Outbreak Investigation

Outbreak Investigation EPIET Introductory course 2011 Lazareto, Menorca, Spain Maaike van Veen

Objectives for this session • Describe • the principles of outbreak investigation • the steps in outbreak investigation • Using practical example • Outbreak of Hepatitis A among European Tourists to Egypt, Summer of 2004 (Christina Frank et al. EID 2007) • This afternoon (throughout the course) • some operational and epidemiological aspects of outbreak investigation

What is an outbreak ? Occurrence of more cases of disease than expected • in a given area • over a particular period of time • among a specific group of people

Why investigate outbreaks? • Stop the outbreak • Understand what happened and why • Prevent future outbreaks • Improve our knowledge • Improve surveillance and outbreak detection • Training

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

Specific demands when investigating outbreaks • Unexpected event • Act quickly • Rapid control • Interdisciplinary coordination • Work carried out in the field Systematic approach

Control measures Steps of an outbreak investigation • Confirm outbreak and diagnosis • Form Outbreak Control Team • Define a case (case definition) • Identify cases and obtain information • Describe data by time, place, person • Develop hypothesis • Test hypothesis: analytical studies • Additional studies • Communicate results: • outbreak report, publication • Implement control measures

Hepatitis A European Tourists to Egypt Summer 2004 Initial Information • Friday, 13th of August: Local Health Department in Germany notified of 4 cases of hepatitis A, all were in same hotel in Hurghada • Within days, 50+ cases were known from all over Germany • Egypt = major tourist destination (2004: >1 million visitors from Germany) • Hotel not aware of ill guests Med. Cairo Hurghada Red Sea N Egypt C. Frank et al. EID 2007

Routine surveillance Clinical / Laboratory General public Media Detection

Control measures Steps of an outbreak investigation • Confirm outbreak and diagnosis • Form Outbreak Control Team • Define a case • Identify cases and obtain information • Describe data by time, place, person • Develop hypothesis • Test hypothesis: analytical studies • Additional studies • Communicate results: • outbreak report, publication • Implement control measures

Confirm outbreak 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)

Confirm diagnosis • Laboratory confirmation • serology • isolates, typing of isolates • toxic agents • Meet attending physicians • Examine some cases • Contact (visit) the laboratories Not always necessary to confirm all the cases but confirm a proportion throughout the outbreak

Hepatitis A European Tourists to Egypt Summer 2004 OutbreakConfirmation • Hepatitis A notifiable disease in Germany • Surveillance case definition: • clinical disease • plus laboratory confirmation • 2001-3:  30 cases / year from Egypt • Other European countries registered cases who had stayed in same hotel • Later: cases infected with same virus strain C. Frank et al. EID 2007

Further investigation? Immediate control measures? Outbreak confirmed  - prophylaxis - exclusion / isolation - public warning - hygienic measures - others - etiological agent - mode of transmission - vehicle of transmission - source of contamination - population at risk - exposure causing illness

Form Outbreak Control Team Team coordinatesfield investigation Outbreak confirmed, further investigations warranted Epidemiologist Microbiologist Clinician Environmentalist Engineers Veterinarians Others

Descriptive epidemiology • Who are the cases? (person) • - Where do they live? (place) • - When did they become ill? (time)

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

Case definition • Simple, practical, objective • Sensitive? • Specific? • Multiple case definitions • confirmed • probable • possible • CD can be adjusted, if new information becomes available

Hepatitis A European Tourists to Egypt Summer 2004 Case definitions • Primary case • Initial: Any person • with IgM antibodies to Hepatitis A Virus and • clinical hepatitis A disease, • who had been to Egypt <50 days before onset • Later: Any person 1., 2. and • who had stayed at hotel X <50 days before onset • Secondary case • Any person 1., 2. and • who had not been to Egypt <50 days before onset • who had been exposed to a primary case C. Frank et al. EID 2007

Hepatitis A European Tourists to Egypt Summer 2004 Case-finding • German cases: • Passive reporting of cases in German infectious disease notification system • Note in German Epidemiological Bulletin, asking to specify the hotel for hepatitis A cases who had been to Egypt • Other European cases: • Note in European Early Warning Network (EWRS), asking other countries to inform Germany of cases possibly associated with this outbreak C. Frank et al. EID 2007

notifications hospitals, GPs laboratories schools workplace, etc Identifying information Demographic information Clinical details Exposures and known risk factors Identify & count cases Obtain information

Hepatitis A European Tourists to Egypt Summer 2004 Obtaininginformation • Cases: Trawling questionnaire • period of stay in hotel • activities inside and outside of hotel • impression of hotel hygiene • some basic food questions • Hotel: • restaurants, meal plans • food suppliers • source of drinking water • method of watering gardens • differences to other hotels in Hurghada • health of staff C. Frank et al. EID 2007

Organize information: Line list • Names • Date of birth • Addresse • Onset of symptoms • Treating physician • Hospital stay • Laboratory results

Line List

Describe in - time - place - person Identify & count cases Obtain information Descriptive study

Time: Epidemic Curve • Histogram • Distribution of cases by time of onset of symptoms, diagnosis or identification • time interval depends on incubation period Cases Days

Epidemic 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

Examples of Epidemic curves Common persistent source Common point source cases cases hours days Propagated source cases Common intermittent source cases weeks days

The Netherlands, Q-fever cases by date of symptom onset, 2007-2010 Number of cases J. Whelan et al. ESCAIDE 2010

Hepatitis A European Tourists to Egypt Summer 2004 Epicurve, German cases among hotel guests C. Frank et al. EID 2007

Estimation of time or period of exposure max incubation cases min exposure

Place • Place of residence • Place of possible exposure • work • meals • travel routes, • day-care • leisure activities Maps • identify an area at risk

Outbreak Rubella 2004 -2005 • 392 cases • “Bible belt” • transmission to Canada (305 cases) Susan Hahné et al. Pediatr Infect Dis J. 2009

Hepatitis A European Tourists to Egypt Summer 2004 Cases geographically • Germany: • 271 primary cases, guests of hotel X • 7 secondary cases, persons who had not traveled but were infected in Germany by guests of hotel X • Elsewhere in Europe(A, S, DK, NL, B, I, CH, GB): • 60 primary cases • Secondary outbreak with 13 cases in Austria C. Frank et al. EID 2007

Person • Distribution of cases • age • sex • occupation, etc • Distribution of these variables in population • Attack rates

Hepatitis A European Tourists to Egypt Summer 2004 Cases by sex and age group, % hospitalized C. Frank et al. EID 2007

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?

Hepatitis A European Tourists to Egypt Summer 2004 Basis for hypothesis • Exploration: • many guests had not left hotel • visible hotel hygiene described as good • Hotel: • did not recall ill staff members • most hotel aspects shared with most hotels in Hurghada (e.g. source of water) • 2 unique food suppliers: • ice cream • orange and grapefruit juices C. Frank et al. EID 2007

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

Testing hypothesis • Cohort • attack rate exposed group • attack rate unexposed group • Case control • proportion of cases exposed • proportion of controls exposed

Hepatitis A European Tourists to Egypt Summer 2004 Case-control study • among hotel guests • in hotel during supposed infectious period • residents of 3 German states • one control per case, unmatched • no history of hepatitis A disease or vaccination (not checked by serology) • telephone interviews C. Frank et al. EID 2007

Hepatitis A European Tourists to Egypt Summer 2004 Cases and controlsby exposure C. Frank et al. EID 2007

Verify hypothesis Additional investigations • Microbiological investigation of food samples • Environmental investigation • Veterinarian investigation • Molecular Typing • Trace back investigations (origin of foods) • Meteorological data • Entomological investigations

Outbreak Investigation