EPID 600; Class 13

Outbreak! Concepts in infectious disease

epidemiology
University of Michigan School of Public Health

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 Infectious disease

“An illness due to a specific infectious agent or its toxic

products that arises through transmission of that agent or
its products from an infected person, animal or inanimate
reservoir to a susceptible host; either directly or indirectly
through an intermediate plant or animal host, vector or the
inanimate environment”

Benensen AS, editor. Control of Communicable Diseases Manual. Sixteenth Edition, 1995. 2
 Dynamics of disease transmission

HOST
Epidemiologic
Triad

VECTOR

AGENT ENVIRONMENT

Human disease results from interaction between the host, agent and
the environment. A vector may be involved in transmission.
Host susceptibility to the agent is determined by a variety of factors,
including genetic background, nutritional status, vaccination, prior
exposure, context

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 Factors associated with increased risk of
human disease
Host Characteristics Agent Environmental Factors

Age Biologic (Bacteria, viruses) Temperature

Sex Chemical (Poison, smoke) Humidity
Race Physical (Trauma, radiation) Altitude
Occupation Nutritional (Lack, excess) Crowding
Marital Status Housing
Genetics Neighborhood
Previous Diseases Water
Immune Status Food
Air Pollution

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 Modes of disease transmission

The potential for a given agent to cause an outbreak depends

on the characteristics of the agent, including the mode of
transmission of the agent

Two basic modes of transmission

Direct
Indirect

Certain diseases can be transmitted directly or indirectly

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 Direct mode of disease transmission

In an infectious setting, immediate and direct transfer of an

agent to a host by an infected person or animal
Touching, biting, or sexual intercourse are classic examples
Measles virus: airborne by droplet spread or direct contact
with nasal/throat secretions of infected persons

In a noninfectious setting, the host may have direct contact

with the agent in the environment
Children ingesting lead paint from playground equipment

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 Indirect mode of disease transmission

Vehicle-borne
Transmission through contaminated inanimate objects (toys, food,
water, surgical utensils, or biological products such as blood, tissues
or organs)

Vector-borne
Transmission through simple contamination by animal or arthropod
vectors or their actual penetration of the skin or mucous membranes

Airborne
Transmission occurs when microbial, particulate, or chemical agents
are aerosolized and remain suspended in air for long periods of time

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 Incubation period

Interval from receipt of infection to the time of onset of clinical

illness (signs and symptoms)
Different diseases have different incubation periods
No precise incubation period but a range is characteristic for
a disease

What accounts for this delay?

Time needed for the pathogen to replicate to the “critical
mass” necessary for clinical disease
Site in the body at which the pathogen replicates
Dose of the infectious agent received at time of infection

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 Outcomes of exposure to an agent

The spectrum of severity varies by disease:

1.  Exposure, No infection

2.  Carrier - Individual harbors the pathogen but does not show
evidence of clinical illness; a potential source of infection
(can transmit the agent)
3.  Subclinical Infection - Disease that is not clinically apparent; leads
to immunity, carrier, or non-immunity
4.  Clinical Infection - Apparent disease characterized by signs and
symptoms; results in immunity, carrier, non-immunity, or severe
consequences such as death

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 Endemic, epidemic, pandemic

Endemic - The habitual presence (or usual occurrence) of a disease

within a given geographic area
Epidemic - The occurrence of an infectious disease clearly in excess
of normal expectancy, and generated
from a common or propagated source
Pandemic - A worldwide epidemic affecting an exceptionally high
proportion of the global population

Number
of Cases
of “Endemic”
Disease

“Epidemic”

Time 10
 Deaths in Greater London;
December 1 – 15, 1952

Period of Dense Fog

1.000
Number of Deaths

800

600

400

200

0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
December 11
 Disease Outbreaks

Typically, sudden and rapid increase in the number of cases of a

disease in a population

Common Source
Cases are limited to those who share a common exposure
Food-borne, water

Propagated
Disease often passed from one individual to another
Measles, STDs

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Essential Steps in an Outbreak
Investigation

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 Steps of an Outbreak Investigation

1.  Establish the existence of an outbreak

2.  Verify the diagnosis
3.  Define and identify cases
4.  Describe and orient the data in terms of person, place
and time
5.  Develop hypotheses
6.  Evaluate hypotheses
7.  Refine hypotheses and carry out additional studies
8.  Implement control and prevention measures
9.  Communicate findings

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 Step 1: Establish the existence of an
outbreak
Before you decide whether an outbreak exists, you must first
determine the expected or usual number of cases for the given
area and time

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 Step 1: Establish the existence of an
outbreak
Data sources
Health department surveillance records for a notifiable
disease
Sources such as hospital discharge records, mortality
records and cancer or birth defect registries
for other diseases and conditions
If local data is not available, make estimates using data
from neighboring states or national data

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 Step 1: Establish the existence of an
outbreak
Whether or not an outbreak is investigated or control measures are
implemented is not strictly tied to verifying that an epidemic exists…
Other factors may come into play, including:
Severity of the illness
Potential for spread
Political considerations
Public concern and pressure from community
Availability of resources

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 How do we know when we have an
excess over what is expected?
Public Health Surveillance
“The ongoing and systematic collection, analysis, and
interpretation of outcome-specific data for use in the
planning, implementation, and evaluation of public health
practice”.

Thacker, Berkleman. Epidemiologic Reviews 1988;10:164-90 18

 Notifiable disease

Disease for which regular, frequent, and timely information

regarding individual cases is considered necessary for the
prevention and control of disease

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 Step 2: Verify the diagnosis

Two goals in verifying a diagnosis

Ensure that the problem has been properly diagnosed
Ensure that the outbreak really is what it has been reported to be

Review clinical findings and laboratory results for affected people

Visit or talk to several of the people who became ill
For outbreaks involving infectious or toxic chemical agents, be certain
that the increase in diagnosed cases is not the result of a mistake in
the laboratory.

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 Step 3: Define and identify cases

Establish a case definition - a standard set of criteria for deciding

whether a person should be classified as having the disease under
study
In many outbreaks, a working definition of the disease syndrome
must be drawn up that will permit the identification and reporting of
cases
As the investigation proceeds and the source, mode of transmission
and/or etiologic agent becomes better known, you can modify the
working definition

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 Step 3: Define and identify cases

A case definition includes four components

1.  Clinical information about the disease

2.  Characteristics about the people who are affected
(person)
3.  Information about the location (place)
4.  A specification of time during which the outbreak
occurred (time)

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 Step 3: Define and identify cases

To increase sensitivity & specificity of reporting, we use three classifications of

cases that reflect the degree of certainty regarding diagnosis:
1. Confirmed
2. Probable
3. Possible

The case definition is used to actively search for more cases beyond the early
cases and the ones that presented themselves.

Confirmed Case Probable Case Possible Case

Laboratory
Verification +
Clinical
Features + ++ +
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 Step 3: Define and identify cases

The following information should be collected from every affected

person in an outbreak:

1. Identifying information - name, address, phone

2. Demographic information - e.g., age, sex, race, occupation
3. Risk factor information
4. Clinical information
Verify the case definition has been met for every case
Date of onset of clinical symptoms to create an epidemic curve

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 Step 3: Define and identify cases

The first cases to be recognized are usually only a small proportion of

the total number

To identify other cases, use as many sources possible

Passive Surveillance - Relies on routine notifications by healthcare

personnel (recall Notifiable Diseases)

Active Surveillance - Involves regular outreach to potential reporters

to stimulate reporting of specific conditions; investigators are sent to
the afflicted area to collect more information
Contact physician offices, hospitals, schools to find persons with
similar symptoms or illnesses
Send out a letter, telephone or visit the facilities to collect information
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 Step 4: Describe and orient the data in
terms of time, place and person
Characterizing an outbreak by time, place and person is
called descriptive epidemiology
Descriptive epidemiology is important because
You can learn what information is reliable and informative
(e.g., similar exposures)
And what may not be as reliable (e.g., many missing
responses to a particular question)
Provides a comprehensive description of an outbreak by
showing its trend over time, its geographic extent (place)
and the populations (people) affected by the disease

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 Step 4: Describe and orient the data in
terms of time
The time course of an epidemic is shown by the distribution of the
times of onset of the disease, called the Epidemic Curve
Graph of the number of cases of the health event by their date of
onset
Provides a simple visual display of the magnitude and time trend of
the outbreak
May stratify epidemic curves by place (residence, work, school, etc.)
or by personal traits (age, gender, race, etc.) to assess whether time
of onset varies in relation to place or person characteristics

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 Step 4: Describe and orient the data in
terms of place
Assessment of the outbreak by place provides
Information on the geographic extent of the problem
A “spot map” indicating place of occurrence of cases may
show clusters or patterns that provide clues to the nature
and source of the outbreak
Patterns reflecting water supply, wind currents, or
proximity to a restaurant, swimming pool, school room or
workplace
If the size of overall population varies between
comparison areas, a “spot map” of the area may be
misleading because it only shows number of cases
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 Step 4: Describe and orient the data in
terms of person
Examine risks in subgroups of the affected population
according to personal characteristics, as well as
interaction between characteristics
Age, race, sex, occupation, social group, medical status
Characterizing an outbreak by person helps to determine
which subgroups of the population are at risk

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Examples of epidemic curves

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 Step 5: Develop hypotheses

Though we generate hypotheses from the beginning of

the outbreak, at this point, the hypotheses are sharpened
and more accurately focused.
Use existing knowledge (if any) on the disease, or find
analogies to diseases of known etiology
Hypotheses should address
Source of the agent
Mode of transmission
Exposures associated with disease and should be
proposed in a way that can be tested

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 Step 6: Evaluate hypotheses

Generally, after a hypothesis is formulated, one should be able to

show that
All additional cases, lab data, and epidemiologic evidence are
consistent with the initial hypothesis; and
No other hypothesis fits the data as well

Observations that add weight to validity

The greater the degree of exposure (or higher dosage of the
pathogen), the higher the incidence of disease
Higher incidence of disease in the presence of one risk factor
relative to another factor

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 Reminder....attack rate

An attack rate is the proportion of a well-defined

population that develops illness over a limited period of
time, such as during an epidemic or outbreak
Useful for comparing the risk of disease in groups with
different exposures
Remember..an attack rate is an incidence proportion
(even though it is called a “rate”)
Often expressed as a percent

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 Attack rate

Attack Rate = Number of new cases occurring in a given time period

Population at risk at the start of the time period

= Number of people at risk who develop a certain illness

Total number of people at risk

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 Calculating an Attack Rate in a
food-borne outbreak
In a foodborne outbreak occurring among people attending a social
function or common geographical site
Calculate an attack rate for people who ate a particular item
(exposed) and an attack rate for those who did not eat the item
(unexposed)
The attack rate is calculated by dividing the number who
became ill and consumed the item by the total number
of people who consumed that item

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 Identifying the source of an outbreak

Look for an item with

A high attack rate among those exposed
AND
A low attack rate among those not exposed (so the ratio of attack
rates for the two groups is high)
Ideally, most of the people who became ill should have been
exposed to the proposed agent so that the exposure could explain
most, if not all, of the cases.

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 Step 7: Refine hypotheses and carry out
additional studies
Additional epidemiologic studies
What questions remain unanswered about the disease?
What kind of study used in a particular setting would answer these
questions?
When analytic studies do not confirm the hypotheses reconsider the
original hypotheses orlook for new vehicles or modes of
transmission

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 Step 7: Refine hypotheses and carry out
additional studies
Laboratory and environmental studies
Epidemiologic studies can implicate the source of infection,
and
guide appropriate public health action
But sometimes laboratory evidence can “clinch” the
findings
Environmental studies often help explain why an outbreak
occurred and may be very important in certain settings

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 Case control methods applied to a
food-borne outbreak
The usual approach is to apply the case-control
methodology to determine what exposures ill people had
that well people did not have
List all of the relevant items on the menu
Determine the proportions of ill and of non-ill persons who
ate each of the items by questionnaire
Identify the food item with the largest difference in attack
rates between cases (ill) and controls (non-ill)

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 Step 8: Implementing control and
prevention measures
The practical objectives of an epidemic investigation are to
stop the current epidemic and establish measures that would
prevent similar outbreaks in the future
Preliminary control measures should be implemented as soon
as possible

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 Ro = βcD

R o = Reproductive Rate
(number of secondary infections/infected case)

β = average probability susceptible partner will be infected

over duration of relationship

c = average rate of acquiring new partners

D = average duration of infectiousness

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 To sustain an epidemic

Ro > 1 but also

β > 0 (transmission must be possible)

can block with barriers

c>0 (new susceptibles) can reduce contacts

D>0 (maintain infectiousness)

can treat infection

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 Therefore, elements of epidemic control

The elements of epidemic control include:

Controlling the source of the pathogen (if known)
e.g., Remove or inactivate the pathogen
Interrupting the transmission
e.g., Sterilize environmental source of spread; vector control
Controlling or modifying the host response to exposure
e.g., Immunize the susceptibles; use prophylactic
chemotherapy

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 Step 9: Communicate findings

At the end of the investigation, communicate findings to

others who need to know
Prepare a final report
Provide information on the nature, spread, and control
measures employed
The report can take several forms:
1. An oral briefing for local health authorities
2. A written report to a journal [note: MMWR]
3.  Formal presentation of recommendations

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 Diarrhea at a high school dinner

In November 2006, between 200-300 students and teachers reported

gastroenteritis after attending a school function in Denmark
The cause was determined to be primarily enterotoxigenic E. coli.
Enterotoxigenic E. coli is transmitted through fecally contaminated food or
water, and mainly diagnosed as travelers’ diarrhea in industrialized
countries
So how did this happen at a dinner in Denmark?

45 2006.
Pakalniskiene et al. A foodborne outbreak of enterotoxigenic E. coli and Salmonella Anatum infection after a high-school dinner in Denmark, November
Epidemiol Infect. 2008; 1-6
 Diarrhea at a high school dinner

Pasta salad with pesto has the highest

number of exposed cases (98%), and a
high attack rate; bread rolls come in at a
close second: exposure=96%

46 2006.
Pakalniskiene et al. A foodborne outbreak of enterotoxigenic E. coli and Salmonella Anatum infection after a high-school dinner in Denmark, November
Epidemiol Infect. 2008; 1-6
 Diarrhea at a high school dinner

So which is it? Bread rolls or pesto?

Eating more
portions of
pasta had a
dose response
effect on the
risk ratio; this
was not true of
the bread rolls

47 2006.
Pakalniskiene et al. A foodborne outbreak of enterotoxigenic E. coli and Salmonella Anatum infection after a high-school dinner in Denmark, November
Epidemiol Infect. 2008; 1-6
 Diarrhea at a high school dinner

None of the food preparers had a history of recent illness or

foreign travel; nor did their stool samples test positive for E coli
Investigators concluded that basil in the pesto was the likely
culprit
The basil had been imported from a country that uses surface
and run-off water for irrigation
Basil from that same country has been linked to various other
outbreaks as well
[aside: the purported producer of the basil denies having grown
basil in the four years prior to the investigation]

48 2006.
Pakalniskiene et al. A foodborne outbreak of enterotoxigenic E. coli and Salmonella Anatum infection after a high-school dinner in Denmark, November
Epidemiol Infect. 2008; 1-6