Outbreak Investigation

Best Practice/Methods
Practical Reference Points

SEARO – CSR Training on Outbreak Investigation

 Learning Objectives

• At the end of the session, the participants

will be able to:
– List down the objectives of outbreak
– Describe steps in outbreak investigation
– Explain the importance of conducting timely
outbreak investigation

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Detecting an outbreak

Routine surveillance
Detection Clinical/laboratory
Rumor verification
General public
Media

Is this an
Outbreak?

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Is it an outbreak?

• More than expected cases

– Illustrates the importance of surveillance and timely
analysis
• Clustered in time, place or person
– Pattern recognition
• Concern from a HCW, school or media
– Rumour verification
– Encourage participation in the system

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Why investigate outbreaks?

• Stop the epidemic (outbreak)

• Increase our knowledge
• Prevent new episodes
• Evaluate the surveillance system
• Establish a surveillance system
• Learn field epidemiology by doing

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Specific objectives of an investigation
Identify:
• Causal agent
• Mode of transmission
• Source
• Carrier
• Population at risk
• Exposure causing disease (risk factors)

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Real time vs. retrospective
investigation
• Epidemic in existence for several
days, weeks, months.
• Based on the memory of the people
• Data already collected
– To be or not to be used

It is never to late,
but it can also be more difficult
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Preparation
• Collect preliminary information
– Available data
– Consult experts (microbiologist, veterinarian,
entomologist etc)
– Check search engines e.g., PUBmed
– Search from both formal and informal surveillance
system (event based and indicator based)
– Prepare a short memo
• Inform the concerned
• Get authorization, travel itinerary
• Investigation committee
– Multidisciplinary
– Assign person in charge
– Define tasks

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Example: Community epidemic due to S.
Typhimurium, Jura, May-June 1997
Context
• Alert: PH medical officer
• 80 cases of salmonellosis in 5 weeks
• Salmonella Typhimurium
• Clustered in the South department of Jura
• No connection (a priori) among cases
• Pressure of media, of politicians
• Local Department of Public Health, Veterinary
Services, Centre National Reference, National
Institute of Public Health

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Steps in Outbreak Investigation
the sequence is not important !

• Descriptive steps
1) Is it an outbreak?
2) Confirm the diagnosis:
– Which diseases are we talking about?
3) Define, find, count the cases
4) Analyse data:
– When? (Time)
– Where? (Place)
– Who? (Person)
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Steps in Outbreak Investigation
the sequence is not important !

• Analyse
5) Generate hypotheses
6) Test the hypotheses
7) Compare each hypothesis with facts
8) Conduct complementary studies

• Synthesis and action

9) Write a report, communicate findings
10) Control measure and prevention

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 1. Confirm the outbreak

• Outbreak
– n° observed cases > n° expected cases

• Expected cases?
– Surveillance data
– Clinicians, hospital registers
– Hospital investigation, lab, doctors, schools..

• Be careful of artefacts!
– Seasonal variation: (diarrhoea)
– Notification variation: (new surveillance system in
place)
– Diagnostic variation: (new technique)
– Diagnostic mistake: (“false epidemic")
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Number of Legionella cases per week, France
January 1996 – August 1997

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 2. Confirm diagnosis

• Laboratory
– serology
– isolation, serotype, lysotype, etc.
– toxic agent
• Meet the doctors
• See the patients
• Visit the laboratories

It is not necessary to confirm all the cases

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Define a case

• A case definition is a standard set of criteria for

deciding whether an individual should be
classified as having the health condition of
interest
• Includes:
– clinical criteria
– restrictions by time, place and person (epidemiological
link)
– laboratory findings (generally)

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 3.1. Define a case

• Suspected • Confirmed
cases cases
– clinical case – stool samples
definition – laboratory
– enough for – few cases (10-20)
immediate action

Do not wait for laboratory results to

start treatment and control activities!
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Example: Case Definition
Outbreak of S. Typhimurium, Jura, May-June 1997

Confirmed Probable
Clinical Diarrhoea (> 2 liquid Diarrhoea (> 2 liquid
stools/day) stools/day)
or Fever > 38°C ( + one or Fever > 38°C ( + one
day) day)
AND

Place, resident in Jura or resident in Jura or

neighbourhood neighbourhood
Person
Time Since 12 May 1997 Since 12 May 1997

Biological Identification of S. None, but contact with

Typhimurium confirmed case
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 3.2. Find and count the cases
• Information sources
– All possible sources (NGOs, local leaders, etc)
– Hospitals, health centres, laboratories, doctors,
nurses
– schools, camps, settlements
– Radio, door to door
– « snow ball »
– Laboratory
• How many? No strictly all
• Collected information
– Demographics
– clinical and biological
– eventual exposure
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 4. Descriptive Epidemiology

• Time
• Place
• Persons

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 4. Data description: TIME
epidemic curve
• Case distribution over time (according to
the date - hour, week - of onset of signs)
• Onset, peak, importance, time, end of
epidemic
• Abnormal cases
• Allow to make hypothesis:
– incubation period, pathogen responsible
– source, mode of transmission
– time of exposure
• Epidemic evolution
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Example: Epidemic curve of Cases due to S.Typhimurium
by week of onset of symptoms of isolated bacteria,
Jura, May- June 1997.
Number
Nombreof de
Cases
cas

30
1One
casCase

25

20

15

10

14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
21
Avril Mai Juin Juillet
–April
Best May
Practices/ MethodsJune July
Outbreak Investigation Semaines d’isolement ou de début des symptômes
SEARO – CSR Training on Outbreak Investigation
 4. Data description: PLACE

• Residence
• Place of exposure
– work, food places, journeys, tour
• Maps (points, attack rate)

Identify areas at risk,

Identify population at risk
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 4. Data description: PERSON

• Distribution of cases by age, sex, profession,

etc (Numerator)
– ex: 50 women, 100 men
• Distribution of variables in the population from
where cases are coming (Denominator)
– ex: 1500 women, 1000 men
• Compute attack rate
– ex: women 50/1500 , men 100/1000

=> Identification of sub-group(s) at risk

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Example: Data Description - Person
Infection by S.Typhimurium
Attack Rate by age group, Jura, May-June 1997
Age group Number of
(years) Cases
<1 2

1–5 36
6 – 14 22
15 – 64 29
> 65 9
Total 98

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Example: Data Description - Person
Infection by S.Typhimurium,
Attack Rate by age group, Jura, may-June 1997

Age Group Number of Cases Population Attack Rate/

(years) 100,000
<1 2 522 383
1–5 36 16,014 225
6 – 14 22 30,385 72
15 – 64 29 157,989 18
> 65 9 41,948 22
Total 98 246,858 40

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 5. Formulating hypotheses
Starting from:
– Descriptive information (TPP)
– Knowledge of the disease
– Exploratory study on some cases

Explaining:
– Causal agent
– Source
– Way of transmission
– Carrier

DIFFICULT !!!!
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Example: Formulating Hypothesis
Infection of S.Typhimurium
• Descriptive data:
– Agent: S. Typhimurium lysotype 12 atypical
– Time, epidemic curve: persistent common
source
– Place: cases clustered in the south of Jura
– Persons:
• Attack rate higher among children
• All ages affected
• Muslim among the cases

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Example: Formulating Hypothesis
Infection S.Typhimurium
May – June 1997

Descriptive information Hypothesis

S. Typhimurium
South of Jura
Children more affected
Muslim among cases
Meat (cow), salami, poultry,
milk products, etc
Regional products, local
distribution
Consumed products (also) by
some children
Pork less probable

Good weather condition Barbecue, poultry

Documentation Epidemic of roasted poultry

described
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 5. Formulating Hypothesis
Exploratory Survey

• Formulate hypothesis
• Interview some cases:
– Open questionnaire and complete
• Common exposure?

Example Jura:
• Big questionnaire, inclusion of regional
products (cheese)
• 17 cases interviewed 29
Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Example: Results of Exploratory Survey
Exposure of cases to specific food
Jura, May - June 1997
Food No. of people No. of % of cases
who ate respondents exposed
Chipolatas 6 15 40
Cooked chicken 58 17 29
Raw chicken 7 16 44
Minced beef 7 17 41
Pork 9 17 53
Veal 8 17 47
Cheese (comte) 13 17 77
Cheese A 14 16 88
(Fromage a)
Rochfort (Bleu de 6 10 60
Gex) 30
Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 6. Testing the hypothesis
• Objectives
– Specific exposure: the carrier and the source
– Factors facilitating or protective
• host, agent, environment

• Survey to identify aetiology:

– Cohort
• uses attack rates
• best in a small, well-defined population
– Case-control
• odds ratio quantifies the relationship b/w exposure and
disease

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 6. Testing the hypothesis
Case-control
• Compare
– Proportion of exposed among cases
– Proportion of exposed among the non cases (controls)

• Compute Odds Ratio (OR) and Confidence Interval

(CI) at 95%

• Select controls
– “Not sick”
– Susceptible (e.g., not immunised)
– Coming from the same population of cases
– The same chances of being exposed
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Exposure of Cases and Controls to specific food
Jura, May - June 1997
Food No (%) of Odds Ratio CI 95%
exposed cases
(N = 42) (N = 42)

Patés 11 (26) 17 (40) 0.5 0.2 – 1.3

Sausage 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
(cheese)

Bleu de Gex 12 (35) 10 (24) 3.0 0.6 – 14.9

(blue cheese)

Comté (cheese) 36 (86) 37 (88) 0.8 0.3 – 2.7

Fromage A 33 (83) 23 (55) 6.5 1.4 – 28.8
(cheese)
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 7. Compare the hypothesis with the results
• Compare the results
– clinical observation
– biological examinations
– epidemiological studies
– statistical tests
• The hypothesis should be:
– plausible
– biologically acceptable
– explain causal agent, source,
mode transmission, time of exposure
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Example:
Comparison of hypotheses with observed facts,
Jura, May-June 1997

Cheese A
• Raw milk (plausible)
• Consumed by children (data persons)
• Regional product (data place)
• Collect cheese among the cases (data
microbiological)
– S. Typhimurium identified in 3 cheeses A
– Other cheeses negatives

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 8. Complementary studies

• At the same time, and oriented by the

epidemiological survey
– Environmental survey
– Microbiological survey

• Plan more systematic studies

– More cases, more controls
– Dose-effect, facilitating factors..

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Example: Complementary studies
Epidemic of S. Typhimurium
Jura, May-June, 1997
• Microbiological survey:
– Food collection among cases
– Sample collection among cases suppliers
– Comparison of human specimens and food
products

• Survey on the distribution network of cheese A

• Survey among the producers:

– Veterinary
– Labour medicine
– Environmental
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Example: Complementary studies
Epidemic of S. Typhimurium
Jura, May-June, 1997

Survey distribution network

Wholesaler

Cheese
dairy

CREMERIE

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 9. Writing a Report

• To be written on site
• Promotes synthesis (of the objectives)
• Documents the event (for evaluation/ legal
purposes)
• Allows communication of results
• Provides recommendations
• Pedagogical tool (training material)

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 10. Take some measure of control and
prevention
• Don’t wait for the end of the investigation :
– General measures at beginning
– Specific measures according to the results

• Kinds of measures to control :

– The source (e.g.: chlorination of water)
– The transmission (e.g.: hygiene measures)
– The carrier (e.g.: recall a lot of suspected cheese)
– Reduce the susceptibility of host (e.g.: vaccination)

• Example Jura:
– Personal Hygiene
– Adequate cooking of meat
– Recall of the incriminated product (Fromage A)
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 " The art of epidemiological reasoning is to
make some reasonable conclusions
starting from imperfect data"

George W. Comstock

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 But better information… leads to better results

• This means having:

– A good description of Time, Place, Person
(TPP)
– Good data collection and preservation of
samples
– A well coordinated multidisciplinary team

Immediate Immediate Reduced morbidity

detection response and mortality

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Outbreak Detection and Response

First Detection/
Case Lab
Reporting
Confirmation Response

90
80
70
60 Opportunity
CASES 50 for control
40
30
20
10
0
43
10

13

16

19

22

25

28

31

34

37

40
1

Outbreak Investigation – Best Practices/ Methods

DAY
SEARO – CSR Training on Outbreak Investigation
 Outbreak Detection and Response
First
Detection/
Case Lab
Reporting
Confirmation
Opportunity
Response
90
for control
80
70
60
CASES 50

40
30
20
10
0
10

13

16

19

22

25

28

31

34

37

40
1

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Outbreak Investigation – Best Practices/ DAY
Methods
SEARO – CSR Training on Outbreak Investigation
 Ethical Aspect

• Securing consent (participants)

• Informing local authorities,
communities
• Ethical treatment of animals

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 Best practices

• Establish clear and concise policies and

procedures
• Careful documentation and proper
recording of events/results
• Effective communication skills
• Evaluate and review responses
• Expect the unexpected
– Key people away, new, emerging pathogen,
demystifying rumour, etc. 46
Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 References

• De Valk, Henriette, French Institute for

Public Health Surveillance (Institut de veille
sanitaire, InVS)
• European Programme on Intervention
Epidemiology Training

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation