Outbreak Investigation EPIET Introductory course 2009 Lazareto, Menorca, Spain

Outbreak InvestigationOutbreak Investigation

EPIET

Introductory course 2009

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 among

European Tourists to Egypt, Summer of 2004

• 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

Vector,Reservoir

Investigation

Co-ordination

Specific demands when investigating outbreaks

• Unexpected event

• Act quickly

• Rapid control

• Interdisciplinary coordination

• Work carried out in the field

Systematic approach

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

Initial Information

• Friday, 13th of August: Local Health Department in Germany notified of 4 cases of hepatitis A, all were in same hotel in Hurghada

• Within days, 50+ cases were known from all over Germany

• Egypt = major tourist destination (2004: >1 million visitors from Germany)

• Hotel not aware of ill guests

Hepatitis A European

Tourists to Egypt

Summer 2004

N

Med.

RedSea

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)

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

OutbreakConfirmation

• Hepatitis A notifiable disease in Germany• Surveillance case definition:

– clinical disease – plus laboratory confirmation

• 2001-3: 30 cases / year from Egypt

• Other European countries registered cases who had stayed in same hotel

• Later: cases infected with same virus strain


Tourists to Egypt

Summer 2004

Outbreak confirmed

Immediate control measures?

Further investigation?

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

- etiological 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

• CD can be adjusted, if new information becomes available

Case definitions

• Primary case– Initial: Any person

1. with IgM antibodies to Hepatitis A Virus and

2. clinical hepatitis A disease,

3. who had been to Egypt <50 days before onset

– Later: Any person 1., 2. and

3. who had stayed at hotel X <50 days before onset

• Secondary case– Any person 1., 2. and

3. who had not been to Egypt <50 days before onset

4. who had been exposed to a primary case


Tourists to Egypt

Summer 2004

Identify & count cases

notificationshospitals, GPslaboratoriesschoolsworkplace, etc

Case-finding

• German cases:

– Passive reporting of cases in German infectious disease notification system

– Note in German Epidemiological Bulletin, asking to specify the hotel for hepatitis A cases who had been to Egypt

• Other European cases:

– Note in European Early Warning Network (EWRS), asking other countries to inform Germany of cases possibly associated with this outbreak


Tourists to Egypt

Summer 2004


Obtain information

Identifying information

Demographic information

Clinical details

Exposures and known risk factors

Obtaininginformation

• Cases: Trawling questionnaire– period of stay in hotel

– activities inside and outside of hotel

– impression of hotel hygiene

– some basic food questions

• Hotel:– restaurants, meal plans

– food suppliers

– source of drinking water

– method of watering gardens

– differences to other hotels in Hurghada

– health of staff


Tourists to Egypt

Summer 2004

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

…

…

…


Obtain information

Descriptive studyDescribe 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

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° ca

ses Shortest incubation period: 3

Longest incubation period: 60 suspected caseprobable caseconfirmed case

Muehlen et al, Eurosurveillance, 2006

Epicurve, German cases among hotel guests


Tourists to Egypt

Summer 2004

Period infected guests stayedat hotel “X“

Aug. 13th Information

of RKI

Min. period withinfections

0

20

40

60

80

27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42

Erkrankungsdaten

Fä

lle

Secondary cases among travelers

23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 June July August Sept Oct 2004

Symptom onset (week)

Cas

es

Calendarweek

15 -50 days pre 1. case 15 -50 days pre last case

Place

• Place of residence• Place of possible exposure

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

Maps– identify an area at risk

Cases geographically Hepatitis A European

Tourists to Egypt

Summer 2004

• Germany:– 271 primary cases, guests of hotel X

• age: 2-67 years, median 34 years• 54% male

– 7 secondary cases, persons who had not traveled but were infected in Germany by guests of hotel X

• Elsewhere in Europe(A, S, DK, NL, B, I, CH, GB):– 60 primary cases– Secondary outbreak with 13 cases in

Austria

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 by sex and age group, % hospitalized


Tourists to Egypt

Summer 2004

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?

Basis for hypothesis

• Exploration:– many guests had not left hotel– visible hotel hygiene described as good

• Hotel:– did not recall ill staff members– most hotel aspects shared with most hotels

in Hurghada (e.g. source of water)– 2 unique food suppliers:

• ice cream• orange and grapefruit juices


Tourists to Egypt

Summer 2004

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

• among hotel guests, max. 1 person / houshold

• in hotel during supposed infectious period

• residents of 3 German states

• one control per case, unmatched

• no history of hepatitis A disease or vaccination (not checked by serology)

• telephone interviews


Tourists to Egypt

Summer 2004

Cases and controlsby exposure


Tourists to Egypt

Summer 2004

No difference between groups regarding:- age, sex- consumption of ice cream, salads- excursions, bathing habits, etc

But:

Cases

n=69

Controls

n=36 OR 95% CI

Orange juice / breakfast 82.3% 63.9% 2.6 1.1-6.6

Days drinking orange juice0 days (Reference)1-6 days7-13 days14+ days

17.713.232.436.8

36.130.516.716.7

Ref.0.94

4,5

-0.3-2.91.2-13.11.4-14.8

Dose-response, levels of exposure


Tourists to Egypt

Summer 2004

0

10

20

30

40

50

0 1-6 7-13 14+Number of days on which orange juice was consumed (breakfast)

Pro

po

rtio

n o

f g

rou

p (

%)

cases (n=68) controls (n=36)

OR: 0.9 (0.3-2.9)

OR: 4.0 (1.2-13.1)

Reference

OR: 4.5 (1.4-14.8)

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 seemingly three different groups of cases (guests of hotels, employees)

– 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

• Holiday destinations: improve food safety

• Travel companies: inform tourists (catalogues etc.)

• Travelers:

– seek pre-travel health advice accoding to destination

– follow vaccination recommendation for travel to endemic areas

– respect basic food safety rules


Tourists to Egypt

Summer 2004

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….

Outbreak suspected

time

Confirmation

Form Outbreak Control Team

Confirm Diagnosis

Site visit

Case definition

Line list

Organize Data

Descripitve Epidemiology

Control measures

AnalyticalEpidemiology

Recommendations

ReportPublication

Documents

Outbreak Investigation EPIET Introductory course 2009 Lazareto, Menorca, Spain