Influenza AH5N1 in Humans: Outbreak Investigation in an International Setting

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Influenza A(H5N1) in Humans Outbreak
Investigation in an International Setting

• Case Study 2

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Learning Objectives

• Define the surveillance objectives, methods of
  hospital selection, and key data collection
  priorities for sentinel surveillance for seasonal
  influenza and severe respiratory diseases
• List appropriate surveillance strategies and
  trigger criteria needed for the early detection
  of Influenza A(H5N1) in hospitals and communities
• List appropriate surveillance strategies and
  trigger criteria needed for a broader pandemic
  early warning system

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Learning Objectives (Continued)

• Describe the benefits of integrating
  population-based Influenza A(H5N1) surveillance
  in humans within a sentinel site seasonal
  influenza surveillance system
• Identify five ways to enhance surveillance
  activities in areas where there are known
  Influenza A(H5N1) outbreaks in poultry

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Outline

• Review of the preparation for an outbreak
  investigation
• Description of the situation and available
  details on the case, surrounding events/history
  and environment
• Engage in outbreak investigation activities
• Case definition
• Clinical / laboratory findings, samples,
  recommendations
• Line listing
• Contract Tracing
• Treatment options/ recommendations

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Introduction

• Be sure to have materials needed to take notes
  and create a line list

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Republic of Pegu Setting

• Developing country
• Southeast Asia
• 21 provinces
• Population 50 million

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Trigger Event 1

• Mass deaths in chicken, geese, and waterfowl
  flocks
• Beginning March 2006
• Southeastern region
• Ministry of Agriculture (MOA) reported 3 test
  results weakly positive for avian influenza
  (H5N1)
• Came from three dead chickens sent to national
  lab in Anawrahta (April, 2006)
• No systemic surveillance exists for H5N1 in
  poultry, wild bird or animal populations

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Question 1

• To respond to trigger event 1, you need to put
  together a Rapid Response Team (RRT) - Which of
  the following skills or persons should be
  represented in this RRT?

• Team Leader
• Epidemiologist
• Veterinary Liaison
• Respiratory Therapist
• Medical Officer / Clinician
• Data Manager
• Marketing Assistant
• Laboratorian or Lab tech
• Logistician
• Communications Specialist

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Question 2

• Match who should be notified about the
  investigation on the left with the reason they
  should be notified on the right.

• Veterinary Health Authority
• Government officials (MOH and other govt offices
  or ministries)
• Healthcare personnel
• The community
• Non-governmental organizations
• The laboratory

• To give you advice and direction
• To satisfy their interest and offer education
• To be ready for samples that will be coming
• To conduct evaluation of diseased poultry
• So they know you are coming to investigate
• To serve as a resource for medical resources

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Question 2

• Answer
• 1. Veterinary health d. Evaluate diseased
  poultry
• 2. Government officials a. Advice and direction
• 3. Healthcare personnel e. Knowledge that you
  will investigate
• 4. Community b. Interest and education
• 5. NGOs f. Medical personnel/supplies resource
• 6. Laboratory c. Prepare for incoming samples

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Question 3a

• Which of the following are NOT documents that you
  would need to bring with you to the field?

• Proof of employment
• Birth certificate
• Case information
• SOPs (case management, lab specimen procedures
• Laboratory testing procedures
• WHO request for assistance (PPE, antivirals,
  personnel)
• WHO guidelines for investigation

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Question 3b

• Below are 6 categories of supplies needed when
  you go to the field. Match the list of supplies
  to the general category.

Categories Epidemiological, Medical,
Laboratory, Educational, PPE, Decontamination

• Case definitions
• Antiviral medication
• Goggles
• Gloves
• Graph paper
• Solution for decontaminating homes or hospital
  room
• Transportation containers
• Pens
• Gown and cap
• Reporting forms

• Specimen collection materials
• Ice
• Guidelines for contacts, family members, and
  healthcare workers
• Notebook/laptop
• Portable GIS unit
• Viral transport media
• Simple messages
• Respirators

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Question 3b Answers

• Answer
• Epidemiological a. Case definitions, j.
  reporting forms, n. notebook/laptop, h. Pens, e.
  graph paper, o. portable GIS unit
• Medical b. Antiviral medication
• Laboratory k. Specimen collection materials, g.
  Transportation containers, l. Ice, p. Viral
  transport media
• Educational materials q. Simple messages, m.
  Guidelines for contacts, family members, and
  healthcare workers
• Personal Protective Equipment (PPE) r.
  Respirators, d. gloves, i. gown and cap, c.
  goggles
• Decontamination f. Solution for decontaminating
  homes or hospital rooms

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Trigger Event 2
JULY 15

• July 15th
• Dava Ghar hospital has admitted 2 patients with
  SARI
• Reported to District Health Office
• They suspect avian influenza due to poultry
  outbreaks in area
• Patients are related
• 65 year old grandmother (JAM)
• 10 year old grandson (AAJ)

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Character Details
JULY 15

• Grandfather AWM
• Mother NJC
• Caretaker of son (AAJ)

• 65 year old grandmother JAM
• Chronically ill
• Caretaker of grandson
• 10 year old grandson AAJ
• Ill July 11
• Uncle JRO

Setting Small, mountain village in Pelu Jaghai
province
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Exposure Onset Details
JULY 15

• AAJ, NJC, JRO attended live-market (Murg
  Market)

• AAJ becomes ill on July 10th

• JAM cares for him starting July 11th

• July 13th AAJ brought to hospital with fever
  (38.7), cough, diarrhea and shortness of breath

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AAJ Clinical Presentation and Further Evidence
JULY 15

• Arrived in unstable condition on the night of
  13th
• Admitted early on 14th
• Rapidly deteriorated
• Respiratory distress led to endotracheal
  intubation and ventilatory support
• Cefriaxone treatment started

10 year old child (AAJ) CXR on Admission
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Caretaker Health Status at Hospital
JULY 15

• Mother (NJC) and grandfather (AWM) are
  asymptomatic or deny symptoms
• Grandmother (JAM) reports respiratory condition
  suddenly worsened on July 9th
• Symptoms fever, cough and dyspnea SARI
• Admitted to hospital on July 14th
• Denied contact with Murg Market or poultry

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Rumor Surveillance
JULY 15

• May be additional sick persons with respiratory
  symptoms in Pelu Jaghai
• May continue to be wide-spread chicken deaths

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Question 4a

• How would you classify AAJ into the WHO influenza
  A(H5N1) case definition? Information on AAJ is
  given for your reference.
• Under investigation
• Suspected
• Probable
• Confirmed
• Answer The Chest X-ray and clinical
  deterioration extend the suspected A(H5N1)
  status to C, a probable case designation.

Clinical Fever, cough, diarrhea and shortness
of breath Epidemiological Exposure to
live-market on July 8th where influenza A(H5N1)
infections in animals were confirmed in the last
month. Laboratory No lab specimens available.
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Question 4b

• How does patient JAM fit into the WHO influenza
  A(H5N1) case definition?
• Under investigation
• Suspected
• Probable
• Confirmed
• Answer The above information is supportive of a
  designation of a. person under investigation

Clinical Fever, cough, and shortness of
breath Epidemiological Close contact (within 1
meter) with a person who is a suspected,
probable, or confirmed H5N1 case. Close contact
with probable case occurred 2 days after onset
of symptoms. Laboratory No lab specimens
collected at time of questioning.
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Question 5

• Create a line list What variables should be
  included?

• ID
• Demographics (age, gender, patient contact)
• Possible exposure to infected animals within 7
  days of symptoms
• Possible contacts with suspect or confirmed human
  case within 7 days

• Occupation
• Symptom onset
• Date of onset
• Hospital test results
• H5 Laboratory diagnosis
• Antivirial treatment
• Status (Case or Contact)
• Disposition (Hospitalized, deceased, etc)

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Suggested Line List Format
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Question 6
JULY 15

• Update the line list with the cases as of July
  15th mid-day

F Fever C Cough D Diarrhea S Shortness of
breath M Myalgias URI upper respiratory
syx DG Dava Ghar PJ Pelu Jaghai
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Question 7a

• When should you begin assessing contacts of this
  probable case?
• As soon as you become aware of the case
• Once you have determined the case status as being
  suspect or highter
• Once you have determined the case status as being
  probable or higher
• Once you have a confirmed diagnosis
• Answer a.

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Question 7b

• Note whether the following statements used to
  define who is a close contact of this probable
  case are true or false.

Answers False True True False True True

• Anyone who came within 1 meter of the case
  patient
• Anyone who had shared space within 1 meter of the
  case patient
• Close contact 1 day before through 14 days after
  onset of symptoms
• Close contact 7 days before through 14 days after
  the onset of symptoms
• Someone who kissed, embraced or shared utensils
  with the case patient
• Someone who spoke with or touched the case
  patient

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Review Identifying Contacts

• Potential contacts
• Household members
• Friends
• Healthcare providers
• Pharmacists
• Traditional healers
• Workplace contacts

• Contact tracing activities
• Prioritize high probability of influenza A(H5N1)
  case patients
• Prioritize contacts by duration, proximity, and
  intensity of exposure to the case patient

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Question 8a

• Assuming that neuraminidase inhibitors are
  available
• Should AAJ be given anti-viral treatment?
• Should JAM be given anti-viral treatment?
• Answer
• Yes
• No

Hint If antiviral drugs are available,
treatment doses should be provided to suspected,
probable and confirmed cases as classified
according to the WHO case definition.
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Question 8b

• Should JAM receive anti-viral prophylaxis?
• Should asympomatic close contacts of AAJ be given
  anti-viral prophylaxis?
• Should close contacts of JAM receive antiviral
  prophylaxis?
• Answer
• Yes
• Yes
• No

Hint The WHO Rapid Advice Guidelines on
pharmacological management of humans infected
with avian influenza A (H5N1) virus suggests that
prophylaxis doses should be provided to all
identified close contacts of confirmed cases, and
if resources allow, to close contacts of
strongly suspected cases as well.
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Question 9

• If there are not enough antiviral resources for
  everyone, persons in the community should be
  prioritized for antiviral prophylaxis. Match the
  Risk Group on the left with the description on
  the right.
• High Risk
• Moderate Risk
• Low Risk

• Personnel culling likely non-infected animals
• Personnel handling sick animals or
  decontaminating environments using insufficient
  PPE
• Personnel handling sick animals or
  decontaminating environments using adequate PPE
• Unprotected close/direct exposure to H5N1
  infected animals
• Healthcare or laboratory personnel in close
  contact with strongly suspected or confirmed
  patients or their samples with insufficient PPE
• Healthcare workers not in close contact
• Healthcare workers with close contact using
  adequate PPE
• Close household contact of strongly suspected or
  confirmed patients

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Question 9 AnswersHigh and Moderate Risk Groups

• High risk exposure groups
• h. Household or close family contacts of a
  strongly suspected or confirmed H5N1 patient
• Moderate risk exposure
• b. Personnel involved in handling sick animals or
  decontaminating affected environments
• d. Individuals with unprotected and very close
  direct exposure to sick or dead animals infected
  with the H5N1 virus
• e. Health care or laboratory personnel with
  unprotected close contact with strongly suspected
  or confirmed H5N1 patients or their clinical
  samples

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Question 9 AnswersLow Risk Groups

• Low risk exposure groups
• f. Health care workers not in close contact
• g. Health care workers using adequate PPE
• a. Personnel involved in culling non-infected or
  likely non-infected animal populations
• c. Personnel involved in handling sick animals or
  decontaminating affected environments using
  adequate PPE
• Explain (tactfully!) to contacts the scarcity of
  antivirals, and that they will be monitored.
• NOTE Drug allocation plans for treatment and
  prophylaxis should be made in advance

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Update July 16thThe RRT arrives at Dava Ghar
JULY 16

• AAJ Update

• JAM Update

• Admission
• Fever 39 C
• Heart rate 120
• 34 breaths/minute
• Blood pressure 90/60
• O2 saturation 88
• Outcome
• Intubated Jul 14
• Hypotensive with renal failure
• Died on the 16th
• Respiratory and sputum samples of poor quality

• Admission
• Temperature 38.5 C
• 28 breaths/minute
• Blood pressure 160/95
• O2 saturation 90
• Initial laboratory findings
• High lymphocyte count
• High leukocyte count

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Specimens Needed
JULY 16

• You will need to quickly determine whether youre
  dealing with H5N1 or some other communicable
  pathogen
• You send biological samples from the grandmother
  to the National laboratory for testing.

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Question 10a

• What specimens need to be collected from the
  grandmother?
• Endotracheal fluid
• Broncho-alveolar lavage
• Throat swab (oropharyngeal)
• Nasal swab (nasopharyngeal)
• Blood
• Acceptable answers
• c. Throat swab, and/or e. Blood specimens

Remember! It is vital to use proper safety
equipment including goggles and PPE for the
protection of the individual(s) carrying out the
procedure(s). Treat all clinical samples as
though they are potentially infected with avian
influenza!!!
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Question 10b

• Which of the following statements about specimen
  collection is NOT true?
• It should begin as soon as possible after
  symptoms begin
• It should begin before antiviral medications are
  administered
• Sample should be collected even if symptoms began
  more than one week ago
• Multiple samples should be collected on multiple
  days if possible
• None of the above (all statements are true)
• Answer e.
• Remember it is better to collect too many
  specimens than not enough

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Specimen Collection Kit
JULY 15
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Question 11
Put the following steps for collecting an
oropharyngeal specimens in the proper order
Answers 1. 4. 3. 2. 5.

• Have the patient open his/her mouth wide open
• Slowly remove the swab while slightly rotating
• The patient should try to resist gagging and
  closing the mouth
• The swab touches the back of the throat near the
  tonsils
• Put tip of swab into vial containing VTM,
  breaking/cutting applicators stick

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Question 12a

• Here is an image of a properly packed specimen.
  Label the packaging using the answer choices
  given.

1) 3 layers of _________
2) Absorbent _________
3) Labeling of the _________ as UN3373
diagnostic specimens

• Answer choices
• contents
• packing material
• identification
• outer package
• packaging
• biohazard

5) Specimen______
4) Itemized list of ______
6) _______ label
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Question 12a

• Here is an image of a properly packed specimen.
  Label the packaging using the answer choices
  given.

1) 3 layers of e. packaging.
2) Absorbent b. packing material
3) Labeling of the d. outer package as UN3373
diagnostic specimens
5) Specimen c. identification
4) Itemized list of a. contents
6) f. Biohazard label
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Question 12b

• Determine whether the following statements about
  storing specimens in VTM are true or false.
• Store specimens can be stored at 4 C within 48
  hours of collection both before and during
  transportation.
• Store specimens at -70 C beyond 48 hours (if you
  will not be able to immediately transport
  specimen to laboratory)
• Never store specimens on dry ice
• Specimens may be stored in standard freezer

Answers True True False False
Avoid freeze thaw cycles. It is better to keep
a sample on ice even for a week, than to allow
the sample to freeze and thaw multiple times.
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Question 12c

• When transporting specimens from potential cases
  of avian influenza from the field to the
  laboratory, you should follow which regulations?
• WHO guidelines for safe transport of infectious
  substances and diagnostic specimens
• Local regulations on the transportation of
  infectious material
• Neither a nor b
• Both a and b
• Answer d.

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Transportation Considerations
JULY 16

• Documents to include
• Itemized list of specimens with identification
  numbers
• Instructions for the laboratory
• Information to maintain
• Identification numbers, linking to epidemiologic
  data forms
• Case demographics
• When and where a specimen was collected
• Type of specimen
• Coordinate shipment with the laboratory so they
  are prepared when the specimens arrive

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Contact Identification
JULY 16

• You have finished collecting patient specimens
  and have sent them off to the national laboratory
  
• You want to identify all potentially exposed
  individuals who have had contact with the
  probable case (AAJ)
• In a team meeting you determine that the contacts
  are
• Mother (NJC)
• Uncle (JRO),
• Grandparents (JAM AWM)

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Question 13
Below is shown the line list from mid-day, July
15th. Update the line listing with all known
contacts as of July 16th a.m.
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Question 13 Answer

• Line list as of July 16th a.m.

F Fever C Cough D Diarrhea S Shortness of
breath M Myalgias URI upper respiratory
syx DG Dava Ghar PJ Pelu Jaghai
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Beyond the Given Scenario

• Also think beyond the nuclear family
• Village health workers
• Traditional healers
• Taxi drivers
• Other people a case may have had close contact
  with while infectious

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Question 14a

• You want to know whether there are more contacts
  you should be concerned about. Which of the
  following places would NOT be one that you would
  visit at this point to determine if there are
  more cases and/or contacts?
• Health care facilities (hospitals, clinics,
  traditional healers)
• Patient (or family proxy)
• Patients village/neighborhood
• Patients school/workplace
• Answer
• d. At this point in time, the appropriate
  information on close contacts can be gathered
  from the patient/proxy

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Question 14b

• In conducting contact tracing interviews, in
  which of these places would you need to wear
  personal protective equipment (PPE)?
• Health care facilities (hospitals, clinics,
  traditional healers)
• Patient (or family proxy)
• Patients village/neighborhood
• Answer b.

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Question 14c
Match the information source on the left with
the contract tracing activities that should be
conducted there on the right.

• Hospital or other medical facility
• Patient (or proxy)
• Patients home and village

• Administer case finding questionnaire to
  determine if the interviewee knows of anyone else
  who is sick, to ask about possible exposures, and
  to ask about possible contacts
• Retrace the steps of the patient and try to
  determine if there were any close contacts
  without adequate PPE.
• Find out more details about suspected exposures,
  conduct an environmental survey, and determine if
  there are any outbreaks among animals.

Answer 1. b 2. a 3. c
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Question 15a

• Questions to ask the case patients family
  covering situations with potential for H5N1
  exposure should include which of the following?
• Contact with confirmed or suspect human H5 cases
• Awareness of clusters of severe respiratory
  illness in family, friends and co-workers
• Awareness of H5N1 outbreaks occurring outside the
  country
• Exposure to animals and their environment
• Exposure to contaminated environments
• Exposure to cooked chicken products
• Inquire about illness or deaths in birds, cats,
  swine, or other animals in the household and
  neighboring area

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Question 15b

• When interviewing at a patients home or in their
  village, which of the following are important
  contextual factors to observe and analyze?
• Poultry in and around the house
• Number of people living in the home
• Construction material of the home
• Mapped location or photograph of house and
  surroundings
• Culture-specific risk factors
• Annual community festival days
• Live bird markets or other occupationally related
  exposures

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Case Finding Results
JULY 16

• Child with unexplained respiratory illness
  reported in nearby province, Pelu Jaghai
• Director of Epidemiology recommends that your
  team meet the Ministry of Health field workers
  there and make site visits to hospitals and
  villages

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New Case and Contact
JULY 16

• 11-year-old boy, TMU
• Fever, cough shortness of breath starting July 12
• Admitted July 15
• Critically ill, not intubated
• You and your team don PPE, evaluate the patient,
  review medical chart, and interview available
  family members
• Mother (ACM)
• Reports boy visited Murg market on July 8

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Question 16

• Update the line list with the current information
  as of the afternoon of July 16.

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Question 16 Answer
Line list as of July 16th p.m.
F Fever C Cough D Diarrhea S Shortness of
breath M Myalgias URI upper respiratory
syx DG Dava Ghar PJ Pelu Jaghai
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Differential Diagnoses

• Human influenza

• Influenza A(H5N1)

• Upper respiratory infection
• Fever, headache, cough, sore throat
• Muscle ache, exhaustion
• Other respiratory symptoms
• Recovery 2-7 days
• Can progress to pneumonia and respiratory failure
  in some cases

• Lower respiratory infection
• Fever, headache, cough, sore throat
• Muscle ache, exhaustion
• Difficulty breathing, respiratory distress
• Crackling on inhalation
• Increased respiratory rate
• Sputum production, possibly with blood
• Limited data diarrhea

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Non-Influenza Differential Diagnoses

• Viral

• Bacterial

• Human influenza viruses
• Parainfluenza viruses
• Respiratory syncytial virus
• Adenovirus
• Rhinovirus
• Flaviviruses (e.g. Dengue)
• Coronaviruses (including SARS-CoV)
• Human metapneumovirus
• Hantavirus
• New / emerging viruses, such as bocavirus

• Mycobacteria tuberculosis
• Yersinia pestis (pneumonic plague)
• Streptococcus pneumoniae
• Staphylococcus aureus
• Hemophilus influenzae
• Burkholderia pseudomallei
• Legionella spp.
• Chlamydia pneumoniae
• Mycoplasma pneumoniae
• Coxiella burnetii(Q fever)

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Question 17

• Do you think TMU has Influenza A(H5N1) infection?

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Move on to Outbreak Investigation, Part 2