How to conduct an Outbreak Investigation

Outline of the class

Steps of the outbreak investigation:
Step-7: Develop hypothesis
Steps-8: Testing hypothesis
Steps-9:
Step 7: Develop hypothesis
 Develop hypothesis

Although the next conceptual step in an investigation is

formulating hypotheses, in reality, investigators usually begin to
generate hypotheses at the time of the initial telephone call.
Depending on the outbreak, the hypotheses may address the
source of the agent, the mode (and vehicle or vector) of
transmission, and the exposures that caused the disease. The
hypotheses should be testable, since evaluating hypotheses is the
next step in the investigation.
 Develop hypothesis

In an outbreak context, hypotheses are generated in a variety of

ways.
Consider first what you know about the disease itself: What is the
agent's usual reservoir? How is it usually transmitted? What
vehicles are commonly implicated? What are the known risk
factors? In other words, by being familiar with the disease, you
can, at the very least, "round up the usual suspects.“
Hypothesis Generation
 Goals

Discuss the importance of hypothesis generation

Describe approaches to generating hypotheses
Present Internet resources useful for literature reviews
 What is Hypothesis Generation and Why is it
Important?

A hypothesis is an educated “guess” about the source

of the outbreak
Generating hypotheses enables the investigators to
test these hypotheses in an analytic study
The success of the investigation depends upon the
quality of the hypotheses
 Overview of Hypothesis Generation Strategy

Ways to approach generating hypotheses about the cause of

the outbreak
Examine the line listing data
Review the existing body of knowledge
Administer open-ended hypothesis-generating
questionnaire to several cases
Develop specific hypotheses
Test the hypotheses in an analytic study using a structured
questionnaire concerning the specific hypotheses
 Overview of Hypothesis Generation Strategy
Literature reviews help identify organisms, risk factors, and
sources of exposures that have been observed in the past
Example: diarrheal disease
Some outbreaks are caused by unrecognized agents or
through unrecognized modes of transmission
Examples: hantavirus and West Nile virus
 Using the Internet

Sources of electronic full-text information

Centers for Disease Control and Prevention (CDC):
http://www.cdc.gov
Morbidity and Mortality Weekly Report (MMWR):
http://www.cdc.gov/mmwr
General searches on the Internet can also be helpful
Example: http://www.google.com
Not all information on the Internet is accurate: be mindful of the
potential credibility of different Internet-based sources
 Using the Internet

PubMed allows individuals to search journal abstracts

from biomedical literature for free
http://www.ncbi.nlm.nih.gov/PubMed
Some states or academic institutions also have
agreements to provide access to journal abstracts or full-
texts
Articles may be available for free online
Hypothesis generation should be guided by:
Descriptive epidemiology from the outbreak
Information learned from past outbreaks
However, keep an open mind and always consider
alternative explanations
Example: Legionnaires’ Disease
 Generating hypothesis

Hypothesis generation is a critical step in any outbreak

investigation
A literature review may be necessary
The Internet is a useful resource
Preliminary data collection with standardized questionnaires may
implicate hypotheses that warrant additional data
Open-ended interviews can be a useful tool to obtain this
information
Hypothesis-Generating Interviews
 Goals

Discuss the uses of hypothesis-generating interviews

Present information on case-patient selection, questions
to ask and when and where to conduct hypothesis-
generating interviews.
Provide useful tips on how to conduct an interview
during an outbreak.
 Why use hypothesis-generating interviews?

To obtain initial clues on possible sources of exposure

To develop a hypotheses-testing questionnaire
To identify signs and symptoms of the disease
To help develop or refine the case definition
To develop a demographic profile and identify the population at
risk
To develop a list of potential exposures
 Whom Do We Interview?

Case-patients
8 to 10
Differing demographic profiles
Typical clinical presentation
Occurring in the middle of the outbreak
Family member or friend if case-patient is unavailable
Parent or guardian if case-patient is a child
Health care providers, lab workers, clinical staff
 Who Do We Interview?

Examples:
1984-1985 Minnesota outbreak of Thyrotoxicosis
1997 Michigan and Virginia Salmonella outbreaks
 What Do We Ask?

Basic demographic information

Clinical details
Activities
Food consumption
 What Do We Ask?

Known or suspected agent

Likely exposures
Known reservoirs
Modes of transmission
Activities occurring during a specific period based on known
incubation period and date of onset
Unknown agent
Broad, less specific questions
Activities, clinical signs and symptoms
 When And Where Do We Conduct The Interview
Early in the investigation
Case-patients’ homes or health care setting
Other settings
e.g. the local health department, if several case-patients need to be brought
together
Unusual approaches may be required
1981 epidemic of listeriosis in Canada
1983 epidemic of listeriosis in Massachusetts
How Do We Conduct The Interview?

Standardized forms
Types of questions
Closed-ended
Open-ended
How Do We Conduct The Interview?
Tips:
Review the literature
Obtain background information
Enhance interviewing and people skills
Act friendly and professional
Use memory aids
How Do We Conduct The Interview?
Tips:
Introduce yourself and give your credentials
Explain the purpose of the interview and tell the case-
patient how long the interview will take
Be systematic but flexible when questioning
Provide contact information
Thank the interviewee for participating
Acknowledge his or her contribution to the investigation
How Hypothesis generating interview helps

Hypothesis-generating interviews increase

efficiency of outbreak investigations by
helping confirm the existence of an outbreak
providing insights on potential causative agents
identifying potential sources of exposure and modes of
transmission
From the information obtained, investigators
create case definitions
construct epi-curves
proceed to test hypotheses through analytic studies
Step 8: Testing Hypothesis
 Testing of Hypothesis:

-By comparing the attack rates in various groups

for those exposed and those not exposed to each
suspected factor or source of infection.
-Case control and Cohort
studies will be the basis to test hypothesis.

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 Testing of Hypothesis:
In general, the case-control study design is suitable for
investigating outbreak because-
Multiple etiologic hypothesis (exposures) can be tested
concurrently
Makes efficient use of time and resources
Analysis does not require full enumeration of the whole
cohort

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 Testing of Hypothesis:
In case-control study design at first
classify persons on the basis of infection status
compare odds of exposed to suspected causal agent
between cases and control subjects
Example: Several college students presented with GI
related symptoms thought to have been associated with
food served in the cafeteria

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 Testing of Hypothesis:
Hypothesis: contaminated salad was the source
of infection
Exposure Cases Controls
status
Ate salad 12 4
12×14
OR=
4×6
Did not eat 6 14 OR= 7.0
salad

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 Testing of Hypothesis:
In a closed population retrospective cohort study
design maybe conducted
Classify persons on the basis of exposure to the
suspected source of infection
Compare attack rate (AR) between exposed and non-
exposed persons

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 Testing of Hypothesis:
Example of retrospective cohort study design:
Of 72 persons who attended in a birthday party, 46
became ill within several hours
Hypothesis: contaminated vanilla ice cream was the
source of infection

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 Testing of Hypothesis:

Exposure N Became ill Attack Relative

status rate Risk

Did not eat 18 3 16.7%

ice cream
4.9%
Ate ice 54 43 79.6%
cream

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Step 9: Implement control
and prevention measures
 Implement control & prevention measures

In most outbreak investigations, the primary goal is control of the outbreak
and prevention of additional cases. Indeed, although implementing control and
prevention measures is listed as Step 9 in the conceptual sequence, in practice
control and prevention activities should be implemented as early as possible.
The health department's first responsibility is to protect the public's health, so
if appropriate control measures are known and available, they should be
initiated even before an epidemiologic investigation is launched. For example,
a child with measles in a community with other susceptible children may
prompt a vaccination campaign before an investigation of how that child
became infected.
 Implement control & prevention measures
Confidentiality is an important issue in implementing control measures.
Healthcare workers need to be aware of the confidentiality issues relevant to
collection, management and sharing of data. For example, in the treatment of
tuberculosis (TB), the relationship between the patient and the healthcare worker
is extremely important because of the serious consequences of treatment failure.
Some interventions are aimed at blocking the mode of transmission. Interruption
of direct transmission may be accomplished by isolation of someone with
infection, or counseling persons to avoid the specific type of contact associated
with transmission. Similarly, to control an outbreak of influenza-like illness in a
nursing home, affected residents could be cohorted, that is, put together in a
separate area to prevent transmission to others.
 Implement control & prevention measures
Vehicle borne transmission may be interrupted by elimination or decontamination
of the vehicle. For example, contaminated foods should be discarded, and
surgical equipment is routinely sterilized to prevent transmission.
Efforts to prevent fecal-oral transmission often focus on rearranging the
environment to reduce the risk of contamination in the future and on changing
behaviors, such as promoting hand washing.
For airborne diseases, strategies may be directed at modifying ventilation or air
pressure, and filtering or treating the air. To interrupt vector borne transmission,
measures may be directed toward controlling the vector population, such as
spraying to reduce the mosquito population that may carry MaliriaWest Nile
virus.
 Implement control & prevention measures

Some simple and effective strategies protect portals of entry. For example,
bed nets are used to protect sleeping persons from being bitten by
mosquitoes that may transmit malaria.
Some interventions aim to increase a host's defenses. Vaccinations promote
development of specific antibodies that protect against infection.
Step 10: Initiate or maintain surveillance
 Initiate or maintain surveillance
Once control and prevention measures have been implemented, they must
continue to be monitored. If surveillance has not been ongoing, now is the
time to initiate active surveillance. If active surveillance was initiated as part
of case finding efforts, it should be continued.
The reasons for conducting active surveillance at this time are twofold:
First, you must continue to monitor the situation and determine whether the
prevention and control measures are working. Is the number of new cases
slowing down or, better yet, stopping? Or are new cases continuing to
occur? If so, where are the new cases? Are they occurring throughout the
area, indicating that the interventions are generally ineffective, or are they
occurring only in pockets, indicating that the interventions may be effective
but that some areas were missed?
 Initiate or maintain surveillance

Second, we need to know whether the outbreak has spread outside

its original area or the area where the interventions were targeted.
If so, effective disease control and prevention measures must be
implemented in these new areas.
THANK YOU