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

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

Detecting an outbreak

Detection

Routine surveillance Clinical/laboratory Rumor verification General public Media

Is this an Outbreak?

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

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

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)

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) 6) 7) 8) Generate hypotheses Test the hypotheses Compare each hypothesis with facts 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
Surveillance data Clinicians, hospital registers Hospital investigation, lab, doctors, schools.. Seasonal variation: (diarrhoea) Notification variation: (new surveillance system in place) Diagnostic variation: (new technique) Diagnostic mistake: (false epidemic")
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Expected cases?

Be careful of artefacts!

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 cases
clinical case definition enough for immediate action

Confirmed cases
stool samples 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
Clinical
Diarrhoea (> 2 liquid stools/day) or Fever > 38C ( + one day) resident in Jura or neighbourhood Since 12 May 1997 Identification of S. Typhimurium

Probable
Diarrhoea (> 2 liquid stools/day) or Fever > 38C ( + one day) resident in Jura or neighbourhood Since 12 May 1997 None, but contact with confirmed case
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AND

Place, Person Time Biological

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.
Nombre de cas Number of Cases

30

1 casCase One

25

20

15

10

14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

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July Outbreak Investigation Semaines disolement ou de dbut des symptmes SEARO CSR Training on Outbreak Investigation

April Best

Avril

May Practices/

Mai

MethodsJune

Juin

Juillet

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 (years) Number of Cases <1 15 6 14 2 36 22

15 64
> 65

29
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 15 6 14 15 64 > 65

2 36 22 29 9

522 16,014 30,385 157,989 41,948

383 225 72 18 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
S. Typhimurium South of Jura Children more affected Muslim among cases Good weather condition Documentation

Hypothesis
Meat (cow), salami, poultry, milk products, etc Regional products, local distribution Consumed products (also) by some children Pork less probable Barbecue, poultry 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
Outbreak Investigation Best Practices/ Methods SEARO CSR Training on Outbreak Investigation

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Example: Results of Exploratory Survey Exposure of cases to specific food Jura, May - June 1997
Food Chipolatas Cooked chicken Raw chicken Minced beef Pork Veal Cheese (comte) Cheese A (Fromage a) Rochfort (Bleu de Gex) No. of people who ate No. of respondents % of cases exposed

6 58 7 7 9 8 13 14 6

15 17 16 17 17 17 17 16 10

40 29 44 41 53 47 77 88 60
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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 odds ratio quantifies the relationship b/w exposure and disease

Case-control

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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 exposed cases
(N = 42) (N = 42)

Odds Ratio

CI 95%

Pats Sausage Beef

11 (26) 24 (57) 32 (78)

17 (40) 28 (67) 33 (79)

0.5 0.7 1

0.2 1.3 0.3 1.6 0.3 3.5

Pork
Veal Chicken Munster (cheese) Bleu de Gex
(blue cheese)

23 (59)
22 (54) 30 (71) 4 (10) 12 (35) 36 (86) 33 (83)

29 (76)
19 (46) 34 (81) 1 (2) 10 (24) 37 (88) 23 (55)

0.5
1.4 0.6 4.0 3.0 0.8 6.5

0.2 1.5
0.6 3.4 0.2 1.7 0.5 35.8 0.6 14.9 0.3 2.7 1.4 28.8 33

Comt (cheese) Fromage A

(cheese)

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

Dont 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 detection

Immediate response

Reduced morbidity and mortality

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

Outbreak Detection and Response

First Case
90 80 70 60 CASES 50 40 30 20 10 0

Detection/ Reporting

Lab Confirmation Response

Opportunity for control

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

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Outbreak Detection and Response

First Detection/ Case Lab Reporting Confirmation Response
90 80 70 60 CASES 50 40 30 20 10 0

Opportunity for control

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