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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? • • • • • • 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 • • • • • • • • • 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 • • • • • • • 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