Pan American Health Organization
Pan American Sanitary Bureau, Regional Office of the World Health
Organization
Modules of the Principles of Epidemiology for
Disease Control
For the English-Speaking Caribbean
Adapted Second Edition
Unit 5.1:Field Epidemiology: the Study of Outbreaks
MOPECD Unit 5: Epidemiologic field study
2
CONTENT AND OBJECTIVES
This unit covers epidemiological field investigation as applied to local health outbreaks
and epidemics. The unit presents procedures to collect data and develop information in a
timely manner for the detection, characterization, confirmation, and control of outbreaks
and epidemiological alert situations.
The objectives of the present unit are:

To recognize alert situations that require epidemiological field study

To present the principles, methods, and basic procedures for epidemiological field
study in the investigation of outbreaks

To lay the foundation for organizing epidemiological field study at the local health
level

To analyze in detail the real case of an epidemiologic field study applied to the
study of an outbreak in the community
INVESTIGATION IN PUBLIC HEALTH
Health services have expanded to not only include treatment and health promotion, but
also the surveillance, prevention, and control of health problems. In the past health services
only focused on communicable diseases but now often include surveillance and control
programs for chronic diseases, lifestyle risk factors, genetic disorders, occupational health
events, environmental risks, disabilities and many more areas of concern.
The collection and analysis of data from public health surveillance systems are
necessary for effective disease control. Control interventions for many emergent serious
health problems often require additional information acquired through rapid focused
epidemiological investigations.
Identifying risk factors for risk of disease or adverse health events in the population is
essential for the designing effective interventions for the prevention and control of disease
or health event. In epidemiological alert situations, control measures require rapid efficient
implementation to successfully suppress or eliminate sources of infection or exposure,
interrupt transmission in the population and reduce susceptibility.
Epidemiological field study is divided into descriptive and analytical epidemiology.
These methods are used for investigating and controlling outbreaks and epidemics of
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infectious disease or other acute events. Descriptive epidemiology characterizes the
disease or adverse events, the times and places of those events and the persons impacted.
Analytical epidemiology generates inferences and predictions about the probable exposure
and mode of transmission associated with risk of disease or health event. This information
is used to plan appropriate interventions for the control of the health problem. The strength
of the association between possible risk factors and disease or event, especially in outbreaks
and epidemics, can provide biologically/socially plausible evidence for initiating effective
control measures in the absence of laboratory confirmation. Thus, analytical epidemiology
can be a driving force for successful public health action.
Epidemiological field study is also used to identify why control measures may be
ineffective. For example, every measles outbreak should be investigated routinely to
evaluate the effectiveness of the vaccine and immunization program for measles. Generally,
measures designed to control an outbreak should always be monitored for effectiveness.
Epidemiological field study can sometimes conflict with socially and culturally
sensitive issues in the community. Thus, the epidemiological field study should always
ensure a balance between the need for rapid response and the need for responding in a
sensitive and ethical manner, protecting the dignity and rights of the community.
In outbreaks and emergencies, epidemiological investigations require rapid deployment.
Rapid implementation of investigations leads to early interventions to protect the
population. For example, prompt identification of contaminated foodstuff can prevent
future cases, hospitalizations and deaths, avoid overloading health services and reduce the
socio-economic costs to the community. The investigation of outbreaks is retrospective or
at best concurrent. The success of a field investigation often depends on the memories and
recollections of people about activities such as consumption of food, routes of travel taken
and contacts. Memories fade, so data needs to be collected as soon as possible. Sometimes
also, the window of opportunity for carrying out an investigation is limited to a few hours
or days, especially where food or other evidence is discarded, where laboratory tests
required freshly contaminated/infected samples, or where an outbreak occurs among
travelers in transition.
Rapid epidemiological assessment none-the-less must be balanced against conducting a
careful comprehensive methodologically-sound investigation to avoid mistakes which
might have serious consequences. Field epidemiologists may have to persuade local
government authorities, industries, and/or the general public to take actions that may not
necessarily be welcomed. Premature findings in error as a result of misleading spurious
associations, biases or confounding factors negatively impact the credibility of local health
team and produce ineffectual and costly interventions. Seriously mistaken findings could
lead to the closure of schools and hospitals, bankruptcy of commercial establishments, labor
and legal disputes, social stigma and civil disorders. The findings of epidemiological field
studies can have a major impact on policy-making and the setting of safety standards on a
national scale. In the Caribbean islands, outbreaks in hotels and on ships not only impact
the health of the Caribbean people and island tourists, but also have negative economic
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consequences for the tourist trade. Thus care must always be taken in field investigation,
balancing this with the demands of speed to resolve the problem and protect the population.
The epidemiological study of outbreaks by local health teams can impact the immediate
health of the community and provide opportunities for in-service training. The history of
such investigations include many notable examples, from the famous study by John Snow
of the cholera outbreak in London in the mid-1800’s to the more recent study of the firstrecognized Legionnaires’ disease outbreak in the United States. Both studies are found in
the annex of this unit. Many epidemiological field studies are also underway in both the
Caribbean countries and elsewhere to investigate emerging disease epidemics such as
HIV/AIDS and remerging disease outbreaks of diseases such as dengue and malaria.
There are two major design groups in epidemiological research. One is randomized
trials or randomized controlled trials. Randomized trials such as clinical trials (where
individuals are assigned exposures) and community trials (where communities are assigned
exposure) attempt to control undue distorting influences on findings by random assignments
of exposure. Clinical trials is considered the “gold standard” of epidemiological study designs
but often cannot be implemented due to logistical, cost or ethical considerations. Randomized
trials attempt to emulate very-controlled scientific experiment. The other study design group
is observational studies. In observational studies there are no assignments of exposure to
participants as there is in randomized trials; exposure status is only observed as it naturally
occurs. One of the classifications of observational study designs is descriptive studies, which
describe the characteristics of frequency and distribution of disease over time and space, and
by person. The other classification of observational study designs is the analytical or
comparative studies, which investigate determinants/risk factors of disease or health event and
evaluate hypotheses (Figure 5.1).
FIGURE 5.1 EPIDEMIOLOGICAL STUDY DESIGNS
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Clinical trial
Therapeutic trial
Prevention trial
Intervention trial
Field trial
Randomized trial
Community trial
Descriptive study
Case-report study
Case series study
Ecological study (correlation)
Cross-sectional study (prevalence)
Observational
study
Analytical study
Case-control study
Case-crossover study
Case-cohort study
Cohort study
Outbreak epidemiological field studies investigate unexpected health problems that
often require immediate response and timely intervention.
Computer technology can support epidemiological field studies when used
appropriately. As previously noted the software EpiInfo which is free as a download from
the internet can be useful in the collection and analysis of outbreak data. Computerized
geographic information systems (GIS) likewise can be helpful in producing maps of risk for
an outbreak, among other applications.
INVESTIGATION OF OUTBREAKS
Local capacity to response to an outbreak in a timely manner requires that the public
health surveillance system is capable of triggering an alert to investigate a potential
outbreak and that the local health team has the capacity to systematically investigate and
control the outbreak. This unit will cover these two areas.
Any suspicion at the local level of an outbreak should be communicated immediately to
the next highest health level. Communicating the suspicion that there may be an outbreak
is important because:




a local outbreak without early response and control could turn into a major epidemic
of larger proportions and more harmful consequences,
a local outbreak could be the first sign of an outbreak that is occurring in other
locations and more threatening than initially believed,
already extant control measures in other areas may be applied locally immediately
for early control if the outbreak is identified early, and
epidemiological technical assistance from higher levels can be mobilized early,
including resources for epidemiological field study.
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Clusters, outbreaks, and epidemics
It is important to define three related terms in alert emergency situations to have a
common language for epidemiological field study and response. A cluster is an unusual
concentration of cases geographically or over time. A cluster of cases would be greater in
number than what would be expected by chance. A cluster of cases on investigation would
be the earliest way of detecting an outbreak. In practice, the search for clusters can be based
on rumors, surveillance reports, hospital or health center registries or by observations from
health professionals.
An outbreak is an epidemic limited geographical to one defined locality, such as a
school, hospital, barracks or monastery. An outbreak is an unusual increase in the number
of cases with at least two epidemiologically-related cases which appear suddenly and
exhibit a localized spread in a defined area. Timely detection and response to an outbreak
is an effective way of preventing a subsequent epidemic. In practice, the detection of
outbreaks is a basic activity of surveillance systems and the investigation of outbreaks is a
requisite for implementing timely and effective prevention and control measures at the local
level.
An epidemic is an “outbreak” exceeding the geographic and population limits of an
outbreak, though these exceeded limits are not clearly defined. An epidemic is the
occurrence of cases of disease or other health events with a greater than expected incidence
for a given geographical area and time period. The expected incidence of disease varies
according to the agent, the characteristics of exposed population, previous experience of
exposure to the disease and the place and time of occurrence. Because acute polio due to
wild poliovirus is eradicated in the western hemisphere, the incidence of even one
confirmed case in the Caribbean exceeds expectations and is considered an epidemic.
Unexpected increases in the incidence of disease are due an increase in the transmission
of disease. Observed increases in the incidence of disease is often attributable to common
cause(s) among the cases. Sometimes greater than expected increases in incidence may not
be an outbreak or an epidemic. For example, changes in the case definition, notification
procedures, type of surveillance (such as switching from a passive surveillance system to an
active surveillance system), access to health services, or improvements in diagnostic
procedures can lead to a sudden apparent "excess" of cases. Sometimes an epidemic or
outbreak will not increase the overall total numbers of cases observed in the population.
For example, health authorities concluded that there was no measles epidemic during
epidemiological week 12 in 1992 because the number of observed cases of measles of 392
in one administrative area did not exceed the expected number of 412 for that week in that
area; however, more than 65% of the observed cases (n=258) were in children older than
two years-of-age, where the expected percent of cases from this age group out of the total is
14% (n=58). The epidemic of measles in this age group in this area for this week went
unnoticed.
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WHEN TO INVESTIGATE
The capacity to identify outbreaks requiring investigation generally depends on the
ability of the local public health surveillance system to alert health teams of a problem. An
investigation requires a significant investment of resources, so the decision whether to
investigate should be made on set criteria. Table 5.1 offers a list of criteria to decide when
to investigation.
TABLE 5.1 EPIDEMIOLOGICAL FIELD STUDY: WHEN DO WE
INVESTIGATE?

When the disease or health event is a priority

When the cases occurs more than expected

When cases seem to have a common source

When the health event seems to be more serious than expected

When the disease is new, emerging or "unknown" in the area

When the disease or health event is of public interest

When the disease or health event is due to disaster
When the disease or health event is a priority
Health authorities sometimes prioritize diseases or health events and mandate that every
reported case of a particular disease or health event be investigated. This requirement to
conduct an investigation derives from general disease/event control objectives of the health
system. Such disease priority lists are usually based on established national and
international epidemiological criteria. Such diseases include those targeted for eradication
and elimination, for which international notification is compulsory and those defined as reemerging.
When cases occurs more than expected
An investigation has to be made when the incidence of a disease or health event in a
specific population in a given time period and geographic area is greater than expected. In
general, a disease should be investigated in situations in which its frequency is greater than
expected. For a specific population and time period it is also possible to detect increases in
the determinants of disease, including risk behaviors and lifestyles, if the surveillance
system is designed to monitor these determinants.
The construction and maintenance of endemic corridors or channels and epidemic
curves for diseases under surveillance helps determine when an epidemiological field study
should be conducted. The identification of temporal clusters, unusual grouping of cases in
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over a short period of time, can trigger investigations of such clusters. Outbreaks are often
identified early by investigating clusters of cases.
When cases seem to have a common source
Diseases or health events that have apparent common cause(s) should be investigated.
Investigating the first occurrence of cases can lead to prompt identification and resolution
of an outbreak before it grows. Prompt investigation is especially important for clusters
caused by food or water borne disease and environmental toxins.
Clusters may be identified by the notification by health professionals of unusual patterns
of disease or health event. Clusters may also be discovered through analyses of surveillance
data or morbidity reports of associations between factors such as sex, age, place of
residence or work, surnames and date of onset with health event. A common date of onset
of symptoms is especially suspicious. Mapping cases geographically may also reveal spatial
clusters. Even rumors in the community can lead to clusters of cases, especially for
outbreaks associated with social and public events.
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When the health event seems to be more serious than expected
If the severity of disease increases, this should be investigated. If there is an increase in
the case fatality based on the information from the surveillance system or hospitalization
rates based on information from hospital records, this warrants investigation.
The development of drug resistant pathogens is increasing the severity of certain
diseases, thus drug surveillance systems are becoming more important. Declines in timely
access to health services or therapies, or reduced quality of care can enhance the relative
severity of disease in the community.
Those diseases with declining severity should also be investigated. Such a decline in
severity may reflect reduced quality of surveillance, thus the surveillance system and the
cases should be investigated.
When the disease is new, emerging or “unknown” in the area
A disease that may have occurred for the first time or rarely should be investigated.
Similarly, cases with clinical symptoms different from any known disease should be
investigated.
The majority of emerging, and re-emerging diseases should be investigated. Increasing
numbers of emerging and re-emerging diseases require more sensitive health surveillance
systems capable of detecting new syndromes and unexpected combinations of symptoms.
Syndromic surveillance systems that monitor symptoms and combinations of symptoms are
especially suited for such surveillance. Increased mobility of people and the expansion of
trade of foodstuffs have globalized risks of diseases and health events.
When the disease or health event is of public interest
Certain health events or disease sometimes capture the attention of the public and raise
concern about a particular disease or health event. Often public concern triggers a response
by health authorities, leading to an investigation.
When the disease or health event is due to disaster
Emergencies and disasters are often accompanied by disease outbreaks due to the
movement of populations and a failure of sanitary infrastructure leading to the
contamination of water, curtailment of waste and refuse disposal and overcrowding.
HOW TO INVESTIGATE
The principal objective of an epidemiological field study is to identify the causal factors
driving a disease outbreak. In general, this requires the determination of the causal agent, its
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source and mode of transmission, the population groups at greatest risk, and the exposures
that predispose the population to the disease.
The epidemiological field study for an outbreak has two objectives:
1) to describe the outbreak, determining the source and mode of transmission and
identifying the individuals at risk. Hypotheses of risk associations are developed
to support early rapid deployment of control measures and
2) to analyze associations for source, mode of transmission, risk factors, and major
exposures with disease and to test hypotheses. Analysis compares groups of
cases and healthy people to identify and quantify strengths of the association
between exposures and risk of disease. Findings are used to fine-tuned control
measures.
The steps for epidemiological field study steps of outbreaks are as follows:
TABLE 5.2 STEPS OF AN EPIDEMIOLOGICAL FIELD STUDY

1. Confirm the outbreak

2. Organize the field work

3. Establish an operational case definition

4. Carry out active case-finding

5. Characterize the outbreak in time, space, and person

6. Generate hypotheses for immediate deployment of control
measures

7. Evaluate hypotheses and conduct analytical field study

8. Implement specific control measures

9. Evaluate the control measures

10. Prepare a technical report on the field study
1. Confirm the outbreak
Confirming an outbreak requires 1) verification that the diagnosis of cases is accurate
and 2) determination that the incidence rate of these cases is higher than expected. For
diagnostic verification medical and laboratory records of the reported cases must be
reviewed. A frequency table of symptoms and signs should be constructed and used to
identify laboratory testing requirements to verify future cases and for excluding some
reported cases from the case count.
Once the clinical signs and symptoms and laboratory findings for cases have been
defined and the final case count is completed, it must be determined if the observed
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incidence rate of disease exceeds the expected incidence rate to qualify as an outbreak.
This analysis must also compare observed and expected incidence rates within subpopulations, such as specific age-groups or those residing in specific localities, and not only
for the total number of cases.
FIGURE 5.1 TYPHOID ENDEMIC CHANNEL 1989-1999 AND EPIDEMIC CURVE
FOR 2000 IN COUNTRY X
70
60
case notifications
3rd Quartile
50
40
Median
30
1st Quartile
20
10
0
J
F
M
A
M
J
J
A
S
O
N
D
months
Figure 5.1 displays a typhoid endemic corridor the epidemic curve for country X. This
graph can be used to determine if observed incidence exceeded expected incidence and
whether we have an outbreak/epidemic. Given that cases are already verified, from June to
at least September 2000 there is an apparent outbreak/epidemic that warrants investigation.
The possibility that observed incidence rate increases are due to factors other than true
increases in disease counts need to be considered and excluded before concluding that this
is a true outbreak/epidemic.
2. Organize the field work
The local health team should plan the field work with attention to three requirements:

Administrative needs. Adequate contact and coordination should be established
with the health, political and civil authorities of the community. As needed, their
active cooperation can be enlisted.

Logistic needs. Field coordination should ensure the provision of minimum
resources, organize people, distribute tasks properly and supervise the general
execution of the field work.

Technical needs. Pertinent technical information should be available, including
reported data, demographic information, maps, standard questionnaires, outbreak
investigation procedures manual, relevant clinical and laboratory information, and
statistical and epidemiological technical assistance.
Prior to implementation of the investigation, it is important to ensure a adequate supply
of laboratory supplies for the verification of cases, including material for the collection,
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storage, and transportation of biological samples and for data processing and analysis. If
investigation includes For any investigation conducted with healthy individuals and cases,
the survey form should be standardized and previously field-tested. Confidentiality and
security of the data collected should be guaranteed. The local health team should always be
previously prepared to respond to outbreaks, epidemics and emergencies.
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Exercise 5.1
Analyze the information contained in Figure 5.2 and then answer the following questions.
FIGURE 5.2 INCIDENCE RATE OF HIV INFECTION FOR WOMEN IN
COUNTRY B IN 2000
incidence per million
New HIV-Identified Cases per Million
30
25
20
15
10
5
0
1
4
7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52
Epidemiological
epidemiologic Week
weeks
Question 1. Based on the information on the graph above, do you think that an epidemic
of HIV infection started in the female population of country B in 2000?
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Question 2. In mid-month May 2000, the national office for the prevention and control
of AIDS in country B announced a program promoting HIV-testing among pregnant women
with the free distribution of antiretroviral treatment to every woman in this program testing
HIV-positive. With this new information, do you think that an epidemic of HIV infection
started in the female population of country B in 2000?
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3. Establish an operational case definition
The third step in field study of outbreaks is to establish a case definition. A case
definition for investigating outbreaks frequently differs from the definitions routinely used
in the public health surveillance system. Case definitions used in field work are also subject
to modifications.
A case definition is a standard criteria used to classify a suspected case as a case or not.
A case definition should be used systematically and uniformly to find additional cases and
to ascertain the true magnitude of the outbreak.
In general, the operational case definition includes the following criteria:

Clinical criteria: the symptoms and signs of the disease most frequently observed
in reported cases. These criteria can include the sequence with which the symptoms
appear and their average duration.

Laboratory criteria: the biochemical, pathological or microbiological test results
of infection or disease for the verification of reported cases.

Epidemiologic criteria: the distribution of reported cases over time, geography and
by person and characteristics of the agent, host and environment. Inclusion/
exclusion criteria for being a case may be based on the incubation period, probable
exposure period, contact with index case and secondary cases, common source, type
of exposure and restriction to a defined time period and geographic area.
The study of the outbreak of Legionnaires’ disease (see annex) offers an example of a case
definition. As an example, the investigators of the Legionnaires’ disease outbreak (see
annex) decided on a case definition with clinical criteria and epidemiological criteria. The
clinical criteria included having an onset of symptoms between l July and 18 August of
1976, a fever of 39C or higher and a dry cough, or fever and pneumonia confirmed by a
chest x-ray. Because this clinical definition was not very specific, with criteria symptoms
typical of viruses, bacteria, rickettsiae, fungi and chemical toxins, epidemiological criteria
restricted cases to persons having attended the American Legion Convention or to having
been present in the Bellevue Stratford Hotel, headquarters of the convention and principal
meeting site, after l July 1976.
The case definition should be simple and clear. The sensitivity and specificity of the
case definition should also be adequate for study purposes.
Sensitivity is the capacity of the case definition (or test) to correctly identify true cases out
of all true cases and is presented as a percent. It is calculated as the number of true cases
identified by the case definition divided by all true cases (identified and not identified)
multiplied by 100% to change to a percent.
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Specificity is the capacity of the case definition (or test) to correctly identify non-cases out
of all true non-cases and is also presented as a percent. It is calculated as the number of true
non-cases identified by the case definition divided by all true non-cases (identified and not
identified) multiplied by 100% to change to a percent.
Once the case definition is established it should be used equally and uniformly to
investigate the outbreak in all the people under investigation.
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Exercise 5.2
Table 5.3 shows the frequency of signs and symptoms of the 46 cases of an acute
disease initially reported to a local health center. All the cases turned out to be foreign
health professionals who had attended a technical meeting of the national program for the
control of leishmaniasis that was held at a nearby rural hotel complex. The meeting hosted
192 participants, lasted five days and was closed-door. The study of the outbreak eventually
identified a total of 108 cases and implicated the consumption of a ham and cheese
sandwich offered during the afternoon break on the second day of the meeting. The causal
agent in the outbreak was identified as staphylococcal bacteria.
TABLE 5.3 OUTBREAK OF STAPHYLOCOCCAL POISONING (N=46)
Symptoms
Nausea
Vomiting
Diarrhea
Abdominal pain
Intestinal bloating
Headache
Tenesmus
Chills
Thirst
Dizziness
Mucus in stools
No. of cases
46
44
32
29
18
13
12
10
9
4
1
Question 1. What was the attack rate of the disease based on the local health center data?
What was the attack rate of the disease based on the outbreak study findings?
Question 2. Using the information available, what case definition would you propose?
Compare your proposed case definition with those of the other members in the group and
establish a case definition by consensus.
Individual:
Group:
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4. Carry out active case-finding
If the outbreak has already been verified, the local team is already organized and an
operational case definition has been established, the next step is to search for cases, which
involves field work. To effectively find cases, an intensive focused surveillance system is
necessary. Such a surveillance system may include switching from passive surveillance to
active surveillance, expanding the frequency and means of reporting (such as daily
telephone calls) and using case and contact investigation cards.
Case-finding methods vary depending on the disease being investigated and the local
setting. In general, outbreaks target certain groups more than others, so case-finding can be
relatively focused on higher risk groups. Active case-finding through physicians,
laboratories, hospitals, schools, factories or public media can locate many unreported cases.
However, more intensive efforts are sometimes required to locate cases, including
serological surveys, door-to-door interviews and surveys for professional health workers.
Regardless of the method chosen, the local team develops an effective system for case
finding and reporting during the investigation of the outbreak.
5. Characterize the outbreak in time, place, and person
Time
An epidemic curve is an effective presentation of an outbreak over time. Important
characteristics of an outbreak to be measured over time include the duration of the outbreak,
the nature of the outbreak, and the probable exposure period.
The duration of an outbreak or epidemic depends on the following factors:





The speed of the outbreak as it relates to infectivity of the agent and mode of
transmission
The size of the susceptible population
The intensity of the exposure of the susceptible population
The incubation period of the disease
The effectiveness of the deployed control measures
Figure 5.3 presents the epidemic curve of a rubella outbreak with 37 cases that occurred
between the 21st and 29th of June, with a duration of 9 days.
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FIGURE 5.3 EPIDEMIC CURVE FOR A RUBELLA OUTBREAK,
10
9
Number
of Cases
c asos
8
7
6
5
4
3
2
1
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
días
Days of June
Mes de junio
Duration
Days
duración == 99 días
The nature of outbreaks/epidemics include:
Epidemics with a common source are outbreaks where the source of exposure is the
same for all persons at risk for disease. The common source of infection can be a singleexposure or continuous-exposure.

In single-exposure common source or explosive epidemic, exposure is to a
common source during a very brief moment in time, such as an exposure to
contaminated food served at a social event or luncheon. The time of exposure to the
onset of symptoms for median case is the median incubation period for this disease.
(Figure 5.4).

In a continuous-exposure common source outbreak, the duration of exposure to
the common source is prolonged and can even be intermittent for persons exposed,
such as the exposure to fecal contaminants in water supply networks.

Person-to-person or propagated epidemics are where transmission of disease is
from person to person (Figure 5.5).
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FIGURE 5.4 EPIDEMIC CURVE
FOR A SALMONELLA SINGLE-EXPOSURE COMMON SOURCE OUTBREAK
20
18
Number
of Cases
cases
16
14
12
10
8
6
4
2
0
11
10
9
8
7
6
5
4
3
2
1
14
13
12
15
(August)
Days days
in August
FIGURE 5.5 EPIDEMIC CURVE FOR A VIRAL HEPATITIS A PERSON-TOPERSON OUTBREAK
14
Number
casos of Cases
12
10
8
6
4
2
0
7
JUN
21
June
5
19
JUL
July
2
16
AGO
Aug
30
13
27
Sept
11
25
Oct
8
22
Nov
6
20
DIC
Dec
3
17
ENE
Jan
31
14
Feb
28
14
Mar
28
11
25
Apr
Semanas
Weeks
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In single-source common-exposure epidemics the median incubation period is the
period of time from exposure to the median onset of symptoms. If the median incubation
period is known for the disease from prior sources, this can be used to quickly estimate the
probable exposure date to the causal agent of the outbreak by subtracting the time of the
median incubation period from the peak of the epidemic curve. Figure 5.6 illustrates this
method with the outbreak of rubella described, where the median incubation period of 37
cases was 18 days.
FIGURE 5.6 RUBELLA EPIDEMIC CURVE WITH PROBABLE DATE OF
EXPOSURE
fecha probable
de exposición
10
9
Date of Probable Exposure
Numberc asos
of Cases
8
7
6
5
4
3
2
Peak of
pico del brote
Epidemic
Curve
18 días
periodo de incubación
Median Incubation Period = 18
Days
1
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
días
Days
Duration=9
duración = 9 Days
días
For a single-source common-exposure outbreak the probable exposure period to the
causal agent during an outbreak is estimated using the range of the incubation period,
available from published sources. The probable exposure period is computed by subtracting
the minimum incubation period from the date of the occurrence of the first case of the
outbreak and then subtracting the maximum incubation period from the date of the
occurrence of the last case of the outbreak. The range of dates between these two limits is
the probable period of exposure to the causal agent. Figure 5.7 illustrates this method with
the rubella outbreak, with the range of the incubation period of rubella from 14 to 21 days.
This method doesn’t apply to outbreaks with person-to-person transmission.
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FIGURE 5.7 RUBELLA OUTBREAK, EPIDEMIC CURVE PROBABLE PERIOD
OF EXPOSURE
10
Number
of Cases
casos
9
8
21Maximum
días: máximo
Incubation
Period =
periodo de incubación
21 Days
Probable
periodo
Exposure
probable
Period
de
exposición
7
Minimum
Incubation
Period =
14 días: mínimo
periodo14
de Days
incubación
6
5
4
3
2
1
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Days in June
días
Duration=
9 Days
The probable exposure period in Figure 5.7 corresponds to June
7th and
duración
= 98th.
días
Junio
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Exercise 5.3
Figure 5.8 shows the epidemic curve for a leptospirosis outbreak. A total of cases were
reported during the outbreak. Based on this information, compute the duration of the
outbreak and estimate the probable period of exposure to the causal agent. Leptospirosis has
a range of reported incubation periods of 4 to 19 days. Answer the following questions and
then discuss them with your group.
FIGURE 5.8 THE EPIDEMIC CURVE FOR A LEPTOSPIROSIS OUTBREAK AT
SITE X ON APRIL 2000
20
cases
16
12
8
4
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
days (April, 2000)
Question 1. The duration of the outbreak was: ____________
Question 2. The probable exposure period was: ______________
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Figure 5.9 shows the epidemic curve for an outbreak of meningococcal meningitis in
the pediatrics ward of hospital M during the month of May 1999. There were nine cases.
Based on this information, establish the duration of the outbreak and estimate the probable
period of exposure to the causal agent. Meningococcal meningitis has a range of reported
incubation periods of two to 10 days (range = eight days). Answer the following questions
and then discuss them with your group.
FIGURE 5.9 THE EPIDEMIC CURVE FOR MENINGOCOCCAL MENINGITIS
HOSPITAL M FOR THE MONTH OF MAY 1999
5
4
cases
3
2
1
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
days (May, 1999)
Question 3. The duration of the outbreak was: ________________
Question 4. The probable exposure period was: ________________
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Place or Space
Place in an outbreak is the geographical/spatial distribution of case counts, incidence
rates and case characteristics. This information defines the geographical limits of the
outbreak and clarifies the etiology, exposure, and spread of disease.
Place can include the site of occurrence of the cases, the place of residence, workplace,
the relevant geographical features geographical (such as rivers, spillways, wells, landfills,
the neighborhoods), distance to health services and the place of medical care.
Place descriptive information can be presented on tables such as table 5.4, on a bar
chart such as figure 5.10, or on a map such as figure 5.11.
TABLE 5.4: INCIDENCE RATE OF LEGIONNAIRES’ DISEASE BY LOCATION
OF LODGING
Location of Lodging
Hotel A
Hotel D
Hotel E
Hotel F
Hotel G
Another hotel
Residence
Unknown
Total
Number
of Cases
Number of
Hosts
Attack Rate
(%)
75
21
19
12
4
7
8
3
1,161
1,046
403
312
104
210
294
153
6.5
2.0
4.7
3.8
3.8
3.3
2.7
2.0
149
3,683
4.0
On maps cases are often marked as points by hand or by using computer programs like
EpiMap (EpiInfo) or more sophisticated programs like ArcView.
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FIGURE 5.10 TYPHOID OUTBREAK CASE DISTRIBUTION BY PARISH
incidence per 100,000 inhabitants
0
10
20
30
40
50
60
70
80
90
100
San Andrés
San Jorge
Victoria
Caroni
San Patricio
Nariva-Mayaro
Maps with plotted cases help identify clusters and provide evidence for common
sources of infection and risk exposures which can lead to the rapid deployment of control
measures. The classic example of such application, shown in figure 5.11, was by John
Snow to study and control the cholera epidemic in London between 1849 and 1854 (see
annex).
FIGURE 5.11 DEATHS FROM CHOLERA AND WATER SOURCES,
SOHO, LONDON IN 1855
Commercial water pumps for domestic water
use
Cholera
deaths
Source: Snow J, 1885.
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Person
Person includes the distribution of cases by relevant case characteristics. The following
tables (tables 5.5 and 5.6) provide the distribution of cases by sex and age groups:
TABLE 5.5 TYPHOID FEVER OUTBREAK DISTRIBUTION OF CASES BY AGE
Age (years)
Cases
Population
Attack Rate
(per 100,000)
0-4
5-9
10 -14
15 - 19
20 - 29
30 - 39
40 - 49
50 - 59
60 and older
Total
4
44
58
10
3
5
3
0
1
148,300
152,200
131,050
105,200
156,050
109,550
89,250
69,650
59,300
2.7
28.9
44.3
9.5
1.9
4.6
3.4
0.0
1.7
128
1,020,550
12.5
TABLE 5.6 TYPHOID FEVER OUTBREAK DISTRIBUTION OF CASES BY SEX
AND AGE
Age
(years)
Males
Cases
Population
Females
AR
Cases
population
(per 100,000)
AR
(per 100,000)
0-4
5-9
10 -14
15 - 19
20 - 29
30 - 39
40 - 49
50 - 59
60 and older
1
19
18
5
1
1
1
0
1
75,150
77,550
65,800
52,900
76,600
55,400
43,950
35,750
27,050
1.3
24.5
27.4
9.5
1.3
1.8
2.3
0.0
3.7
3
25
40
5
2
4
2
0
0
73,150
74,650
65,250
52,300
79,450
54,150
45,300
33,900
32,250
4.1
33.5
61.3
9.6
2.5
7.4
4.4
0.0
0.0
Total
47
510,150
9.2
81
510,400
15.9
Not only are numerator data important for the calculation of rates, but population-at-risk
data for the denominator is also essential.
6. Generate hypotheses for immediate deployment of control measures
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Generating hypotheses for immediate response is based on the synthesis of available
evidence. We have two sources for this evidence:

General medical information on the disease or health condition that could be
causing the outbreak.

Descriptive epidemiological information on the time, place and person of the
outbreak.
The hypotheses (plausible conjectures or provisional explanations) should attempt to
resolve the following:



The probable source of the causal agent of the outbreak
The probable mode of transmission in the outbreak
The exposure associated with a greater risk of developing disease
These hypotheses should lead directly to provisional control measures for immediate
deployment. Such control measures should target the removal, isolation, suppression,
elimination, or correction of the suspected common source. Where transmission is personto-person and the agent is highly pathogenic or virulent, control measures should focus on
cases and the protection of susceptible persons.
7. Evaluate hypotheses and conduct analytical field study
Epidemiologists compare population groups to determine underlying determinants for
developing diseases or health events, translating into effective control measures and health
interventions. During most outbreaks more information is needed than can be provided by
surveillance. To fill this knowledge gap, an epidemiological analytical study design called
case-control is often conducted during outbreaks. A case-control study design compares
outbreak cases with a usually easily accessible population of healthy people in the vicinity.
These epidemiological studies can rapidly produce findings leading to the protection of the
community health and the effective planning of health authorities. They also provide
stimulating opportunities for in-service training of local health teams.
The case-control study requires the selection of two groups, a case group who have the
disease and a control group without the disease. The history of exposure to the source(s) of
disease and suspected risk factors are investigated in both cases and controls using a
standardized questionnaire. The results can be arranged in 2x2 tables, one table for each
source and suspected risk factor. Thus the prevalence of exposure in both groups for each of
the exposures and suspected risk factors are compared. If a suspected factor is associated
with the outbreak, then the prevalence of exposure to this factor will be higher in cases
(people with disease) than in controls (people without disease). In case-control studies the
odds ratio (OR) is the measure of the strength of association between the exposure and
disease, and the statistical significance of the association can be tested using the chi-square
statistic.
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To conduct a case-control study, cases, controls and suspected risk factors must be
selected by the investigator. Cases should be verified using the case definition for the
investigation. Cases and controls should be comparable in factors that are not under study.
For comparability, controls should be representative of the population from where the cases
derive. It is important that all study factors be measured in the same way for both cases and
controls. The number of suspected risk factors included in the study should be kept to a
necessary minimum for testing the hypotheses. The selected study factors and their
categories should have been field-tested prior to use and operational definitions of each
should be included with the study survey. This survey form should be field-tested before
being used with cases and controls.
A basic analytical tool for case-control studies is the 2x2 table. These case-control study
tables have the following components (Table 5.7):
TABLE 5.7 CROSS-TABULATION TABLE FOR A CASE-CONTROL STUDY
Case
Control
Exposed
a
b
a+b
Not
Exposed
c
d
c+d
a+c
b+d
n
a = number of exposed cases
b = number of exposed controls
c = number of unexposed cases
d = number of unexposed controls
a + c = case total
b + d = control total
a + b = exposed total
c + d = unexposed total
n = a + b + c + d== total cases and controls
For case-control studies, the prevalence of exposure of the cases and the controls are
compared:
a
Prevalence of Exposure in the Case Group
=
ac
Prevalence of Exposure in the Control Group =
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If the suspected factor is a true risk factor, then the prevalence of exposure to this factor
will be higher in cases than in controls. The statistical significance of the association
between exposure and disease is determined with the chi-square test:
χ
2

n.(ad  bc) 2
(a  c).(b  d).(a  b).(c  d)
If this statistic is greater than 3.84, then the null hypothesis is rejected and it is
concluded that there is an association between exposure and disease, with statistical
significance lower than 5%.
The odds ratio (OR) is computed as the ratio of cross-products in the 2x2 table:
OR 
ad
bc
The odds ratio (OR) is the measure that we can calculate for case-control studies and is
a good estimate of the relative risk for rare diseases (prevalence<10%). An OR= 1 indicates
that there is no association between exposure and disease; an OR greater than 1 indicates an
association between exposure and increased risk, and an OR less than 1 indicates a
protective association between exposure and risk of disease.
Let us consider the following example. During the second week of an outbreak of
listeria infection the possibility that exposure to unpasteurized butter was a determinant of
the outbreak was examined. A case-control study was conducted with 40 cases and 120
selected controls of the community. The results were the following:
Exposed
Not
Exposed
Case
31
Control
61
9
59
40
120
92
68
160
Prevalence of Exposure in Case Group:
31
 100  77 .5%
40
Prevalence of Exposure in Control Group:
61
 100  50 .8%
120
As an example, to explore the association between unpasteurized butter and listeria
infection we design a case-control study with the following results (listeria infection is
rare):
Using the chi-square statistic we have
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X2 
31
160  [(31  59 )  (61  9)] 2
 8.73
40 120  92  68
Because 8.73 is greater than 3.84, we conclude that there is a statistically significant
association between exposure to the unpasteurized butter and the presence of listeria
infection (p<0.05).
The odds ratio between exposure to unpasteurized butter and the listeria infection is:
OR 
31  59
 3.3
61  9
In short, the case-control study found a statistically significant association between the
consumption of unpasteurized butter and the presence of listeria infection; furthermore, the
group who consumed unpasteurized butter had approximately 3.3 times the risk of
developing listeria infection compared those that did not consume the unpasteurized butter.
Outbreaks in confined quarters such as hotels, ships, hospitals, schools and barracks
occur with relative frequency. Outbreaks often occur in social activities where exposure to a
single common source is suspected, usually a contaminated food. In such situations where
the entire at-risk population is well-defined, a cohort study can be readily used for the
investigation. For a cohort study of outbreaks, a standardized survey is applied to the entire
population at risk (sick and not sick) to determine history of exposure to each suspected risk
factor. Then the attack rates between exposed and unexposed groups for different exposures
are compared. The exposure with the largest attack rate in the exposed will often be the
source of illness. The following is a 2x2 table for cohort studies:
TABLE 5.8 CROSS-TABULATION TABLE FOR A COHORT STUDY
Cases
Non
Cases
Exposed
a
b
a+b
Not Exposed
c
d
c+d
a+c
b+d
n
a = number of exposed cases
b = number of exposed non-cases
c = number of not exposed cases
d = number of not exposed non-cases
a + b = total exposed
c + d = total not exposed
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a + c = total number of cases
b + d = total number of non-cases
n = a + b + c + d== total number of exposed and not exposed
Cohort studies compare attack rates in people exposed and not exposed:
Attack Rate among Exposed People
=
Attack Rate among Not Exposed People
a
ab
=
c
cd
If the exposure is a risk factor for disease, then the attack rate or incidence rate will be
higher in the exposed people than in the not exposed people. The statistical significance of
the association between exposure and disease can be tested with the chi-square test. The
measure of the strength of association for a cohort study is the relative risk (RR), the ratio
of the incidence rates of exposed persons to unexposed as follows:
RR 
a/(a  b)
c/(c  d)
Using the outbreak example in Exercise 5.2, we have 192 participants at a technical
meeting with information collected using a survey on what foods they consumed during the
first three days. The results for the ham and cheese sandwich served during the afternoon
break on the second day of the meeting are presented below:
Case
Exposed
Not
exposed
89
Noncase
23
19
61
108
84
112
80
192
Attack Rate among Exposed People=
89
100  79 .5%
112
Attack Rate in Not Exposed People=
19
 100  23 .8%
80
To determine the statistical significance of the association between eating the sandwich
and diarrhea we use the chi-square statistic, as follows:
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χ2 
33
192  [(89  61)  (23 19 )]2
 58 .86
108  84 112  80
Because 58.86 is much greater than 3.84 (p<<.05), we conclude that there is a statistically
significant association between exposure to the ham and cheese sandwich and the presence
of acute diarrheal disease. The strength of this association is measured by the relative risk as
follows:
RR 
79 .5%
 3.3
23 .8%
Findings indicate that the group who consumed the sandwich had 3.3 times greater risk
of developing diarrhea than those who did not eat it.
8. Implement specific control measures
All available evidence should be considered to plan final control measures, including
information on outbreak characteristics and the effectiveness of the earlier control measure.
Sources of disease should be removed, isolated, suppressed or eliminated. In person-toperson transmission, control measures should be directed toward patients and the protection
of susceptible persons, such as immunization, treatment, and prophylaxis. Health education
and promotion campaigns can be very effective in control and prevention of future
outbreaks and epidemics.
9. Evaluate the efficacy of the control measures
The epidemiological field study should also monitor and evaluate control measures. We
should continue surveillance of disease as an outcome measure of evaluation, being
especially watchful for modifications in disease patterns. Control measures can be evaluated
by comparing observed disease patterns and trends with expected disease patterns and
trends if control measures were effective.
10. Prepare a technical report of the field study
During the investigation and implementation of control measures for the outbreak,
valuable information is generated. The health team involved in the outbreak is advised to
synthesize this information into a consistent, understandable, and convincing technical
report that documents the process and its context. The technical report is an instructional
document disseminated to agencies and institutions responsible for public health. It is an
ideal teaching tool.
The technical research report should include an introduction and background,
justification, materials and methods, results, discussion, recommendations, control
measures, and references. It should communicate the results in a scientifically objective way
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using clear and convincing language and justify the appropriate recommendations for
action. The technical report can also serve as basis for the publication of a scientific article
to contribute to the knowledge of epidemiology and public health. It also serves as a guide
for presentations and summaries for local authorities, press and the general public.
This Unit is accompanied by the Comprehensive Exercise in Epidemiologic
Field Study: “Outbreak of icteric disease in a rural area”
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Unit 5.1:Field Epidemiology: the Study of Outbreaks
Annex: Supplementary Readings
Complementary Reading No. 1:
Classic methods in epidemiological research
Cholera Epidemic in London
John Snow (1813-1858)
Adapted from: Terris M. Bank of epidemiology exercises; New York Medical School, 1967.
The problem
Cholera was not recognized outside of India until almost 1820 when it spread widely throughout
the world, causing numerous epidemics. One such cholera epidemic occurred at the end of August
in 1854 in a subdistrict of the city of London. As a result of thorough study, John Snow formulated
a hypothesis of the transmission of disease and produced recommendations for its control. Below is
an extract of the classic and fascinating monograph of Snow “On the Mode of Communication of
Cholera”, second edition, 1854 (Snow on Cholera. The Commonwealth Fund, New York, 1936),
which allows the reader to see how Snow compiled evidence and how it was evaluated.
“...A long time would be needed to report the advance of cholera in different parts of the world, in
some of which it produced great devastation, while it passed lightly through others, and even left
some untouched. Unless this account could be accompanied by a description of the physical
conditions of the places and the habits of the people, which is impossible, it would be of little use
to attempt this. However, there are certain circumstances related to the progression of cholera that
can be established as general rules. Cholera spreads through the major routes of transit, never as
rapidly as people do, but almost always more slowly. Its exact route between one town and another
cannot always be mapped, but it never has appeared in places where it could not have been taken
by the movement of people.”
Person-to-person transmission
“There are also countless examples that convincingly show the transmission of cholera by
individual or unique cases; these examples are free of any source of error, as will be seen below. I
went to take reports on the death of the wife of a worker that occurred at New Leigham Road,
Streatham. I knew that one of her sons had traveled to its house afflicted with an intestinal disease,
of which he died one or two days later, on 18 August. His mother, who had attended him, began to
feel ill the next day and died one day later, on 20 August. During the disease of the lady, whose
family name was Barnes, her mother (who lived in Tockwith, a healthy community five miles from
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Moor Monkton) was called to care for her. She arrived at house of her daughter and remained for
two days caring for her and washing her linens, after which she returned to Tockwith in apparently
good health. However, while on the road she became ill and collapsed. She was transported home
and placed in bed beside her husband; he and a daughter who lived with them acquired the disease
and all three died in the course of two days. A nurse who attended the patient became ill and died
when she returned to her house, near Everton. The nurse who attended her also was attacked and
died. No case had occurred beforehand in that neighborhood and none appeared in the next fifteen
days.”
“In addition to the aforementioned facts, which demonstrate that cholera is transmitted from one
person to another, there are others that show: first, that living with a patient in the same room and
attending the patient does not necessarily expose the person to the action of the morbid poison; and
second, that it is not always an indispensable requisite that the person come very close to the
patient to be attacked, because the morbid matter can be transmitted over a distance. If it is
accepted that cholera is a contagious or communicable disease, it should spread through the
effluvia that emanate from the patient into the air that surrounds the patient and penetrating the
lungs of those who inhale them. This assumption has produced very contradictory opinions about
the illness. However, by reflecting a little we can see that we do not have the right to limit the ways
by which a disease can spread, since the communicable diseases of which we have correct
knowledge spread in very different ways, as occurs with pruritus and other diseases of the skin,
syphilis, and intestinal parasitic infestations, all which have ways of spreading that differ from each
other.”
Spread of the morbid material through the digestive tract
“Considering the cholera pathology, it is possible to find the way in which it is transmitted. If it
started with fever or any other general symptom, we would not obtain any clue about the route of
entry of the morbid substance into the organism; it could enter by the digestive tract, lungs, or in
some other form; however, this point must be determined by circumstances unrelated to the
pathology of the disease. From all that I have been able to learn about cholera, both by personal
observation and from the descriptions of other authors, I can state that cholera starts invariably with
disorders of the digestive system that often are preceded by only mild malaise, which makes the
patient not realize the danger that he is running, or to consult, or to request advice about his health
until the disease is already very advanced. In truth, there are few cases that present dizziness,
intense weakness, and general abatement before the gastrointestinal discharges appear. However,
there is no doubt that these symptoms depend on exudation from the mucous membrane, which
immediately is abundantly evacuated. In all cases of cholera that I have attended, the loss of fluids
from the stomach and intestine was sufficient to produce collapse; the previous general condition of
the patient should be taken into account together with the abrupt appearance of fluid loss and the
fact that absorption processes seem to have been suspended.”
“We have seen that cholera starts as a disease of the digestive tract, and that at the beginning of the
disease, the blood is not under the action of any poison; as a result, it can be thought that the
material or morbid substance that produces the disease penetrates the organism by the digestive
tract, being swallowed accidentally by people who would not swallow it purposely; the increase of
this morbid substance or poison must then be carried out in the stomach and intestine. It would
seem that when the aforementioned poison is produced in sufficient quantity, it acts as an irritant
for the gastrointestinal mucous membrane; or, what is more likely, by removing fluid from the
circulating blood of the capillaries by a mechanism analogous to that which the epithelial cells of
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several organs use to absorb different secretions in the healthy body. Since the morbid substance of
cholera has its own way of reproducing, it must have a structure similar to that of a cell. This
viewpoint is not contradicted by the fact that the cholera poison cannot be recognized by
microscope, since the materials of chickenpox and chancre can only be recognized by their effects,
and not by their physical properties.”
“The time elapsed between the entry of the morbid substance into the organism and the beginning
of the disease is called the incubation period, which is actually the period of reproduction of the
morbid substance; thus, the disease results from the action of a small quantity of poison initially
introduced. In cholera, this incubation or reproduction period is much shorter than in other
epidemic or communicable diseases. Such a short incubation period, as well as the amount of
morbid substance transported in the feces, means that sometimes cholera spreads with a speed
unknown in other diseases.”
Cholera near the Golden Square
“The most terrible outbreak of cholera that has occurred in this kingdom is probably the one that
appeared on Broad Street (Golden Square) and contiguous streets a few weeks ago. Within 250
yards of the place where Cambridge Street joins Broad Street, 500 fatal cases of cholera occurred
in a period of ten days. Such a high mortality in such a small area had never occurred in the
country, not even in the time of the plague; its appearance was very fast and a large number of
cases died within a matter of hours. The mortality surely would have been greater if the population
had not fled. The first ones to escape were those who lived in inns, followed by those of other
houses; they abandoned their furniture and household effects that they had moved after finding a
place where to store them. Many houses were closed upon the death of their owners and a large
number of merchants sent their families away; thus, in less than six days after the onset of the
outbreak, the streets most attacked were deserted, with only one fourth of their inhabitants.”
”There were a few cases of cholera on the last days of August among the neighbors of Broad Street
(Golden Square); the outbreak that started on the night between 31 August and 1 September was, as
in similar examples, only a violent increase of the disease. As soon as I learned about the existence
and spread of cholera, I thought about the contamination of the water from the pump most
frequented on Broad Street, which is located near the corner with Cambridge Street; but upon
examining the water on the afternoon of 3 September, I found so few impurities of an organic
nature that I refused to draw that conclusion. However, later research demonstrated to me that there
were no other circumstances or common agents that could explain the rapid increase confined to a
certain locality and not disseminated to others, except for the water from the aforementioned pump.
I also found that the amount of organic impurities in the water in the form of white particles, which
were visible to the naked eye when examined closely, varied on the next two days; this suggested to
me that at the beginning of the outbreak, the water was even more impure. I decided to request
permission from the General Office of Registry to prepare a list of all those dead from cholera in
the subdistricts of Golden Square—Berwick, St. Ann, and Soho—during the week that ended on 2
September, and was kindly given permission. In the three subdistricts, 89 deaths were registered
during that week; of these, only 6 occurred on first four days of the week and 4 on Thursday, 31
August; the remaining 79 occurred on Friday and Saturday. Thus, I had to assume that the outbreak
had started Thursday and I carefully investigated the 83 deaths that occurred on the last three days
of the week.”
”Examining the area, I found that almost all the deaths had occurred in the houses close to the
Broad Street well, and that only l0 deaths had occurred in houses closer to the wells of other
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streets. In 5 of these cases, the relatives of the dead informed me that they always fetched water
from the well on Broad Street because they preferred it, despite having other wells closer to their
households. Another 3 of these cases were children who attended school close to the well
mentioned; in 2 of them it was confirmed that they drank this water and the parents of the third
child thought that their child also drank it. The other 2 deaths that occurred in the district distant
from the well mentioned represented the mortality from cholera that occurred before the outbreak
started. Upon reviewing the deaths that occurred in the vicinity of the Broad Street well, they
informed me that 61 of those who died took water from the aforementioned well, either regularly or
occasionally. In 6 cases I could not obtain any information about this point because the people
connected with the death had gone elsewhere; in another 6 cases I found that the people who died
had not taken water from that well before becoming ill. The investigation demonstrated that there
was no increase or other cholera outbreaks in this part of London, except in people who had the
habit of taking water from the well mentioned.”
“On the afternoon of Thursday, 7 September, I had a meeting with the Council of Guards of the
jurisdiction of St. James and I described and explained the circumstances. As a result of what I told
them, they removed the pump handle from the well the next day. The Table shows the chronologic
features of this terrible cholera outbreak:”
“date
August 19
20
21
22
23
24
25
26
27
28
29
30
31
September 1
2
3
4
5
6
7
8
9
10
No. of
fatal
cases
1
1
1
0
1
1
0
1
1
1
1
8
56
143
116
54
46
36
20
28
12
11
5
deaths
1
0
2
0
0
2
0
0
1
0
1
2
3
70
127
76
71
445
37
32
30
24
18
Date
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
unknown date
TOTAL
No. of
fatal
cases
5
1
3
0
1
4
3
3
0
0
2
1
1
1
1
1
1
0
0
0
45
617
deaths
15
6
13
6
8
6
5
2
3
0
0
2
3
0
0
2
0
2
1
0
0
1016
”Of the 56 cases that appeared on 31 August, it is certain that very few started in the late hours of
the afternoon. The appearance of the outbreak was extremely rapid (as I was informed by a
physician who lives in the center of the district where the attack occurred) and began in the night
between 31 August and 1 September. Only a few of those who became ill in the first three days
presented a history of diarrhea and the physicians who attended them informed me that very few
recovered.”
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“The first of September—immediately after the onset of the outbreak—was the day on which the
largest number of cases (143) occurred; a day later, the number declined to 116, and on the
following day, to 54. When studying the table, we see that the number of cases continued to
decrease day by day. On 8 September, the day on which the pump handle was removed, 12 cases
occurred; on day 9, 11 cases; 10, 5 cases; 11, 5 cases; and on day 12 only 1 case. After this, no
more than 4 cases occurred on the same day. As the epidemic declined, the daily deaths were more
numerous than the new cases and they occurred in people who had suffered fever for several days.
There is no doubt that mortality declined, as I already mentioned, due to the flight of the population
as soon as the outbreak appeared. Nevertheless, the attacks only decreased until use of the water
was stopped; this makes it impossible to determine if the well continued to contain the cholera
poison in active state, or, by some cause had been freed of it.”
“There is a beer brewery on Broad Street, near the well, where none of the workers died of cholera.
When I found out about this I visited Mr. Huggins, the owner of the brewery, who informed me that
he had close to 70 men working in the brewery, of which none suffered cholera, or at least the
severe form, and only 2 workers felt mildly indisposed when the disease was prevalent. The men
were assigned an amount of malt liquor and Mr. Huggins believed that they did not drink water at
all and did not use water from the Broad Street well.”
“A survey conducted among 418 people of the 896 residents on Broad Street revealed the relations
between the disease and consuming water from the incriminated pump, as follows: among the
consumers, 80 became ill and 57 did not; among the people who did not take water from the Broad
Street pump, 2 became ill and 279 did not become ill. This means that among the patients with
cholera, the relation between consumption and nonconsumption was 80/2. Among those who
escaped the disease, the relation was 57/279.”
became ill
did not
become ill
consumed water
80
57
137
did not consume
water
2
279
281
82
336
418
“The total case rate [attack rate] was 19.6% (82/418x100). In order to establish the importance
of the water pump as a source of contamination, it is necessary to compare the case rate of those
who took water with the case rate of those who did not take water:”
80
100  58%
137
2
care rate among those who did not consume water 
100  0.7%
case
281
case rate among those who consumed water 
case
relative risk =
58 %
 82 .9
0. 7 %
“This study demonstrated the transmission by water of the outbreak.”
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“While contamination of the water of Broad Street with the evacuations of the disease exactly
explains the terrible outbreak of the jurisdiction of St. James, there is no other circumstance that
offers another explanation, no matter what hypothesis is adopted about the nature and cause of the
disease....”
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Complementary Reading No. 2:
Contemporary methodology of epidemiologic investigation
Legionnaires’ Disease
Adapted from Sharrar RC. Legionnaire’s disease: stalking a killer epidemic. A scientific detective team
discovers the Philadelphia Killer. Encyclopedia Britannica, Book of Science and the Future, 1979.
The problem
When the American Legion Convention of the State of Pennsylvania, which had been convened
from 21 to 24 July 1976 at the Hotel Bellevue Stratford in Philadelphia, was almost reaching its
end some of the participants became ill. Almost all of them attributed it to the intense program of
the convention.
Upon returning to their respective cities, however, some of them complained about headache, high
fever, chills, a dry cough, and muscular pains, symptoms of acute infectious disease. On the 27th of
July, an elderly legionnaire died in Athens, Pennsylvania. However, not much attention was paid
to the case because the individual suffered heart problems. By Friday, the 30th of July, five more
legionnaires had already died and others had been hospitalized. Over that weekend five more died.
On the morning of Monday, the 2nd of August, the epidemiologist of the State of Pennsylvania
called the head of the Unit of Communicable Disease Control of the Department of Health of
Philadelphia and declared an alert for the entire State. The alert stated that “there have been 11
deaths due to pneumonia recorded and all the people who died attended the American Legion
Convention last week in Philadelphia.”
In that same period, the country was preparing to combat a possible epidemic of swine flu and the
public health authorities in all the states were preparing to implement a federal program of mass
vaccination. The epidemiologists immediately considered swine flu and initiated epidemiological
investigations as recommended by the Centers for Disease Control in Atlanta, Georgia. The search
involved the participation of hundreds of people from various professions and became the most
intense epidemiological investigation carried out in the modern history of medicine since the
advent of AIDS.
Beginning the search
As a response to the extensive coverage provided by the communications media, which called this
respiratory disease “Legionnaires’ disease” and the “Philadelphia Killer”, each suspected case was
reported and investigated. The existence of an epidemic was confirmed rapidly. However, it was
impossible to confirm the diagnosis with laboratory tests because the pathogen was unknown.
Many cases of pneumonia were being reported to the health authorities and it was necessary to
distinguish between disease from the outbreak and other diseases. Therefore, the investigators
established a case definition: the first symptoms occurred between the 1st of July and the 18th of
August 1976, including a fever of 39ºC or more and a dry cough, or fever and pneumonia
confirmed by x-rays of the lungs. This clinical definition was very broad and included symptoms
that could be attributed to a virus, bacterium, rickettsia, fungus, or a chemical toxin. Thus, the
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following was added to the case definition: an individual had to have attended the American Legion
Convention or to have been in the Bellevue Stratford Hotel, headquarters of the convention and
principal site of the meeting, after the first of July.
Those falling under the case definition were called “cases of legionnaires’ disease.” One other case
definition was also used: Cases with pneumonia and were a block from the hotel on Broad street,
the principal access to the hotel, were “cases of Broad Street pneumonia”. All the other cases
occurring in Philadelphia were classified as common pneumonia.
The people who participated in the July convention came from every corner of the State and could
be classified into four groups: delegates with the right to vote, non-delegates, relatives of the
participants and members of the Women’s Auxiliary Group. The latter was holding its 56th Annual
Convention concurrently. Participants were lodged primarily in five main downtown hotels. Most
of the activities of the American Legion Convention took place in the Bellevue Stratford Hotel,
while those of the Women’s Auxiliary Group were held in the Benjamin Franklin Hotel, about
seven blocks away.
The legionnaires rarely ate or drank in the restaurants and bars of the hotel. Instead, they frequented
the restaurants around the hotel and drank at their private meetings, so it was very difficult to
identify all the activities in which they participated over the four days.
The hotel building had several intermediate floors with storerooms, restaurants, bars, offices, a
ballroom and meeting rooms. Between floors 2 and 16 there were 725 guest rooms. Floor 18 had
several conference rooms and a banquet hall. Under the vestibule there were three more floors: the
kitchen, the basement containing several cabinets and storerooms, and the lower basement with an
incinerator, machine room, water coolers for the air conditioning system, electric power
distribution equipment, sewer pipes and water pumps. Finally, on the terrace of the hotel was the
chimney of the incinerator, several air outlets and an air conditioning plant.
The air conditioning system was investigated because it could potentially disseminating pathogens
by air. A child had tossed powder used by magicians in an air conditioning outlet of the hotel a
week before the convention. The powder was examined and it was found to be innocuous. The
drinking water in the hotel, originating from the Philadelphia municipal system was also examined.
In addition, detailed inspections of kitchens, elevators and waste and sanitation equipment were
made and samples of suspicious substances were collected throughout the hotel. The bars and
restaurants located outside the hotel were also thoroughly examined. By the 6th of August, 22
people had died and 130 had been hospitalized.
Characteristics of person, place, and time
The investigators needed information on cases and all others who had attended the Convention.
Neither the American Legion nor the hotels could identify with certainty all of the Convention
participants. Accordingly, a survey was conducted to determine who had attended the Convention
and their activities during the Convention, with questions such as “were you sick before attending
the convention?”, “when did you begin to feel ill?”, “what room did you stay in?” and “what
restaurants did you go to?” Ten thousand two-page questionnaires were delivered to the 1002
American Legion posts throughout the State. The commanders of each post received instructions to
deliver the questionnaire to each participant so that they could fill it out and return it.
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To determine if the outbreak was citywide, investigators reviewed the admissions records of three
downtown hospitals and those of patients seen for diseases similar to the legionnaires’ disease in
the emergency services of 11 hospitals. The number of deaths from pneumonia and flu reported
weekly was compared with the corresponding weeks of the three previous years. None of the
studies showed a notable increase in the number of cases of pneumonia in Philadelphia.
Apparently, the legionnaires’ disease outbreak was not citywide.
Other studies were conducted to determine if the problem of legionnaires’ disease was continuing.
No secondary cases were detected among the relatives of the Convention participants or among the
medical personnel who attended the outbreak cases at different hospitals. Fortunately, it appeared
that the disease was not transmitted person-to-person. The people who stayed at the four hotels
between the 6th of July and the 7th of August were surveyed to determine if new cases were
occurring. No new cases were verified among the guests who arrived after the week of the 18th to
the 24th of July, the week of the Convention. The findings indicated that legionnaires’ disease
outbreak was not continuing and was limited to the dates of the Convention.
Based on the investigations and a flow of information from medical and hospital sources, a clear
clinical description of Legionnaires’ disease was gradually pieced together. The typical case started
from 2 to 10 days after being exposed to the agent (incubation period) and the majority of the
victims became ill after returning home. The first symptoms consisted of malaise, muscular pains,
headache, and a dry cough. Shortly afterwards, a fever of 39 to 41ºC and chills appeared. Many
patients had symptoms of respiratory distress, chest pain and gastrointestinal disorders. In general,
they saw a physician two or three days after the onset of symptoms. At that time the chest X-ray
revealed abnormal respiratory sounds, but up to that time there were no signs of condensation,
when the lung tissue fills with fluid and cellular matter as in the case of pneumonia. More than
80% of the cases were hospitalized and 29 patients died, which represented a case-fatality rate of
16%. Deaths occurred mainly in elderly patients who had chronic diseases and short incubation
periods for legionnaires’ disease. Patients treated with erythromycin and tetracycline had greater
odds of surviving.
Laboratory test results for cases did not help in diagnosis. Lab findings included some
abnormalities that indicated a recent infection, but the information was not specific. Symptoms of
low blood oxygen saturation were observed. Ninety percent of the cases had abnormal chest
radiographs, mainly lung edema, that terminated with general condensation of the lungs. About
50% of the most advanced cases presented radiographic abnormalities in a single lung. On
examining the lungs of the dead, several inflamed and condensed areas were observed that
suggested a diagnosis of pneumonia. No abnormalities were observed in any other organ or system.
Figure 5.1A shows the distribution of cases in time and the epidemic curve for the 182 cases
classified as legionnaires’ disease and the 39 cases of Broad Street pneumonia. The cases of
legionnaires’ disease included 149 Convention participants and 33 non-participants. The similarity
of the two curves indicated that both groups were part of the same outbreak. The persistence of the
disease among people who did not participate in the Convention during the first part of the month
of August indicated that the source of infection remained active but less intense.
In Tables 5.1A and 5.2A, the results of the survey among the legionnaires are presented. Table
5.1A shows the case rate by subgroup of participants and place of lodging. The 3,683
questionnaires processed included those of 1,849 delegates. Based on the number of delegates who
voted in the Convention, it is estimated that between 80% and 85% of the forms were returned. The
table also shows that the attack rate was higher among the delegates and their families and lower
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among the non-delegates and the members of the Women’s Auxiliary Group. This group held its
meetings seven blocks away from the Bellevue Stratford. The guests of hotel “A”, the Bellevue
Stratford, had the highest attack rate. Table 5.1A shows the attack rate by age and sex. This
increased with age and was greater for men than for women. The general attack rate was 4%.
Source and mode of transmission
Findings from the investigation conducted after the Convention among the relatives of the
legionnaires indicated no person-to-person transmission. Likewise, there was no cluster of cases
within rooms of the hotel, as would have been expected if the transmission were person-to-person.
Number
of Cases
cases
FIGURE 5.1A EPIDEMIC CURVES FOR LEGIONNAIRES’ DISEASE
6
Broad Street
Broad
Street
pneumonia
Pneumonia
5
4
3
2
1
0
26
Legionnaires’
Legionnaires'
disease
Disease
24
Convention Participants
Convention Non-Participants
22
20
Convention
Number of
Cases
cases
18
16
14
12
10
8
6
4
2
0
6
7
8
9
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 1 2
JUL
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17
AUG
July
August
no participantes participantes
A study of the 28 restaurants and bars in the neighborhood of the Bellevue Stratford found no
associations between consumed food and drink and risk of disease. Likewise, the investigation of
the two banquets at the Convention also yielded no association between consumed food and drink
and risk of disease. Though a case-control study found that cigarette smokers had a greater risk of
contracting disease, smokers were generally more susceptible to respiratory tract disease. No link
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was found between disease and consumption of alcoholic beverages or drinking water in the
Bellevue Stratford. Likewise, the investigators found no association between insect bites or
exposure to animals and disease.
With no evidence emerging to point to the source of disease, speculators filled the gap with favorite
theories like sabotage, biological warfare, several toxins and even paranormal and occult
phenomena. The news media drew attention to some of these theories. Unfortunately, none of these
speculations were supported by the epidemiological, clinical, and laboratory evidence.
TABLE 5.1A LEGIONNAIRES’ DISEASE DISTRIBUTION BY TYPE OF
PARTICIPATION AND LODGING
Category
Number of
Cases
Number of
Responses
Attack Rate (%)
Delegate
Auxiliary
Companion
Non-Delegate
Stranger
Total
125
4
17
3
0
149
1,849
701
268
762
103
3,683
6.8
0.6
6.3
0.4
0.0
4.0
Hotel A
Hotel D
Hotel E
Hotel F
Hotel G
Another Hotel
House
Stranger
Total
75
21
19
12
4
7
8
3
149
1,161
1.046
403
312
104
210
294
153
3,683
6.5
2.0
4.7
3.8
3.8
3.3
2.7
2.0
4.0
TABLE 5.2A LEGIONNAIRES’ DISEASE DISTRIBUTION BY SEX AND AGE
Category
Number of
Cases
Number of
Responses
Attack Rate (%)
less than 40 years
40 to 49 years
50 to 59 years
60 to 69 years
70 and more years
Unknown
Total
11
25
58
36
19
0
149
610
805
1,428
538
254
48
3,683
1.8
3.1
4.1
6.7
7.5
0.0
4.0
Male Sex
Female Sex
Unknown
Total
123
26
0
149
2,292
1,380
11
3,683
5.4
1.9
0.0
4.0
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Identification of the agent
The search for the cause of Legionnaires’ disease involved obtaining and analyzing hundreds of
biological samples from patients. The search for a possible microbiological agent included nine
methods of visual microscopic screening, 14 different culture media to isolate bacteria and fungi,
and 13 host systems for isolating viruses. In addition, tests of blood sera were made with 77 known
infectious agents to seek the presence of antibodies. Tissue and urine samples were examined to
detect abnormal concentrations of over 30 metals and several toxic organic compounds. Though
these tests excluded many causal agents, none was able to identify the cause of Legionnaires’
disease. One by one, all known agents were excluded as possible causes of legionnaires’ disease.
At the end of December in the year of the outbreak, two microbiologists from the Division of
Leprosy and Rickettsiae in the Centers for Disease Control, Joseph E. McDade and Charles C.
Shepard, in tissue samples isolated a new agent suspected as the cause of legionnaires’ disease.
These findings were published in January 1977.
The agent was isolated with the laboratory techniques commonly used to detect rickettsiae.
Samples of lung tissue from a dead victim were homogenized and injected in guinea pigs. After a
period of incubation of one to two days, the young guinea pigs presented symptoms of fever, teary
eyes and prostration. Suspensions from the spleen of the symptomatic animals were prepared and
used to inoculate chicken embryo vitelline sacs. These embryos died after 4-6 days and microscopic
examination of stained sections of the vitelline sac revealed rod-shaped bacteria. Once the causal
agent was isolated, a laboratory test was developed to detect the presence of antibodies to the agent
in the blood serum of cases. This test could detect disease events long after the disease was
resolved. Thus, five and a half months after the epidemic began the epidemiologists finally had a
laboratory test that could confirm diagnoses. In the year after the outbreak, using the new blood test
for this disease the following findings were reported:
1. The bacterium was isolated in five cases of pneumonia recorded in Philadelphia, 4 met the
investigators’ case definition of legionnaires’ disease and one was a Broad street pneumonia
case.
2. The antibody assay showed that more than 90% of the cases of legionnaires’ disease and 64%
of the cases of Broad street pneumonia from specimens of blood serum were positive for the
pathogen.
3. The samples of blood serum of patients who were exposed for a single day on the 21st , 22nd or
23rd of July, and two of the nine victims of the disease who attended another meeting in
Philadelphia from August 1st to the 8th confirmed the existence of a recent infection of this
disease, indicating that the source of infection infected persons for at least two weeks.
4. Blood samples were collected from over 500 people who lived or worked in central
Philadelphia to determine the prevalence of antibodies against the bacterium. The studies
demonstrated that less than the 5% of the general population had an appreciable concentration
of antibodies of that class. Testing at the national level of patients diagnosed with pneumonia
of non-bacterial origin found that 1% to 2% of these cases could be legionnaires’ disease.
These studies found that legionnaires’ disease was caused by a biological agent and not by a toxin
and that the victims of Broad street pneumonia who never entered the Bellevue Stratford were part
of the epidemic. It was concluded that the period of exposure of the microorganism was at least two
weeks. Although this bacterium can cause major epidemics, it maintains a low endemic level. It’s
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improbable that this pathogen would maintain high rates of disease continually in a given
geographic region.
Protection of the public
The investigation initiated in August 1976 finally led to the discovery of a biological pathogen that
until then had been unknown. Later studies revealed that this organism has caused epidemics in the
past and that it has low-grade endemic activity during the year over a broad geographical area.
Current situation
With time, legionnaire’s disease was recognized as an acute bacterial disease with two clinicalepidemiological manifestations:


Legionnaires’ disease
Pontiac fever
Pontiac fever is not associated with pneumonia or death and patients recover spontaneously within
2 to 5 days without treatment; it’s more similar to an allergic reaction elicited by inhaling an
antigen than a bacterial invasion.
The responsible pathogen, a gram-negative bacillus, was named Legionella pneumophila. Eighteen
serogroups of L. pneumophila are currently recognized. The one most associated with disease is
serogroup 1.

The earliest known case of legionnaire’s disease occurred in 1947 and the earliest known
outbreak occurred in 1957 in Minnesota. The disease has been identified in North America,
Australia, Africa, South America and Europe. Cases and sporadic outbreaks occur
throughout the year, although it is more common in summer and fall. The attack rate of
legionnaires’ disease in community outbreaks generally ranges from 0.5% to 5%. On the
other hand, Pontiac fever has shown a high attack rate of around 95% in several outbreaks.
The pathogen’s primary reservoir is water. It frequently spreads through hot water systems such as
showers. The mode of transmission is through the air. The incubation period can range from 2 to
10 days but most often falls between 5 to 6 days.
Person-to-person transmission is not significant. The disease appears in older patients; the majority
of cases are at least 50 years old. It’s more likely to cause disease in smokers, patients with chronic
diseases and men, with a man-woman ratio of 2.5:1. It is extremely rare in people under 20 yearsof-age, though some outbreaks have been recorded in hospitalized patients in this age group.
There are now effective control measures and treatment for the disease. The investigation of the
legionnaires’ disease outbreak demonstrates how epidemiology can clarify problems early and lay
the foundation for control and treatment even when the disease is not fully understood.
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Second Edition, MOPECD 2001
Special Program for Health Analysis.
Pan American Health Organization
MOPECD Unit 5: Epidemiologic field study
Second Edition, MOPECD 2001
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Special Program for Health Analysis.
Pan American Health Organization