1. Outbreak Investigation Methodological aspects Jurgita Bagdonaite, Jolita Mereckiene Jurmala, Latvia, 2006 Based EPIET material

2. Objectives for this session Describe –the principles of outbreak investigation –the steps in outbreak investigation Using practical examples –Salmonella outbreak in Jura, France Next lecture –some operational and logistical aspects of outbreak investigation

3. What is an outbreak ? Occurrence of more cases of disease than expected –in a given area –among a specific group of people –over a particular period of time

4. Food-or waterborne outbreak (WHO definition) two or more persons similar illness after ingestion of the same type of food or water from the same source epidemiological evidence - the food or the water - the source of the illness

5. Why investigate outbreaks? Stop the outbreak –Find and neutralise the source (cause) –Prevent additional cases Prevent future outbreaks Improve surveillance and outbreak detection Improve our knowledge Keep the publics confidence Training

6. Retrospective investigation Often the outbreak exists since days, weeks, months Many cases already occurred Count on the memory of people Many data already collected; use them or start all over? Never too late, but more difficult

7. Community wide outbreak of Salmonellosis, Jura, spring 1997 Context Alert: District medical officer 80 cases of salmonellosis in 5 weeks Salmonella Typhimurium No link identified between cases High political and media profile Local outbreak team set up Cases continued to occur

8. Specific demands when investigating outbreaks Unexpected event Act quickly Rapid control Bias caused by media reports Legal and financial pressure Interdisciplinary coordination Work carried out in the field Systematic approach

9. 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

10. Role of the Epidemiologist Systematic Description Identification of risk factors (by descriptive or analytical means) Identification of interventions Work with others to implement control measures Evaluate the impact of control measures YOU MAY BE THE ONE TO COORDINATE !

11. Steps of an outbreak investigation Confirm outbreak and diagnosis Define a case Identify cases & obtain information Describe data collected and analyse Develop hypothesis Test hypothesis: analytical studies Special studies Communicate results, –including outbreak report Implement control measure Control measures

12. Detection Routine surveillance Clinical / Laboratory General public Media

13. Surveillance and outbreak detection: Salmonella Goldcoast strains by month of isolation, 1993-1996 Month Number of isolates 1993199419951996 Epidemic threshold facilitates detection

14. Confirm outbreak and diagnosis 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)

15. 3691215182124273033 Week of notification Number of cases 19961997

16. 3691215182124273033 Week of notification Number of cases 19961997 National meeting: legionellosis diagnosis and reporting

17. Confirm outbreak and diagnosis Laboratory confirmation –serology –isolates, typing of isolates –toxic agents Contact (visit) the laboratories Meet attending physicians Examine some cases Not always necessary to confirm all the cases but confirm a proportion throughout the outbreak

18. 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

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

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

21. 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

22. Case definition Simple, practical, objective Sensitive? Specific? Multiple case definitions –confirmed –probable –possible

23. Case definition Outbreak of salmonellosis in the Jura, spring 1997 Confirmed case diarrhoea (> 2 liquid stools per day) or fever (> 38°C, at least one day) and isolate of S. Typhimurium in a resident of Jura or neighbouring communities after May 1997 Probable case diarrhoea (> 2 liquid stools per day) and contact (same household) with confirmed case in a resident of the Jura or neighbouring communities after May 1997

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

25. Salmonellosis outbreak in the Jura case finding All laboratories in the Jura district Major laboratories in neighbouring districts National reference laboratory Food borne outbreak notifications Interview of cases

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

27. Salmonellosis in the Jura Obtaining information Trawling questionnaire: Attendance of events Places visited Food histories including, regional products

28. Identify & count cases Obtain information Analysis of descriptive data Describe in - time - place - person

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

30. 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

31. Epicurves hours cases days weeks Common point sourceCommon persistent source Propagated source

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

33. Outbreak of typhoid fever, Germany, 2004 (source, Marion Muehlen)

34. Cases of Salmonella Typhimurium infection by week of onset of symptoms, Jura, May - June 1997.

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

36. Distribution of cases of cholera, London 1854

37. Person Distribution of cases by age, sex, occupation,etc (numerator) –60 female –50 male Distribution of these variables in population (denominator) –600 females –350 males Attack rates –female: 60/600 –Males: 50/350

38. S.Typhimurium infection distribution of cases by age group, Jura, May - June 1997 Age groups (years) No cases <12 1 - 536 6 - 14 22 15 - 6429 > 659 Total98

39. S.Typhimurium infection attack rates by age group, Jura, May - June 1997

40. 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?

41. Outbreak of S. Typhimurium infections, Jura, spring 1997

42. Food consumption by cases, outbreak of Salmonellosis, Jura, spring 1997

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

44. Testing hypothesis Cohort -attack rate exposed group -attack rate unexposed group Case control -% of cases exposed -% of controls exposed

45. Food consumption by cases and controls, outbreak of salmonellosis, Jura, spring 1997

46. Verify hypothesis Special investigations/studies Microbiological investigation Environmental investigation Veterinarian investigation Trace back investigations (origin of foods) Meteorological data Entomological investigations

47. Special complementary investigations, outbreak of S. Typhimurium infections, Jura, spring 1997 Microbiological investigations –cheese samples cases homes, retail shops –human and food isolates by phage and molecular typing Trace back investigation supply channels Production plant –veterinarian (herds supplying milk) –occupational medicine –environmental

48. Investigation of supply channels CREMERIE Whole saler Production plant

49. Morbier vehicle of infection? Raw cows milk Eaten by children Regional product Morbier sampled at the residence of cases –S. Typhimurium isolated from 3 Morbiers leftovers –all other cheeses sampled tested negative Trace back: single producer No source of contamination identified

50. 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

51. Control measures, Outbreak of S. Typhimurium infections, Jura, 1997 At the beginning of the outbreak Personal hygiene advice Thorough cooking of meat and poultry After the investigation Recall of the incriminated batches of Morbier cheese

52. 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

53. Steps of an outbreak investigation Confirm outbreak and diagnosis Define case Identify cases and obtain information Descriptive data collection and analysis Develop hypothesis Analytical studies to test hypotheses Special studies Communication, including outbreak report Implement control measures control measures

54. Laboratory confirmation Source Outbreak control team meeting - urgent! TV inter view The Tasks ! Control measures ? Meet minister