Download What is an outbreak

Outbreak 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?
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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
Investigation
Dead
Surveillance
Exposed
Prediction
Epidemiology
Vector,
Reservoir
Supply
channels
Trace
back
Sick
Clinicians
Co-ordination
Food safety
Laboratory
Clinical
Specimen
transfer
Investigation
Diagnostic
Media
Authorities
Decisions
Infrastructure
Regulations
Vaccinations etc
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
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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
Hepatitis A
European Tourists
to Egypt
Initial Information
Summer 2004
• 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
Med.
N
• Egypt = major tourist destination
(2004: >1 million visitors from Germany)
• Hotel not aware of ill guests
Red
Sea
Detection
Routine surveillance
Clinical / Laboratory
General public
Media
Notified cases of S. Bovismorbificans,
Germany 2002-2005
no. cases
120
100
80
60
40
20
0
2002
(n=184)
2003
(n=150)
2004
(n=153)
2005
Confirm outbreak
Is 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 cases
but confirm a proportion
throughout the outbreak
Hepatitis A
European Tourists
to Egypt
Summer 2004
Outbreak
Confirmation
• 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
Outbreak confirmed 
Immediate control
measures?
- prophylaxis
- exclusion / isolation
- public warning
- hygienic measures
- others
Further
investigation?
- etiological agent
- mode of transmission
- vehicle of transmission
- source of contamination
- population at risk
- exposure causing illness
Outbreak confirmed,
further investigations warranted
Form Outbreak
Control Team
Team coordinates
field investigation
Epidemiologist
Microbiologist
Clinician
Environmentalist
Engineers
Veterinarians
Others
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
Hepatitis A
European Tourists
to Egypt
Case definitions
Summer 2004
•
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
Identify &
count cases
notifications
hospitals, GPs
laboratories
schools
workplace, etc
Hepatitis A
European Tourists
to Egypt
Case-finding
Summer 2004
• 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
Identify &
count cases
Obtain
information
Identifying information
Demographic information
Clinical details
Exposures and known
risk factors
Hepatitis A
European Tourists
to Egypt
Summer 2004
Obtaining
information
• 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
Organize information: Line list
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Names
Date of birth
Addresse
Onset of symptoms
Treating physician
Hospital stay
Laboratory results
Line List
Case
No.
Name
1
2
3
4
5
6
XY
AB
CD
…
…
…
Date
Addresse
of birth
Date of
onset
Lab
results
Identify &
count cases
Obtain
information
Descriptive study
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
10
9
8
7
6
5
4
3
2
1
0
1
2
3
4
5
6
7
Days
8
9
10
11
12
Epi curve
• Describe
– start, end, duration
– peak
– importance
– atypical cases
Cases
10
9
8
7
6
5
4
3
2
1
0
1
• Helps to develop hypotheses
–
–
–
–
–
incubation period
etiological agent
type of source
type of transmission
time of exposure
2
3
4
Days
5
6
7
8
9
10
11
12
Examples of Epicurves
Common persistent
source
Common point source
cases
cases
10
9
6
8
7
6
5
4
5
4
3
2
3
2
1
1
0
0
1
2
3
4
5
6
7
8
1
hours
12
10
cases
10
9
8
7
6
8
6
2
5
4
3
2
0
1
0
4
1
2
3
4
5
6
7
weeks
3
4
5
6
7
8
9
10
11
12
days
Propagated source
cases
2
8
9
10
11
12
13
Common
intermittent source
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
days
Estimation of time
or period of exposure
max incubation
cases
6
5
min
4
3
2
1
0
1
2
3
4
exposure
5
6
7
8
Outbreak of typhoid fever,
Germany 2004
suspected case
probable case
confirmed case
Longest incubation period: 60
N° cases
Shortest incubation period: 3
6
15
April
25
May
26
27
28
29
30
31
1
2
June
Probable time period of infection
Muehlen et al, Eurosurveillance, 2006
3
4
5
6
7
8
9
10
11
5
2
3
1
4
12
13
14
15
Hepatitis A
Epicurve, German cases
among hotel guests
European Tourists
to Egypt
Summer 2004
80
Erkrankungsdaten
Symptom
onset (week)
Cases
Fälle
60
40
Secondary cases among travelers
20
0
Calendar
week
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
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
Min. period with
infections
Period infected guests stayed
at hotel “X“
15 -50 days pre 1. case
Aug. 13th
Information
of RKI
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
Hepatitis A
European Tourists
to Egypt
Cases geographically
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
2002 - S. Agona notifications
2003
30
25
25
20
20
age (years)
age (years)
70+
60-69
50-59
40-49
30-39
25-29
20-24
15-19
10-14
5-9
4
3
70+
60-69
50-59
40-49
30-39
25-29
20-24
15-19
10-14
0
5-9
0
4
5
3
5
2
10
1
10
2
15
1
15
<1
No. Cases
30
<1
No. cases
2002
Hepatitis A
European Tourists
to Egypt
Summer 2004
Cases by sex and age
group, % hospitalized
50
70
male
Cases
40
female
57
62
% hospitalized
30
42
20
10
44
30
25
0
0
<10
10 - 19
20 - 29
30 - 39
Age group
40 - 49
50+
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?
Hepatitis A
European Tourists
to Egypt
Basis for hypothesis
Summer 2004
• 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
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
Hepatitis A
European Tourists
to Egypt
Case-control study
Summer 2004
• 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 controls
by exposure
No difference between groups regarding:
- age, sex
- consumption of ice cream, salads
- excursions, bathing habits, etc
But:
Orange juice / breakfast
Cases
n=69
Controls
n=36
OR
95% CI
82.3%
63.9%
2.6
1.1-6.6
17.7
13.2
32.4
36.8
36.1
30.5
16.7
16.7
Ref.
0.9
4
4,5
0.3-2.9
1.2-13.1
1.4-14.8
Days drinking orange juice
0 days (Reference)
1-6 days
7-13 days
14+ days
Hepatitis A
European Tourists
to Egypt
Dose-response,
levels of exposure
Summer 2004
Proportion of group (%)
50
40
Reference
OR: 0.9
(0.3-2.9)
30
OR: 4.0 (1.213.1)
OR: 4.5
(1.4-14.8)
20
10
0
0
1-6
7-13
14+
Number of days on which orange juice was consumed (breakfast)
cases (n=68)
controls (n=36)
Verify hypothesis
Additional 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
NL
Schleswig-Holstein
Mecklenburg-Vorpommern
Hamburg
Bremen
Niedersachsen
Berlin
Brandenburg
Sachsen-Anhalt
Nordrhein-Westfalen
Sachsen
Thüringen
Hessen
Rheinland-Pfalz
Saarland
Bayern
Baden-Württemberg
Outbreak of
S. Bovismorbificans,
Germany 2004
Implement control measures
May (must) occur at any
time during the outbreak!!
At first, general measures
According to findings,
more specific measures
1) Control the source of pathogen
2) Interrupt transmission
3) Modify host response
Hepatitis A
European Tourists
to Egypt
Recommendations
Summer 2004
• 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
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….
time
Confirmation
Site visit
Recommendations
Case definition
Report
Publication
Organize Data
Confirm Diagnosis
Outbreak
suspected Form Outbreak
Control Team
Descripitve
Epidemiology
Line list
Analytical
Epidemiology
Control measures