Outbreak Investigation Methodological aspects

1. Outbreak InvestigationMethodological 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) • twoor 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 public’s 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. Systematic approach 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

9. Co-ordination Dead Sick Investigation Surveillance Exposed Prediction Clinicians Epidemiology Vector Reservoir Food safety Laboratory Clinical Supply channels Specimen transfer Trace back Investigation Diagnostic Authorities Decisions Infrastructure Regulations Vaccinations etc Media

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. Control measures 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

12. Routine surveillance Clinical / Laboratory General public Media Detection

13. Surveillance and outbreak detection: Salmonella Goldcoast strains by month of isolation, 1993-1996 Number of isolates Epidemic threshold facilitates detection 1993 1994 1995 1996 Month

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. Cases of legionellosis by week of notification France, January 1996 - August 1997 8 7 6 5 4 3 2 1 0 1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 Number of cases 3 6 9 12 15 18 21 24 27 30 33 1996 1997 Week of notification

16. Cases of legionellosis by week of notification France, January 1996 - August 1997 8 7 6 5 4 3 2 1 0 1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 Number of cases National meeting: legionellosis diagnosis and reporting 3 6 9 12 15 18 21 24 27 30 33 1996 1997 Week of notification

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. Further investigation? Immediate control measures? Outbreak confirmed  - 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. Form Outbreak Control Team? Team coordinatesfield investigation Outbreak confirmed, further investigations warranted Epidemiologist Microbiologist Clinician Environmentalist Engineers Veterinarians Others

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. 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 Case definitionOutbreak of salmonellosis in the Jura, spring 1997

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

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

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

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

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

29. TimeEpi 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 Cases • 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 Days

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

32. max incubation min Estimation of time or period of exposure 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. X PUMP B WORK HOUSE POLAND STREET MARSHALL STREET CARNABY STREET X BERWICK STREET PUMP A BROAD STREET BREWERY SILVER STREET REGENT STREET GREAT PULTENEY STREET GOLDEN X SQUARE PUMP X PUMP C X N PUMP W E S 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. Age groups No cases (years) <1 2 1 - 5 36 22 6 - 14 15 - 64 29 > 65 9 Total 98 S.Typhimurium infection distribution of cases by age group, Jura, May - June 1997

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

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 Whole saler Production plant CREMERIE

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