tunis, 27th october 2014 -...
TRANSCRIPT
Investigating an outbreak
Tunis, 27th October 2014
Dr Isme Humolli Institute of Public Health, Kosovo
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
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. 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
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. Recommendation and implementation of
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(%)
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. 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
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. Recommendation and implementation of
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
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. Recommendation and implementation of
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
Point common source
Persistante commune source
time
time
Number cases
Number cases
TIME – EPIDEMIC CURVE
time
temps
Number cases
Number cases
Human-to-human transmission
Point common source + human to human transmission
TIME – EPIDEMIC CURVE
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
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
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. 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
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. Recommendation and implementation of
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
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 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
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. 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
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. Recommendation and implementation of
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