1. Insert name of presentation on Master Slide Epidemiology Toolkit for Outbreak Investigation Meirion Evans Communicable Disease Surveillance Centre

2. What is an outbreak? Occurrence of more cases of disease than expected Over a particular period of time In a given area Among a specific group of people (incidents, clusters)

3. Key questions What is going on?ASSESS Who is affected?DESCRIBE What is the cause?ANALYSE What should be done?ACT

4. 1.Confirm existence of an outbreak 2.Corroborate diagnosis 3.Define and identify cases 4.Collect and collate data 5.Characterise cases (person - place - time) 6.Develop hypotheses 7.Test hypotheses 8.Verify biological coherence 9.Communicate results and write report 10.Implement control measures ASSESS ANALYSE ACT 10 steps in outbreak investigation DESCRIBE

5. Confirm existence of an outbreak Corroborate diagnosis 3.Define and identify cases 4.Collect and collate data 5.Characterise cases (person - place - time) 6.Develop hypotheses 7.Test hypotheses 8.Verify biological coherence Communicate results and write report Implement control measures ANALYSE 10 steps in outbreak investigation DESCRIBE Descriptive epidemiology Analytical epidemiology

6. Descriptive epidemiology Define & identify cases Develop hypotheses Characterise cases Collect & collate data

7. To refine the case definition To develop a demographic profile To identify people at risk To develop hypotheses about Potential sources of exposure Potential routes of transmission Descriptive epidemiology OBJECTIVES

8. Case definition Set of criteria… for deciding if a person should be classified as having the disease for the purposes of that stage of the investigation Clinical and/or laboratory criteria Time Place Person Tiered definitions: confirmed, probable, possible

9. Case definition outbreak of salmonellosis in Swansea, 2011 Confirmed case diarrhoea (> 2 liquid stools per day) and/or fever > 38°C (for at least one day) and an isolate of S. Typhimurium in a resident of Swansea after May 2011 Probable case diarrhoea (> 2 liquid stools per day) and contact (same household) with a confirmed case in a resident of Swansea after May 2011

10. Case definition sensitivity vs. specificity Possible ProbableConfirmed Low Specificity High Specificity High Sensitivity Low Sensitivity

11. Identify & count cases Collect data demographics clinical details (outcome) risk factors (exposure) reports from staff laboratory data occupational health hospitals records GPs, etc

12. Collect data Detailed interviews symptoms and date of onset case characteristics all relevant exposures in relevant period Visit (examine) some cases Speak with clinicians Obtain lab confirmation

13. Collect data Collate data Line listing

14. Example line list Case No. Name Date of birth Date of onset Date of report Lab results 123456123456 XY AB CD …

16. Line listing - principles Constitutes a unique MASTER LIST avoids confusion with multiple versions suitable for sharing Contains unique identifier for each record Ensures confidentiality Contains essential information on each case time, place, person, clinical, lab, etc. Can be updated as the investigation develops Prepares data for simple descriptive analysis

17. Collect data Collate data Characterise cases describe in - person - place - time

18. Characterise cases Who are the cases? Where do they live, work, etc.? When did they become ill? Classify cases by: Person Place Time

19. Person Place Time Characterise cases Develop hypotheses Pathogen? Source? Transmission?

20. Person WHO is getting the disease? Sex and age group Ethnicity Pre-existing conditions Medication Invasive procedures Surgical treatment

21. Person C. difficile outbreak in peri-partum women

22. Place WHERE is the disease occurring? In the community Place of residence Place of work In hospital Floor Ward or unit Operating theatre Outpatient departments

23. Place Measles outbreak in a local community

24. Figure. Cases of gastroenteritis (n=45) in Hospital X, Wales by date of onset, January and February 2012 1 patient case 1 staff case Time WHEN does the disease occur?

25. To describe the outbreak Start date, end date, duration Peak, shape, magnitude Outliers and atypical cases To develop hypotheses Incubation period Aetiological agent Type of source and transmission Time of exposure Time - use of the epidemic curve

26. Time C. difficile outbreak timeline

27. Time Pseudomonas on a neonatal ICU

28. What is the disease? Who is at risk of becoming ill? What is the source and the vehicle? What is the mode of transmission? Develop hypotheses

29. Analytical epidemiology Test hypotheses Verify biological coherence

30. To test hypotheses Is there an association between exposure and disease? How strong is the association? What proportion of cases are explained by the exposure? Is there an increased risk of disease with increased exposure (dose-response)? Analytical epidemiology OBJECTIVES

31. Test hypotheses Analytical studies Cohort study Case-control study These must test specific hypotheses Compare the predictions of your hypotheses with further investigations

32. Testing hypothesis - comparing groups Cohort study - attack rate exposed group - attack rate unexposed group = risk ratio Case control study - proportion of cases exposed - proportion of controls exposed = odds ratio

33. Cohort Study Identify a cohort Categorise individuals based on whether or not they were exposed Compare attack rates  exposed vs unexposed Suitable when a cohort is easily identifiable e.g. specific ward(s), operating theatre list(s)

34. Case-Control Study Identify cases that meet the case definition Select non-diseased individuals from the same population to act as controls Compare proportions exposed cases vs. controls Suitable when a distinct group is not easily identifiable e.g. long-term outbreak, OPD

35. Cohort study two-by-two table Calculate association between exposure & disease dc ba NTotal c + d Unexposed a + b Exposed TotalWellIll Risk ratio [RR] = a/(a+b) / c/(c+d)

36. CC study two-by-two table Calculate association between disease & exposure dc ba NTotal Unexposed Exposed TotalControlCase Odds ratio [OR] = ad/bc

37. Table from a case control study Risk factors for MRSA bacteraemia Exposure Cases n=42 Controls n=90 Odds Ratio On admission Indwelling catheter on admission533.9 Prior admission35661.8 On or during admission Bed sore5112.0 Skin ulcer552.3 During admission Central line during admission17160.5 Urinary catheter during admission22248.4 Blood transfusion1576.6

38. Verify biological coherence Corroborative studies Microbiological investigation  suspected sources or vehicles of transmission  typing and molecular diagnostics Environmental investigation Traceback investigations (origin of supplies) Air circulation data

39. The reality…. Outbreak suspected time Confirmation Form Outbreak Control Team Confirm Diagnosis Site visit Case definition Line list Organise data Descriptive Epidemiology Control measures Analytical Epidemiology Recommendations Outbreak report

40. Methodological issues Keep things simple Stick to basic principles Get as much information as possible Be clear what the key questions are Design investigations to test hypotheses appropriately