Outbreak InvestigationOutbreak InvestigationMethodological aspectsMethodological aspects

Jurgita Bagdonaite, Jolita Mereckiene

Jurmala, Latvia, 2006

Based EPIET material

Objectives for this session

• Describe – the principles of outbreak investigation– the steps in outbreak investigation

• Using practical examples– Salmonella outbreak in Jura, France

• Next lecture– some operational and logistical aspects

of outbreak investigation

What is an outbreak ?

• Occurrence of more cases of disease than expected

– in a given area – among a specific group of people – over a particular period of time

Food-or waterborne outbreak (WHO definition)

• two or more persons

• similar illness

• after ingestion of the same type of food or water

• from the same source

• epidemiological evidence - the food or the water - the source of the illness

Why investigate outbreaks?

• Stop the outbreak

– Find and neutralise the source (cause)– Prevent additional cases

• Prevent future outbreaks

• Improve surveillance and outbreak detection

• Improve our knowledge

• Keep the public’s confidence

• Training

Retrospective investigation

• Often the outbreak exists since days, weeks, months

• Many cases already occurred

• Count on the memory of people

• Many data already collected; use them or start all over?

Never too late, but more difficult

Community wide outbreak of Salmonellosis,

Jura, spring 1997

Context

• Alert: District medical officer

• 80 cases of salmonellosis in 5 weeks

• Salmonella Typhimurium

• No link identified between cases

• High political and media profile

• Local outbreak team set up

• Cases continued to occur

Specific demands when investigating outbreaks

• Unexpected event

• Act quickly

• Rapid control

• Bias caused by media reports

• Legal and financial pressure

• Interdisciplinary coordination

• Work carried out in the field

Systematic approach

Epidemiology

Food safety

Clinicians

Laboratory

Media AuthoritiesDiagnostic

Clinical

Specimen transfer

Dead Sick

Exposed

SurveillanceInvestigation

Prediction

Supply channels

Trace back

DecisionsInfrastructureRegulationsVaccinations etc

VectorReservoir

Investigation

Co-ordination

Role of the Epidemiologist

• Systematic Description

• Identification of risk factors (by descriptive or analytical means)

• Identification of interventions

• Work with others to implement control measures

• Evaluate the impact of control measures

YOU MAY BE THE ONE TO COORDINATE !

Steps of an outbreak investigation

• Confirm outbreak and diagnosis• Define a case • Identify cases & obtain information• Describe data collected and analyse• Develop hypothesis• Test hypothesis: analytical studies • Special studies• Communicate results,

– including outbreak report

• Implement control measure

Co

ntro

l measu

res

Detection

Routine surveillanceClinical / LaboratoryGeneral publicMedia

Surveillance and outbreak detection: Salmonella Goldcoast strains

by month of isolation, 1993-1996

0

20

40

60

J M M J S N J M M J S N J M M J S N J M M J

Goldcoast

Threshold

Month

Number of isolates

1993 1994 1995 1996

Epidemic threshold facilitates detection

Confirm outbreak and diagnosis

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)

Cases of legionellosis by week of notificationFrance, January 1996 - August 1997

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1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 3 6 9 12 15 18 21 24 27 30 33

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Number of cases

1996 1997

Cases of legionellosis by week of notificationFrance, January 1996 - August 1997

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Number of cases

1996 1997

National meeting: legionellosis diagnosis and reporting

Confirm outbreak and diagnosis

• Laboratory confirmation – serology– isolates, typing of isolates– toxic agents

• Contact (visit) the laboratories• Meet attending physicians• Examine some cases

Not always necessary to confirm all the casesbut confirm a proportion throughout the outbreak

Outbreak confirmed

Immediate control measures?

Further investigation?

- prophylaxis- exclusion / isolation- public warning- hygienic measures- others

- aetiological agent- mode of transmission- vehicle of transmission- source of contamination- population at risk- exposure causing illness

EpidemiologistMicrobiologistClinicianEnvironmentalistEngineersVeterinariansOthers

Team coordinatesfield investigation

Outbreak confirmed, further investigations warranted

Form Outbreak Control Team?

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

Case definitionOutbreak of salmonellosis in the Jura,

spring 1997Confirmed case

• diarrhoea (> 2 liquid stools per day) or fever (> 38°C, at least one day)

and • isolate of S. Typhimurium

• in a resident of Jura or neighbouring communities

• after May 1997

Probable case

• diarrhoea (> 2 liquid stools per day)

and• contact (same household)

with confirmed case • in a resident of the Jura

or neighbouring communities

• after May 1997

Identify & count cases

notificationslaboratorieshospitals, GPsschoolsworkplace,cases, media, etc

Salmonellosis outbreak in the Jura

case finding

• All laboratories in the Jura district

• Major laboratories in neighbouring districts

• National reference laboratory

• Food borne outbreak notifications

• Interview of cases

Identify & count cases

Obtain information

Identifying information

Demographic information

Clinical details

Exposures and known risk factors

Salmonellosis in the JuraObtaining information

Trawling questionnaire:

• Attendance of events

• Places visited

• Food histories including, regional products

Identify & count cases

Obtain information

Analysis of descriptive data

Describe in

- time

- place

- person

TimeEpi Curve

• Histogram

• Distribution of cases by time of onset

of symptoms, diagnosis or identification– time interval depends on incubation period

Cases

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1 2 3 4 5 6 7 8 9 10 11 12

Days

Epi curve• 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

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Epicurves

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hours

cases

cases

cases

days

weeks

Common point source Common persistent source

Propagated source

Estimation of time or period of exposure

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max incubation

min

cases

exposure

Outbreak of typhoid fever, Germany, 2004(source, Marion Muehlen)

5 2

6 3 1 4

15 25 26 27 28 29 30 31 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

April May

Probable infection time period

J une

N° c

ases

Shortest incubation period:

Longest incubation period: 60 suspected caseprobable caseconfirmed case

Number of cases

30

1 case

25

20

15

10

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14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 April Mai June July

Week of onset of symptoms

Cases of Salmonella Typhimurium infection by week of onset of symptoms, Jura, May - June 1997.

Place

• Place of residence• Place of possible exposure

– work– meals– travel routes – day-care– leisure activities

• Maps– identify an area at risk

WORKHOUSE

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BROAD STREET

SILVER STREET

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GOLDEN

SQUARE

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PUMP B

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PUMP A

PUMP

Distribution of cases of cholera, London 1854

Person• Distribution of cases by age, sex, occupation,etc

(numerator)– 60 female– 50 male

• Distribution of these variables in population (denominator)– 600 females– 350 males

• Attack rates– female: 60/600– Males: 50/350

S.Typhimurium infection distribution of cases by age group,

Jura, May - June 1997

Age groups(years)

No cases

<1 2

1 - 5 36

6 - 14 22

15 - 64 29

> 65 9

Total 98

S.Typhimurium infection attack rates by age group,

Jura, May - June 1997

Age groups (years)

nr of cases population Attack rate per 100,000

<1 2 3,200 63

1 - 5 36 16,000 225

6 - 14 22 30,300 72

15 - 64 29 159,500 18

> 65 9 39,100 22

Total 98 248,100 40

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?

Outbreak of S. Typhimurium infections, Jura, spring 1997

Descriptive data Hypotheses

No common place, event Most likely food borne

S.Typhimurium Meat (beef), pork meat andmeat products, poultry, dairyproducts, etc

South of Jura district Regional product, localdistribution

Young childen most affected Product eaten by children

Several cases moslim Pork products less likely

Period of warm weather Barbeque, take away grilledchicken

Publications Outbreak linked to take awaygrilled chicken

Food consumption by cases, outbreak of Salmonellosis, Jura, spring 1997

Food have eaten Total replies

% of cases exposed

Chipolatas 6 15 40 Take away chicken

5 17 29

Chicken bought raw

7 16 44

Minced beef burger

7 17 41

Pork 9 17 53 Veal 8 17 47 Comté 13 17 77 Morbier 14 16 88 Bleu de Gex 6 10 60

Compare hypotheses with facts

Test specific hypotheses

Analytical studies- cohort studies- case-control studies

Testing hypothesis

• Cohort - attack rate exposed group- attack rate unexposed group

• Case control- % of cases exposed- % of controls exposed

Food consumption by cases and controls, outbreak of salmonellosis, Jura, spring 1997

Foods nr (%) of cases

have eaten

(n=42)

nr (%) of controls

have eaten

(n=42)

OR

matched CI 95%

Pâtés 11 (26) 17 (40) 0,5 0,2 - 1,3

Sausages 24 (57) 28 (67) 0,7 0,3 - 1,6

Beef 32 (78) 33 (79) 1 0,3 - 3,5

Pork 23 (59) 29 (76) 0,5 0,2 - 1,5

Veal 22 (54) 19 (46) 1,4 0,6 - 3,4

Chicken 30 (71) 34 (81) 0,6 0,2 - 1,7

Munster 4 (10) 1 (2) 4,0 0,5 - 35.8

Bleu de Gex 12 (35) 10 (24) 3,0 0,6 - 14,9

Comté 36 (86) 37 (88) 0,8 0,3 - 2,7

Morbier 33 (83) 23 (55) 6,5 1,4 - 28,8

Verify hypothesisSpecial investigations/studies

• Microbiological investigation

• Environmental investigation

• Veterinarian investigation

• Trace back investigations (origin of foods)

• Meteorological data

• Entomological investigations

Special complementary investigations, outbreak of S. Typhimurium infections, Jura, spring 1997

• Microbiological investigations– cheese samples cases homes, retail shops– human and food isolates by phage and

molecular typing

• Trace back investigation supply channels

• Production plant – veterinarian (herds supplying milk)– occupational medicine– environmental

Investigation of supply channels

CREMERIE

Whole saler

Production plant

Morbier vehicle of infection?

• Raw cows’ milk

• Eaten by children

• Regional product

• Morbier sampled at the residence of cases – S. Typhimurium isolated from 3 Morbiers leftovers– all other cheeses sampled tested negative

• Trace back: single producer

• No source of contamination identified

Implement control measures

1) Control the source of pathogen

2) Interrupt transmission

3) Modify host response

May (must) occur at any time during the outbreak!!

At first, general measures

According to findings, more specific measures

Control measures, Outbreak of S. Typhimurium infections, Jura, 1997

At the beginning of the outbreak• Personal hygiene advice• Thorough cooking of meat and poultry

After the investigation• Recall of the incriminated batches

of Morbier cheese

Outbreak report

• Regular updates during the investigation

• Detailed report at the end

– communicate public health messages

– influence public health policy

– evaluate performance

– training tool

– legal proceedings

Steps of an outbreak investigation

• Confirm outbreak and diagnosis• Define case • Identify cases and obtain information• Descriptive data collection and analysis• Develop hypothesis• Analytical studies to test hypotheses• Special studies• Communication,

including outbreak report• Implement control measures

con

tr ol m

easures

Laboratory confirmation

Source

Outbreak control team

meeting - urgent!

TV inter view

The Tasks !

Control measures ?

Meet minister