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