outbreak investigation epiet introductory course 2009 lazareto, menorca, spain
TRANSCRIPT
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
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
Hepatitis A European
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
Hepatitis A European
Tourists to Egypt
Summer 2004
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
Identify & count cases
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
Hepatitis A European
Tourists to Egypt
Summer 2004
Organize information: Line list
• Names• Date of birth• Addresse• Onset of symptoms• Treating physician• Hospital stay• Laboratory results
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
Hepatitis A European
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
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
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
Hepatitis A European
Tourists to Egypt
Summer 2004
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
Dose-response, levels of exposure
Hepatitis A European
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
Hepatitis A European
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