Investigation - UNC Center for Public Health Preparedness
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Transcript Investigation - UNC Center for Public Health Preparedness
Investigation of Suspected Cases of
Human Infection with
Avian Influenza A (H5N1) Virus
1
Learning Objectives
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Know when and how to prepare for the investigation of
suspected human H5N1 cases
Understand the objectives of outbreak investigation of
suspected, probable, or confirmed H5N1 cases
Understand the mechanics of an outbreak investigation of
suspected, probable, or confirmed H5N1 cases
Describe how to analyze and communicate findings from
case investigations
2
Outline
• Pre-investigation and response planning
• Gathering initial evidence
• Specimen collection
• Case finding and clusters
• Contract tracing
• Managing data
• Reporting and evaluation
3
An important
resource for
H5N1
case
investigations
4
Investigating Cases to Protect Public
Health
• Confirm or exclude H5N1 virus infection
• Reduce morbidity and mortality through rapid
identification, isolation, treatment, clinical management
of cases and follow-up of contacts
• Reduce spread of H5N1 virus infection through
identification of exposure sources and implementation of
control measures
• Determine if cases or cluster of cases represent the
beginning of a potential pandemic
5
Investigating Cases to Gather and
Disseminate Data
• Determine key epidemiological, clinical, and
virologic characteristics of cases
• Enhance surveillance
• Ensure timely communication to facilitate informed
decision-making
6
Phases of a Case Investigation
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Pre-Investigation
Plan the Response
Investigation
1. Gather epidemiologic evidence: Create case definitions,
assess exposure and risk, collect clinical specimens
2. Conduct case/cluster finding, contract tracing
3. Manage and analyze data, study epidemic curves and
patterns
4. Prevention and control activities
Post-Investigation
Write a summary report and evaluation of performance
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Pre-Investigation and
Response Planning
Phase 1
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Define: Trigger
Trigger: A series of events or occurrence of cases which
initiates an epidemiologic investigation
•
May be used for avian influenza
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May be used for any emerging pandemic
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More sensitive than standard WHO case definitions alone
Epidemiologic links to H5N1
Early warning
Clusters of severe, unknown respiratory disease
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Triggers With Possible H5N1 Link
Any person that meets the WHO
definition of: suspect, probable
or confirmed case of human
H5N1 infection
OR
SARI cases in workers in
poultry industry or among
those with other relevant
occupational exposures
Photo: Tony Mounts, CDC
Photo: Tony Mounts, CDC
10
Additional H5N1 Triggers
• Poultry events: excessive deaths
• Rumors from informal data sources
News media
Information hotlines
Photo: Diane
CDC
Photo:Gross,
Diane Gross,
CDC
11
Triggers Without Clear H5N1 Link
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Severe, acute, respiratory cases in health care workers
who care for patients with SARI or pneumonia
Clusters of 2 or more SARI cases in a 2 week period
2 people in a family
Cases in a small geographic area
Cases with social or occupational connection
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Increases in cases at a hospital compared to the same time
in previous years
Change in the epidemiology of cases
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Preliminary Data Collection
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How many suspected cases are there?
Among those, how many would meet the WHO suspect case
definition for H5N1?
What are the signs, symptoms and clinical characteristics?
How serious is the condition of the case(s)?
What is the date of onset fever and other symptoms?
What is the geographic location of these cases?
Has this area had a recent bird or poultry H5N1 epizootic?
Have the suspected cases had any relevant exposures, including
poultry or other bird exposures, or exposure to people with SARI?
Has any testing for seasonal influenza, avian influenza A (H5N1) or
other novel influenza subtypes been undertaken?
! Consider the security situation in the area !
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Rapid Response Team (RRT)
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Team leader
Epidemiologists
Medical officer
Veterinary officer
Laboratory scientist
Communications
specialist
Logistician
Data Manager
Photo: Tim Uyeki, CDC
14
Resources to Use
• People
Physicians and nurses caring for case-patient
Agricultural and animal health workers,
veterinarians, clinical and laboratory experts,
support personnel
Local district, city, and provincial public health
staff
• Other
Security
Communication devices, money
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Institutional Resources
• Ministry of Health, and Ministry of Agriculture
Advice, guidance, additional personnel
Background information on organization of health care
system
• World Health Organization (WHO)
Request for assistance: PPE, antiviral, personnel
WHO guidelines for investigation of human
cases of avian influenza A (H5N1)
• Other Non-governmental Organizations
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Logistics and Documentation
• Proof of employment
• Information on cases already gathered
• List of important contacts or resources
• Manuals or Standard Operating Procedures
(SOPs)
Case management, laboratory procedures
• Local currency
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Supplies
• Epidemiological
Case definitions, reporting forms, questionnaires
• Medical
Antiviral medications
• Laboratory
Specimen collection materials, transportation containers, labels,
viral transport media
• Personal Protective Equipment (PPE)
Respirators, gloves, gown, goggles
• Decontamination
Solution for homes or hospital rooms
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Supplies, cont
• Electronic equipment
Cell phone
Laptop (with epidemiologic software)
• Educational materials
H5N1 information brochures and posters
Simple messages, culturally appropriate
Guidelines for contacts, family members, and
healthcare workers
Ccommunication materials
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Stakeholders
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Veterinary Health Authorities
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Government Officials
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Health Care personnel
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Community
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Non-governmental organizations
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Laboratory
Centers for Disease Control and Prevention
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Review Question #1
What are some of the logistic and planning
documents you need to prepare as part of the
pre-investigation?
Answer: Many are possible. Examples include:
Case reporting forms
WHO and national guidance documents
Standard protocols and procedures
Specimen collection forms
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Collaborative Investigation
• Public health investigators should work
together with human, animal, and
environmental health investigators
Plan joint visits to affected areas
• Animal health investigators help assess
appearance and health of animals and
surrounding environment
• Coordinate and share test results and
surveillance data
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Investigation Step 1:
Gathering Initial Evidence
Centers for Disease Control and Prevention
Phase 2: Investigation
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Evidence From a Suspect Case
• Epidemiological findings
Exposures
• Clinical evidence
• Laboratory evidence
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Key Questions to Address in H5N1
Case/Cluster Investigations
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?
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What are the likely H5N1 virus exposure sources
for the case(s)?
Has human-to-human transmission of H5N1 virus
likely to have occurred?
Is there evidence of human-to-human H5N1 virus
transmission beyond two generations?
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H5N1 Avian Exposures
• Unprotected exposure to H5N1 virus-infected poultry
or wild birds (ill or dead)
• Consumption of raw poultry
products infected or contaminated
with H5N1 virus
• Visiting a live poultry market
• Contact with ducks and geese
• Unprotected contact with
Source: Tim Uyeki, CDC
contaminated environment
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Human H5N1 Exposures
• Exposures to a H5N1 case
Contact (within one meter) with a person
(e.g. caring for, speaking with or touching)
who is a suspected, probable or confirmed
H5N1 case
From one day before to 14 days after the
case patient’s illness onset
Source: Josh Mott, CDC
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Other Possible H5N1 Exposures
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Exposure to other H5N1 virusinfected animals
Touching or consuming an H5N1 virus
infected animal (cat, dog, pig)
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Laboratory exposure
Unprotected exposure while processing
samples suspected of containing H5N1
virus
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Other environmental exposure
Residence or visit to an area where
H5N1 virus is suspected or confirmed
Centers for Disease Control and Prevention
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Risk Stratification:
Based on Exposures
• High risk exposure
Household or close family contacts
• Moderate risk exposure
Other exposed persons who were not wearing appropriate
PPE
• Low risk exposure
Unexposed persons or those wearing appropriate PPE)
*
WHO Rapid Advice Guidelines on pharmacological management of
humans infected with avian influenza A (H5N1) virus
http://www.who.int/csr/disease/avian_influenza/guidelines/pharmamanagement/en/index.html
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Why Use Risk Stratification?
• Helps prioritize limited resources
A priori rationale for who will, and will not,
receive resources
• Is used in WHO’s recommendations for
guiding post-exposure antiviral
chemoprophylaxis
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Review Question #2
Which of these are possible exposure routes for H5N1
infection in humans?
• Uncooked poultry meat
• Close contact with a suspected case
• Virus in home environment
• Occupational exposure (work with poultry, poultry
products)
• Infected domestic pets
• Cooked poultry meat
Answer: All are possible exposures except cooked poultry meat
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Case Definitions
• “Standardizes” the investigation
• Clear criteria
Signs
Symptoms
Epidemiological data
Lab results
• Unique for every outbreak
• Objective measures
• Person, place, and time
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WHO Case Definitions for Human Infection
with Avian Influenza A (H5N1) Virus*
• Person under investigation
• Suspected Case
• Probable Case
• Confirmed Case
*WHO case definitions for human infections with influenza
A(H5N1) virus; 29 August 2006
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Person Under Investigation
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Person whom public health authorities have decided
to investigate for possible H5N1 virus infection
Photo: Reuters / Amr Dalsh
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Suspected Case
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A person presenting with unexplained acute lower
respiratory illness with fever (>38°C) and cough,
shortness of breath, or difficulty breathing;
AND
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Potential exposure to H5N1 virus in the 7 days prior to
symptom onset
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WHO Suspected Case Exposures
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Exposure to poultry or wild birds ,their
remains, or areas contaminated by their feces
in area with suspected/confirmed H5N1 in
the last month
Consumption of raw or undercooked poultry
products
Close contact (within 1 meter) with a person
who is a suspected, probable, or confirmed
H5N1 case
Close contact with a confirmed H5N1
infected animal other than poultry or wild
birds
Handling samples (animal or human)
suspected of containing H5N1 virus in a
laboratory or other setting
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Probable Case
Probable definition 1
• A person meeting the criteria for a suspected case
AND
Exhibit infiltrates or evidence of an acute pneumonia on chest
radiograph plus evidence of respiratory failure (hypoxemia,
severe tachypnea)
OR
Have a positive laboratory confirmation of an influenza A
infection but insufficient evidence for H5N1 virus infection
Probable definition 2
• A person dying of an unexplained acute respiratory illness who
is considered to be epidemiologically linked by time, place, and
exposure to a probable or confirmed H5N1 case
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Confirmed Case
• A person meeting the criteria for a suspected or
probable case
AND
• A positive test result accepted as “confirmatory” by
WHO, and was conducted in a national, regional or
internationally accepted* influenza laboratory
* Accepted by WHO
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Confirmatory Test Results for
H5N1 Virus Infection
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Isolation of an H5N1 virus
Positive H5 PCR results from tests using two different PCR
targets
Fourfold or greater rise in H5N1 neutralizing antibody titer
from acute serum specimen (collected 7 days or less after
symptom onset) and a convalescent serum specimen
(convalescent titer must be 1:80 or higher)
An H5N1 neutralizing antibody titer of 1:80 or greater in a
single serum specimen collected at day 14 or later after
symptom onset and a positive result using a different
serological assay
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Review Question #3
Is this case a suspect, probable, or confirmed case
based on WHO definitions:
A 8 year old boy dying of an unexplained acute
respiratory illness who was a neighbor of a
previously confirmed H5N1 case
Answer: probable case
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Investigation Step 2: Case Finding,
Clusters, Contract Tracing
Photo: Diane Gross, CDC
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Case Finding and Clusters
Photo: Diane Gross, CDC
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Importance of Case Finding
• Identify all possible cases in a community
Treat affected persons, determine exposure
sources, and prevent further transmission
• May provide information about potential
human-to-human transmission
Obtain information on cases related in time and
location to other cases or clusters
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What is Case Finding?
• Attempt to identify additional cases
Persons who may have been exposed to the same
H5N1 source as the case
Persons with bird/animal exposures or healthcare
workers caring for H5N1 patients
Persons with unexplained SARI (with fever AND
either cough, difficulty breathing, or shortness of
breath)
Persons who died of an unexplained acute
respiratory illness
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Close contacts of the case
Methods of Case Finding
Active: Search effort by public
health workers in an area
where a case has occurred
Passive: Suspect cases that are
reported without efforts by
public health staff
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House-to-house searches
Visits to health care facilities
Private practitioners
Traditional healers
Laboratories
Routine surveillance
Rumor hotlines
Public information messages
in the affected communities
Any cases meeting H5N1 or pandemic early warning trigger
criteria must be referred for specimen testing and appropriate
medical care!
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Whom to Interview
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Suspected, probable, confirmed
H5N1 cases, other persons meeting
trigger criteria
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Family members/Household contacts
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Health care providers, health workers
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Co-workers, if occupational
exposures are suspected
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Type of Information to Collect
• Demographic data
Age, sex, household members
• Epidemiology data
Occupational, home, avian or other environmental exposures (7
days before illness onset)
Contact with confirmed or suspect H5N1 cases (7 days before
illness onset)
Travel history
• Clinical data
Signs & symptoms, underlying conditions, physical exam, vitals,
Hospital admission, treatments, laboratory results, chest x-ray
results, complications
Outcome
• Laboratory results
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How to Interview
• Generate list of potentially exposed contacts for
each case
• Collect as much information as reasonably possible
Structure and unstructured components to the interviews
• Repeat critical questions for accuracy, validity, and
additional details
• Understand that family members may be grieving
for deceased cases
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Interview Tips
• Be friendly, but professional
• Identify yourself and your institution
• Explain purpose of interview
• Stress importance of information you will collect
• Inform respondents that all information will be kept
confidential
• If appropriate, conduct the interview in private place
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Specimen Collection
Confirm the Diagnosis
Centers for Disease Control and Prevention
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Specimen Collection
• Safe and correct collection
• What samples to collect?
• What to wear for protection?
• How to transport specimens?
• Procedures for diagnosis?
Who to collect from (trigger criteria)?
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What to Collect
Collect multiple specimens from different sites on
different days
• Lower respiratory tract specimens (best)
Endotracheal aspirates
Bronchiolalveolar lavage (BAL)
Pleural fluid from chest tubes
BAL or pleural fluid should only be tested if they were collected
for another purpose
• Upper respiratory tract specimens
Throat swabs preferred
Nasal swabs (can help detect human influenza viruses)
• Collect acute and convalescent serum
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Review Question #4
What types of information do you need solicit during an
interview?
Environmental exposures
Clinical symptoms
Travel information
Potential contacts
Poultry exposure during last month
Answer: All of these EXCEPT poultry exposure in last
month (should be in last 7 days before symptom onset)
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Common Challenges to Case
Finding
• Even with active case finding, all cases may
not be identified:
Physicians may not suspect H5N1 virus infection
Some H5N1 virus-infected persons may not seek
medical care
Secrecy about poultry outbreaks to avoid culling of
poultry
Presentation may be atypical
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Enhancing Surveillance
• Location
• Implement in areas where H5N1 cases live or
where animal outbreaks are occurring
• Active surveillance at healthcare facilities or
healers, private laboratories;
• Active surveillance among health care workers,
persons exposed to birds/animals
• Duration
• Minimum of 2 weeks after the last human H5N1
case is identified (2 incubation periods)
• Maintain for longer periods if H5N1 poultry
outbreaks are not controlled
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Methods to Enhance Surveillance
among Medical Community
• Conduct
trainings at health care facilities in the area
to recognize trigger events and reporting process
• Ask health care facilities in the area to report all cases
of SARI for the next 2-4 weeks
• Notify pharmacists and dispensers to report increases
in medications for respiratory illnesses
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Methods to Enhance Surveillance
among General Community
• Expand sensitization training to key community
members
• Ask village leaders, traditional healers, and
religious leaders to report trigger events
• Notify teachers and school administrators to
report increases in student absenteeism
• Pharmacists may also report any unusual
increases in prescription practices
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Clusters of Severe Acute
Respiratory Illness
PHOTO: AP / Binsar Bakkara
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A Cluster May Exist When:
• Two or more people with moderate or severe
acute respiratory illness
Unexplained by other causes
May have died from the illness
Onset within two weeks of each other
AND
• History suggests exposure to H5N1 virus or
another person with SARI
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Determining Human-to-Human
Transmission of H5N1 Virus
• Documented exposure to a confirmed, probable, or
suspected human H5N1 case, AND
• The time interval between contact with a suspected,
probable, or confirmed H5N1 case and illness onset is
7 days or less, AND
• No other sources of H5N1 exposures (such as
exposures to birds, other animals, feathers, droppings,
fertilizers made of fresh bird droppings, live poultry
markets, contaminated environments, or laboratory
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specimens)
Review Question #5
If you recognize a cluster of human H5N1 cases
with contact with a confirmed H5N1 case and onset
within one incubation period of that case, would you
conclude that human-to-human transmission of
H5N1 virus has occurred?
• Answer: No. A detailed epidemiologic
investigation would need to take place to ensure
that no other plausible source of infection should
be of concern.
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Contact Tracing
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What is Contact Tracing?
The identification and diagnosis of persons who may
have been in close contact with an infected individual
during the infectious period
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Purpose of Contact Tracing during
an Influenza A(H5N1) Investigation
• Find new suspected human cases of H5N1 or other
cases meeting trigger criteria
• Decrease risk of illness and interrupt further
transmission through methods such as:
Active surveillance for illness
Antiviral chemoprophylaxis of exposed
Early treatment of ill persons
Collection of specimens for H5N1 testing
Educational information to prevent transmission
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How to Identify Contacts
1. Review the case patient’s activities for the 1 day
before onset of symptoms through 14 days after
onset of symptoms
2. Identify all close contacts (within 1 meter) of the
case
3. Identify additional individuals with exposure to
birds and other animals suspected of being infected
with H5N1 virus
4. Verify all information collected
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Prioritize Contact Identification
• If number of contacts is large, focus on:
Contacts of probable and laboratory confirmed
H5N1 cases
Contacts with prolonged close exposures to a
suspected H5N1 case
Household contacts sharing the same sleeping and
eating space, persons providing bedside care
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Key Information for Contact Tracing
• Who did the case come into close contact with?
• What activities was case doing at the time?
• Where did these activities take place?
• When did case come into contact with this person?
• Other key information:
Contact information, health status
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General Guidelines for
Interviewing Contacts
• Do not alarm contacts
• Communicate preventive
information
• Refer symptomatic
individuals to a designated
healthcare facility
• Consider if Personal
Protective Equipment (PPE)
is necessary
Centers for Disease Control and Prevention
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Information from Contacts
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Demographic and contact information
Name, Address
Occupation, age, gender, relationship to the case
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Exposure History
Contact with case-patient
Poultry and wild bird exposure
Other high-risk exposures such as contact with SARI cases
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Physical Exam and Clinical information
Health status
Temperature, other vital signs
Presence of signs or symptoms of acute respiratory infection
(feverishness, fever, sore throat, coughing)
Hospital lab findings (such as blood work, chest xray findings) 69
Monitoring and Managing Contacts
• Actively (daily) monitor contacts for signs of illness for
7 days after exposure
Encourage self-health monitoring
Instruct to report onset of fever or respiratory symptoms
Visit or phone daily to monitor for illness
Refer contacts with fever or respiratory illness to medical
care, isolation, treatment; obtain respiratory specimens for
H5N1 testing
• MOH may request (voluntary) home quarantine of all
•
contacts for 7 days post exposure
Consider antiviral chemoprophylaxis, if available
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Investigation Step 3: Managing
Data
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Data Management
• Line listing of cases, contacts
• Record keeping
• Validation and Cross-Checking
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Line Listing
An organized way to view all cases in an investigation
Case Age Sex Status
#
Occupation
1
5
M
Probable
Child
Yes
7 July
2
55
F
Suspect
Caretaker of case
#1
Yes
9 July
3
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M
Suspect
Poultry Farmer
No
7 July
Information included:
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Difficult
breathing
Date of Onset
Demographic, Epidemiological
(exposures)
Clinical, Laboratory data
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Record Keeping
• Where will records be
kept?
• How will records be kept?
• Who is assigned to record
keeping?
• Maintain confidentiality!!
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Validation and Cross-Checking
• Check line lists against medical charts and
interviews
• Validation
Ask same question in different ways
Ask same question at different times
Ensure answers are consistent
Double-entry of data
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Creating an Epidemic Curve and
Analyzing Data
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What is an Epidemic Curve?
An epidemic curve
(‘Epi’ curve) is a
graph or histogram of
the number of cases
of illness by the date
of illness onset
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How Can an Epidemic Curve Help in an
Outbreak?
Provides information on the characteristics of an
outbreak
• Pattern of spread or transmission pattern
• Magnitude of epidemic
• Outliers (case outside expected time frame)
• Time trend
• Disease incubation period, possible timing of
exposure
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Epidemic Curves and Transmission
• Epidemic curves have different patterns depending on
transmission
Infectious agent transmitted between people
Infectious agent transmitted from one source to multiple
people
• Can be used to assess whether human-to-human
transmission is occurring
• Patterns easier to identify with larger number of cases
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Epi Curve for Human to Human
Transmission
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Epi Curve for Human Cases from
Single Source
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Key Analytic Questions
• Do data suggest greater spread of H5N1 virus among
humans?
Large increase in human H5N1 cases?
Increase in cluster frequency, duration of illness?
Cases in non-family member contacts?
Mild or moderately ill cases?
Absence of animal/bird exposures?
Change in age distribution?
Multiple generations of human-to-human transmission
suspected?
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Investigation Step 4:
Prevention and Control Activities
Photo: Reuters / Bobby Yip
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Prevention and Control Activities
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Animal health and
control measures
Culling, disinfection,
surveillance,
vaccination
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Infection control
Isolation of suspected
and confirmed cases
PPE, infection control
precautions
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Treatment of ill
patients
Contact tracing &
contact surveillance
Voluntary quarantine
of well contacts
Antiviral
chemoprophylaxis
Enhanced (active)
surveillance and case
finding
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Reporting and Evaluation
Phase III: Post Investigation
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Multiple Levels of Reporting
• Local Level: Who is responsible for submitting H5N1
case reports? When should this be done?
• National Level: Who needs to be updated on the
investigation and receive the final report on number
of H5N1 cases? Who is responsible for assuring that
this occurs?
• International Level: Probable, and confirmed H5N1
cases should be reported immediately to WHO. The
WHO IHR National Focal Point should be
responsible for notifying WHO.
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International Health Regulations (IHR)
• Compulsory notification of any human infection
with a novel subtype of influenza A
• Under IHR (2005) all probable and confirmed
H5N1 cases in humans must be immediately
reported to WHO
• Compliance with these standards is required to
strengthen early detection, reporting, and
response
87
How and When to Report
Use standard reporting forms
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Case/Lab specimen
based forms, linelists, weekly and
monthly reporting
forms, contacts
follow-up forms
Immediate reporting
of cases/clusters to
next levels
Share information
Case Reporting
site
Feedback
(all levels)
Local Health
Department
Local
Laboratories &
Agencies
District
Epidemiology
Offices
District Animal /
Agriculture
Offices
National /Ministry
of Health
National Agencies
/Ministry of
Agriculture88
Writing a Summary Report
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Why communicate the findings?
• A document for action
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Control and prevention measures
To share new insights
To obtain national and international resources
Documents the investigation
To assist other nations districts or countries with
investigation
Inform the public
Help prevent future outbreaks
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Content of a Summary Report
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Summary
Introduction and Background
Outbreak Description
Methods and Results
Discussion
Lessons Learned
Recommendations
Acknowledgements
Supporting Documentation
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Evaluate Performance
Onset
Detection
Response
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Why Evaluate the Investigation
• To summarize the events that occurred
• To learn from experience
Make recommendations for future investigations
Take lessons from what worked well
Take lessons from mistakes
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What to Evaluate
• Timeliness of response
Detection
Response time
Control measures
Communication
• Completeness of the
investigation
Case finding
Data collection
Analysis
• Accuracy of the data
• Inter-agency
coordination
• Lessons for better
practice in the future
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Case Investigation Summary
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Be aware of epidemiologic triggers
Prepare investigation logistics and supplies in advance
Investigation begins with gathering clinical, epidemiologic,
and laboratory information
If warranted, conduct active case finding, cluster
investigation, and contact tracing activities
Initiate prevention and control measures at any time it is
necessary
Maintain a system for collecting, managing, storing,
analyzing, and reporting data
After the response is concluded, evaluate the investigation
performance
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Glossary
Trigger
A series of events or cases which initiate an epidemiologic
investigation. Diseases have different and specific triggers. For
example, a single suspect case of human H5N1 is a sufficient
trigger for avian flu investigation. However, multiple cases of
gastrointestinal disease would be required to trigger a salmonella
investigation.
Rapid response team (RRT)
A multi-disciplinary group of investigators and medical scientists
who are quickly mobilized in response to a disease outbreak or
adverse health event. Teams can consist of epidemiologists,
medical providers, veterinarians, laboratory and communication
specialists, data managers, infection control nurses, etc.
Glossary
Stakeholder
A person or group who is affected by, or involved in the
investigation and its outcomes
Risk Stratification
Grouping individuals according to specific risk attributes
such as degree of exposure or severity of illness
Case finding
The concerted effort of public health professionals to
search for and identify any potential cases of disease in
order to treat or contain an illness
Glossary
Cluster
An unusual grouping, or excess number of disease cases in
a geographical location or point in time
Case-patient
Index case, or patient who initiated the investigation
Line listing
A way to organize and present important information that
is collected about each potential case or contact
References
• WHO Guidelines for the Investigation of
Human Cases of Avian Influenza A (H5N1),
Jan 2007. Accessed from:
http://www.who.int/csr/resources/publications/influen
za/WHO_CDS_EPR_GIP_2006_4r1.pdf
99