Outbreak Investigation EPIET Introductory course 2006 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 in Ibiza, Spain September 2000 - January 2001 Tomorrow some operational and logistical aspects of outbreak investigation

Clinicians Epidemiology Co-ordination Food safety Laboratory Dead Sick Investigation Surveillance Prediction Exposed Clinicians Epidemiology Co-ordination Vector Reservoir Food safety Laboratory Clinical Supply channels Specimen transfer Trace back 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

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 Control measures 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 Detection

Notified cases of S. Bovismorbificans, Germany 2002-2005 2004 (n=153) 2003 (n=150)

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 Meet attending physicians 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

Immediate control measures? Further investigation? Outbreak confirmed  Immediate control measures? Further investigation? - prophylaxis - exclusion / isolation - public warning - hygienic measures - others - 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 Identify & count cases

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 Date of birth Addresse Date of onset Lab results 1 2 3 4 5 6 XY AB CD …

Analysis of descriptive data 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 Days

Epi curve Describe Helps to develop hypotheses atypical cases start, end, duration peak importance atypical cases Helps to develop hypotheses incubation period etiological agent type of source type of transmission time of exposure Days

Common intermittent source Examples of Epicurves Common persistent source Common point source cases cases hours days Propagated source cases Common intermittent source cases weeks days

Cases of Hepatitis A in Ibiza by week of onset, 2000/2001

Estimation of time or period of exposure cases max incubation min exposure

Outbreak of typhoid fever, Germany 2004

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 2003

Cases of Hepatitis A in Ibiza by age group, 2000/2001

Develop hypotheses - What is the disease? - 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)

Test specific hypotheses 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 Cases (n=38) Controls (n=38) matched OR 95% CI Restaurant 22 (57.9%) 5 (13.2%) 9.0 2.1-38.8 Shop 13 (34.2%) 6 (15.8%) 4.5 0.97-20.8

Cases of Hepatitis A and controls by exposure to food items, Ibiza 2000/2001 Restaurant Cases n = 22 Controls n = 5 Matched OR 95% CI Salad 18 undef. Shop n = 13 n = 6 Sausages 11 3 5.5 0.4-87.3 Meat 10 4 1.67 0.1-21.1 Vegetables Fish 9 1.13 0.1-12.6 Bread 8 0.8 0.1-8.6

Additional investigations 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

Outbreak of S. Bovismorbificans, Germany 2004 Food trace-back NL Outbreak of S. Bovismorbificans, Germany 2004

Implement control measures 1) Control the source of pathogen 2) Interrupt transmission 3) Modify host response At first, general measures According to findings, more specific measures May (must) occur at any time during the outbreak!!

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 Site visit Case definition Recommendations Report Publication Confirmation Organize Data Descripitve Epidemiology Confirm Diagnosis Info: Outbreak suspected Line list Analytic Epidemiology Form Outbreak Control Team Control measures