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

International Setting

Case Study 2

11

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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3

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

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

44

Introduction

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

5

Republic of Pegu: Setting

• Developing country

• Southeast Asia

• 21 provinces

• Population: 50 million

66

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

7

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.

1. Veterinary Health Authority

2. Government officials (MOH and other gov’t offices or ministries)

3. Healthcare personnel

4. The community

5. Non-governmental organizations

6. The laboratory

a. To give you advice and direction

b. To satisfy their interest and offer education

c. To be ready for samples that will be coming

d. To conduct evaluation of diseased poultry

e. So they know you are coming to investigate

f. 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?

a. Proof of employmentb. Birth certificatec. Case informationd. SOP’s (case management, lab specimen

procedurese. Laboratory testing proceduresf. WHO request for assistance: (PPE, antivirals,

personnel)g. 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

a. Case definitionsb. Antiviral medicationc. Gogglesd. Glovese. Graph paperf. Solution for decontaminating

homes or hospital roomg. Transportation containersh. Pensi. Gown and capj. Reporting forms

k. Specimen collection materials

l. Icem. Guidelines for contacts,

family members, and healthcare workers

n. Notebook/laptopo. Portable GIS unitp. Viral transport mediaq. Simple messages r. 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 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)

JULY 15

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Character Details

• 65 year old grandmother = JAMChronically illCaretaker of grandson

• 10 year old grandson = AAJ Ill July 11

• Uncle = JRO

• Grandfather = AWM

• Mother = NJC Caretaker of son (AAJ)

Setting: Small, mountain village in Pelu Jaghai

province

JULY 15

15

Exposure & Onset Details

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

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

July 8th

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

• AAJ becomes ill on July 10th

• JAM cares for him starting July 11th

Dava Ghar hospital: 60 km away from village

July

13th

JULY 15

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AAJ Clinical Presentation and Further Evidence

• 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

JULY 15

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Caretaker Health Status at Hospital

• 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

JULY 15

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Rumor Surveillance

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

• May continue to be wide-spread chicken deaths

JULY 15

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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.

a. Under investigation

b. Suspected

c. Probable

d. 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?

a. Under investigation

b. Suspected

c. Probable

d. 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

ID Age Gender

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)22

Suggested Line List Format

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ID #

Initials Loc Age Sex EPI relation

Occ Syx Onset - July

Poss. Exp.

Lab Status

Case vs. Contact

Outcome

Question 6

Update the line list with the cases as of July 15th mid-dayID #

Initials Loc Age Sex EPI relation Occ Syx Onset - July

Poss. Exp.

1 AAJ DG 10 M Child (exp at live market)

Child F,C,S 10 Live Mkt: July 8th

Grandmother: July9th

2 JAM DG 65 F Grandmother of #1 (AAJ)

Retired F,C,S 9 Caretaker of #1

Timing - ?

ID Initials

Lab

Status

Case status definition

(Case v. Contact)

Outcome

1 AAJ No lab specimen Probable Case Hospitalized on ventilator, pneumonia, respiratory failure

2 JAM Pending Person under invest. Hospitalized

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

JULY 15

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Question 7a

When should you begin assessing contacts of this probable case?

a. As soon as you become aware of the case

b. Once you have determined the case status as being “suspect” or highter

c. Once you have determined the case status as being “probable” or higher

d. Once you have a confirmed diagnosis

Answer: a.25

Question 7b

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

1. Anyone who came within 1 meter of the case patient

2. Anyone who had shared space within 1 meter of the case patient

3. Close contact 1 day before through 14 days after onset of symptoms

4. Close contact 7 days before through 14 days after the onset of symptoms

5. Someone who kissed, embraced or shared utensils with the case patient

6. Someone who spoke with or touched the case patient

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Answers:

False

True

True

False

True

True

Review: Identifying Contacts

• Potential contactsHousehold membersFriendsHealthcare providersPharmacistsTraditional healersWorkplace contacts

• Contact tracing activitiesPrioritize 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:

1.Should AAJ be given anti-viral treatment?

2.Should JAM be given anti-viral treatment?

Answer: 1.Yes2.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

1. Should JAM receive anti-viral prophylaxis?

2. Should asympomatic close contacts of AAJ be given anti-viral prophylaxis?

3. Should close contacts of JAM receive antiviral prophylaxis?

Answer:

1. Yes

2. Yes

3. 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 9If 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.

1. High Risk

2. Moderate Risk

3. Low Risk

a. Personnel culling likely non-infected animalsb. Personnel handling sick animals or decontaminating

environments using insufficient PPE c. Personnel handling sick animals or decontaminating

environments using adequate PPE d. Unprotected close/direct exposure to H5N1 infected

animalse. Healthcare or laboratory personnel in close contact with

strongly suspected or confirmed patients or their samples with insufficient PPE

f. Healthcare workers not in close contactg. Healthcare workers with close contact using adequate

PPEh. Close household contact of strongly suspected or

confirmed patients 30

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 31

Question 9 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 32

Update: July 16th

The RRT arrives at Dava Ghar

AAJ 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

JAM Update

• Admission Temperature 38.5 °C 28 breaths/minute Blood pressure 160/95 O2 saturation 90%

• Initial laboratory findings High lymphocyte count High leukocyte count

JULY 16

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Specimens Needed

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

• You send biological samples from the grandmother to the National laboratory for testing.

JULY 16

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Question 10a

What specimens need to be collected from the grandmother?

a.Endotracheal fluidb.Broncho-alveolar lavagec.Throat swab (oropharyngeal) d.Nasal swab (nasopharyngeal) e. 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?

a.It should begin as soon as possible after symptoms begin

b.It should begin before antiviral medications are administered

c.Sample should be collected even if symptoms began more than one week ago

d.Multiple samples should be collected on multiple days if possible

e.None of the above (all statements are true)

Answer: e.

Remember – it is better to collect too many specimens than not enough 36

Specimen Collection Kit

Collection vials with VTM

Polyester fiber-tipped applicators

Sterile saline which is 0,85% NaCI

A sputum or mucus trap

Tongue depressors

Specimen collection cups or Petri dishes

Transfer pipettes A secondary

container Ice pack

Items for collection of blood

Personal Protective Equipment (PPE)

Field collection forms

A pen or marker for labeling samples

JULY 15

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Question 11

• 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 applicator’s stick

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

1.

4.

3.

2.

5.

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Question 12aHere is an image of a properly packed specimen. Label the packaging using the answer choices given.

1) 3 layers of _________

2) Absorbent _________

5) Specimen______

6) _______ label

4) Itemized list of ______

3) Labeling of the _________ as UN3373 diagnostic specimens

Answer choices:a.contentsb.packing materialc.identificationd.outer packagee.packagingf.biohazard 39

Question 12aHere 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

5) Specimen c. identification

6) f. Biohazard label

4) Itemized list of a. contents

3) Labeling of the d. outer package as UN3373 diagnostic specimens

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Question 12b

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

1.Store specimens can be stored at 4 °C within 48 hours of collection both before and during transportation.

2.Store specimens at -70 °C beyond 48 hours (if you will not be able to immediately transport specimen to laboratory)

3.Never store specimens on dry ice

4.Specimens may be stored in standard freezer

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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.

Answers:

True

True

False

False

Question 12c

When transporting specimens from potential cases of avian influenza from the field to the laboratory, you should follow which regulations?

a. WHO guidelines for safe transport of infectious substances and diagnostic specimens

b. Local regulations on the transportation of infectious material

c. Neither a nor b

d. Both a and b

Answer: d.

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Transportation Considerations

• 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 43

JULY 16

Contact Identification

• 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 areMother (NJC) Uncle (JRO),Grandparents (JAM & AWM)

JULY 16

44

Question 13

45

ID #

Initials Loc Age Sex EPI relation

Occ Syx Onset - July

Poss. Exp.

Lab Status

Case vs.

Contact

Outcome

1 AAJ DG 10 M Index case

Child F,C,S

10 Live Mkt: July 8th

Grandmother: July9th

No lab specimen

Probable Case

Hospitalized on ventilator, pneumonia,respiratory failure

2 JAM DG 65 F Grandmother of #1 (AAJ)

Retired F,C,S

9 Caretaker of #1

Timing - ?

Pending Person under invest.

Hospitalized

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.

Question 13 AnswerLine list as of July 16th a.m.

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

ID #

Initials Loc Age Sex EPI relation

Occ Syx Onset - July

Poss. Exp.

Lab Status

Case vs.

Contact

Outcome

1 AAJ DG 10 M ‘index’ case

Child F, C, D, S

10 Live-Mkt: July 8

No lab specimen

ProbableCASE

Died (7/16)

2 JAM DG 65 F Grandmother (# 1)

Retired F, C, S

9 Caretaker of # 1

Pending PUI/Contact

Hospitalized

3 AWM DG 70 M Grandfather (# 1)

Retired Caretaker of # 1

Contact

4 NJC DG 36 F Mother (# 1)

Home-maker

Caretaker of # 1; Live-Mkt: July 8

Contact

5 JRO DG 27 M Uncle (# 1)

Farmer Live-Mkt: July 8

Contact

46

Beyond the Given Scenario

Also think beyond the nuclear familyVillage health workersTraditional healersTaxi 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?

a.Health care facilities (hospitals, clinics, traditional healers)b.Patient (or family proxy)c.Patient’s village/neighborhoodd.Patient’s school/workplace

Answer: d. At this point in time, the appropriate information on close contacts can be gathered from the patient/proxy

48

Question 14b

In conducting contact tracing interviews, in which of these places would you need to wear personal protective equipment (PPE)?

a.Health care facilities (hospitals, clinics, traditional healers)

b.Patient (or family proxy)

c.Patient’s village/neighborhood

Answer: b.

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Question 14c

1. Hospital or other medical facility

2. Patient (or proxy)

3. Patients home and village

a. 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

b. Retrace the steps of the patient and try to determine if there were any close contacts without adequate PPE.

c. Find out more details about suspected exposures, conduct an environmental survey, and determine if there are any outbreaks among animals.

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

Answer: 1. b 2. a 3. c 50

Question 15a

Questions to ask the case patient’s family covering situations with potential for H5N1 exposure should include which of the following?

Contact with confirmed or suspect human H5 casesAwareness of clusters of severe respiratory illness in family, friends and co-workersAwareness of H5N1 outbreaks occurring outside the countryExposure to animals and their environmentExposure to contaminated environmentsExposure to cooked chicken productsInquire 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 patient’s home or in their village, which of the following are important contextual factors to observe and analyze?Poultry in and around the houseNumber of people living in the homeConstruction material of the homeMapped location or photograph of house and surroundingsCulture-specific risk factorsAnnual community festival daysLive bird markets or other occupationally related exposures

52

Case Finding Results

• 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

JULY 16

53

New Case and Contact

• 11-year-old boy, TMUFever, cough shortness of breath starting July 12Admitted July 15Critically 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

54

JULY 16

Question 16

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

55

Question 16 Answer

56

Line list as of July 16th p.m.

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

ID #

Initials Loc Age Sex EPI relation

Occ Syx Onset - July

Poss. Exp.

Lab Status

Case vs.

Contact

Outcome

1 AAJ DG 10 M ‘index’ case

Child F, C, D, S

10 Live-Mkt: July 8

No lab specimen

ProbableCASE

Died (7/16)

2 JAM DG 65 F Grandmother (# 1)

Retired F, C, S

9 Caretaker of # 1

Pending PUI/Contact

Hospitalized

3 AWM DG 70 M Grandfather (# 1)

Retired Caretaker of # 1

Contact

4 NJC DG 36 F Mother (# 1)

Home-maker

Caretaker of # 1; Live-Mkt: July 8

Contact

5 JRO DG 27 M Uncle (# 1)

Farmer Live-Mkt: July 8

Contact

6 TMU PJ 11 M Playmate (# 1)

Child F, C, D, M

12 Live-Mkt: July 8

Pending SuspectCASE

Hospitalized

7 AMC PJ 29 F Mother of # 6

Mother Caretaker of # 6

Contact

Differential Diagnoses

Human influenza

• 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

Influenza A(H5N1)

• 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

57

Non-Influenza Differential Diagnoses

Viral

• 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

Bacterial

• Mycobacteria tuberculosis

• Yersinia pestis (pneumonic plague)

• Streptococcus pneumoniae

• Staphylococcus aureus

• Hemophilus influenzae

• Burkholderia pseudomallei

• Legionella spp.

• Chlamydia pneumoniae

• Mycoplasma pneumoniae

• Coxiella burnetii(Q fever) 58

Question 17

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

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Move on to Outbreak Investigation, Part 2

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