outbreak investigation epiet introductory course 2011 lazareto, menorca, spain maaike van veen

Outbreak InvestigationOutbreak Investigation

EPIET Introductory course 2011Lazareto, Menorca, Spain

Maaike van Veen

Objectives for this session

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

• Using practical example– Outbreak of Hepatitis A among European Tourists to Egypt,

Summer of 2004 (Christina Frank et al. EID 2007)

• This afternoon (throughout the course)

– some operational and epidemiological aspects of outbreak investigation

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

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 (case definition)• 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

C. Frank et al. EID 2007

Detection

Routine surveillanceClinical / LaboratoryGeneral publicMedia

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

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

Hepatitis A European

Tourists to Egypt

Summer 2004

C. Frank et al. EID 2007

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

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

EpidemiologistMicrobiologistClinicianEnvironmentalistEngineersVeterinariansOthers

Team coordinatesfield investigation

Outbreak confirmed, further investigations warranted

Form Outbreak Control Team

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

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

Hepatitis A European

Tourists to Egypt

Summer 2004

C. Frank et al. EID 2007

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

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

Hepatitis A European

Tourists to Egypt

Summer 2004

C. Frank et al. EID 2007

Identify & count cases

Obtain information

Identifying information

Demographic information

Clinical details

Exposures and known risk factors

notificationshospitals, GPslaboratoriesschoolsworkplace, etc

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

Hepatitis A European

Tourists to Egypt

Summer 2004

C. Frank et al. EID 2007

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

Descriptive studyDescribe in

- time

- place

- person

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

Time: Epidemic 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

Epidemic 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 Epidemic curves

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

The Netherlands, Q-fever cases by date of symptom onset, 2007-2010

Num

ber

of c

ases

J. Whelan et al. ESCAIDE 2010

Epicurve, German cases among hotel guests

Hepatitis A European

Tourists to Egypt

Summer 2004

C. Frank et al. EID 2007

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

Place

• Place of residence• Place of possible exposure

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

Maps– identify an area at risk

• 392 cases

• “Bible belt”

• transmission to Canada (305 cases)

Outbreak Rubella 2004 -2005

Susan Hahné et al. Pediatr Infect Dis J. 2009

Cases geographically Hepatitis A European

Tourists to Egypt

Summer 2004

• Germany:– 271 primary cases, guests of

hotel X– 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

AustriaC. Frank et al. EID 2007

Person

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

• Distribution of these variables in population

• Attack rates

Cases by sex and age group, % hospitalized

Hepatitis A European

Tourists to Egypt

Summer 2004

C. Frank et al. EID 2007

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

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

Hepatitis A European

Tourists to Egypt

Summer 2004

C. Frank et al. EID 2007

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

• 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

Hepatitis A European

Tourists to Egypt

Summer 2004

C. Frank et al. EID 2007

Cases and controlsby exposure

Hepatitis A European

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

C. Frank et al. EID 2007

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

Verify hypothesisAdditional investigations

• Microbiological investigation of food samples

• Environmental investigation

• Veterinarian investigation

• Molecular Typing

• Trace back investigations (origin of foods)

• Meteorological data

• Entomological investigations

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

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

Recommendations

• Holiday destinations: improve food safety

• Travel companies: inform tourists (catalogues etc.)

• Travelers:

– seek pre-travel health advice according to destination

– follow vaccination recommendation for travel to endemic areas

– respect basic food safety rules

Hepatitis A European

Tourists to Egypt

Summer 2004

C. Frank et al. EID 2007

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

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

Acknowledgements

• Viviane Bremer

• Christina Frank

• Susan Hahné

• Jane Whelan

• EPIET

Questions??