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Outbreak InvestigationOutbreak InvestigationStep by StepStep by Step

Darin Areechokchai MD., DTM&H., MCTM.Surveillance and Investigation Section

Bureau of Epidemiology, Department of Disease ControlMinistry of Public Health, Thailand

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Outline

Introduction: Epidemiology is …

Outbreak: Definition, Type, Detection

Investigation: Steps

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What is Epidemiology?

Disease Occurrence Population

•Distribution of disease by person, place, and time

•Determinants (Risk Factors)

Study of

DiseaseControl

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Roles of Epidemiology in Public Health

Surveillance

Outbreak Investigation

Epidemiological StudyEvaluation of PH measures*RM Page, et al. “Basic epidemiological methods and biostatistics, 1995 p.32

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Definition of Outbreak

The occurrence of cases of an illness, specific health-related behaviour, or other health-related events clearly in excess of normal expectancy. The area and the period in which the cases occur are specified precisely.

What is

the

normal e

xpectan

cy?

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Excess of Normal ExpectancyMore than

Median number of cases in previous 5 years orAverage number of cases + 2sd of previous 5 yr

Number of Cholera case by month, District A

0

10

20

30

40

50

60

70

Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

# ca

ses

2003 Median 1998 - 2002

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Cases linked to the same factors

Judged to be an outbreak

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A single case of disease that has never

been occurred before.

1997:A 3-year old boy, case of Avian Flu (H5N1) in Hong Kong alerted the public health people around the world to start a full scale investigation.

Judged to be an outbreak

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TermsEndemic = Disease that routinely occurs in a given place

Epidemic = Outbreak(outbreak -> sense of urgency,

Epidemic -> sense of wide spreading)

Cluster = An aggregation of cases in a given place & time

Pandemic = Epidemic that spreads over many countries of regions of the world

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1918 flu pandemic (Spanish flu)

50 50 –– 100 million deaths worldwide in 18 months100 million deaths worldwide in 18 months

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Detection of the outbreak

Sources of outbreak news:

Surveillance data that are collected and analyzed timely

Health care provider or citizen who knows of “several cases”

Media: Newspaper, TV, Internet

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Media reports outbreak

2 deaths and 118 coma cases after eating raw park salad in a cremation

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Surveillance for outbreak detection

0

10

20

30

40

50

60

70

80

Jan Mar May July Sep Nov Jan Mar May July Sep Nov Jan Mar May July Sep Nov Jan Mar May July Sep Nov Jan Mar May July

1995 1996 1997 1998 1999

Reported Cholera cases in Khonkaen, Thailand January 1995 - July 1999

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Outbreak patterns

Common source outbreak

Propagated source outbreak

(Person-to-person)

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Common Source Outbreak

0123456789

10

# ca

se

Date of onset

Common sourceFood

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Propagated Source Outbreak

0

5

10

15

20

25

30

# ca

ses

Date of onset

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Outbreak: the basicsDefinition

More than normal expectancy

Cases with epidemiological linkage

New disease (emerging disease)

DetectionSurveillance

Health care providers

media

Pattern and epidemic curveCommon source

Propagated source

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Steps of Steps of Outbreak InvestigationsOutbreak Investigations

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Why investigate an outbreak?

Characterize a public health problem

Identify preventable risk factors

Recommend control and prevention measures

0

20

40

60

80

100

1 5 9 13 17 21 25 29 33 37

PrimaryCase

1st case at HC

Report to DMO

Lab result

Samplestaken

Responsebegins

Days

Opportunity for control

“Usual” sequence of events

0

20

40

60

80

100

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39

“Ideal” sequence of events

Days

Potential cases prevented

PrimaryCase

Responsebegins

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Steps of an outbreak investigationSteps of an outbreak investigationSteps of an outbreak investigationIm

pl emen t c on tro l m

ea su re s

1. Prepare for Field Work : Rapid Response Team2. Confirm outbreak and diagnosis3. Define case and start case-finding4. Descriptive data collection and analysis5. Develop hypothesis6. Analytical studies to test hypotheses7. Special studies (e.g. environmental study)8. Communicate the conclusion and recommend

control measures9. Follow-up the control implementations

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1. Team members and roles

2. Necessary Knowledge and equipments; specimen collection & transport method, etc.

3. Lines of communication

I. Preparing for field works

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II. Confirm outbreak and diagnosis

Is this anoutbreakoutbreak?

Link between cases?Higher than expected?

What is the diagnosisdiagnosis?

Clinical manifestationLaboratory result

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Scenario 1Scenario 1Scenario 1

Many adults in a remote village were sick with fever, severe joint and muscle pain and rash over the body

• Is this an outbreak?• What is the likely diagnosis?• Should we start the investigation?•Which intervention should be started?

Outbreak confirmed Maybe measles, rubella, dengue etc. Investigation warrantedShall we start the vaccination or spray mosquitoes?

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To Investigate or not to Investigate

Consider the following factors when deciding whether or not to investigate an outbreak

It could be “true” outbreak with common cause

It could be unrelated cases of the same disease

Severity of illness

Transmissibility

Local politics

Public concern

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EpidemiologistClinicianMicrobiologistEnvironmentalistGovernmentPress officerOthers

Team coordinatesfield investigation

Outbreak confirmed, further investigations warranted

Form Outbreak Investigation & Control

Team

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ea su re s

1. Prepare for Field Work : Rapid Response Team2. Confirm outbreak and diagnosis3. Define case and start case-finding4. Descriptive data collection and analysis5. Hypothesis generation6. Analytical studies to test hypotheses7. Special studies (e.g. environmental study)8. Communicate the conclusion and recommend


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Which one is longer?

Standard measurement

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Case Definition

Standard criteria for deciding if a person should be classified as suffering from the disease under investigation

Clinical criteria, restrictions of time, place, person

Simple, practical, objective

Sensitivity versus specificity

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Case definition: example

Patient older than 5 years with severe dehydration or dying of acute watery diarrhoea in town “x” between 1 June and 20 July 1999.

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Case DefinitionsCan emphasize sensitivity or specificity in case definition

SENSITIVITYSPECIFICITYmany false positives

many specimens to test low % tested specimens +ve

Sensitivity: Most cases detected, but …

Overload

Specificity: Cases missed, but …SENSITIVITY

SPECIFICITY few false positivesfewer specimens to test

high % tested specimens +veUnderload

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Case DefinitionCategories of cases

SuspectedSymptoms reported but not confirmedNo lab or epidemiologic link

ProbableSymptoms confirmedEpidemiologic linkInitial lab test

ConfirmedLab testEpidemiologic link

> 5 yr in town X

Suspected

With diarrhea symptoms

Probable

Mucous bloody diarrhea

WBC, RBC in stool exam

Confirmed

RSC found Shigella sonnei

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(Passive cases)

(Active cases)

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Why is Case Finding Important?

In an outbreak:

There are usually more cases than are reported to the health department

Reported cases may not be representative of all cases

To identify exposure and/or outcome investigator needs information from persons who represent all cases

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Why is Case Finding Important?

To refine the case definition as more information is garneredTo define the exposed population for the purposes of developing control measures

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How to Find CasesPassive strategies involve review of information available

OPD, IPD log book in hospitals, Health center

Laboratory log book

Active strategiesScreening unit in

the affected area

Door to door

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Information to Collect during Case Finding Process

Demographic information Age, gender, race, occupation

Clinical information Symptoms, date of onset, lab results, severity of illness

risk factor information to collectVaries by type of outbreak

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Survey of hepatitis B cases in a male juvenile detention, Saraburi, Thailand, November 1999

Date of interview Interviewer's name Patient number

Patient's name-Surname Age (in years) Number of domitory (1-5)

Study field 1. Machanic 2. Carpanter 3. Electric

4. Barber 5. Music 6. Agriculture

Clinical symptoms (sick inside the juvenile detention, since 1 Jan 99) Possible risk factors

No Yes Y N

Homosexual Y N

Injected drug user Y N

This hepatitis cases is laboratory confirY N

Fatigue

Onset of symptoms Tatooing

Jaundice

Nausia/Vomiting

Clinical info.Risk factors

Demographic info.

Identifying info.

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Line Listing: What and Why?

It provides organized information about the cases

Can be quickly reviewed and updated

Create a table in which each row represents a case and each column represents a variable of interest

Line listing of streptococcus meningitis cases after eating raw pork

ID Sex Age Onset Alcohol 25/4/07 26/4/07

27/4/07

26/4/07

27/4/07

27/4/07

26/4/07

26/4/07

27/4/07

26/4/07

27/4/07

BF LUN DIN BF LUN DIN

1 M 50 Yes Raw Raw - Cook Cook Cook

2 M 41 Yes Raw Raw - - - -

3 M 43 Yes Raw Raw - - - -

4 M 62 Yes Raw Raw Cook - - -

5 M 71 No - Raw - - - -

6 M 56 Yes - Raw - - - -

7 M 51 Yes - Raw - - Cook -

8 M 50 Yes Raw Raw - - - -

9 F 49 Yes - Raw - - - -

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Using Information from a Line Listing

Frequency distributions of demographics

May provide information about exposure and/or risk of disease

Frequency distributions of potential exposures

May provide information about source or route of transmission

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Descriptive data analysisTime:

Epidemic curvePlace:

spot maparea mapAttack rate (incidence) by place

PersonFrequencySpecific attack rate (incidence)

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Epidemic Curve: How Can it Help in an Outbreak?

An epidemic curve (epi curve) is a graphical depiction of the number of cases of illness by the date (time) of illness onset

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What is an Epidemic Curve and How Can it Help in an Outbreak?

An epi curve can provide information on the following characteristics of an outbreak:

Pattern of spreadMagnitudeOutliersTime trendExposure and/or disease incubation period

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Epi curve: Outbreak Pattern of Spread

The overall shape of the epi curve can reveal the type of outbreak

Common source

Propagated

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Epi curve: Outbreak Time Trend

Allow information about the time trend of the outbreak to be gleaned

Consider:Date of illness onset for the first case

Date when the outbreak peaked

Date of illness onset for the last case

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Epi curve: Outbreak Outliers

Outliers are cases at the very beginning and end that may not appear to be relatedIf they are not an error, they may represent

Baseline level of illnessOutbreak sourceA case exposed earlier than the othersAn unrelated caseA case exposed later than the othersA case with a long incubation period

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Epidemic curve: Exposure period

0

2

4

6

8

10

12

14

Date of onset

Num

ber o

f cas

es

suspect first case

active

passive

16 21 23 25 28 October

Exposure period = (Onset of the first case – Shortest incubation period) to

(Onset of the most cases – the average incubation period)

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How do I Make an Epi Curve?

Plot the number of cases of disease reported during an outbreak on the y-axis

Plot the time or date of illness onset on the x-axis

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Technical tips

Choice of time unit for x-axis depends upon the incubation period

Begin with a unit approximately one quarter of the incubation period

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Epi curves are histograms

There should not be any space between the x-axis categories

Label each axis

Provide a descriptive title

Include the pre-epidemic period to show the baseline number of cases

0

1

2

3

4

5

6

7

8

w k1 w k2 w k3 w k4 w k5 w k6 w k7 w k8 w k9 w k10 w k11 w k12 w k13 w k14

num

ber o

f cas

es13 10 8

9111214

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7

15

4

3

2

1

Burma

Measles case distribution by sector, Nupo camp, Tak, Jan – Mar 2007

Epidemic curve by week of onset (N = 27)

Case in week 2Case in week 6Case in week 7Case in week 8Case in week 9Case in week 10

Case in week 11Case in week 12Case in week 13

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Distribution of avian influenza casesThailand, Jan – Mar 2004

11 cases in 8 provinces

Male : Female = 8 : 3

Median age 7 (2 - 58 years old)

8 died (CFR 72.7%) :

- Age <15 years CFR 85.7%

- Age >15 years CFR 50.0%died (N=8)

improved (N=3)

Area of poultry outbreak

0 10 20 30 40 50 60 70 80 90 100

Pediatric (N=7) Adult (N=4)

Fever

Cough

Sputum

Dyspnea

Rhinorrhea

Diarrhea

Vomiting

Wbc<5000

Platelet<106

Pleural effus.

Percent of cases

Clinical manifestations of confirmed AI casesThailand, Jan – Mar 2004

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Area map: Human brain

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Cases

0

5

10

15

20

25

1 2 3 4 5 6 7 8 9 10

0

200

400

600

800

1000

1200

0-4 '5-14 '15-44 '45-64 '64+

Age Group

Evaluate information

Pathogen? Source? Transmission?

Person Place Time

Set Hypothesis from all information

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- Who is at risk of becoming ill?- What is the source and the vehicle?- What is the mode of transmission?

Examples

• Tatooing was the risk of getting hepatitis B infection, because 13 out of 15 cases had new tatooes.

• A shallow well was the source of shigella, because most of case used water from there.

• Juice from the school cafeteria caused the illness, because a pass-by visitor got sick after drank a glass of juice. (outlier case)

Hypothesis generation

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Develop hypotheses

- Who is at risk of becoming ill?- What is the source and the vehicle?- What is the mode of transmission?

Analytical studies to test hypotheses

Analytic study- study design; case-control, cohort- sampling control (non-cases)- data collecting: more detailed

questionnaire

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Steps in creating a questionnaire

1. Identify the leading hypotheses about the source of the problem

2. Identify the information needed to test the hypotheses

3. Identify the information needed for logisticsof the study and to examine confounding

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Steps in creating a questionnaire

4. Write the questions to collect this information

5. Organize the questions into questionnaire format

6. Test the questionnaire

7. Revise the questionnaire

8. Train interviewers to administer the questionnaire

9. Ethics

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About Analytic Studies

We can use analytic studies to test hypotheses.

We want to know:Whether there is an association between exposure and disease,

How strong the association is,

What proportion of cases are due to exposure, and

Whether there is an increased risk of disease with increased exposure (a dose-response relationship).

Two common types of analytic studies are cohort study and case-control study.

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What is a Cohort?

A “cohort” is a group of people who have something in common.

Can represent the source population—the population from which cases of disease arise.

Examples of cohorts:All employees in an office building

Everyone who attended a football game

All the residents of a neighborhood

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Cohort StudiesTend to be retrospective (exposures in the past in relation to disease that has already happened).

Occurrence of disease in exposed group compared to occurrence of disease in unexposed group = risk ratio.

Risk ratio tells whether disease is associated with exposure and strength of association.

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Cohort study

Expose Non-exp

AteNot eat

Case

Non-case

Case

Non-case

Case Non-case Total

Ate 9 16 25

Not eat 7 113 120

RR = 6.2, 95%CI 2.5, 15.1

In a shigellosis outbreak, fermented vegetable was suspected to be the implicated food

A person who ate the fermented vegetable was 6.2 times more likely to be ill than a person who did not eat...

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Case-Control StudiesThe most frequently used type of study in outbreaks

Can be quickly implemented

Can be used when cohort study might be large and time-consuming

Identify people with disease (case-patients) and people without disease (controls), then ask everyone about past exposures

You already know who is case

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Case-Control Studies

Calculate odds ratio to measure strength of association between illness and exposure

Compare odds of exposure among case-patients to odds of exposure among controls

Cannot calculate risk ratio in case-control study

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Case-control study

ControlCase

Case Control Total

Ate 13 4 17

Not eat 1 62 63

OR = 201, 95%CI 18, 5410

In a botulism outbreak, home-canned bamboo shoots was suspected to be the implicated food

A person who ate the bamboo shoots was 201 times more likely to be ill than a person who did not eat...

Cases Controls

Exposed

Non-exp.

Exposed

Non-exp.

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Case-Control or Cohort: Which one is right?

The choice depends on the situationAlways think about the source population:

Are members of the group easily identifiable? Can you interview all or a sample of them?

Use a cohort study

Is the cohort difficult to identify or too large to contact all members?

Use a case-control study design

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Environmental study:Traceback Investigations

Process used to determine the production and distribution chain of a vehicle implicated in an outbreakHelps determine if (and where) you can conduct an environmental health assessmentUsed to clarify the point at which the implicated vehicle may have become contaminatedNecessary investigation to identify contributing factors (implement control measures)

Simmer with

ingredients

Processing of rice with red pork with eggin an outbreak of shigellosis in school A

Soaking in water & peeloff eggshell

Critical Critical pointpoint

TEXT

Mixed &divideTEXT TEXT

Boiling pork~ 1-1.5 hrs Boiling eggs

Slice red pork

Splitting egg by thread &

knife

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Outbreaks Involving Clinical Specimens

Human clinical specimens from cases, contactsBloodSerumUrine

Type of specimen depends on the outbreakSpecimens from environments, animals

SalivaHairFeces

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Implement control measures

May occur at any time during the outbreak!!

Control measuresControl measures

Control the source of pathogenInterrupt transmissionModify host response

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Control the source of pathogen

• Remove source of contamination• Remove persons from exposure• Isolate and/or treat infected persons

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Interrupt transmission

Interrupt environmental transmission

Control vector transmission

Improve personal sanitation

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Modify host response

Immunise susceptibles

Use prophylactic chemotherapy

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Main reference: http://www.sph.unc.edu/nccphp/focus/

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Thanks for Thanks for your kind attentionyour kind attention

The International Field Epidemiology Training Program, Thailand

Many slides in this presentation are from the World Health Organization, the European Programme for Intervention Epidemiology Training and work of

our trainees here in the Thai-FETP

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