Influenza A(H5N1) 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 Part 2

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2
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 coordination priorities
  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.

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3
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

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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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5
Introduction
6
Situation Review

• Dava Ghar
• Severe respiratory illness in boy (AAJ) and
  grandmother (JAM)
• Boy has died, grandmother is hospitalized
• Pelu Jaghai
• Severe respirtoary illness in boy (TMU)
• Mother (ACM) followed as a contact

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July 17
JULY 17

• Suspect or probable cases of Influenza A(H5N1)
• Dava Ghar
• Pelu Jaghai
• Contacts are being monitored
• Concern about healthcare worker safety

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Question 1

• Which of the following are standard precautions?
• Patient placement into single room/cohorting for
  influenza A(H5N1) cases
• Hand hygiene
• Respiratory and cough etiquette
• Personal protective equipment (PPE), depending on
  risk of contact with patient bodily fluids
• Safe injection practices
• Surgical mask on entry into room
• Environmental control
• Answer b, c, d, e, and g

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Question 2

• Which of the following are droplet precautions?
• Private room/cohorting for patients with the
  same infection
• Surgical mask on entry to patients room (and on
  patient when outside the room)
• Patients should be places in negative air
  pressure airborne isolation rooms
• Eye protection
• Change of PPE and hand hygiene between patients
• Respirator for entry into patient room
• Daily cleaning and disinfection of surfaces in
  patient room
• Answer a b, d, e, and g.

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Question 3

• You provide advice about infection control to the
  hospital. When should each of the following sets
  of precautions be taken? Match the precaution to
  its appropriate use.
• Answer a) 2 b) 1 c) 3

Precautions Use
Standard precautions 1. During routine care of suspect, probable, or confirmed influenza A(H5N1) cases
Contact / droplet precautions 2. At all times
Airborne precautions 3. When performing aerosol-generating procedures on influenza A(H5N1) cases
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Epidemiologic Connection
JULY 17

• TMU
• 11 year-old boy in Pelu Jaghai
• AAJ
• 10 year-old boy in Dava Ghar
• Both at Murg market
• Chased a slow and unsteady chicken

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Murg Market
JULY 17

• You collect respiratory specimens from TMU
• You learn AAJs uncle, JRO, took him to the
  market
• You return to Dava Ghar, anxious that you are
  missing other suspected cases of influenza
  A(H5N1)

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July 18 Grandparents
JULY 18

• Patient rounds
• Grandmother (JAM)
• Not progressing to respiratory failure
• Laboratory tests negative for influenza A(H5N1)
• Suggestive of tuberculosis
• Grandfather
• Fever and myalgia
• Stayed by JAMs bedside with respirator
• On Oseltamivir chemoprophylaxis, but rapidly
  worsening
• Hospitalized

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H5 Test Results
JULY 18

• TMU (11-year-old) specimen is positive for H5
  influenza by real-time PCR
• Chicken specimen also positive for H5

Apisarnthanarak A, Kitphati R, Thongphubeth K, et
al. Atypical avian influenza (H5N1). Emerg Infect
Dis 10(7)1321-1324, 2004.
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Market Closure
JULY 18

• Murg market is closed
• Perimeter for culling and surveillance
• Active surveillance at source farms
• Cases reported to WHO
• WHO mobilizing to assist

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Update the line list given below to be current up
until the afternoon of July 18
JULY 16th, PM
ID Initials Vill-age Age Sex Possible exposures and date EPI relation SYX Onset - July Lab Status Case Status Outcome
1 AAJ DG 10 M Live-Mkt July 8 index case F, C, D, S 10 No lab specimen Probable CASE Died (7/16)
2 JAM DG 65 F Caretaker of 1 Grandmother ( 1) F, C, S 9 Pending PUI/Contact Hospitalized
3 AWM DG 70 M Caretaker of 1 Grandfather ( 1) CONTACT
4 NJC DG 36 F Caretaker of 1 Live-Mkt July 8 Mother ( 1) Contact
5 JRO DG 27 M Live-Mkt July 8 Uncle ( 1) Contact
6 TMU PJ 11 M Live-Mkt July 8 Playmate ( 1) F, C, D, M 12 Pending Suspect CASE Hospitalized
7 AMC PJ 29 F Caretaker of 6 Mother of 6 Contact
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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Linelist as of July 18th, Afternoon
ID Initials Vill-age Age Sex Possible exposures and date EPI relation Syx Onset date Lab Status Case status Outcome
1 AAJ DG 10 M Live-Mkt July 8 Index case F, C, D, S 10 No lab specimen Probable CASE Died (7/16)
2 JAM DG 65 F Caretaker of 1 Grandmother ( 1) F, C, S 9 Negative H5N1 CONTACT Hospitalized
3 AWM DG 70 M Caretaker of 1 Grandfather ( 1) F, S, M 18 Pending Suspect CASE Hospitalized
4 NJC DG 36 F Caretaker of 1 Live-Mkt July 8 Mother ( 1) CONTACT
5 JRO DG 27 M Live-Mkt July 8 Uncle ( 1) CONTACT
6 TMU PJ 11 M Live-Mkt July 8 Playmate ( 1) F, C, D, M 12 Positive H5N1 - PCR Confirmed CASE Hospitalized
7 AMC PJ 29 F Caretaker of 6 Mother of 6 CONTACT
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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Public Alert
JULY 18

• A reporter from a regional newspaper has
  contacted the Director of Epidemiology about ill
  patients, and has learned about the potential
  exposures at the July 8th live-market
• The reporter wants to write an article notifying
  the public
• The Director of Epidemiology wants you to prepare
  talking points to share with the Ministry of
  Healths Public Information Officer

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Question 4

• Place yourself in the shoes of the Pegu Ministry
  of Health. What would be the three concepts that
  it would be most important to convey with this
  messages?
• Show empathy, openness, and understanding
• Indicate that the government is taking steps to
  address this problem
• Assure the public that no more people will get
  sick
• Indicate that the MOH are the scientific experts
  on this complicated issue and the public has
  nothing to worry about
• Indicate what the public can do for themselves
• Answer a, b, and e

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Question 5

• Form a small group with those seated around you.
  Choose one of the communication types from the
  previous question, and develop a message for this
  situation.

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Question 6

• You begin working on a situation report. Which
  one of the following would NOT be a section in
  your situation report?

1. Current staff in the field
2. Update on human cases
3. Changed case classifications since last report
4. Close contacts being monitored
5. Update on active/enhanced human surveillance
   activities
6. Update on animal surveillance and animal outbreak
   control activities

1. Epidemiologic assessment and likelihood of human
   to human transmission
2. Laboratory tests pending
3. Hospital infection control update
4. Outbreak control measures being implemented
5. Planned next steps
6. Material / personnel assistance needed

• Answer All!

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Question 7

• Match the statements on the right to the
  appropriate section of the situation report on
  the left.

• Active surveillance is being undertaken among
  poultry owners that supplied birds to the Murg
  Market
• There is a new suspected case of influenza
  A(H5N1)
• Efforts to identify additional cases beyond close
  contacts
• The uncle of the 10-yr-old decedent, who attended
  the live bird market on July 8

1. Update on current suspect, probable, and
   confirmed human cases of influenza A(H5N1)
2. Close contacts of suspect, probable, or confirmed
   cases being monitored
3. Update on active/enhanced human surveillance
   activities
4. Planned next steps

• Answers
• 1) b 2) d 3) a 4) c

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A New Problem
JULY 18

• Family of case AAJ have refused voluntary
  quarantine
• Mother (NJC)
• Uncle (JRO)
• Symptoms of family include weakness, tiredness,
  aches

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Question 8

• The goal of quarantine is to protect the public
  health by
• restricting the movement of an ill individual.
• separating persons exposed to a communicable
  disease from the general population.
• limiting the activities of persons exposed to a
  communicable disease.
• limiting the activities of an ill individual.
• Answer b

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Question 9

• The ethical justification of quarantine requires
  that
• person-to-person spread of a disease is possible.
• only lower SES individuals should be placed into
  quarantine.
• quarantine only be used if influenza A(H5N1) is
  suspected, and not another pathogen.
• voluntary quarantine is used before more
  restrictive measures are used.
• physical needs are met and psychological affects
  are minimized.
• quarantined individuals are closely monitored for
  onset of symptoms.
• Answer a, d, e, and f

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Question 10

• In this situation whose responsibility is it to
  determine whether the family members refusing
  voluntary quarantine should be forced into
  quarantine?
• Yours
• The local and national authorities of Pegu
• The World Health Organizations
• UN Secreteriat for Respectful Quarantine (UNSRQ)
• Answer b.

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Key Point Quarantine

• Ethical justification of quarantine or isolation
  requires that
• There is a possibility of person-to person spread
  of disease and the necessity of quarantine
• The least restrictive measures be used. Voluntary
  quarantine should be used before more restrictive
  measures are enacted.
• Society provide necessary support services for
  those in quarantine
• Public health officials justify their actions and
  allow for a process of appeal
• Quarantined individuals be closely monitored to
  detect onset of symptoms

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Visit to NJC and RJO
JULY 18

• Persuasion
• Local religious leaders help NJC and JRO accept
  voluntary quarantine
• Interview
• 19-year-old brother, DKS, was exposed during
  family vigil July 12-13
• DKS returned to university July 14

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July 19 Late Evening Updates
JULY 19

• TMU (11 yr-old boy) intubated
• JRO (uncle of AAJ) admitted
• NJC (mother of AAJ) admitted
• JAM (grandmother of AAJ) cared for AAJ
• AWM (grandfather of AAJ) cared for AAJ

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July 20 MOH Updates
JULY 20

• DKS (19 yr-old student) symptom onset today
• Returned to home province
• Denied live-market or poultry exposure
• Affirmed exposure to his ill brother
• AWM (grandfather) died
• Multiple complications renal failure,
  encephalitis, ventricular arrhythmias
• PCR for influenza A(H5N1)

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Update the line list given below to be current up
until the afternoon of July 20
JULY 18th, PM
ID Initials Vill-age Age Sex Possible exposures and date EPI relation Syx Onset date Lab Status Case status Outcome
1 AAJ DG 10 M Live-Mkt July 8 Index case F, C, D, S 10 No lab specimen Probable CASE Died (7/16)
2 JAM DG 65 F Caretaker of 1 Grandmother ( 1) F, C, S 9 Negative H5N1 Contact Hospitalized
3 AWM DG 70 M Caretaker of 1 Grandfather ( 1) F, S, M 18 Pending Suspect CASE Hospitalized
4 NJC DG 36 F Caretaker of 1 Live-Mkt July 8 Mother ( 1) Contact
5 JRO DG 27 M Live-Mkt July 8 Uncle ( 1) Contact
6 TMU PJ 11 M Live-Mkt July 8 Playmate ( 1) F, C, D, M 12 Positive H5N1 - PCR Confirmed CASE Hospitalized
7 AMC PJ 29 F Caretaker of 6 Mother of 6 Contact
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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Line List July 20th
ID Initials Vill-age Age Sex Possible exposures and date EPI relation Syx Onset date Lab Status Case status Outcome
1 AAJ DG 10 M Live-Mkt July 8 Index case F, C, D, S 10 No lab specimen Probable CASE Died (7/16)
2 JAM DG 65 F Caretaker of 1 Grandmother ( 1) F, C, S 9 Negative H5N1 CONTACT Recovered
3 AWM DG 70 M Caretaker of 1 Grandfather ( 1) F, S, M 18 Positive H5N1 - PCR Confirmed CASE Died (7/20)
4 NJC DG 36 F Caretaker of 1 Live-Mkt July 8 Mother ( 1) F, C, S, M, D, URI 19 Pending Probable CASE Hospitalized
5 JRO DG 27 M Live-Mkt July 8, NJC Uncle ( 1) F, C, S 19 Pending Probable CASE Hospitalized
6 TMU PJ 11 M Live-Mkt July 8 Playmate ( 1) F, C, D, M 12 Positive H5N1 - PCR Confirmed CASE Hospitalized
7 AMC PJ 29 F Caretaker of 6 Mother of 6 CONTACT
8 DKS DG 19 M Caretaker of 1 Sibling (1) F, C 20 Pending Suspect CASE Hospitalized
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 11

• Do any of these recent events give you any
  further evidence about the possible reason for
  AAJs death?
• a. Yes
• b. No
• Answer a. Yes. AWM was been confirmed with
  influenza A (H5N1) infection and his only
  reported exposure so far was to AAJ

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New Concerns from Healthcare Workers
JULY 20

• Respiratory technician on duty when AAJ admitted
  felt droplets, has a fever
• Nurse 1 gave end-of-life and post-mortem care to
  grandfather, is unsure of PPE use
• Nurse 2 scared but adhered to precautions
• All of these individuals request antiviral
  therapy.

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Question 12

• Assuming Oseltamivir is available.
• Should the respiratory therapist receive therapy?
  If so, what dose should he receive?
• Yes 150 mg per day, given as 75 mg twice a day
  for at least five days
• Yes 75 mg once per day for 7-10 days
• No, dont give him any oseltamivir
• Answer a. Yes 150 mg per day, given as 75 mg
  twice per day for at least 5 days

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Question 13

• Assuming Oseltamivir is available.
• Should Nurse 1 receive therapy? If so, what dose
  should she receive?
• Yes 150 mg per day, given as 75 mg twice a day
  for at least five days
• Yes 75 mg once per day for 7-10 days
• No, dont give him any oseltamivir
• Answer b. Yes. 75 mg/day, once a day for 7-10
  days

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Question 14

• Assuming Oseltamivir is available.
• Should Nurse 2 receive therapy? If so, what
  dose should she receive?
• Yes 150 mg per day, given as 75 mg twice a day
  for at least five days
• Yes 75 mg once per day for 7-10 days
• No, dont give him any oseltamivir
• Answer No
• KEY POINT Consistent and appropriate use of PPE
  is the first line of defense against infection.

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Evening of July 20
JULY 20

• Colleagues return from Pelu Jaghai
• DKS has radiologically confirmed pneumonia
• Teams gather to update line lists and review
  epidemiologic data

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Reminder of the Linelist
JULY 20th, PM
ID Initials Vill-age Age Sex Possible exposures and date EPI relation Syx Onset date Lab Status Case status Outcome
1 AAJ DG 10 M Live-Mkt July 8 Index case F, C, D, S 10 No lab specimen Probable CASE Died (7/16)
2 JAM DG 65 F Caretaker of 1 Grandmother ( 1) F, C, S 9 Negative H5N1 CONTACT Recovered
3 AWM DG 70 M Caretaker of 1 Grandfather ( 1) F, S, M 18 Positive H5N1 - PCR Confirmed CASE Died (7/20)
4 NJC DG 36 F Caretaker of 1 Live-Mkt July 8 Mother ( 1) F, C, S, M, D, URI 19 Pending Probable CASE Hospitalized
5 JRO DG 27 M Live-Mkt July 8, NJC Uncle ( 1) F, C, S 19 Pending Probable CASE Hospitalized
6 TMU PJ 11 M Live-Mkt July 8 Playmate ( 1) F, C, D, M 12 Positive H5N1 - PCR Confirmed CASE Hospitalized
7 AMC PJ 29 F Caretaker of 6 Mother of 6 CONTACT
8 DKS DG 19 M Caretaker of 1 Sibling (1) F, C 20 Pending Suspect CASE Hospitalized
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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Epidemic Curve in Pegu
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Question 15

• Considering the estimated incubation period for
  influenza A(H5N1), look at the epi curve and
  infer the exposure that most likely occurred for
  each of the following cases. Arrows on the epi
  curve indicate timing of potential exposure
  sources (live market and family vigil).

Case Potential exposure
AAJ TMU NJC AWM JRO DKS Murg live bird market Contact with AAJ Family vigil Uncertain or multiple possible Contact with NJC

• Answer
• 1) a 2) a 3) b 4) b 5) d
  6) c

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Update!
JULY 21-23

• Confirmed positive for Influenza A(H5N1)
• Mother (NJC)
• Uncle (JRO)
• Sibling (DKS)
• Remaining contacts tested negative
• Respiratory therapist positive for Influenza
  A(H3N2)

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Diagram of the Outbreak
44
Blank Diagram of the Outbreak
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Components

• Exposure
• Case
• Possible zoonotic transmission
• Possible human-to-human transmission

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Possible Exposure Sources
Murg Market July 8
Family Vigil for AAJ July 11-13
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Probable and Confirmed Cases
AAJ
NJC
Jul 10
Jul 19
Murg Market July 8
AWM
Jul 18
TMU
Jul 12
JRO
Jul 19
DKS
Jul 20
Family Vigil for AAJ July 11-13
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Links to Possible Exposures
2 days
AAJ
9 days
NJC
11 days
6-8 days
Murg Live Bird Market July 8
12 days
AWM
10 hours
4 days
TMU
5-7 days
JRO
7-9 days
DKS
Family Vigil for AAJ July 11-13
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Diagram Summary
Probable or Confirmed Case Potential Exposure Calculated Incubation Plausibility of Incubation Based on Suspected Exposure
AAJ Market 2 days Plausible
AWM Vigil 5-7 days Plausible
NJC Market 11 days A little long
JRO Market 11 days A little long
JRO (option 2) NJC 10 hours A little short
TMU Market 4 days Plausible
DKS Vigil 7-9 days Plausible
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Human-to-Human Transmission Criteria

• Well documented exposure to a confirmed,
  probable, or suspect human case
• AND
• The time interval between contact with a human
  case and illness onset is 7 days or less
• AND
• Absence of an alternative source of exposure such
  as exposures to birds, animals, feathers,
  droppings, fertilizers made of fresh bird
  droppings, contaminated environments, or
  laboratory specimens
• OR
• Several generations of transmission linked to a
  primary case

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Question 26Assessing Human-to-Human Transmission
ID INITIALS LOC STATUS Case vs. Contact Human-to-human transmission? Possible Sources of Exposure
1 AAJ DG Probable CASE
3 AWM DG Confirmed CASE
4 NJC DG Confirmed CASE
5 JRO DG Confirmed CASE
6 TMU PJ Confirmed CASE
8 DKS DG Confirmed CASE

• Label as
• Likely
• Not likely
• Possible

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Human-to-Human TransmissionSuggested Answers
ID INITIALS LOC STATUS Case vs. Contact Human-to-human transmission? Possible Sources of Exposure
1 AAJ DG Probable CASE Not likely Live-Mkt July 8
3 AWM DG Confirmed CASE Likely Caretaker of 1, no reported poultry exposure.
4 NJC DG Confirmed CASE Possible Caretaker of 1 Live-Mkt July 8
5 JRO DG Confirmed CASE Possible Live-Mkt July 8, Exposure to NJC may be more likely source given incubation periods
6 TMU PJ Confirmed CASE Not likely Live-Mkt July 8. Exposed to AAJ, prior to AAJs symptom onset.
8 DKS DG Confirmed CASE Likely Caretaker of 1. Exposed at vigil, denies poultry exposure.
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Outbreak Progress
JULY 21-31

• Case patient updates
• Mother (NJC) dies
• Uncle (JRO) and sibling (DKS) survive
• Boy at Pelu Jaghai (TMU) dies
• No more acute unexplained respiratory infections
  with an underlying epidemiologic link to cases,
  contacts or sick poultry have arisen

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Question 16

• How long must you wait before you can consider
  this investigation closed, and the outbreak(s)
  over?
• At least 1 day
• At least 7 days
• At least 14 days
• At least 30 days
• Answer c. 14 days, or about 2 incubation periods

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Question 17

• At this stage, you should do all of the
  following, EXCEPT
• Sustain and enhance ongoing surveillance in
  humans and animals
• Sustain and enhance biosecurity in farms,
  backyard flocks, and markets
• Ask the laboratory to only test probable cases at
  this point
• Continue to provide prevention and control
  measures for case patients and contacts in
  communities and healthcare facilities
• Review and improve pandemic plans for interagency
  coordination and resource allocation
• Answer c.

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Conclusion
JULY 31

• All H5N1 viral isolates were identical and
  classified in the same clade of virus strains
• Testing revealed they were sensitive to
  Oseltamivir and Zanamirvir, but resistant to
  amantadine and rimantadine
• You return home!