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 outbreak (new cases)

• 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
• Outbreaks 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) Determine existence of an outbreak
2) Confirm the diagnosis:
– Which diseases are we talking about?
3) Define a case; find and count cases
4) Orient data as to:
– Time (When?)
– Place (Where?)
– Person (Who?)
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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) Plan a more systematic study

• 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. Determine existence of an 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 the 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
 3. Define a case; find and count cases

• 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 cases • Confirmed cases

– clinical case definition – Collect relevant
– enough for immediate samples
action – laboratory
– few cases (10-20)

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, Person resident in Jura or resident in Jura or

neighbourhood neighbourhood

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. Orient data as to:

• Time
• Place
• Persons

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Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 4.1 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 Cases
de 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
Outbreak Investigation –April
Best May
Practices/ Methods June July
Semaines d’isolement ou de début des symptômes

SEARO – CSR Training on Outbreak Investigation

 4.2 Data description: PLACE

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

Identify areas at risk,

Identify population at risk
Identify priority areas for control activities 22
Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 4.3 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 (years) Number of 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 (years) Number of Cases Population Attack Rate/ 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. Generate 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: Generating 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 Meat (cow), salami, poultry, milk
products, etc
South of Jura Regional products, local
distribution
Children more affected Consumed products (also) by some
children
Muslim among cases 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. Generate 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
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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 cases who No. of respondents % of cases exposed
ate
Chipolatas
6 15 40
Cooked chicken
5 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 (Fromage
a)
14 16 88
Rochfort (Bleu de 6 10 60
Gex) 30
Outbreak Investigation – Best Practices/ Methods
SEARO – CSR Training on Outbreak Investigation
 6. Test 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. Test 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 exposed Odds Ratio CI 95%
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 (cheese) 4 (10) 1 (2) 4.0 0.5 – 35.8

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

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 facts
• 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 (meets persons affected by the
outbreak)
• Regional product (meets place affected)
• 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. Plan a more systematic study

• At the same time, and oriented by the

epidemiological survey
– Environmental survey
– Microbiological survey

• Plan more systematic studies (if needed)

– 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. Write a report; communicate findings

• 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. Control measures 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)
– Communicate risk if outbreak is affecting the public

• 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 (1915-2007)

Physician and Professor Emeritus
Johns Hopkins Bloomberg School of Public Health

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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.
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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