Outbreak Investigation Step by Step

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1 Outbreak Investigation Step by Step Darin Areechokchai MD., DTM&H., MCTM. Surveillance and Investigation Section Bureau of Epidemiology, Department of Disease Control Ministry of Public Health, Thailand 1

2 Outline Introduction: Epidemiology is Outbreak: Definition, Type, Detection Investigation: Steps 2

3 What is Epidemiology? Study of Disease Occurrence Distribution of disease Population by person, place, and time Determinants (Risk Factors) Disease Control 3

4 Roles of Epidemiology in Public Health Surveillance Outbreak Investigation Epidemiological Study Evaluation of PH measures *RM Page, et al. Basic epidemiological methods and biostatistics, 1995 p.32 4

5 Definition of Outbreak The occurrence of cases of an illness, specific health-related behaviour, or other health-related events clearly in excess of normal expectancy. The area and the What is the period in which the cases occur are specified precisely. normal expectancy? 5

6 Excess of Normal Expectancy More than Median number of cases in previous 5 years or Average number of cases + 2sd of previous 5 yr Number of Cholera case by month, District A # cases Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 2003 Median

7 Judged to be an outbreak Cases linked to the same factors 7

8 Judged to be an outbreak A single case of disease that has never been occurred before. 1997: A 3-year old boy, case of Avian Flu (H5N1) in Hong Kong alerted the public health people around the world to start a full scale investigation. 8

9 Terms Endemic = Disease that routinely occurs in a given place Epidemic = Outbreak (outbreak -> sense of urgency, Epidemic -> sense of wide spreading) Cluster = An aggregation of cases in a given place & time Pandemic = Epidemic that spreads over many countries of regions of the world 9

10 1918 flu pandemic (Spanish flu) million deaths worldwide in 18 months 10

11 Detection of the outbreak Sources of outbreak news: Surveillance data that are collected and analyzed timely Health care provider or citizen who knows of several cases Media: Newspaper, TV, Internet 11

12 Media reports outbreak 2 deaths and 118 coma cases after eating raw park salad in a cremation 12

13 Surveillance for outbreak detection Reported Cholera cases in Khonkaen, Thailand January July Jan Mar May July Sep Nov Jan Mar May July Sep Nov Jan Mar May July Sep Nov Jan Mar May July Sep Nov Jan Mar May July

14 Outbreak patterns Common source outbreak Propagated source outbreak (Person-to-person) 14

15 Common Source Outbreak Food # case Common source Date of onset 15

16 Propagated Source Outbreak # cases Date of onset 16

17 Outbreak: the basics Definition More than normal expectancy Cases with epidemiological linkage New disease (emerging disease) Detection Surveillance Health care providers media Pattern and epidemic curve Common source Propagated source 17

18 Steps of Outbreak Investigations 18

19 Why investigate an outbreak? Characterize a public health problem Identify preventable risk factors Recommend control and prevention measures 19

20 Usual sequence of events Primary Case 1st case at HC Report to DMO Samples taken Lab result Response begins Opportunity for control Days

21 Ideal sequence of events Primary Case Response begins Potential cases prevented Days 14

22 Steps of an outbreak investigation 1. Prepare for Field Work : Rapid Response Team 2. Confirm outbreak and diagnosis 3. Define case and start case-finding 4. Descriptive data collection and analysis 5. Develop hypothesis 6. Analytical studies to test hypotheses 7. Special studies (e.g. environmental study) 8. Communicate the conclusion and recommend control measures 9. Follow-up the control implementations Implement control measures 22

23 I. Preparing for field works 1. Team members and roles 2. Necessary Knowledge and equipments; specimen collection & transport method, etc. 3. Lines of communication 23

24 II. Confirm outbreak and diagnosis Is this an outbreak? What is the diagnosis? Link between cases? Higher than expected? Clinical manifestation Laboratory result 24

25 Scenario 1 Many adults in a remote village were sick with fever, severe joint and muscle pain and rash over the body Is this an outbreak? What is the likely diagnosis? Should we start the investigation? Which intervention should be started? Outbreak confirmed Maybe measles, rubella, dengue etc. Investigation warranted Shall we start the vaccination or spray mosquitoes? 25

26 To Investigate or not to Investigate Consider the following factors when deciding whether or not to investigate an outbreak It could be true outbreak with common cause It could be unrelated cases of the same disease Severity of illness Transmissibility Local politics Public concern 26

27 Outbreak confirmed, further investigations warranted Form Outbreak Investigation & Control Team Team coordinates field investigation Epidemiologist Clinician Microbiologist Environmentalist Government Press officer Others 27

28 Steps of an outbreak investigation 1. Prepare for Field Work : Rapid Response Team 2. Confirm outbreak and diagnosis 3. Define case and start case-finding 4. Descriptive data collection and analysis 5. Hypothesis generation 6. Analytical studies to test hypotheses 7. Special studies (e.g. environmental study) 8. Communicate the conclusion and recommend control measures 9. Follow-up the control implementations Implement control measures 28

29 Which one is longer? Standard measurement 29

30 Case Definition Standard criteria for deciding if a person should be classified as suffering from the disease under investigation Clinical criteria, restrictions of time, place, person Simple, practical, objective Sensitivity versus specificity 30

31 Case definition: example Patient older than 5 years with severe dehydration or dying of acute watery diarrhoea in town x between 1 June and 20 July

32 Case Definitions Can emphasize sensitivity or specificity in case definition Sensitivity: Most cases detected, but many false positives many specimens Overload to test low % tested specimens +ve SENSITIVITY SPECIFICITY Specificity: Cases missed, but SENSITIVITY SPECIFICITY few false positives fewer specimens Underloadto test high % tested specimens +ve 32

33 Case Definition Categories of cases Suspected Symptoms reported but not confirmed No lab or epidemiologic link Probable Symptoms confirmed Epidemiologic link Initial lab test Confirmed Lab test Epidemiologic link > 5 yr in town X Suspected With diarrhea symptoms Probable Mucous bloody diarrhea WBC, RBC in stool exam Confirmed RSC found Shigella sonnei 33

34 (Passive cases) (Active cases) 34

35 Why is Case Finding Important? In an outbreak: There are usually more cases than are reported to the health department Reported cases may not be representative of all cases To identify exposure and/or outcome investigator needs information from persons who represent all cases 35

36 Why is Case Finding Important? To refine the case definition as more information is garnered To define the exposed population for the purposes of developing control measures 36

37 How to Find Cases Passive strategies involve review of information available OPD, IPD log book in hospitals, Health center Laboratory log book Active strategies Screening unit in the affected area Door to door 37

38 Information to Collect during Case Finding Process Demographic information Age, gender, race, occupation Clinical information Symptoms, date of onset, lab results, severity of illness risk factor information to collect Varies by type of outbreak 38

39 Identifying info. Survey of hepatitis B cases in a male juvenile detention, Saraburi, Thailand, November 1999 Date of interview Interviewer's name Patient number Patient's name-surname Age (in years) Number of domitory (1-5) Study field 1. Machanic 2. Carpanter 3. Electric Demographic info. 4. Barber 5. Music 6. Agriculture Clinical symptoms (sick inside the juvenile detention, since 1 Jan 99) Possible risk factors No Yes Onset of symptoms Tatooing Y N Jaundice Homosexual Y N Nausia/Vomiting Injected drug user Y N Fatigue This hepatitis cases is laboratory confiry N Clinical info. Risk factors 39

40 Line Listing: What and Why? It provides organized information about the cases Can be quickly reviewed and updated Create a table in which each row represents a case and each column represents a variable of interest 40

41 Line listing of streptococcus meningitis cases after eating raw pork ID Sex Age Onset Alcohol 25/4/07 26/4/07 BF LUN DIN BF LUN DIN 1 M 50 27/4/07 Yes Raw Raw - Cook Cook Cook 2 M 41 26/4/07 Yes Raw Raw M 43 27/4/07 Yes Raw Raw M 62 27/4/07 Yes Raw Raw Cook M 71 26/4/07 No - Raw M 56 26/4/07 Yes - Raw M 51 27/4/07 Yes - Raw - - Cook - 8 M 50 26/4/07 Yes Raw Raw F 49 27/4/07 Yes - Raw

42 Using Information from a Line Listing Frequency distributions of demographics May provide information about exposure and/or risk of disease Frequency distributions of potential exposures May provide information about source or route of transmission 42

43 Descriptive data analysis Time: Epidemic curve Place: spot map area map Attack rate (incidence) by place Person Frequency Specific attack rate (incidence) 43

44 Epidemic Curve: How Can it Help in an Outbreak? An epidemic curve (epi curve) is a graphical depiction of the number of cases of illness by the date (time) of illness onset 44

45 What is an Epidemic Curve and How Can it Help in an Outbreak? An epi curve can provide information on the following characteristics of an outbreak: Pattern of spread Magnitude Outliers Time trend Exposure and/or disease incubation period 45

46 Epi curve: Outbreak Pattern of Spread The overall shape of the epi curve can reveal the type of outbreak Common source Propagated 46

47 Epi curve: Outbreak Time Trend Allow information about the time trend of the outbreak to be gleaned Consider: Date of illness onset for the first case Date when the outbreak peaked Date of illness onset for the last case 47

48 Epi curve: Outbreak Outliers Outliers are cases at the very beginning and end that may not appear to be related If they are not an error, they may represent Baseline level of illness Outbreak source A case exposed earlier than the others An unrelated case A case exposed later than the others A case with a long incubation period 48

49 Epidemic curve: Exposure period Exposure period = (Onset of the first case Shortest incubation period) to (Onset of the most cases the average incubation period) Number of cases suspect first case active passive October Date of onset 49

50 How do I Make an Epi Curve? Plot the number of cases of disease reported during an outbreak on the y-axis Plot the time or date of illness onset on the x-axis 50

51 How do I Make an Epi Curve? Technical tips Choice of time unit for x-axis depends upon the incubation period Begin with a unit approximately one quarter of the incubation period 51

52 How do I Make an Epi Curve? Epi curves are histograms There should not be any space between the x-axis categories Label each axis Provide a descriptive title Include the pre-epidemic period to show the baseline number of cases 52

53 Measles case distribution by sector, Nupo camp, Tak, Jan Mar Case in week Case in week 6 3 Case in week 7 4 Case in week 8 15 Case in week 9 Case in week Case in week 11 Burma Case in week 12 Case in week 13 8 Epidemic curve by week of onset (N = 27) 7 6 number of cases w k1 w k2 w k3 w k4 w k5 w k6 w k7 w k8 w k9 w k10 w k11 w k12 w k13 w k14

54 Distribution of avian influenza cases Thailand, Jan Mar cases in 8 provinces Male : Female = 8 : 3 Median age 7 (2-58 years old) 8 died (CFR 72.7%) : Area of poultry outbreak died (N=8) improved (N=3) - Age <15 years CFR 85.7% - Age >15 years CFR 50.0% 54

55 Clinical manifestations of confirmed AI cases Thailand, Jan Mar 2004 Fever Cough Sputum Dyspnea Rhinorrhea Diarrhea Vomiting Wbc<5000 Platelet<10 6 Pleural effus Pediatric (N=7) Adult (N=4) Percent of cases

56 Area map: Human brain 56

57 Cases Person Place Time '5-14 '15-44 '45-64 '64+ 0 Age Group Evaluate information Pathogen? Source? Transmission? Set Hypothesis from all information 57

58 Steps of an outbreak investigation 1. Prepare for Field Work : Rapid Response Team 2. Confirm outbreak and diagnosis 3. Define case and start case-finding 4. Descriptive data collection and analysis 5. Hypothesis generation 6. Analytical studies to test hypotheses 7. Special studies (e.g. environmental study) 8. Communicate the conclusion and recommend control measures 9. Follow-up the control implementations Implement control measures 58

59 Hypothesis generation - Who is at risk of becoming ill? - What is the source and the vehicle? - What is the mode of transmission? Examples Tatooing was the risk of getting hepatitis B infection, because 13 out of 15 cases had new tatooes. A shallow well was the source of shigella, because most of case used water from there. Juice from the school cafeteria caused the illness, because a pass-by visitor got sick after drank a glass of juice. (outlier case) 59

60 Analytical studies to test hypotheses Develop hypotheses - Who is at risk of becoming ill? - What is the source and the vehicle? - What is the mode of transmission? Analytic study - study design; case-control, cohort - sampling control (non-cases) - data collecting: more detailed questionnaire 60

61 Steps in creating a questionnaire 1. Identify the leading hypotheses about the source of the problem 2. Identify the information needed to test the hypotheses 3. Identify the information needed for logistics of the study and to examine confounding 61

62 Steps in creating a questionnaire 4. Write the questions to collect this information 5. Organize the questions into questionnaire format 6. Test the questionnaire 7. Revise the questionnaire 8. Train interviewers to administer the questionnaire 9. Ethics 62

63 About Analytic Studies We can use analytic studies to test hypotheses. We want to know: Whether there is an association between exposure and disease, How strong the association is, What proportion of cases are due to exposure, and Whether there is an increased risk of disease with increased exposure (a dose-response relationship). Two common types of analytic studies are cohort study and case-control study. 63

64 What is a Cohort? A cohort is a group of people who have something in common. Can represent the source population the population from which cases of disease arise. Examples of cohorts: All employees in an office building Everyone who attended a football game All the residents of a neighborhood 64

65 Cohort Studies Tend to be retrospective (exposures in the past in relation to disease that has already happened). Occurrence of disease in exposed group compared to occurrence of disease in unexposed group = risk ratio. Risk ratio tells whether disease is associated with exposure and strength of association. 65

66 Cohort study In a shigellosis outbreak, fermented vegetable was suspected to be the implicated food Not eat Expose Ate Non-exp Case Non-case Total Ate Not eat RR = 6.2, 95%CI 2.5, 15.1 Case Non-case Case Non-case A person who ate the fermented vegetable was 6.2 times more likely to be ill than a person who did not eat... 66

67 Case-Control Studies The most frequently used type of study in outbreaks Can be quickly implemented Can be used when cohort study might be large and timeconsuming Identify people with disease (case-patients) and people without disease (controls), then ask everyone about past exposures You already know who is case 67

68 Case-Control Studies Calculate odds ratio to measure strength of association between illness and exposure Compare odds of exposure among case-patients to odds of exposure among controls Cannot calculate risk ratio in case-control study 68

69 Case-control study Case Control Total Ate Not eat OR = 201, 95%CI 18, 5410 In a botulism outbreak, home-canned bamboo shoots was suspected to be the implicated food Non-exp. Exposed Cases Case Exposed Non-exp. Controls Control A person who ate the bamboo shoots was 201 times more likely to be ill than a person who did not eat... 69

70 Case-Control or Cohort: Which one is right? The choice depends on the situation Always think about the source population: Are members of the group easily identifiable? Can you interview all or a sample of them? Use a cohort study Is the cohort difficult to identify or too large to contact all members? Use a case-control study design 70

71 Steps of an outbreak investigation 1. Prepare for Field Work : Rapid Response Team 2. Confirm outbreak and diagnosis 3. Define case and start case-finding 4. Descriptive data collection and analysis 5. Hypothesis generation 6. Analytical studies to test hypotheses 7. Special studies (e.g. environmental study) 8. Communicate the conclusion and recommend control measures 9. Follow-up the control implementations Implement control measures 71

72 Environmental study: Traceback Investigations Process used to determine the production and distribution chain of a vehicle implicated in an outbreak Helps determine if (and where) you can conduct an environmental health assessment Used to clarify the point at which the implicated vehicle may have become contaminated Necessary investigation to identify contributing factors (implement control measures) 72

73 Processing of rice with red pork with egg in an outbreak of shigellosis in school A Boiling pork ~ hrs Boiling eggs Simmer with ingredients Critical point Soaking in water & peel off eggshell Slice TEXT TEXT red pork Mixed &divide Splitting TEXT egg by thread & knife

74 Outbreaks Involving Clinical Specimens Human clinical specimens from cases, contacts Blood Serum Urine Saliva Hair Feces Type of specimen depends on the outbreak Specimens from environments, animals 74

75 Steps of an outbreak investigation 1. Prepare for Field Work : Rapid Response Team 2. Confirm outbreak and diagnosis 3. Define case and start case-finding 4. Descriptive data collection and analysis 5. Hypothesis generation 6. Analytical studies to test hypotheses 7. Special studies (e.g. environmental study) 8. Communicate the conclusion and recommend control measures 9. Follow-up the control implementations Implement control measures 75

76 Control measures Implement control measures May occur at any time during the outbreak!! Control the source of pathogen Interrupt transmission Modify host response 76

77 77

78 Control the source of pathogen Remove source of contamination Remove persons from exposure Isolate and/or treat infected persons 78

79 Interrupt transmission Interrupt environmental transmission Control vector transmission Improve personal sanitation 79

80 Modify host response Immunise susceptibles Use prophylactic chemotherapy 80

81 Steps of an outbreak investigation 1. Prepare for Field Work : Rapid Response Team 2. Confirm outbreak and diagnosis 3. Define case and start case-finding 4. Descriptive data collection and analysis 5. Hypothesis generation 6. Analytical studies to test hypotheses 7. Special studies (e.g. environmental study) 8. Communicate the conclusion and recommend control measures 9. Follow-up the control implementations Implement control measures 81

82 Main reference: 82

83 Thanks for your kind attention Many slides in this presentation are from the World Health Organization, the European Programme for Intervention Epidemiology Training and work of our trainees here in the Thai-FETP The International Field Epidemiology Training Program, Thailand 83

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