Foodborne Disease Outbreak Investigation Team Training:

Foodborne Disease Outbreak Investigation Team Training: Module 3 – Preliminary Investigation of an Outbreak

Module Learning Objectives At the end of this module, you will be able to • 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 • Develop a case definition for an outbreak. • Generate a hypothesis about the source of an outbreak. • Prioritize an outbreak for further investigation. > Learning objectives

Step 1: Verify Diagnosis Purpose • Make sure illness properly diagnosed • Rule out laboratory and reporting errors • Determine that all cases suffer from same illness > Verify diagnosis

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 > Verify diagnosis

 E. histolytica 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 White blood cells > Verify diagnosis

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 > Search for cases

 All cases (N=20) Why Search for Additional Cases? = Female = Male Female First cases detected (N=10) 80% 50% > Search for cases

 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 > Search for cases

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 > Develop case definition

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) > Develop case definition

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 > Develop case definition

 Class Question Which criterion is more objective (not open to interpretation)? An oral temperature of 100.4 or higher “Fever” OR Which criterion is more discriminating (more likely to distinguish between illness associated with an out-break and illness not associated with that outbreak)? A stool culture that yielded Salmonella ≥3 loose stools in a 24-hour period OR > Develop case definition

 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 > Develop case definition

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 24-hour 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. > Develop case definition

Class Question (cont’d) *Three or more stools in a 24-hour period NA=culture not performed > Develop case definition

 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? > Develop case definition

 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? > Develop case definition

 Class Question (cont’d) All of the ill people ate ice cream. Would you include ice cream in the case definition? > Develop case definition

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 > Generate hypothesis

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.” > Generate hypothesis

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”) > Generate hypothesis

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) > Generate hypothesis

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) > Generate hypothesis

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 > Generate hypothesis

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 > Generate hypothesis

Time – Onset of Illness • 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 Number of Cases 3 2 1 1/11 1/13 1/15 1/17 Date of Onset of Illness > Generate hypothesis

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 > Generate hypothesis

 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 > Generate hypothesis

 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 > Generate hypothesis

 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 January > Generate hypothesis

 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) > Generate hypothesis

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 > Generate hypothesis

 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 > Generate hypothesis

 Place – Example (cont’d) Percent Hispanic population 3-20% 21-39% 40-61% 62-97% > Generate hypothesis

 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 > Generate hypothesis

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 > Generate hypothesis

 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 > Generate hypothesis

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 > Generate hypothesis

 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 > Generate hypothesis

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 > Generate hypothesis

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) > Generate hypothesis

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 > Generate hypothesis

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 > Generate hypothesis

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 > Prioritization for further investigation

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 > Prioritization for further investigation

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

Group Exercise Divide into groups by table. Read the brief description of an E. coli O157:H7 outbreak that occurred in Wisconsin. Answer the questions. Develop a hypothesis about the source of the outbreak. Be prepared to share your answers with the class. Time: 15 minutes

Group Exercise (cont’d) On September 5, the WI Division of Public Health received separate reports of clusters of laboratory-confirmed E. coli O157:H7 infections in three non-contiguous 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.

 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?

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.

Foodborne Disease Outbreak Investigation Team Training: