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Influenza A(H5N1) in Humans: Outbreak Investigation in an International Setting. Case Study 2: Part 1. 1. Learning Objectives.

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Influenza a h5n1 in humans outbreak investigation in an international setting

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

Case Study 2: Part 1


Learning objectives
Learning Objectives

Describe key outbreak management issues that need to be addressed related to supplies, team composition, WHO policy and epidemiologic data management during an internationally located A(H5N1) outbreak investigation.

Identify critical coordinationpriorities involving the interface between animal and human health sectors, key stakeholders such as WHO, CDC and Ministries of Health and communication processes between CDC field staff, CDC Headquarters and relevant subject matter experts.


Learning objectives cont
Learning Objectives (cont.)

  • List appropriate practices and procedures for:

    • Specimen collection and transport

    • Epidemiologic investigation

    • Identification of transmission mechanisms

    • Contact tracing

    • Isolation/quarantine policy

    • Treatment/control policy

    • Risk communication priorities

    • Recommended laboratory specimen protocols methods

    • Ethical considerations


  • 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

      Principles are applicable to outbreaks from other known or newly emerging pathogens




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

Republic of pegu setting
Republic of Pegu: Setting

Developing country

Southeast Asia

21 provinces

Population: 50 million


Epidemiologic setting
Epidemiologic Setting

  • Mass deaths in chicken, geese, and waterfowl flocks

    • Five months ago (March)

    • Southeastern region

  • Ministry of Agriculture (MOA) reported 3 test results “weakly positive” for avian influenza A(H5N1)

    • Came from three dead chickens sent to national lab in Anawrahta (April)

  • No systemic surveillance exists for H5N1 in poultry, wild bird or animal populations

Question 1
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

Question 2
Question 2

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

So they can raise concerns and be aware of possible cases

To be ready for samples that will be coming

So they can undertake enhanced surveillance for sick or dying poultry

So they know you are coming to investigate, can have medical records ready to review, and have appropriate staff available

So they can leverage resources such as medical supplies or additional staff

  • Veterinary Health Authority

  • Healthcare personnel

  • The community

  • Non-governmental organizations

  • The laboratory

Question 2 answers
Question 2 Answers


1. Veterinary health = c. Evaluate diseased poultry

2. Healthcare personnel = d. Knowledge that you will investigate

3. Community = a. Can raise concerns

4. NGOs = e. Medical personnel/supplies and resources

5. Laboratory = b. Prepare for incoming samples

Question 3
Question 3

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 & Communications, PPE, Decontamination

Case definitions

Antiviral medication



Graph paper

Solution for decontaminating homes or hospital room

Transportation containers


Gown and cap

Reporting forms

Specimen collection materials


Guidelines for contacts, family members, and healthcare workers


Portable GIS unit

Viral transport media

Simple messages


Question 3 answers
Question 3 Answers


  • 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

Trigger event
Trigger Event


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)

Character details
Character Details


  • 65 year old grandmother = JAM

    • Chronically ill

    • Caretaker of grandson starting July 11

  • 10 year old grandson = AAJ

    • Onset July 10

  • Uncle = JRO

  • Grandfather = AWM

  • Mother = NJC

    • Caretaker of son (AAJ)

  • Setting: Small, mountain village in Pelu Jaghai province

    Exposure onset details

    July 8th

    Murg Market in Pelu Jaghai: Local market with live animals and location of A(H5N1) confirmed poultry outbreaks

    July 13th

    Dava Ghar hospital: 60 km away from village

    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

    Aaj clinical presentation and further evidence
    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

    Caretaker health status at hospital
    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 about July 9th

      • JAM symptoms: fever, cough and dyspnea = SARI

      • JAM admitted to hospital on July 14th

      • JAM denied contact with Murg Market or poultry

    Rumor surveillance update from local health authorities
    Rumor Surveillance Update from Local Health Authorities

    JULY 15

    • May be additional sick persons with respiratory symptoms in Pelu Jaghai

    • May continue to be wide-spread chicken deaths

    Question 4
    Question 4

    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, Chest x-ray positive for pneumonia

    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.

    Question 5
    Question 5

    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.

    Create a line list

    What variables should be included?

    Create a Line List

    • 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)

    Update the line list
    Update the Line List

    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

    Question 6
    Question 6

    Which of the following would be considered contacts of AAJ?

    • JAM

    • A teacher who last spoke to him 2 weeks ago

    • A tuk-tuk driver who drove him to a friends home on the 6th

    • A neighbor who walked by AAJ but didn’t say anything to him on the 10th

      Answer: a.

    Question 7
    Question 7

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








    • 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

    Review identifying contacts
    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

    Question 8
    Question 8

    Assuming that neuraminidase inhibitors are available:

    • Should AAJ be given anti-viral treatment?

    • Should JAM be given anti-viral treatment?


    • Yes

    • Maybe

    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.

    Question 9
    Question 9

    • 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?


    • 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.

    Question 10
    Question 10

    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

    Question 10 answers high and moderate risk groups
    Question 10 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

    Question 10 answers low risk groups
    Question 10 Answers:Low 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

    Update july 16 th the rrt arrives at dava ghar
    Update: July 16thThe RRT arrives at Dava Ghar

    JULY 16

    AAJ Update

    JAM Update


    Temperature 38.5 °C

    28 breaths/minute

    Blood pressure 160/95

    O2 saturation 90%

    Initial laboratory findings

    High lymphocyte count

    High leukocyte count

    • 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

    Specimens needed
    Specimens Needed

    JULY 16

    • You will need to quickly determine whether you’re dealing with H5N1 or some other communicable pathogen

    • You send respiratory specimens from the grandmother to the National laboratory for testing.

    Question 11
    Question 11

    What specimen type is the top priority to be collected from JAM for laboratory testing for influenza?

    • Endotracheal fluid

    • Broncho-alveolar lavage

    • Throat swab (oropharyngeal)

    • Nasal swab (nasopharyngeal)

    • Blood

      Answer :

      c. Throat swab

      Comment: Nasal swabs should be collected to rule out seasonal influenza. In general, collect multiple samples on multiple days.

    Remember! It is vital to use proper safety equipment including eye protection 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!!!

    Question 12
    Question 12

    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 (but treatment should not be delayed for specimen collection)

    • 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

    Specimen collection kit
    Specimen Collection Kit

    JULY 15

    Question 13
    Question 13

    Put the following steps for collecting an oropharyngeal specimens in the proper order

    • Done appropriate PPE

    • Slowly remove the swab while slightly rotating ; the patient should try to resist gagging and closing the mouth

    • Swab oropharyngeal area behind tonsils

    • Have the patient open his/her mouth wide open

    • Put tip of swab into vial containing VTM, breaking/cutting applicator’s stick







    Question 14
    Question 14

    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

    4) Itemized list of ______

    5) Specimen______

    6) _______ label

    Question 15
    Question 15

    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

    4) Itemized list of a. contents

    5) Specimen c. identification

    6) f. Biohazard label

    Question 16
    Question 16

    Determine whether the following statements about storing specimens in VTM are true or false.

    • 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






    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.

    Question 17
    Question 17

    When transporting specimens from potential human cases of influenza A(H5N1) infection from the field to the laboratory, you should follow which sets of 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.

    Epidemiologic and specimen tracking for transportation
    Epidemiologic and Specimen Tracking for Transportation

    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

    Contact identification
    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)

    • You determine that close contacts are

      • Mother (NJC)

      • Uncle (JRO),

      • Grandparents (JAM & AWM)

    Update the line list1
    Update the Line List

    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.

    Line list as of july 16 th a m
    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

    Beyond the given scenario
    Beyond the Given Scenario

    Also think beyond the nuclear family

    • Village health workers

    • Traditional healers

    • Taxi drivers

    • Other people that may have had close contact with the case during the infectious period

    Question 18
    Question 18

    You want to know whether there are more contacts that 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)

    • Patient’s village/neighborhood

    • Patient’s school/workplace

    • None of the above


      e. Depending on the places visited by a case, any of these places could be important places to undertake additional contact tracing activities

    Question 19
    Question 19

    Which of the following scenarios does NOT list the appropriate PPE measure?

    • You will interview a symptomatic person that could be infected with influenza A(H5N1):

      • Interview from more than 1-2 meters away and wear no PPE

    • You will be within 1-2 meters of a symptomatic person that could be infected with influenza A(H5N1)

      • Wear a fit tested respirator and eye protection

    • You physically examine a person that could be infected with influenza A(H5N1)

      • You need to wear droplet and contact precautions

    • You are entering an environment where poultry products or feces may be contaminated,

      • Wear droplet and contact precautions including boots and undertake appropriate biosecurity/decontamination measures before leaving the premises

        Answer: Scenario 2. Respirators are used for aerosol-generating procedures.

    Question 20
    Question 20

    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 in the facility 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. Look for additional cases

    Answer: 1. b 2. a 3. c

    Question 21
    Question 21

    Questions to ask the case patient/case patient’s family regarding potential H5N1 exposures should cover which of the following?

    • Contact with confirmed , suspect, or probable human H5 cases

    • Exposure to sick or dying animals, wild birds, other animals, or their environment

    • Exposure to environments that may be contaminated with influenza A (H5N1)

    • Exposure to cooked chicken products

    • Handling/preparation of raw poultry and other animal products

    Question 22
    Question 22

    Questions to as the case patient/case patient’s family regarding additional case finding/H5N1 circulation in the community include which of the following?

    • Awareness of additional cases of severe respiratory illness in family, friends and co-workers

    • Awareness of H5N1 outbreaks occurring outside of the country

    • Awareness of illness or deaths in birds, cats, swine, or other animals in the household and neighboring area

    Question 23
    Question 23

    When in a patient’s home or their village, what are important contextual factors to observe?

    • Poultry in and around the house

    • Construction material of the home

    • Mapped location or photograph of house and surroundings

    • Possible unique and culturally-specific mechanisms of exposure

    • Annual community festival days

    • Live bird markets or other occupationally related exposures

    Case finding results
    Case Finding Results

    JULY 16

    • Child with unexplained respiratory illness reported in nearby province, Pelu Jaghai

    • Director of Epidemiology orders your team to meet the Ministry of Health field workers there and make site visits to hospitals and villages

    New case and contact
    New Case and Contact

    JULY 16

    • 11-year-old boy, TMU

      • Fever, cough shortness of breath , date of onset 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

    Line list as of july 16 th p m
    Line List as of July 16 afternoon of July p.m.

    F: Fever; C: Cough; D: Diarrhea; S: Shortness of breath; M: Myalgias; URI – upper respiratory syx

    DG: Dava Ghar

    PJ: Pelu Jaghai

    Differential diagnoses
    Differential Diagnoses afternoon of July 16.

    Human influenza

    Influenza A(H5N1)

    Commonly a lower respiratory infection

    Fever, headache, cough, sore throat

    Muscle ache, exhaustion

    Difficulty breathing, respiratory distress

    Crackling on inhalation

    Leukopenia, lymphopenia

    Increased respiratory rate

    Sputum production, possibly with blood

    Limited data: diarrhea

    • Commonly an 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

    An animal virus that is adapting to humans may have a mixed picture of clinical presentations.

    Non influenza differential diagnoses
    Non-Influenza Differential Diagnoses afternoon of July 16.



    Mycobacteria tuberculosis

    Yersinia pestis (pneumonic plague)

    Streptococcus pneumoniae

    Staphylococcus aureus

    Hemophilus influenzae

    Burkholderia pseudomallei

    Legionella spp.

    Chlamydia pneumoniae

    Mycoplasma pneumoniae

    Coxiella burnetii(Q fever)

    • 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

    Influenza a h5n1 in humans outbreak investigation in an international setting

    Clinical signs and symptoms alone cannot distinguish the severe complications of seasonal influenza from influenza A (H5N1) infection in humans:

    Examine the epidemiology and collect specimens!

    Move on to outbreak investigation part 2

    Move on to Outbreak Investigation, Part 2 severe complications of seasonal influenza from influenza A (H5N1) infection in humans: