Title: Investigation of Suspected Cases of Human Infection with Avian Influenza A (H5N1) Virus
1Investigation of Suspected Cases of Human
Infection with Avian Influenza A (H5N1) Virus
2Learning Objectives
- 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
3Outline
- Pre-Investigation and Response Planning
- Gathering Initial Evidence
- Case Finding and Clusters
- Contract Tracing
- Managing Data
- Reporting and Evaluation
4An important resource for H5N1 case
investigations
5Investigating 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 further 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
6Investigating 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
7Phases of a Case Investigation
- Pre-Investigation
- Plan the Response
- Investigation
- Gather epidemiologic evidence Create case
definitions, assess exposure and risk, collect
clinical specimens - Conduct case/cluster finding, contract tracing
- Manage and analyze data, study epidemic curves
and patterns - Prevention and control activities
- Post-Investigation
- Write a summary report and evaluation of
performance
8Pre-Investigation and Response Planning
9Triggers 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
10Triggers Without Clear H5N1 Link
- 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
- Increases in cases at a hospital compared
to the same time in previous years - Change in the epidemiology of cases
11Other Triggers for Investigation
- Poultry events excessive deaths
- Rumors from informal data sources
- News media
- Information hotlines
Photo Diane Gross, CDC
Photo Diane Gross, CDC
12Preliminary Data Collection
- How many suspected cases are there?
- What are the signs and symptoms?
- How serious is the condition of the case(s)?
- What is the date of illness onset of the
suspected H5N1 case(s)? - 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? - Has any H5N1 testing been done?
- ! Consider the security situation in the area !
13Rapid Response Team (RRT)
- Team leader
- Epidemiologists
- Medical officer
- Veterinary officer
- Laboratory scientist
- Communications specialist
- Logistician
- Data Manager
- Infection Control Nurse
Photo Tim Uyeki, CDC
14Resources 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
15Institutional 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
16Logistics 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
17Supplies
- 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
18Supplies, 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 - UNICEF communication materials
19Stakeholders
- Veterinary Health Authorities
- Government Officials
- Health Care personnel
- Community
- Non-governmental organizations
- Laboratory
Centers for Disease Control and Prevention
20Review 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
21Collaborative 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
22Gathering Initial Evidence
23Evidence From a Suspect Case
- Epidemiological findings
- Exposures
- Clinical evidence
- Laboratory evidence
24Key Questions to Address in H5N1 Case/Cluster
Investigations
- 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?
25H5N1 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 healthy-looking ducks and geese
- H5-vaccinated poultry
- Unprotected contact with contaminated environment
26Human H5N1 Exposures
- Exposures to H5N1 virus-infected persons
- Unprotected extended close contact (within 1
meter) with a probable or confirmed case of H5N1
from one day before to 14 days after the case
patients illness onset - Speaking, touching, providing bedside care,
sleeping with, sharing utensils, or other
prolonged close contact
Source Josh Mott, CDC
27Other H5N1 Exposures
- Exposure to other H5N1 virus-infected animals
- Touching or consuming an H5N1 virus infected
animal (cat, dog, pig) - Laboratory exposure
- Unprotected exposure while processing samples
suspected of containing H5N1 virus - Other environmental exposure
- Residence or visit to an area where H5N1 virus is
suspected or confirmed
Centers for Disease Control and Prevention
28Risk 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/gu
idelines/pharmamanagement/en/index.html
29Why Use Risk Stratification?
- Helps prioritize limited resources
- A priori rationale for who will, and will not,
receive resources - Is used in WHOs recommendations for guiding
post-exposure antiviral chemoprophylaxis
30Review 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
- Infected domestic pets
- Cooked poultry meat
- Answer first five!
31Case Definitions
- Standardizes the investigation
- Clear criteria
- Signs
- Symptoms
- Epidemiological data
- Lab results
- Unique for every outbreak
- Objective measures
- Person, place, and time
32WHO 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
33Person Under Investigation
- Person whom public health authorities have
decided to investigate for possible H5N1 virus
infection
Photo Reuters / Amr Dalsh
34Suspected Case
- A person presenting with unexplained acute lower
respiratory illness with fever (gt38C) and cough,
shortness of breath, or difficulty breathing - AND
- Potential exposure to H5N1 virus in the 7 days
prior to symptom onset
35WHO Suspected Case Exposures
- 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
36Probable 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
37Confirmed 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
38Confirmatory Test Results for H5N1 Virus
Infection
- 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 180 or higher) - An H5N1 neutralizing antibody titer of 180 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
39Review 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
40Specimen Collection
Centers for Disease Control and Prevention
41Specimen 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)?
42What 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
43Investigation Step 2 Case Finding, Clusters,
Contract Tracing
44Case Finding and Clusters
Photo Diane Gross, CDC
45Importance 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
46What 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 acute lower respiratory
infection with fever or persons who died of an
unexplained acute respiratory illness - Close contacts of the case
47Methods of Case Finding
- Passive Suspect cases that are reported without
efforts by public health staff - Routine surveillance
- Rumor hotlines
- Public information messages in the affected
communities
- Active Search effort by public health workers
in an area where a case has occurred - House-to-house searches
- Visits to health care facilities
- Private practitioners
- Traditional healers
- Laboratories
Any cases meeting trigger criteria must be
referred for specimen testing and appropriate
medical care!
48Whom to Interview
- Suspected, probable, confirmed H5N1 cases, other
persons meeting trigger criteria - Family members/Household contacts
- Health care providers, health workers
- Co-workers, if occupational exposures are
suspected
49Type 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
50How 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
51Interview 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
52Review 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)
53Common 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
54Enhancing 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
55Methods 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
56Methods 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
57Clusters
PHOTO AP / Binsar Bakkara
58A 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 strongly suggests exposure to H5N1 virus
59Possible Human-to-Human H5N1 Virus Transmission
- 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 specimens)
60Review Question 5
- If you recognize a cluster of human H5N1 cases,
what would cause you to suspect that
human-to-human transmission of H5N1 virus has
occurred? - Answer Criteria such as contact with a case,
onset within one incubation period, and no other
plausible source of infection should be of
concern.
61Contact Tracing
62What is Contact Tracing?
- The identification and diagnosis of persons who
may have been in close contact with an infected
individual during the infectious period
63Purpose of Contact Tracing
- Find new suspected human cases of H5N1
- Provide interventions to decrease risk of illness
and interrupt further transmission - Active surveillance for illness
- Antiviral chemoprophylaxis of exposed
- Early treatment of ill persons
- Collection of specimens for H5N1 testing
- Educational information to prevent transmission
64How to Identify Contacts
- Review the case patients activities for the 1
day before onset of symptoms through 14 days
after onset of illness - Based on their activities, identify all close
contacts (within 1 meter) of the case - Identify additional individuals with exposure to
birds and other animals suspected of being
infected with H5N1 virus - Verify all information collected
65Prioritize 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
66Key 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
67General 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
68Information from Contacts
- Demographic and contact information
- Name, Address
- Occupation, age, gender, relationship to the case
- Exposure History
- Contact with case-patient
- Poultry and wild bird exposure
- Other high-risk exposures
- 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)
69Monitoring 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
70Investigation Step 3 Managing Data
71Data Management
- Line listing of cases, contacts
- Record keeping
- Validation and Cross-Checking
72Line Listing
An organized way to view all cases in an
investigation
Case Age Sex Status Occupation Difficult breathing Date of Onset
1 5 M Probable Child Yes 7 July
2 55 F Suspect Caretaker of case 1 Yes 9 July
3 48 M Suspect Poultry Farmer No 7 July
- Demographic, Epidemiological (exposures)
- Clinical, Laboratory data
Information included
73Record Keeping
- Where will records be kept?
- How will records be kept?
- Who is assigned to record keeping?
- Maintain confidentiality!!
74Validation 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
75 Creating an Epidemic Curve and Analyzing Data
76What 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
77How 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
78Epidemic 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
79Epi Curve for Human to Human Transmission
80Epi Curve for Human Cases from Single Source
81 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?
82Investigation Step 4 Prevention and Control
Activities
Photo Reuters / Bobby Yip
83Prevention and Control Activities
- Animal health and control measures
- Culling, disinfection, surveillance, vaccination
- Infection control
- Isolation of suspected and confirmed cases
- PPE, infection control precautions
- Treatment of ill patients
- Contact tracing contact surveillance
- Voluntary quarantine of well contacts
- Antiviral chemoprophylaxis
- Enhanced (active) surveillance and case finding
84Reporting and Evaluation
- Phase III Post Investigation
85Multiple 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.
86International Health Regulations (IHR)
- Compulsory notification of highly-pathogenic
strains of avian influenza - 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
87How and When to Report
- Use standard reporting forms
- Case/Lab specimen based forms, line-lists, weekly
and monthly reporting forms, contacts follow-up
forms - Immediate reporting of cases/clusters to next
levels - Information flow
- Information should be shared both vertically
(reporting and feedback) and horizontally (among
team/partners)
88Writing a Summary Report
89Why communicate the findings?
- A document for action
- 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
90Content of a Summary Report
- Summary
- Introduction and Background
- Outbreak Description
- Methods and Results
- Discussion
- Lessons Learned
- Recommendations
- Acknowledgements
- Supporting Documentation
91Evaluate Performance
Detection
Onset
Response
92Why 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
93What to Evaluate
- Timeliness of response
- Completeness of the investigation
- Accuracy of the data
- Inter-agency coordination
94Glossary
- 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.
95Glossary
- 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
96Glossary
- 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
97References
- WHO Guidelines for the Investigation of Human
Cases of Avian Influenza A (H5N1), Jan 2007.
Accessed from - http//www.who.int/csr/resources/publications/i
nfluenza/WHO_CDS_EPR_GIP_2006_4r1.pdf