Outbreak InvestigationOutbreak Investigation

EPIET Introductory course 2006

Lazareto, Menorca, Spain

What is an outbreak ?

Occurrence of more cases of disease than expected

– in a given area – over a particular period of time – among a specific group of people

Why investigate outbreaks?

• Stop the outbreak• Understand what happened and why• Prevent future outbreaks• Improve our knowledge• Improve surveillance and outbreak detection • Training

Objectives for this session

• Describe – the principles of outbreak investigation– the steps in outbreak investigation

• Using practical examples– Outbreak of Hepatitis A in Ibiza, Spain

September 2000 - January 2001

• Tomorrow– some operational and logistical aspects

of outbreak investigation

Epidemiology

Food safety

Clinicians

Laboratory

Media AuthoritiesDiagnostic

Clinical

Specimen transfer

Dead Sick

Exposed

SurveillanceInvestigation

Prediction

Supply channels

Trace back

DecisionsInfrastructureRegulationsVaccinations etc

VectorReservoir

Investigation

Co-ordination

Specific demands when investigating outbreaks

• Unexpected event

• Act quickly

• Rapid control

• Interdisciplinary coordination

• Work carried out in the field

Systematic approach

Outbreak of Hepatitis A in Ibiza (Spain) 2000/2001

• Ibiza is a major tourist destination(2 million visitors in 2000)

• 23-27 October 2000: 5 cases of Hepatitis A notified to local health authorities in Ibiza

• 3 cases of Hepatitis A among German tourists returning from Ibiza

Steps of an outbreak investigation

• Confirm outbreak and diagnosis• Form Outbreak Control Team• Define a case • Identify cases and obtain information• Describe data by time, place, person• Develop hypothesis• Test hypothesis: analytical studies • Additional studies• Communicate results:

– outbreak report, publication

• Implement control measures

Co

ntro

l measu

res

Detection

Routine surveillanceClinical / LaboratoryGeneral publicMedia

0

20

40

60

80

100

120

no. cases

2002(n=184)

20052004(n=153)

2003(n=150)

Notified cases of S. Bovismorbificans, Germany 2002-2005

Confirm outbreakIs this an outbreak?• More cases than expected?• Surveillance data• Surveys: hospitals, labs, physicians

Caution!• Seasonal variations• Notification artefacts• Diagnostic bias (new technique)• Diagnostic errors (pseudo-outbreaks)

Outbreak of Hepatitis A in Ibiza, Spain

• Hepatitis A notifiable disease in Spain• notifications in Ibiza during previous years:

– 1997: 6 cases– 1998: 0 cases– 1999: 4 cases

Confirm diagnosis

• Laboratory confirmation – serology– isolates, typing of isolates– toxic agents

• Meet attending physicians• Examine some cases• Contact (visit) the laboratories

Not always necessary to confirm all the casesbut confirm a proportion throughout the outbreak

Outbreak confirmed

Immediate control measures?

Further investigation?

- prophylaxis- exclusion / isolation- public warning- hygienic measures- others

- aetiological agent- mode of transmission- vehicle of transmission- source of contamination- population at risk- exposure causing illness

EpidemiologistMicrobiologistClinicianEnvironmentalistEngineersVeterinariansOthers

Team coordinatesfield investigation

Outbreak confirmed, further investigations warranted

Form Outbreak Control Team

Descriptive epidemiology

- Who are the cases? (person)

- Where do they live? (place)

- When did they become ill? (time)

Case definition

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

• Criteria

– clinical and/or biological criteria,

– time

– place

– person

Case definition

• Simple, practical, objective

• Sensitive?

• Specific?

• Multiple case definitions

– confirmed

– probable

– possible

Case definition Outbreak of Hepatitis A in Ibiza 2000/2001

Any person

• with IgM antibodies to Hepatitis A VirusAugust 2000 - January 2001

• on the island of Ibiza for at least one day during a 15-50 day period before onset of illness or seroconversion

Identify & count cases

notificationshospitals, GPslaboratoriesschoolsworkplace, etc

Case-findingOutbreak of Hepatitis A in Ibiza 2000/2001

• Contacting clinicians and laboratories on the island

• Note in German Epidemiological Bulletin

• Enquiries through European network

Identify & count cases

Obtain information

Identifying information

Demographic information

Clinical details

Exposures and known risk factors

Obtaining informationOutbreak of Hepatitis A in Ibiza 2000/2001

• Trawling questionnaire

• Place and time of stay on Ibiza

• Food histories:

– What eaten

– Where bought?

– Visit to restaurants

Organize information: Line list

• Names• Date of birth• Addresse• Onset of symptoms• Treating physician• Hospital stay• Laboratory results

Line List

Case

No. Name

Date

of birthAddresse

Date of onset

Lab

results

1

2

3

4

5

6

XY

AB

CD

…

…

…

Identify & count cases

Obtain information

Analysis of descriptive data

Describe in

- time

- place

- person

Time: Epi Curve

• Histogram

• Distribution of cases by time of onset

of symptoms, diagnosis or identification– time interval depends on incubation period

Cases

0

1

2

3

4

5

6

7

8

9

10

1 2 3 4 5 6 7 8 9 10 11 12

Days

Epi curve

• Describe– start, end, duration

– peak

– importance

– atypical cases

• Helps to develop hypotheses– incubation period– etiological agent– type of source– type of transmission– time of exposure

0

1

2

3

4

5

6

7

8

9

10

1 2 3 4 5 6 7 8 9 10 11 12

Cases

Days

Examples of Epicurves

0

1

2

3

4

5

6

1 2 3 4 5 6 7 8

0

1

2

3

4

5

6

7

8

9

10

1 2 3 4 5 6 7 8 9 10 11 12

0

2

4

6

8

10

12

1 2 3 4 5 6 7 8 9 10 11 12 13

hours

cases

cases

cases

days

weeks

Common point source Common persistent source

Propagated source

0

1

2

3

4

5

6

7

8

9

10

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

cases

days

Common intermittent source

cases

10 tourists 9

8 residents76543210

30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 1

week number

JanuaryDecemberAugust September October November

Cases of Hepatitis A in Ibiza by week of onset, 2000/2001

Estimation of time or period of exposure

0

1

2

3

4

5

6

1 2 3 4 5 6 7 8

max incubation

min

cases

exposure

Outbreak of typhoid fever, Germany 2004

5 2

6 3 1 4

15 25 26 27 28 29 30 31 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

April May

Probable time period of infection

June

N° c

ases

Shortest incubation period:

Longest incubation period: 60 dayssuspected caseprobable caseconfirmed case

Place

• Place of residence• Place of possible exposure

– work– meals– travel routes, – day-care– leisure activities

• Maps– identify an area at risk

Cases of Hepatitis A in Ibiza by place of residence, 2000/2001

Portinatx

Ibiza-City

10 km

Person

• Distribution of cases – age– sex– occupation, etc

• Distribution of these variables in population • Attack rates

Outbreak of S. Agona, Germany 2003

2003 - Meldungen S. Agona

0

5

10

15

20

25

30

<1 1 2 3 4

5-9

10-1

4

15-1

9

20-2

4

25-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70+

age (years)

No

. Cas

es

20032002 - S. Agona notifications

0

5

10

15

20

25

30

<1 1 2 3 4

5-9

10-1

4

15-1

9

20-2

4

25-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70+

age (years)

No

. cas

es

2002

Cases of Hepatitis A in Ibiza by age group, 2000/2001

0

5

10

15

20

25

0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59

age (years)

percentage

Develop hypotheses

- Who is at risk of becoming ill?

- What is the disease?

- What is the source and the vehicle?

- What is the mode of transmission?

exploratory interviews among cases of Hepatitis A, Ibiza 2000/01

• 3 potential risk factors:– visited a restaurant in the harbour of Ibiza

town– bought food at a supermarket in the centre

of the town– stayed at Hotel in Portinatx (German

tourists)

Compare hypotheses with facts

Test specific hypotheses

Analytical studies- cohort studies- case-control studies

Testing hypothesis

• Cohort - attack rate exposed group- attack rate unexposed group

• Case control- proportion of cases exposed- proportion of controls exposed

Case-control study Outbreak of Hepatitis A in Ibiza 2000/2001

• among residents of the island

• one control per case

• selected from the data-base of the health registration card

• matching for age and neighbourhood • no history of hepatitis A disease or

vaccination.

Cases of Hepatitis A and controls by exposure to restaurant and shop,

Ibiza 2000/2001

Exposure Cases (n=38)

Controls (n=38)

matched

OR

95% CI

Restaurant 22 (57.9%) 5 (13.2%) 9.0 2.1-38.8

Shop 13 (34.2%) 6 (15.8%) 4.5 0.97-20.8

Cases of Hepatitis A and controls by exposure to food items, Ibiza 2000/2001

Restaurant

Cases

n = 22

Controls

n = 5

Matched

OR 95% CI

Salad 18 0 undef.

Shop n = 13 n = 6

Sausages 11 3 5.5 0.4-87.3

Meat 10 4 1.67 0.1-21.1

Vegetables 11 4 1.67 0.1-21.1

Fish 9 4 1.13 0.1-12.6

Bread 8 4 0.8 0.1-8.6

Verify hypothesisAdditional investigations

• Microbiological investigation of food samples

• Environmental investigation

• Veterinarian investigation

• Molecular Typing

• Trace back investigations (origin of foods)

• Meteorological data

• Entomological investigations

Viral genome sequencing Outbreak of Hepatitis A in Ibiza 2000/2001

• Alignment of aminoterminal region of VP3

• 38 serum samples

• Positive in 11 cases:

– belonging to the three different groups

– 100% homology

Food trace-back

Schleswig-Holstein

Hamburg

Niedersachsen

Bremen

Nordrhein-Westfalen

Hessen

Rheinland-Pfalz

Baden-Württemberg

Bayern

Saarland

Berlin

Brandenburg

Mecklenburg-Vorpommern

Sachsen

Sachsen-Anhalt

Thüringen

NL

Outbreak of S. Bovismorbificans,

Germany 2004

Implement control measures

1) Control the source of pathogen

2) Interrupt transmission

3) Modify host response

May (must) occur at any time during the outbreak!!

At first, general measures

According to findings, more specific measures

Recommendations Outbreak of Hepatitis A in Ibiza 2000/2001

• Emphasise hygiene amongst food handlers

• Strengthen surveillance for foodborne diseases

• Enhance international co-operation

Outbreak report

• Regular updates during the investigation

• Detailed report at the end

– communicate public health messages

– influence public health policy

– evaluate performance

– training tool

– legal proceedings

Steps of an outbreak investigation

• Confirm outbreak and diagnosis• Form Outbreak Control Team• Define a case • Identify cases and obtain information• Describe data by time, place, person• Develop hypothesis• Test hypothesis: analytical studies • Additional studies• Communicate results:

– outbreak report, publication

• Implement control measures

The reality….

Info:Outbreak suspected

time

Confirmation

Form Outbreak Control Team

Confirm Diagnosis

Site visit

Case definition

Line list

Organize Data

Descripitve Epidemiology

Control measures

AnalyticEpidemiology

Recommendations

ReportPublication