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Epidemiology Toolkit for

Outbreak Investigation

Meirion Evans

Communicable Disease Surveillance Centre

What is an outbreak?

Occurrence of more cases of disease

than expected

• Over a particular period of time

• In a given area

• Among a specific group of people

(incidents, clusters)

Key questions

What is going on? ASSESS

Who is affected? DESCRIBE

What is the cause? ANALYSE

What should be done? ACT

1. Confirm existence of an outbreak

2. Corroborate diagnosis

3. Define and identify cases

4. Collect and collate data

5. Characterise cases (person - place - time)

6. Develop hypotheses

7. Test hypotheses

8. Verify biological coherence

9. Communicate results and write report

10. Implement control measures

ASSESS

ANAL

YSE

ACT

10 steps in outbreak investigationDESCRIBE

Confirm existence of an outbreak

Corroborate diagnosis

3. Define and identify cases

4. Collect and collate data

5. Characterise cases (person - place - time)

6. Develop hypotheses

7. Test hypotheses

8. Verify biological coherence

Communicate results and write report

Implement control measures

ANAL

YSE

10 steps in outbreak investigationDESCRIBE

Descriptive epidemiology

Analytical epidemiology

Descriptive epidemiology

Define & identify cases

Develop hypotheses

Characterise cases

Collect & collate data

To refine the case definition To develop a demographic profile To identify people at risk To develop hypotheses about

• Potential sources of exposure

• Potential routes of transmission

Descriptive epidemiology OBJECTIVES

Case definition

Set of criteria… • for deciding if a person should be classified as having the disease• for the purposes of that stage of the investigation

Clinical and/or laboratory criteria Time Place Person

• Tiered definitions: confirmed, probable, possible

Case definitionoutbreak of salmonellosis in Swansea, 2011

Confirmed case

diarrhoea • (> 2 liquid stools per day)

and/or fever > 38°C • (for at least one day)

and

an isolate of S. Typhimurium

in a resident of Swansea after May 2011

Probable case

diarrhoea • (> 2 liquid stools per day)

and contact (same household) with a

confirmed case in a resident of Swansea after May 2011

Case definitionsensitivity vs. specificity

Possible Probable Confirmed

Low Specificity

High Specificity

High Sensitivity

Low Sensitivity

Identify & count cases

Collect data

demographics

clinical details (outcome)

risk factors (exposure)

reports from stafflaboratory dataoccupational healthhospitals recordsGPs, etc

Collect data

Detailed interviews• symptoms and date of onset• case characteristics • all relevant exposures in relevant period

Visit (examine) some cases

Speak with clinicians

Obtain lab confirmation

Collect data

Collate data Line listing

Example line list

Case

No. Name

Date

of birthDate of onset

Date of report

Lab

results

1

2

3

4

5

6

XY

AB

CD

…

…

…

Line listing - principles

Constitutes a unique MASTER LIST• avoids confusion with multiple versions• suitable for sharing

Contains unique identifier for each record Ensures confidentiality Contains essential information on each case

• time, place, person, clinical, lab, etc. Can be updated as the investigation develops Prepares data for simple descriptive analysis

Collect data

Collate data

Characterise cases

describe in - person - place - time

Characterise cases

Who are the cases? Where do they live, work, etc.? When did they become ill?

Classify cases by:• Person

• Place

• Time

Person

Place

Time

Characterise cases

0

5

10

15

20

25

1 2 3 4 5 6 7 8 9 100

200400600800

10001200

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

Age Group

Develop hypotheses

Pathogen? Source? Transmission?

PersonWHO is getting the disease?

Sex and age group Ethnicity Pre-existing conditions Medication Invasive procedures Surgical treatment

PersonC. difficile outbreak in peri-partum women

PlaceWHERE is the disease occurring?

In the community• Place of residence• Place of work

In hospital• Floor• Ward or unit• Operating theatre• Outpatient departments

Place Measles outbreak in a local community

Figure 1. Reported cases of campylobacteriosis (n=45) in Svolvær, Norway, by

date of onset J anuary and February 1997.

10 = 1 primary case

= 1 secondary household case

5

22 23 24 25 26 27 28 29 30 31 1 2 3 4 5 6 7 8 9 10

J anuary February

Figure. Cases of gastroenteritis (n=45) in Hospital X, Wales by date of onset, January and February

2012

1 patient case

1 staff case

TimeWHEN does the disease occur?

To describe the outbreak

• Start date, end date, duration

• Peak, shape, magnitude

• Outliers and atypical cases

To develop hypotheses

• Incubation period

• Aetiological agent

• Type of source and transmission

• Time of exposure

Time - use of the epidemic curve

TimeC. difficile outbreak timeline

TimePseudomonas on a neonatal ICU

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

Develop hypotheses

Analytical epidemiology

Test hypotheses

Verify biological coherence

To test hypotheses• Is there an association between exposure

and disease?• How strong is the association?• What proportion of cases are explained by

the exposure?• Is there an increased risk of disease with

increased exposure (dose-response)?

Analytical epidemiology OBJECTIVES

Test hypotheses

Analytical studies

• Cohort study

• Case-control study

These must test specific hypotheses Compare the predictions of your hypotheses

with further investigations

Testing hypothesis - comparing groups

Cohort study

- attack rate exposed group

- attack rate unexposed group

= risk ratio

Case control study

- proportion of cases exposed

- proportion of controls exposed

= odds ratio

Cohort Study

Identify a cohort• Categorise individuals based on whether or

not they were exposed• Compare attack rates

exposed vs unexposed

Suitable when a cohort is easily identifiable e.g. specific ward(s), operating theatre list(s)

Case-Control Study

Identify cases • that meet the case definition Select non-diseased individuals from the

same population to act as controls Compare proportions exposed• cases vs. controls

Suitable when a distinct group is not easily identifiable e.g. long-term outbreak, OPD

Cohort study two-by-two table

Calculate association between exposure & disease

dc

ba

NTotal

c + dUnexposed

a + bExposed

TotalWellIll

Risk ratio [RR] = a/(a+b) / c/(c+d)

CC study two-by-two table

Calculate association between disease & exposure

dc

ba

NTotal

Unexposed

Exposed

TotalControlCase

Odds ratio [OR] = ad/bc

Table from a case control studyRisk factors for MRSA bacteraemia

ExposureCases n=42

Controls n=90

Odds Ratio

On admission

Indwelling catheter on admission 5 3 3.9

Prior admission 35 66 1.8

On or during admission

Bed sore 5 1 12.0

Skin ulcer 5 5 2.3

During admission

Central line during admission 17 1 60.5

Urinary catheter during admission 22 2 48.4

Blood transfusion 15 7 6.6

Verify biological coherence

Corroborative studies• Microbiological investigation

suspected sources or vehicles of transmission typing and molecular diagnostics

• Environmental investigation

• Traceback investigations (origin of supplies)

• Air circulation data

The reality….

Outbreak suspected

time

Confirmation

Form Outbreak Control Team

Confirm Diagnosis

Site visit

Case definition

Line list

Organise data

Descriptive Epidemiology

Control measures

AnalyticalEpidemiology

Recommendations

Outbreakreport

Methodological issues

Keep things simple Stick to basic principles Get as much information as possible Be clear what the key questions are Design investigations to test

hypotheses appropriately