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 2

1

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. 22

Learning Objectives (cont.)

• List appropriate practices and procedures for: Specimen collection and transport Epidemiologic investigation Identification of transmission mechanismsContact tracing Isolation/quarantine policyTreatment/control policy Risk communication prioritiesRecommended laboratory specimen protocols methodsEthical considerations

3

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

4

Introduction

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 contact6

July 17

• Suspect or probable cases of Influenza A(H5N1)Dava GharPelu JaghaiContacts are being monitored

• Concern about healthcare worker safety

7

JULY 17

Question 1

Which of the following are standard precautions?a. Patient placement into single room/cohorting for influenza

A(H5N1) cases

b. Hand hygiene

c. Respiratory and cough etiquette

d. Personal protective equipment (PPE), depending on risk of contact with patient bodily fluids

e. Safe injection practices

f. Surgical mask on entry into room

g. Environmental control

Answer: b, c, d, e, and g8

Question 2

Which of the following are droplet precautions?a. Private room/cohorting for patients with the same infectionb. Surgical mask on entry to patient’s room (and on patient when

outside the room) c. Patients should be places in negative air pressure airborne

isolation roomsd. Eye protectione. Change of PPE and hand hygiene between patientsf. Respirator for entry into patient roomg. Daily cleaning and disinfection of surfaces in patient room

Answer: a b, d, e, and g.

9

Question 3You 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) 310

Precautions Use

a. Standard precautions

1. During routine care of suspect, probable, or confirmed influenza A(H5N1) cases

b.Contact / droplet precautions

2. At all times

c. Airborne precautions

3. When performing aerosol-generating procedures on influenza A(H5N1) cases

Epidemiologic Connection

• TMU11 year-old boy in Pelu Jaghai

• AAJ10 year-old boy in Dava Ghar

• Both at Murg marketChased a “slow and unsteady” chicken

11

JULY 17

Murg Market

• You collect respiratory specimens from TMU

• You learn AAJ’s uncle, JRO, took him to the market

• You return to Dava Ghar, anxious that you are missing other suspected cases of influenza A(H5N1)

12

JULY 17

July 18: Grandparents

Patient rounds

• Grandmother (JAM)Not progressing to respiratory failureLaboratory tests negative for influenza A(H5N1)Suggestive of tuberculosis

• GrandfatherFever and myalgiaStayed by JAM’s bedside with respiratorOn Oseltamivir chemoprophylaxis, but rapidly worsening Hospitalized

13

JULY 18

H5 Test Results

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

• Chicken specimen also positive for H5

14

JULY 18

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

Market Closure

• Murg market is closedPerimeter for culling and surveillanceActive surveillance at source farms

• Cases reported to WHO

• WHO mobilizing to assist15

JULY 18

Update the line list given below to be current up until the afternoon of July 18

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 specime

n

ProbableCASE

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 SuspectCASE

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 GharPJ: Pelu Jaghai

JULY 16th, PM

Linelist as of July 18th, Afternoon

ID #

Initials Vill-age


EPI relation

Syx Onset date

Lab

Status

Case status

Outcome


‘Index’ case F, C, D, S

10 No lab specime

n

Probable CASE

Died (7/16)


Grandmother (# 1)

F, C, S

9 Negative H5N1

CONTACT

Hospitalized


Grandfather (# 1)

F, S, M


Hospitalized


Mother (# 1) CONTACT


Uncle (# 1) CONTACT


Playmate (# 1)

F, C, D, M

12 Positive H5N1 - PCR

Confirmed CASE

Hospitalized


Mother of # 6

CONTACT

17

F: Fever; C: Cough; D: Diarrhea; S: Shortness of breath; M: Myalgias; URI – upper respiratory syx DG: Dava GharPJ: Pelu Jaghai

Public Alert

• 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 Health’s Public Information Officer

18

JULY 18

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?

a. Show empathy, openness, and understanding

b. Indicate that the government is taking steps to address this problem

c. Assure the public that no more people will get sick

d. Indicate that the MOH are the scientific experts on this complicated issue and the public has nothing to worry about

e. Indicate what the public can do for themselves

Answer: a, b, and e

19

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.

20

Question 6

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

a. Current staff in the field

b. Update on human cases

c. Changed case classifications since last report

d. Close contacts being monitored

e. Update on active/enhanced human surveillance activities

f. Update on animal surveillance and animal outbreak control activities

g. Epidemiologic assessment and likelihood of human to human transmission

h. Laboratory tests pending

i. Hospital infection control update

j. Outbreak control measures being implemented

k. Planned next steps

l. Material / personnel assistance needed

21Answer: All!

Question 7Match the statements on the right to the appropriate section of the situation report on the left.

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

a. Active surveillance is being undertaken among poultry owners that supplied birds to the Murg Market

b. There is a new suspected case of influenza A(H5N1)

c. Efforts to identify additional cases beyond close contacts

d. The uncle of the 10-yr-old decedent, who attended the live bird market on July 8

22

Answers:

1) b 2) d 3) a 4) c

A New Problem

• Family of case AAJ have refused voluntary quarantineMother (NJC)Uncle (JRO)

• Symptoms of family include weakness, tiredness, aches

23

JULY 18

Question 8

The goal of quarantine is to protect the public health by…

a. restricting the movement of an ill individual.b. separating persons exposed to a communicable

disease from the general population.c. limiting the activities of persons exposed to a

communicable disease.d. limiting the activities of an ill individual.

Answer: b24

Question 9

The ethical justification of quarantine requires that…

a. person-to-person spread of a disease is possible.

b. only lower SES individuals should be placed into quarantine.

c. quarantine only be used if influenza A(H5N1) is suspected, and not another pathogen.

d. voluntary quarantine is used before more restrictive measures are used.

e. physical needs are met and psychological affects are minimized.

f. quarantined individuals are closely monitored for onset of symptoms.

Answer: a, d, e, and f 25

Question 10

In this situation whose responsibility is it to determine whether the family members refusing voluntary quarantine should be forced into quarantine?

a. Yours

b. The local and national authorities of Pegu

c. The World Health Organization’s

d. UN Secreteriat for Respectful Quarantine (UNSRQ)

Answer: b. 26

Key Point: Quarantine

Ethical justification of quarantine or isolation requires that:

1. There is a possibility of person-to person spread of disease and the necessity of quarantine

2. The least restrictive measures be used. Voluntary quarantine should be used before more restrictive measures are enacted.

3. Society provide necessary support services for those in quarantine

4. Public health officials justify their actions and allow for a process of appeal

5. Quarantined individuals be closely monitored to detect onset of symptoms

27

Visit to NJC and RJO

• PersuasionLocal religious leaders help NJC and JRO accept

voluntary quarantine

• Interview19-year-old brother, DKS, was exposed during

family vigil July 12-13DKS returned to university July 14

28

JULY 18

July 19: Late Evening Updates

• 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

29

JULY 19

July 20: MOH Updates

• DKS (19 yr-old student) symptom onset todayReturned to home provinceDenied live-market or poultry exposureAffirmed exposure to his ill brother

• AWM (grandfather) diedMultiple complications – renal failure, encephalitis,

ventricular arrhythmiasPCR+ for influenza A(H5N1)

30

JULY 20

Update the line list given below to be current up until the afternoon of July 20

31

ID #

Initials Vill-age


EPI relation Syx Onset date

Lab

Status

Case status

Outcome



10 No lab specimen

Probable CASE

Died (7/16)


Grandmother (# 1)

F, C, S

9 Negative H5N1

Contact Hospitalized


Grandfather (# 1)

F, S, M


Hospitalized


Mother (# 1) Contact


Uncle (# 1) Contact


Playmate (# 1)

F, C, D, M


Confirmed CASE

Hospitalized


Mother of # 6 Contact

F: Fever; C: Cough; D: Diarrhea; S: Shortness of breath; M: Myalgias; URI – upper respiratory syxDG: Dava GharPJ: Pelu Jaghai

JULY 18th, PM

Line List: July 20th

ID #

Initials Vill-age


EPI relation

Syx Onset date

Lab

Status

Case status

Outcome



10 No lab specime

n

Probable CASE

Died (7/16)


Grandmother (# 1)

F, C, S

9 Negative H5N1

CONTACT Recovered


Grandfather (# 1)

F, S, M


Confirmed CASE

Died (7/20)


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


Hospitalized


Playmate (# 1)

F, C, D, M


Confirmed CASE

Hospitalized


Mother of # 6 CONTACT

8 DKS DG 19 M Caretaker of # 1

Sibling (#1) F, C 20 Pending SuspectCASE

Hospitalized


Question 11

Do any of these recent events give you any further evidence about the possible reason for AAJ’s 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

33

New Concerns from Healthcare Workers

• 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.34

JULY 20

Question 12

Assuming Oseltamivir is available….

Should the respiratory therapist receive therapy? If so, what dose should he receive?a. Yes: 150 mg per day, given as 75 mg twice a day for at

least five days

b. Yes: 75 mg once per day for 7-10 days

c. No, don’t give him any oseltamivir

Answer: a. Yes; 150 mg per day, given as 75 mg twice per day for at least 5 days

35

Question 13


Should Nurse #1 receive therapy? If so, what dose should she receive?a. Yes: 150 mg per day, given as 75 mg twice a day for at least

five days



Answer: b. Yes. 75 mg/day, once a day for 7-10 days36

Question 14


Should Nurse #2 receive therapy? If so, what dose should she receive?a. Yes: 150 mg per day, given as 75 mg twice a day for at least five

days



Answer: No

KEY POINT: Consistent and appropriate use of PPE is the first line of defense against infection.

37

Evening of July 20

• Colleagues return from Pelu Jaghai

• DKS has radiologically confirmed pneumonia

• Teams gather to update line lists and review epidemiologic data

38

JULY 20

Reminder of the LinelistID #

Initials Vill-age


EPI relation

Syx Onset date

Lab

Status

Case status

Outcome



10 No lab specime

n

Probable CASE

Died (7/16)


Grandmother (# 1)

F, C, S

9 Negative H5N1

CONTACT Recovered


Grandfather (# 1)

F, S, M


Confirmed CASE

Died (7/20)


Mother (# 1) F, C, S, M, D, URI


Hospitalized

5 JRO DG 27 M Live-Mkt: July 8, NJC

Uncle (# 1) F, C, S


Hospitalized


Playmate (# 1)

F, C, D, M


Confirmed CASE

Hospitalized


Mother of # 6 CONTACT

8 DKS DG 19 M Caretaker of # 1

Sibling (#1) F, C 20 Pending SuspectCASE

Hospitalized


JULY 20th, PM

Epidemic Curve in Pegu

40

Question 15Considering 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).

41

Case Potential exposure

1. AAJ2. TMU3. NJC 4. AWM5. JRO 6. DKS

a. Murg live bird marketb. Contact with AAJc. Family vigild. Uncertain or multiple possiblee. Contact with NJC

Answer:

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

Update!

• Confirmed positive for Influenza A(H5N1)Mother (NJC)Uncle (JRO)Sibling (DKS)

• Remaining ‘contacts’ tested negativeRespiratory therapist positive for Influenza

A(H3N2)42

JULY 21-23

Diagram of the Outbreak

43

Blank Diagram of the Outbreak

44

Components

45

Exposure

Case

Possible zoonotic transmission

Possible human-to-human transmission

Possible Exposure Sources

46

Murg MarketJuly 8

Family Vigil for AAJJuly 11-13

Probable and Confirmed Cases

47

Murg MarketJuly 8


AAJ

AWM

NJC

JRO

DKS

TMU

Jul 10

Jul 18

Jul 19

Jul 19Jul 12

Jul 20

Links to Possible Exposures

48

Murg Live Bird Market

July 8


AAJ

AWM

NJC

JRO

DKS

TMU

2 days

5-7 days

9 days

11 days

6-8

days12 days4 days

7-9 days

10 hours

Diagram Summary

49

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

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 case50

Question 26:Assessing 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

51

Label as: •Likely•Not likely•Possible

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 AAJ’s symptom onset.

8 DKS DG Confirmed CASE

Likely Caretaker of # 1. Exposed at vigil, denies poultry exposure.

52

Outbreak Progress

• Case patient updatesMother (NJC) diesUncle (JRO) and sibling (DKS) surviveBoy at Pelu Jaghai (TMU) dies

• No more acute unexplained respiratory infections with an underlying epidemiologic link to cases, contacts or sick poultry have arisen

53

JULY 21-31

Question 16

How long must you wait before you can consider this investigation closed, and the outbreak(s) over?

a. At least 1 day

b. At least 7 days

c. At least 14 days

d. At least 30 days

Answer: c. 14 days, or about 2 incubation periods

54

Question 17

At this stage, you should do all of the following, EXCEPT:

a. Sustain and enhance ongoing surveillance in humans and animals

b. Sustain and enhance biosecurity in farms, backyard flocks, and markets

c. Ask the laboratory to only test probable cases at this pointd. Continue to provide prevention and control measures for

case patients and contacts in communities and healthcare facilities

e. Review and improve pandemic plans for interagency coordination and resource allocation

Answer: c.55

Conclusion

• 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!

56

JULY 31

Documents

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