1. Outbreak Investigation EPIET Introductory course 2009 Lazareto, Menorca, Spain

2. 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

3. Why investigate outbreaks? Stop the outbreak Understand what happened and why Prevent future outbreaks Improve our knowledge Improve surveillance and outbreak detection Training

4. 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

5. Epidemiology Food safety Clinicians Laboratory Media Authorities Diagnostic Clinical Specimen transfer DeadSick Exposed SurveillanceInvestigation Prediction Supply channels Trace back Decisions Infrastructure Regulations Vaccinations etc Vector, Reservoir Investigation Co-ordination

6. Specific demands when investigating outbreaks Unexpected event Act quickly Rapid control Interdisciplinary coordination Work carried out in the field Systematic approach

7. 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 Control measures

8. 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. Red Sea

9. Detection Routine surveillance Clinical / Laboratory General public Media

10. 2002 (n=184) 2005 2004 (n=153) 2003 (n=150) Notified cases of S. Bovismorbificans, Germany 2002-2005

11. 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)

12. 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

13. 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 Hepatitis A European Tourists to Egypt Summer 2004

14. 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

15. Epidemiologist Microbiologist Clinician Environmentalist Engineers Veterinarians Others Team coordinates field investigation Outbreak confirmed, further investigations warranted Form Outbreak Control Team

16. Descriptive epidemiology - Who are the cases? (person) - Where do they live? (place) - When did they become ill? (time)

17. 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

18. Case definition Simple, practical, objective Sensitive? Specific? Multiple case definitions –confirmed –probable –possible CD can be adjusted, if new information becomes available

19. 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

20. Identify & count cases notifications hospitals, GPs laboratories schools workplace, etc

21. 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

22. Identify & count cases Obtain information Identifying information Demographic information Clinical details Exposures and known risk factors

23. 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 Hepatitis A European Tourists to Egypt Summer 2004

24. Organize information: Line list Names Date of birth Addresse Onset of symptoms Treating physician Hospital stay Laboratory results

25. Line List Case No. Name Date of birth Addresse Date of onset Lab results 123456123456 XY AB CD …

26. Identify & count cases Obtain information Descriptive study Describe in - time - place - person

27. Time: Epi Curve Histogram Distribution of cases by time of onset of symptoms, diagnosis or identification –time interval depends on incubation period Cases Days

28. 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 Cases Days

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

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

31. Outbreak of typhoid fever, Germany 2004 Muehlen et al, Eurosurveillance, 2006

32. Epicurve, German cases among hotel guests Hepatitis A European Tourists to Egypt Summer 2004 Period infected guests stayed at hotel “X“ Aug. 13th Information of RKI Min. period with infections 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) Cases Calendar week 15 -50 days pre 1. case 15 -50 days pre last case

33. Place Place of residence Place of possible exposure –work –meals –travel routes, –day-care –leisure activities Maps –identify an area at risk

34. 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

35. Person Distribution of cases –age –sex –occupation, etc Distribution of these variables in population Attack rates

36. Outbreak of S. Agona, Germany 2003 2003 2002

37. Cases by sex and age group, % hospitalized Hepatitis A European Tourists to Egypt Summer 2004

38. 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?

39. 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

40. Compare hypotheses with facts Test specific hypotheses Analytical studies - cohort studies - case-control studies

41. Testing hypothesis Cohort -attack rate exposed group -attack rate unexposed group Case control -proportion of cases exposed -proportion of controls exposed

42. 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

43. Cases and controls by 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=36OR95% CI Orange juice / breakfast82.3%63.9%2.61.1-6.6 Days drinking orange juice 0 days (Reference) 1-6 days 7-13 days 14+ days 17.7 13.2 32.4 36.8 36.1 30.5 16.7 Ref. 0.9 4 4,5 - 0.3-2.9 1.2-13.1 1.4-14.8

44. Dose-response, levels of exposure Hepatitis A European Tourists to Egypt Summer 2004

45. 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

46. 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

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

48. 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

49. 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

50. 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

51. 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

52. The reality…. Outbreak suspected time Confirmation Form Outbreak Control Team Confirm Diagnosis Site visit Case definition Line list Organize Data Descripitve Epidemiology Control measures Analytical Epidemiology Recommendations Report Publication