disease

Section 4: Time when the disease occurs

4.1: Time when the disease occurs

4.2: Time when the disease occurs

(buttons moves green line left or right)

4.3: Time when the disease occurs

Do disease cases occur close together in time?

4.4: Time when the disease occurs

season for a number of reasons. In temperate climates, there tends to be more

In fact, incidence of vector-borne diseases such as malaria tends to peak in the

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4.5: Time when the disease occurs

For more information about this infection see

4.6: Time when the disease occurs

4.7: Time when the disease occurs

4.8: Time when the disease occurs

4.9: Time when the disease occurs

It shows a close association with the between-year variation in malaria incidence in

4.10: Time when the disease occurs

Interaction: Hyperlink: birth cohorts: output (appears in new window)

Section 5: Place where the disease occurs

5.1: Place where the disease occurs

John Snow plotted the residence of fatal cases of cholera

5.2: Place where the disease occurs

5.3: Place where the disease occurs

Measures of household spread of infection will be discussed in EC03.

5.4: Place where the disease occurs

Interaction: Tabs: 2 : output

Interaction: Tabs: 3 : output

5.5: Place where the disease occurs

3. individuals migrating into the area

Section 6: Person who develops the disease

6.1: Person who develops the disease

6.2: Person who develops the disease

6.3: Person who develops the disease

6.4: Person who develops the disease

6.5: Person who develops the disease

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Section 8: Exercise: A disease of unknown aetiology

8.1: Exercise: A disease of unknown aetiology

Cases appeared to be localised in their geographical distribution. Multiple cases

8.2: Exercise: A disease of unknown aetiology

Section 9: Exercise: Table 1

That's right, the minimum number of cases is 13, in village 'Gr'.

The highest risk of disease is 100.8 per 1000, in village 'In'.

9.1: Exercise: Table 1

RHS remains static (chart)

9.2: Exercise: Table 1

9.3: Exercise: Table 1

9.4: Exercise: Table 1

In fact it is more conventional to put the dependent or outcome variable on

9.5: Exercise: Table 1

9.6: Exercise: Table 1

9.7: Exercise: Table 1

9.8: Exercise: Table 1

1. There are no cases during the first

Interaction: Button: Inferences: output

Section 10: Exercise: Table 3

Section 11: Exercise: Table 4