tunis, 27th october 2014 -...

Investigating an outbreak

Tunis, 27th October 2014

Dr Isme Humolli Institute of Public Health, Kosovo

[email protected]

Competency to be gained from this lecture

• List three reasons why outbreak investigations are important to public health,

• Know steps of outbreak investigation

• Investigate an outbreak to propose effective prevention and control measures

Reasons to Investigate an Outbreak

• Identify the source (and eliminate it),

• Develop the strategies to prevent future outbreaks,

• Evaluate existing prevention strategies,

• Describe new disease and learn more about it,

• Address public concern,

• It’s our JOB!!!!!

When to Investigate an Outbreak

Considering the following factors:

• Severity of the disease,

• Transmissibility,

• Unanswered questions,

• Ongoing illness/exposure,

• Public concern.

Steps of an outbreak investigation

1. Establish the existence of a real outbreak 2. Confirm the diagnosis 3. Define a case 4. Search for cases 5. Generate hypotheses using descriptive findings 6. Test hypotheses based using analytical

epidemiology 7. Draw conclusions 8. Conduct additional investigations 9. Communicate findings 10. Recommendations and implementation of

prevention measures



epidemiology 7. Draw conclusions 8. Conduct additional investigations 9. Communicate findings 10. Recommendation and implementation of

prevention measures

Establish the existence of an outbreak

• Definition of an outbreak: – More number of the cases observed than is expected,

– Increased incidence of certain disease in a place at a given time,

• Elements needed: – Numerator

• Number of cases

– Denominator • Size of the population where cases come from

– Collection of this information over time • Baseline data (surveillance data, ask professionals, villagers)

Pseudo-outbreaks not linked with any recent increase of incidence

• Artifact in the numerator: – Increased awareness

– Change in surveillance practices

– Reporting of prevalent cases as incident cases (e.g., hepatitis C, sleeping sickness)

– Laboratory error

• Variation of the denominator: – Rapidly changing population denominators

• Hospital patients, migrants, refugees, mass gathering




prevention measures

Confirming the diagnosis: A two-stage process

1. Short list diagnoses with clinical information

– Communicate with clinicians, specialists

– Examine the frequency of symptoms among cases

2. Confirm diagnosis with laboratory tests

– Communicate with the laboratory

– Conduct testing for probable diagnoses

• Better predictive positive value if tests guided by clinical picture

Symptoms reported by cases among CCHF patients, Kosovo 2013

69.3

71.6

89.3

49.2

62.4

84.7

70.5

78.2

34.5

13.2

9.6

3.05

Petechie

HSC

Conjunctive Injection

Haemorrhagia in sclera

Epistaxis

Gingivorrhagia

Haematemesis

Melena

Metrorrhagia

Hematoperitoneum

Pleuritis haemorrhagica

Otorrhagia

Frequecy(%)



epidemiology 7. Draw conclusions 8. Conduct additional investigations 9. Communicate findings 10. Execute prevention measures

Case definition

• A case is the occurrence of (these syndromes) in a resident of (this place) between [beginning date] and [end date],

• Standardization of cases for surveillance purposes

• Is set of criteria of person, time, place and clinical features, and/or lab, and/or epidemiological feature,

Case definition

• Different levels of case definition allow:

– Searching for potential cases widely

– Narrowing the search subsequently

• Case definitions may differ at various stages

– Descriptive stage (Case-finding)

• More sensitive

– Analytical stage (Hypothesis testing)

• More specific

Case definition

• Degree of certainty: possible /probable/

confirmed

• Summarize:

Simple, clear, precise and applicable

Can be used by different people

Risks:

Include false cases (too sensitive)

Exclude real cases (too specific)

Case definition

• EXAMPLE: Diarrhoea outbreak in Ìsland X, May 2013

– Person : WHO?

– Clinical/biological criteria : WHAT?

– Time (study period) : WHEN?

– Place: WHERE?

• A case was defined as person with fever and at least one of the following:

diarrhoea, vomiting, abdominal pain or nausea, presented between 1 May

and 31 May 2013 to the health center in Island X




prevention measures

Search for cases

• Time, place and person criteria – From case definition

• Chose a uniform strategy to search for cases – Passive surveillance

• Reports coming to surveillance unit

– Stimulated, passive surveillance • Phone calls / visits to facilities to trigger reporting

– Active surveillance • Search of records in health care facilities

– Door-to-door case search

Search for cases

Create a questionnaire:

– Interview case (or family):

– Demographics: sex, age, place of residence..

– Clinical characteristics

– Expositions: food, activities, travels , behavior, common characteristics,

Line list

The line listing

• Constitutes and updates a database of cases

• Protects the confidentiality of the patients

• Prepares an easy, automated, descriptive analysis

Typical line listing for an outbreak investigation

Uni. ID OnsetDate Street Area City AgeYears Sex Hospital Death HEVIgM HAVIgM

1 1-Mar-05 18 2 HYD 12 1 1 2 1 9

2 3-Mar-05 22 1 HYD 25 2 1 2 2 1

3 5-Mar-05 23 3 HYD 36 1 2 9 9 9

4 6-Mar-05 - - SEC 23 2 1 1 1 2

Unique

identifier

Time

Place

Person

Outcome

Lab

Guiding principles for the line listing

• Is unique – Don’t confuse yourself and others with multiple versions

• Contains a unique identifier for each record (case)

• Ensures confidentiality – Separate list of names on paper kept under lock and key

• Contains essential information on each case – Time, place, person, other (e.g., clinical picture, laboratory)

• Can be updated as the investigation develops

• Allows regular, automated, computerized analysis – Aggregation




prevention measures

Using time, place and person information to generate hypotheses

• Time – Epidemic curve

• Place – Spot map

– Incidence by area

• Person – Incidence by age, sex, etc.

– Trawling questionnaire of cases

– Interview of outliers

TIME: Drawing an epidemic curve

• Epidemic curve shows progression of the disease in the outbreak by time:

– Bar chart

– Time in X axis

– Unit: 1/4 of the incubation period

– Number of cases in Y axis

– No intervals between bars

(1) Describing and (2) interpreting an epidemic curve

• Description – Beginning

– Peak(s) • Number

• Duration

– End

• Interpretation – Point source outbreak

– Persisting common source outbreak

– Person-to-person transmission

Cases of acute gastroenteritis (n=20*) among

guests by date and time of onset, Helsinki, 2012

10

9

8

7

6

5

4

3

2

1

0 8 16 0 8 16 0 8 16 Hours

19 August 20 August 21 August Day

Num

ber

of

cases

Time

0

5

10

15

20

25

30

Number of cases

TIME – EPIDEMIC CURVE

0

5

10

15

20

25

30

start

peak

end

Outlier

case

Range

Number of cases


Point common source

Persistante commune source

time

time

Number cases

Number cases


time

temps

Number cases

Number cases

Human-to-human transmission

Point common source + human to human transmission


Probable and confirmed cases of non-travel-related Salmonella Stanley infections by month of report, August

2011 – 23 January 2013

n=684, 10 countries: Hungary (235), Austria (186), Germany (77), Belgium (41), the United Kingdom (64), Czech

Republic (35), Sweden (18), Italy (14), Slovak Republic (12), and Greece (1)

0

10

20

30

40

50

60

Sept Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug

Month of onset

Num

ber

of ca

ses

Did not report injecting drug use

Reported injecting drug use

1995 1996

Hepatitis A cases by month of onset in Siouxland, Iowa, USA, 1995-1996

Drawing the epidemic curve on the basis of the distribution by time of onset

1. Count cases by

time of onset

2. Eyeball

distribution

to choose interval

3. Finalize

PLACE: Drawing a map

• Geographical distribution of cases: place of

residence, work, other activitis

• Spot map

– Plot of cases (spot) on a rough map in the field

– Does not account for population density

• Incidence by area

– Calculate incidence by area (ward, block)

– Draw chloroplethic map

Cholera cases by residence, Kanchrapara, N-24 Parganas, West Bengal, India, 2004

Rates of confirmed and probable cases of Salmonella Stanley by EU Member State,

1 August, 2011 to 18 September 2012 (N=418)

PERSON: Attack rate

• Case: numerator

– Count the cases by age groups, profession, sex

• Population: denominators

– Describe cases for each age groups, profession, sex

• Risk group identification

– Attack rate AR= (cases/exposed population) x 100

Attack rate of parotitis by age and gender, Gjakova, Kosovo, January – May 2014

Characteristics Number of

cases

Population Attack rate

per 10,000

Age group 10-14 98 57,456 17.1

15-19 87 54,938 15.8

Gender Male 96 57,374 16.7

Female 89 55,020 16.2

Total 185 112,394 16.5

Using outliers to generate hypotheses

• Outliers may have had a different type of exposure

– Different timing

– Different intensity

– Different location

• Outliers may be source patients

• Outliers may correspond to errors in data collection

Using outliers to generate hypotheses: Cases of gastro-enteritis according by

onset time, Oswego, USA, 1940

0

1

2

3

4

5

6

7

8

9

18-

15

18-

16

18-

17

18-

18

18-

18

18-

19

18-

20

18-

21

18-

22

18-

23

19-

00

19-

01

19-

02

19 -

03

19 -

04

19-

05

19 -

06

19-

07

19-

08

19-

09

19-

10

Time (on 18th and 19th of April)

Num

ber

of

case

s

The outlying case-

patient had early

exposure to the

vanilla ice cream,

the source of the

outbreak


1. Establish the existence of a real outbreak 2. Confirm the diagnosis 3. Define a case 4. Search for cases 5. Generate hypotheses using descriptive findings 6. Test hypotheses based using analytical epidemiology 7. Draw conclusions 8. Conduct additional investigations 9. Communicate findings 10. Recommendation and implementation of prevention

measures

Test hypothesis

• Hypothesis is generated using descriptive findings: person, time, place

• Analytical study, test hypotheses to sort out:

– Characteristics common to all individuals

– Characteristics specific to cases

• ANALYTICAL STUDIES:

• RELATIVE RISK (RR): AR in exposed cases / AR in non exposed

Test hypothesis

ill Non - ill

Exposed 10 3

Non exposed 2 25

RR= AR exposed / AR non exposed

RR= (10/13) / (2/27) RR= 10.4

Two different fishermen

Don’t test your hypothesis using the data you used to generate them

Descriptive epidemiological data generates hypotheses

(Throw the nets wide)

Analytical epidemiological data tests hypotheses

(Fish out the answer)

Decision of analytical study?

• Different factor can be consider to decide for analytical study:

– Attack rate,

– Source population (open / closed)

– Human resources,

– Money resource,

– Time

Case control or a cohort approach

during an outbreak investigation

Size of the population Attack rate

Under 5-10 % Above 5-10%

Case control Cohort

Size of the community

Small > Take all All cases Select controls

Cohort of group (Church supper)

Large > Sample Sample cases Select controls

Cohort in a sample of the population

Interpreting the results of an analytical study during an outbreak

• Is the suspected exposure associated with illness? – What is the strength of association?

– Is there a statistical significance?

• Is there a dose response relationship? – Higher exposure, stronger association

• If a single source is suspected: – Does the source of infection identified explain most

cases? • Are most of the cases exposed?

• Is the attributable fraction in the population high?

Incidence of Klebsiella species colonization, according to

selected characteristics, Neonatal Unit, Pilsen region, Czech

Republic, 2012-2013

Characteristics Cumulative

incidence

Relative risk

Among

exposed

(%)

Among

unexposed

(%)

Estimate 95%

Confidence

Interval

Diagnosis Adoption 100 39 2.5 1.8-3.5

Weight lost 100 41 2.5 1.8-3.4

Feeding

Full artificial feeding 88 37 2.4 1.5-3.7

Breast feeding partial 31 60 0.52 0.28-0.95

Artificial

nutrition

Nutrilon 73 37 2.0 1.2-3.3

Invasive

procedures

Stomach probe 67 40 1.7 0.94-3.0

Arterial catheter 67

41 1.6 0.84-3.1

One-page mini-protocol for outbreak investigations

• Background • Objectives • Methods

– Null hypothesis – Study design – Study population – Sample size – Case definition – Case ascertainment – Recruitment of controls – Data collection – Analysis plan

• Expected benefit




prevention measures

Generating and testing an hypothesis during an outbreak investigation

Observe

a situation

Test the

hypothesis

Formulate a

conclusion

Generate a

hypothesis

Does the conclusion explains the initial

observations?

Compare the conclusion with actual knowledge

• Contacts with supervisors

• Literature review

• Medline search

• Internet



epidemiology 7. Draw conclusions 8. Conduct additional investigations 9. Communicate findings 10. Recommendations and implementations of

prevention measures

Planning additional studies guided by the results of the analytical study

• Laboratory studies – Microbiological typing

• Identical isolates among cases

• Identical isolates in source and cases

• Other studies – Environmental

• (e.g., test water, vector studies, visit the kitchen)

– Anthropological • (e.g., understand a practice at risk)

– Health economics

Environmental investigations, Neonatal

Unit, Pilsen Region, Czech Republic,

2012-2013

• Same place used to prepare

newborns diet and staff food

• Environmental cultures:

- Number of taken swabs: 12

- Klebsiella species positive: 4

– Microwave

– Cutlery

– Sewage pipe

– Plates for the staff



epidemiology 7. Draw conclusions 8. Conduct additional investigations 9. Communicate findings 10. Execute prevention measures

Communicate findings

• Tools and methodology

– Depend on audience

• Report, can be:

– Initial and final

• A written report must be left in the field

– Short

– Preliminary (disclaimer)

– Factual

Matrix for the communication of the findings of an outbreak investigation to

various audiences

Audience Medium Focus of the

content

Communication

objective

Epidemiologists,

laboratory

Report Epidemiology Documentation of

the source

Public health

managers

Summary Recommendations Action

Political leaders Briefing Control measures Evidence that the

situation is under

control

Community Press release,

interview

Health education Personal steps

towards prevention

Scientific

community

Presentation,

manuscript

Science Scientific progress

Proposed final reports for the results of an outbreak investigation

• Oral scientific presentation

• Manuscript

• Epidemiological bulletin report




prevention measures

Standard control measures

• General measures may be formulated initially to prevent secondary spread (e.g., infection control)

– Before the results of the investigations

• Type of measures:

– Source – chlorination, elimination of waste

– Transmission -hygiene

– Host - vaccination

Proposing prevention measures following an outbreak investigation

• Short, medium and long term recommendations

• Characteristics of good recommendations Evidence based

Specific

Feasible

Cost effective

Acceptable (Discuss with health officials)

Ethical

Evaluating prevention measures following an outbreak investigation

• Input

– Were the recommendations implemented?

• Process

– How did the implementation work?

• Outcome

– Did the recommendation(s) led to prevention?

The checklist is the final audit of your investigation: Cluster of diarrhea after a christening at my sister’s

Status Implementation

1 ✔ Phone call from sister the day after a christening party

2 ✗ Symptoms suggest norovirus

3 ✔ Any GI symptoms among attendees

4 ✔ Phone call to brothers and sisters

5 ✔ Epicurve, incidence by age and sex

6 ✔ Cohort study -> Carrots associated with illness

7 ✔ Carrots may have been the source

8 ✔ Niece peeled carrots after diarrhea, no hand washing

9 ✔ Spoof letter to family

10 ✔ Family advised to wash hands before peeing vegetables

Pseudo-outbreaks are not pseudo-problems

• The issue is not acute

• The problem is chronic

– There is an accumulation of cases

– The chronic problem also need to be addressed

Summarize

• Ten steps of an outbreak investigation,

• Criteria of case definition: time place person,

• Generate the hypothesis using descriptive findings,

• Test hypothesis – analytical epidemiology,

• Make recommendation,

• Communicate findings,

• Evaluate the implementation of recommendations

Thank you!

Dr Isme Humolli Institute of Public Health, Kosovo

[email protected]

mailto:[email protected]



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