outbreak investigation methodological aspects jurgita bagdonaite, jolita mereckiene jurmala, latvia,...
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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
0
1
2
3
4
5
6
7
8
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
Week of notification
Number of cases
1996 1997
Cases of legionellosis by week of notificationFrance, January 1996 - August 1997
0
1
2
3
4
5
6
7
8
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
Week of notification
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
0
1
2
3
4
5
6
7
8
9
10
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
0
1
2
3
4
5
6
7
8
9
10
1 2 3 4 5 6 7 8 9 10 11 12
Cases
Days
Epicurves
0
1
2
3
4
5
6
1 2 3 4 5 6 7 8
0
1
2
3
4
5
6
7
8
9
10
1 2 3 4 5 6 7 8 9 10 11 12
0
2
4
6
8
10
12
1 2 3 4 5 6 7 8 9 10 11 12 13
hours
cases
cases
cases
days
weeks
Common point source Common persistent source
Propagated source
Estimation of time or period of exposure
0
1
2
3
4
5
6
1 2 3 4 5 6 7 8
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
5
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
CA
RN
AB
Y S
TR
EE
T
MA
RS
HA
LL S
TR
EE
T
RE
GE
NT
ST
RE
ET
GR
EA
T P
ULT
EN
EY
ST
RE
ET
BR
EW
ER
Y
BE
RW
ICK
ST
RE
ET
BROAD STREET
SILVER STREET
X
X
XX
X
PO
LAN
D S
TR
EE
T
GOLDEN
SQUARE
N
S
EW
PUMP B
PUMP
PUMP C
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