Foodborne Disease Outbreak Investigation Team Training: Module 3 – Preliminary Investigation of an Outbreak Preliminary investigation.
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Foodborne Disease Outbreak Investigation Team Training: Module 3 – Preliminary Investigation of an Outbreak Preliminary investigation 1 Module Learning Objectives At the end of this module, you will be able to 1. Describe the initial steps of an outbreak investigation including • Verify the diagnosis • Search for additional cases • Create a case definition • Generate a hypothesis about the source 2. Develop a case definition for an outbreak. 3. Generate a hypothesis about the source of an outbreak. 4. Prioritize an outbreak for further investigation. Preliminary investigation > Learning objectives 2 Step 1: Verify Diagnosis Purpose • Make sure illness properly diagnosed • Rule out laboratory and reporting errors • Determine that all cases suffer from same illness Preliminary investigation > Verify diagnosis 3 Ways to Verify Diagnosis • • • • • Obtain clinical samples for laboratory testing Review medical records and laboratory results Talk with health-care providers of cases Interview (and even examine) cases Consult a qualified microbiologist Preliminary investigation > Verify diagnosis 4 Laboratory Error – Example • Increase in intestinal amebiasis (Entamoeba histolytica infection) in Los Angeles • 38 cases in 4 months (usual: one per month) • Investigation showed no common exposures • Diagnostic slides reexamined E. histolytica White blood cells Preliminary investigation > Verify diagnosis 5 Step 2: Search for Additional Cases • Identified cases often “tip of the iceberg” • Might not represent all cases associated with outbreak • Need to actively search for additional cases to – Determine true magnitude of outbreak – Characterize outbreak accurately – Increase ability of epidemiologic studies to link illness with true cause of outbreak Preliminary investigation > Search for cases 6 Why Search for Additional Cases? = Female = Male First cases detected (N=10) Female 80% All cases (N=20) 50% Preliminary investigation > Search for cases 7 Ways to Search for Additional Cases • Contact implicated establishment to identify other ill customers (e.g., reservations, credit card receipts) • Contact event organizer for list of attendees • Review foodborne illness complaints and notifiable disease reports • Examine laboratory reports and hospital medical records • Ask local health-care providers to look for cases • Ask known cases if they know of other cases • Review death certificates • Make announcements through local media Preliminary investigation > Search for cases 8 Step 3: Develop a Case Definition • Standard set of criteria used to classify ill people as being cases associated with a particular outbreak • Criteria include – Clinical findings (e.g., signs, symptoms, laboratory results) – Restrictions by time, place, and person • Different from a clinical diagnosis, used for epidemiologic purposes only Preliminary investigation > Develop case definition 9 Case Definition - Example For outbreak of salmonellosis at child care center Clinical criteria • ≥3 loose stools in a 24-hour period OR • stool culture that yielded Salmonella Javiana Restrictions • Time: onset from October 24-30 • Place: attended/worked at Child Care Center X • Person: excludes siblings of initial case in a family (if onset of illness after initial case) Preliminary investigation > Develop case definition 10 Case Definition Criteria • Objective – Not open to interpretation • Discriminating – Distinguish between individuals with illness associated with outbreak and those with illness not associated with the outbreak Preliminary investigation > Develop case definition 11 Class Question Which criterion is more objective (not open to interpretation)? An oral temperature “Fever” OR of 100.4 or higher Which criterion is more discriminating (more likely to distinguish between illness associated with an outbreak and illness not associated with that outbreak)? ≥3 loose stools in a 24-hour period OR A stool culture that yielded Salmonella Preliminary investigation > Develop case definition 12 Case Definition • Does not include suspected source of outbreak (i.e., hypothesis you are trying to test) • Can reflect different levels of certainty that person has disease associated with outbreak – Typical signs and symptoms only (“probable case”) – Inclusion of laboratory testing or subtyping (“confirmed case”) • Can change over time as more information about the illness or outbreak is revealed Preliminary investigation > Develop case definition 13 Class Question An outbreak of gastrointestinal illness occurred following a birthday party at a private home on June 10. At the party, a meal was served including potato salad, hamburgers, and ice cream. Ten guests reported becoming ill. Ill persons reported vomiting, diarrhea (3 or more loose stools in a 24hour period), fever, and headache. Develop a case definition for illness associated with this outbreak. A line list of ill guests is provided at the end of this module. Preliminary investigation > Develop case definition 14 Class Question (cont’d) # Sex Age Onset Vomiting Diarrhea* Fever Headache Salmonella Positive Stool Ice Culture Salad Burger Cream 1 F 14 6/12 Y Y Y N Y Y Y Y 2 F 5 6/13 Y Y N N NA Y N Y 3 M 16 6/12 Y Y Y N NA Y Y Y 4 F 18 6/10 N Y Y Y N N Y Y 5 M 16 6/14 Y Y N N NA Y Y Y 6 M 15 6/11 Y N N N NA N N Y 7 M 15 6/13 Y Y N N NA Y Y Y 8 M 17 6/12 N Y N N NA Y N Y 9 F 16 6/20 N Y N N Y N Y Y 10 F 14 6/12 N N Y Y NA Y N Y *Three or more stools in a 24-hour period NA=culture not performed Preliminary investigation > Develop case definition 15 Class Question (cont’d) Looking at the line list, what symptoms are reported among ill persons (and what is their frequency)? Which signs and symptoms would you include in the case definition for the outbreak? Preliminary investigation > Develop case definition 16 Class Question (cont’d) Two ill people had stool cultures positive for Salmonella. Would you include a positive stool culture in the case definition? Would you include restrictions by time, place, and person in the case definition? Preliminary investigation > Develop case definition 17 Class Question (cont’d) All of the ill people ate ice cream. Would you include ice cream in the case definition? Preliminary investigation > Develop case definition 18 Step 4: Generate Hypothesis • Using available information to make an educated guess about the cause and source of an outbreak • Purpose – To direct immediate control measures – To narrow focus of subsequent studies – To determine the need to involve others in investigation • Undertaken by entire team Preliminary investigation > Generate hypothesis 19 Hypothesis • Includes likely causative agent, people at risk, mode of transmission, vehicle, and period of interest • Example: “The outbreak is due to a bacterium that was spread during the first week of November by a food commonly consumed by children.” Preliminary investigation > Generate hypothesis 20 Key Sources of Information • Basic information about causative agent • Information on implicated facility or food • Descriptive epidemiology (i.e., describe cases by time, place, and person) • Case interviews (“hypothesis-generating interviews”) Preliminary investigation > Generate hypothesis 21 Basic Information about Causative Agent • • • • Common reservoirs of causative agent Vehicles in past outbreaks Growth requirements for causative agent Incubation period (time from exposure to onset of illness) Preliminary investigation > Generate hypothesis 22 References on Causative Agents • APHA Control of Communicable Diseases Manual • IAFP Procedures to Investigate Foodborne Illness (Table B) • AMA “Diagnosis and Management of Foodborne Illnesses: A Primer for Physicians” • FDA Bad Bug Book (online) • CDC A-Z Index (online) Preliminary investigation > Generate hypothesis 23 Information on Implicated Facility • Foods produced or served; production, processing, distribution methods; past food safety problems • Help identify high risk foods, likely causative agent, and contributing factors • Sources of information – Online menus – Paperwork from past inspections, Hazard Analysis and Critical Control Point risk assessment, facility plan review – Regulatory inspector Preliminary investigation > Generate hypothesis 24 Descriptive Epidemiology • Simple characterization of outbreak by – Time – Place – Person • Can provide clues about the mode of transmission and vehicle • Comparison group usually needed to put findings in perspective Preliminary investigation > Generate hypothesis 25 Time – Onset of Illness Number of Cases • Time or date of onset of symptoms • Relates back to likely period of exposure • Typically presented as epidemic curve (epi curve) 6 = one case 5 4 3 2 1 1/11 1/13 1/15 1/17 Date of Onset of Illness Preliminary investigation > Generate hypothesis 26 Uses of Epi Curve • • • • Grasp magnitude of outbreak Clarify outbreak’s time course Identify cases that are outliers Draw inferences about pattern of spread – Point source outbreak – Continuous common source outbreak – Propagated outbreak Preliminary investigation > Generate hypothesis 27 Point Source Outbreak • Exposure to same source over brief time • Cases rise rapidly to a peak and fall off gradually • Majority of cases within one incubation period Cryptosporidiosis cases by date of onset of illness, June one incubation period = 7 days Preliminary investigation > Generate hypothesis 28 Continuous Common Source Outbreak • Exposure to same source over prolonged time • Epidemic curve rises gradually • May plateau Infections with Salmonella Enteritidis by date of onset of illness, January and February. one incubation period = 2-3 days January February Preliminary investigation > Generate hypothesis 29 Propagated Outbreak • Spread from person to person • Series of progressively taller peaks • Peaks one incubation period apart Measles cases by date of onset of illness, Aberdeen, South Dakota, October 15 – January 16 one incubation period = 10 days October November December Preliminary investigation > Generate hypothesis January 30 Class Question Thirty seven cases of campylobacteriosis were identified among children attending a summer camp. Based on the epi curve, what is the most likely means of spread: point source, continuous common source, or propagated? (average incubation period 3-5 days) Preliminary investigation > Generate hypothesis 31 Place • Residence of cases (typically) • Distribution reveals clues about source of outbreak – Over broad area commercial product with wide distribution – Clustering locally sold product, point source, or person-to-person spread – Concentrated areas with outliers travel to affected area or importation of product • Typically presented as spot map Preliminary investigation > Generate hypothesis 32 Place – Example • Outbreak of Salmonella Typhimurium with unique PFGE pattern in San Diego • 50 cases among Mexicans and Mexican Americans • Spot map of households of cases Preliminary investigation > Generate hypothesis 33 Place – Example (cont’d) Percent Hispanic population 3-20% 21-39% 40-61% 62-97% Preliminary investigation > Generate hypothesis 34 Place – Example • Outbreak associated with Mexican-style soft cheese sold by street vendors; four vendors cited Case Vendor #1 route Vendor #1 stops Vendor #1 Preliminary investigation > Generate hypothesis 35 Person • Age group, sex, and other characteristics • Influence individual’s susceptibility to illness or opportunities for disease exposure → can provide clues to source of outbreak • Typically presented as percentage of all cases or rate among affected population Preliminary investigation > Generate hypothesis 36 Person – Example • E. coli O104 outbreak in Germany with many cases of hemolytic uremic syndrome (HUS) • 88% of HUS cases ≥20 years (usually 1-10%) • 71% of HUS cases female (usually around 50%) • Think “girl food” • Source of outbreak sprouts from fenugreek seeds from Egypt Preliminary investigation > Generate hypothesis 37 Descriptive Epidemiology Clues • Person-to-person transmission – Clustering in social units – Localized to one part of community – Occurrence of cases in waves • Transmission by public drinking water – Widespread illness – Affecting both sexes and all age groups – Distribution consistent with public water system • Transmission by food – Increased risk among certain groups – Distribution similar to distribution of foods Preliminary investigation > Generate hypothesis 38 Class Question Based on the following case characteristics, what mode of transmission seems likely in each outbreak? Mode of Transmission Cases live in one community; most <3 years of age; attend same child care center; onset of cases in waves Majority of cases live in city limits, age range 1-75 years; 52% female Cases live in two states; high proportion 20-29 years; 65% male Preliminary investigation > Generate hypothesis 39 Hypothesis-Generating Interviews • Extensive exploration of illness and exposures with cases • Purpose – To identify a common location or activity – To shorten list of foods and other exposures for study • Much more detailed than interviews for foodborne illness complaints or pathogen-specific surveillance with hundreds of exposures examined Preliminary investigation > Generate hypothesis 40 Hypothesis-Generating Interviews (cont’d) • Extensive information on food and non-food exposures within incubation period of illness – Open-ended questions on exposures (e.g., restaurants, stores, events, food history) – Lengthy list of specific foods – Details on foods eaten (e.g., brands, where purchased, purchase dates) – Non-food exposures • Use of standard questionnaire www.cdc.gov/outbreaknet/references_resources (example form in Appendix) Preliminary investigation > Generate hypothesis 41 Interpretation of Commonalities If you find commonalities among cases: • Are commonalities unique to cases or a reflection of common exposures in the community? • Comparison group needed – “Controlled” epidemiologic study – Other cases of unrelated foodborne illness interviewed for other reasons (case-case comparisons) – FoodNet Atlas of Exposures Preliminary investigation > Generate hypothesis 42 FoodNet Atlas of Exposures • Population-based survey at FoodNet sites • Exposures among respondents in previous 7 days • Estimates of background rate of exposure • Available at www.cdc.gov/foodnet/studies_pages/pop.htm Preliminary investigation > Generate hypothesis 43 Prioritization for Further Investigation • Ideally, all outbreaks are investigated further to – Prevent others from becoming ill from the outbreak source – Identify problematic food preparation practices or risky foods to prevent future outbreaks – Add to our knowledge of foodborne diseases • Given limited resources, not all outbreaks can be investigated Preliminary investigation > Prioritization for further investigation 44 High Priority Investigations • High public health impact – Life-threatening illness – Population at high risk for complications of illness affected – Large number of affected persons • Exposure likely to be ongoing – Suspicion of continuing source of exposure – Cases still rising – Less than 2 incubation periods since onset of symptoms in last case • Intentional adulteration of food Preliminary investigation > Prioritization for further investigation 45 Ability of Local Team to Respond? • When to ask for help – Scale of outbreak likely to overwhelm local resources – Nature of outbreak or response beyond the experience of local staff – Outbreak suspected to affect multiple counties, states, or countries • How to ask for help – Call State Epidemiologist – Be prepared to share outbreak information Preliminary investigation 46 Group Exercise Divide into groups by table. 1. Read the brief description of an E. coli O157:H7 outbreak that occurred in Wisconsin. 2. Answer the questions. 3. Develop a hypothesis about the source of the outbreak. Be prepared to share your answers with the class. Time: 15 minutes Environmental health investigation 47 Group Exercise (cont’d) On September 5, the WI Division of Public Health received separate reports of clusters of laboratoryconfirmed E. coli O157:H7 infections in three noncontiguous counties: Manitowoc, Ozaukee, and Dane. The Manitowoc County cluster involved five ill persons, four of whom visited an animal exhibition at a county fair. On September 7, WI state epidemiologist was called by the director of the Blood Center of Southeastern Wisconsin regarding 5 adults who received plasma exchanges during the prior 3 days to treat illnesses consistent with hemolytic uremic syndrome. Three had a lab-confirmed E. coli O157:H7 infection. Environmental health investigation 48 Group Exercise (cont’d) A total of 30 E. coli O157:H7 infections were reported in one week. (On average, 15 E. coli O157:H7 infections are reported in WI each month.) Question 1: Do these cases represent an outbreak? What explanations might explain the increase? What information might help you determine if the increase represents an outbreak? Environmental health investigation 49 Group Exercise (cont’d) Molecular subtyping of 8 of the E. coli O157:H7 isolates showed seven had PFGE patterns that were indistinguishable. Infections with this strain had only been reported sporadically in the past. The PFGE patterns from the four Manitowoc County fairgoers did not match this pattern. Officials from the WI Division of Public Health decided that the cases of E. coli O157:H7 infection with the indistinguishable PFGE pattern represented a possible outbreak and assembled the outbreak investigation team to consider the situation. Environmental health investigation 50 Group Exercise (cont’d) Question 2: What are the modes of transmission for E. coli O157:H7? What vehicles have been associated with E. coli O157:H7 in past outbreaks? What is the average incubation period of E. coli O157:H7? Environmental health investigation 51 Group Exercise (cont’d) To search for additional cases of E. coli O157:H7 infection, the WI Division of Public Health staff used the WI Health Alert Network and e-mail to notify local, regional, and tribal health departments; laboratories; infection control professionals; hospitals; emergency departments; and clinics of the suspected outbreak. For the investigation, a case was defined as a patient who was infected with the outbreak strain of E. coli O157: H7, who resided in WI and had onset of symptoms since August 1. Environmental health investigation 52 Group Exercise (cont’d) A total of 49 WI residents from 10 counties had illness meeting the case definition. The most frequently reported signs and symptoms among cases included diarrhea (96%), abdominal cramps (96%), bloody diarrhea (88%), fatigue (80%), watery diarrhea (63%), and chills (57%). Among cases, illness onset dates occurred from August 20 through September 14. (Figure 1) Case ages ranged from 1 to 84 years; 38 (78%) cases were ≥ 20 years of age. Of the 49 cases, 35 (71%) were female, 24 (49%) were hospitalized, and 9 (18%) had hemolytic uremic syndrome. Environmental health investigation 53 Group Exercise (cont’d) Figure 1. Onset of illness among persons infected with outbreak strain of E. coli O157:H7, Wisconsin. Environmental health investigation 54 Group Exercise (cont’d) Question 3: Interpret the descriptive epidemiology of the outbreak. Were symptoms among patients consistent with infection with E. coli O157:H7? Does the epi curve suggest a mode of transmission? Was clustering of cases by selected demographic characteristics apparent? Environmental health investigation 55 Group Exercise (cont’d) Staff at local health departments and the WI Division of Public Health conducted telephone interviews of cases using a standard comprehensive enteric disease questionnaire. Of the initial 9 cases interviewed, 7 (78%) ate potatoes, 5 (56%) ate romaine lettuce, and 8 (89%) ate fresh spinach. Question 4: Using the excerpt from the FoodNet Atlas of Exposures, are these exposures unusual? Environmental health investigation 56 Group Exercise (cont’d) Question 5: State your hypothesis about the source of this outbreak including causative agent, people at risk, mode of transmission, vehicle, and period of interest. Question 6: How would you prioritize this outbreak for investigation? Why? Environmental health investigation 57 Quick Quiz Preliminary investigation 58 Quick Quiz 1. Why is it important to identify as many cases associated with an outbreak as possible? A. Determine true magnitude of outbreak B. Characterize outbreak accurately C. Increase the ability of epidemiologic studies to link illness with true cause of outbreak D. All of the above Preliminary investigation 59 Quick Quiz 2. A case definition might include all of the following EXCEPT: A. Symptoms of the illness B. Laboratory test results C. Food that is the suspected source of the outbreak D. Date of illness onset Preliminary investigation 60 Quick Quiz 3. Development of a hypothesis early in an outbreak helps direct subsequent steps of an outbreak investigation and should involve all investigation team members. A. True B. False Preliminary investigation 61 Quick Quiz 4. A cluster of E. coli O157:H7 infections is detected through PulseNet with cases from 30 states. Among cases, 66% were under 19 years of age and 71% were female. What is the most likely mode of transmission in this outbreak? A. Person-to-person B. Public water supply C. Recreational water D. Food Preliminary investigation 62 Quick Quiz 5. Which of the following characteristics would make an outbreak the highest priority for further investigation? A. It has been 3 months since onset of illness for the last case. B. Affected persons are limited to staff who attended an office potluck. C. Listeria is the causative agent. D. A total of 8 cases of campylobacteriosis were identified after searching for additional cases. Preliminary investigation 63