Outbreak Investigation
Dr.Kedar Karki
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 in Ibiza, Spain September 2000 - January 2001 • Tomorrow – some operational and logistical aspects of outbreak investigation
Investigation
Surveillance
Dead
Sick
Prediction
Exposed
Epidemiology
Vector Reservoir
Clinicians
Co-ordination
Food safety
Supply channels Trace back
Laboratory
Clinical
Investigation
Specimen transfer 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
Outbreak of Hepatitis A in Ibiza (Spain) 2000/2001
• Ibiza is a major tourist destination (2 million visitors in 2000)
• 23-27 October 2000: 5 cases of Hepatitis A notified to local health authorities in Ibiza
• 3 cases of Hepatitis A among German tourists returning from Ibiza
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
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)
Outbreak of Hepatitis A in Ibiza, Spain
• Hepatitis A notifiable disease in Spain • notifications in Ibiza during previous years: – 1997: 6 cases – 1998: 0 cases – 1999: 4 cases
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
Outbreak confirmed
Immediate control measures?
- prophylaxis - exclusion / isolation - public warning - hygienic measures - others
Further investigation?
- aetiological 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
Epidemiologist Microbiologist Clinician Environmentalist Engineers Veterinarians Others
Team coordinates field investigation
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
Case definition
Outbreak of Hepatitis A in Ibiza 2000/2001
Any person • with IgM antibodies to Hepatitis A Virus August 2000 - January 2001 • on the island of Ibiza for at least one day during a 15-50 day period before onset of illness or seroconversion
Identify & count cases
notifications hospitals, GPs laboratories schools workplace, etc
Case-finding
Outbreak of Hepatitis A in Ibiza 2000/2001
• Contacting clinicians and laboratories on the island • Note in German Epidemiological Bulletin • Enquiries through European network
Identify & count cases
Obtain information
Identifying information Demographic information
Clinical details
Exposures and known risk factors
Obtaining information
Outbreak of Hepatitis A in Ibiza 2000/2001 • Trawling questionnaire • Place and time of stay on Ibiza • Food histories:
– What eaten
– Where bought?
– Visit to restaurants
Organize information: Line list
• • • • • • • Names Date of birth Addresse Onset of symptoms Treating physician Hospital stay Laboratory results
Line List
Case No.
Name XY AB CD … … …
Date Addresse of birth
Date of onset
Lab results
1 2 3 4 5 6
Identify & count cases
Obtain information
Describe in - time - place - person
Analysis of descriptive data
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 8 9 10 11 12
Days
Epi curve
• Describe
– start, end, duration – peak – importance
Cases
10 9 8 7 6 5 4 3 2 1 0 1 2 3 4 5 6 7 8 9 10 11 12
– atypical cases – – – – – incubation period etiological agent type of source type of transmission time of exposure
• Helps to develop hypotheses
Days
Examples of Epicurves
Common point source
cases
6 5 4 3 2 1 0 1 2 3 4 5 6 7 8
cases
10 9 8 7 6 5 4 3 2 1 0 1 2
Common persistent source
3
4
5
6
7
8
9
10
11
12
hours cases
12 10 8 6 4 2 0 1 2 3 4 5 6 7 8 9 10 11 12 13
days cases
10 9 8 7 6 5 4 3 2 1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Propagated source
Common intermittent source
weeks
days
Cases of Hepatitis A in Ibiza by week of onset, 2000/2001
cases
10 9 8 7 6 5 4 3 2 1 0
tourists residents
30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 1
week number
August September October November December January
Estimation of time or period of exposure
cases
6 5 4 3 2 1 0 1 2 3
max incubation min
4
5
6
7
8
exposure
Outbreak of typhoid fever, Germany 2004
Longest incubation period: 60 days suspected case probable case confirmed case
N° cases
Shortest incubation period:
5 6 15 April 25 May 26 27 28 29 30 31 1 J une 2 3 4 5 6 7 8 9 10 11 3 12
2 1 13 4 14 15
Probable time period of infection
Place
• Place of residence • Place of possible exposure – work – meals – travel routes, – day-care – leisure activities • Maps – identify an area at risk
Cases of Hepatitis A in Ibiza by place of residence, 2000/2001
Portinatx
Ibiza-City
10 km
Person
• Distribution of cases – age – sex – occupation, etc • Distribution of these variables in population • Attack rates
Outbreak of S. Agona, Germany 2003
2002 - S. Agona notifications
2002
2003 - Meldungen S. Agona
2003
30 25 20
30 25 20 15 10 5 0
No. cases
15 10 5 0
No. Cases
10-14
15-19
20-24
25-29
30-39
40-49
50-59
10-14
15-19
20-24
25-29
30-39
40-49
50-59
60-69
age (years)
age (years)
60-69
70+
70+
1
2
3
<1
4
5-9
5-9
1
2
3
<1
4
Cases of Hepatitis A in Ibiza by age group, 2000/2001
percentage 25 20 15 10 5 0 0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 age (years)
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?
exploratory interviews
among cases of Hepatitis A, Ibiza 2000/01
• 3 potential risk factors:
– visited a restaurant in the harbour of Ibiza town – bought food at a supermarket in the centre of the town – stayed at Hotel in Portinatx (German tourists)
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
Outbreak of Hepatitis A in Ibiza 2000/2001
• among residents of the island • one control per case • selected from the data-base of the health registration card • matching for age and neighbourhood • no history of hepatitis A disease or vaccination.
Cases of Hepatitis A and controls by exposure to restaurant and shop, Ibiza 2000/2001
Exposure Cases (n=38) 22 (57.9%) 13 (34.2%) Controls (n=38) 5 (13.2%) 6 (15.8%) matched OR 9.0 4.5 95% CI
Restaurant Shop
2.1-38.8 0.97-20.8
Cases of Hepatitis A and controls by exposure to food items, Ibiza 2000/2001
Restaurant
Salad
Cases n = 22
18
Controls n=5
0
Matched OR
undef.
95% CI
Shop Sausages Meat Vegetables Fish Bread
n = 13 11 10 11 9 8
n=6 3 4 4 4 4 5.5 1.67 1.67 1.13 0.8 0.4-87.3 0.1-21.1 0.1-21.1 0.1-12.6 0.1-8.6
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 the three different groups
– 100% homology
Food trace-back
NL
Schleswig-Holstein Mecklenburg-Vorpommern Hamburg Bremen Niedersachsen Berlin Brandenburg Sachsen-Anhalt Nordrhein-Westfalen Sachsen Thüringen Hessen
Outbreak of S. Bovismorbificans, Germany 2004
Rheinland-Pfalz Saarland
Bayern Baden-Württemberg
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
Recommendations
Outbreak of Hepatitis A in Ibiza 2000/2001
• Emphasise hygiene amongst food handlers • Strengthen surveillance for foodborne diseases
• Enhance international co-operation
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 Report Publication
Case definition Organize Data Confirm Diagnosis Info: Outbreak suspected Form Outbreak Control Team Descripitve Epidemiology Line list
Analytic Epidemiology Control measures