Influenza A(H5N1) in Humans: Outbreak Investigation in an International Setting Case Study 2 Welcome to the Outbreak Investigation portion of the Avian.

Influenza A(H5N1) in Humans: Outbreak Investigation in an International Setting
Case Study 2 Welcome to the Outbreak Investigation portion of the Avian Influenza training. 1

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 The learning objectives for this module are to: 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 2 2

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 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 In this session, we will continue working through a case study set in a fictional country, Pegu. It will be your responsibility to make decisions and recommendations for influenza surveillance in this country as we go along. We will begin by briefly reviewing the geography and infrastructure given for Pegu in the scenario. Throughout the case study, you will be given descriptions of the situation and the available details on cases, events, and the environment. The concepts you will work through include the following: Creating a case definition Collecting clinical samples, interpreting laboratory findings, and making recommendations Creating a line list Conducting contact tracing, and Evaluating treatment options and giving recommendations. 4 4

Be sure to have materials needed to take notes and create a line list
Introduction Be sure to have materials needed to take notes and create a line list Just as you would in a ‘real-life’ epidemic investigation, take notes on any and all details that are presented as you walk through this case study. Actively record pertinent epidemiological and clinical information, important dates and locations, and relevant policies and procedures. Given the complexity of the upcoming story line, it is recommended that you start a line list on your own. You will be provided a line list in the case study, but as it is part of the simulation, you should not look ahead. Note to instructor: A graphical representation of cases, onset dates, sources of exposure and incubation periods is included in the slides. When discussed in a later question, it might be helpful to use paper or a white board to create and update this graphic with the group (along with the line-lists) as the scenario progresses. Also note: This case study is focused on a human health investigation. If there are veterinarians present in the class, please have them occasionally summarize the parallel agricultural investigations that would be occurring during this study.

Republic of Pegu: Setting
Developing country Southeast Asia 21 provinces Population: 50 million Remember, you are working in Pegu to assist or advise the Pegu MOH with their public health needs. They are your partners and it is vitally important that that you are working together with them, and in direct communication with them at all times. 6 6

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 Beginning in March 2006 there have been a series of reports from different media sources indicating mass deaths of flocks of chickens, geese, and other waterfowl. These deaths have primarily occurred in the southeastern region of Pegu. The Ministry of Agriculture (MOA) sent investigators into this region to follow-up on these rumored reports, and has reported test results from three samples collected from dead chickens sent to the national laboratory in Anawrahta to be “weakly positive” for avian Influenza A(H5N1) in April, There is no systematic surveillance for avian Influenza A(H5N1) in poultry, wild bird, or other animal populations.

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 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? Note to instructor: In a classroom setting, you can have different students each write one person or skill on the whiteboard or flip chart, or one person can write while they brainstorm as a group. Make sure they also describe and understand the different roles/activities of each RR Team member. Core team members should have skills that include: A team leader whose role is to oversea the team, outline investigation plans, assign roles and responsibilities, and communicate with other officials and the media An epidemiologist whose role it is to verify the outbreak, establish a case definition, lead case finding activities, supervise data collection and analysis, identify risk factors, and coordinate control measures A medical officer/clinician whose role it is to advise and assist in managing sick patients and supervise institution of infection control measures. They may also advise and assist in collection of clinical specimens and advise and institute infection control measures A veterinary Liaison should be designated whose role it is to coordinate with the veterinary/agricultural response and also to possibly provide expertise related to detection, prevention and control of H5N1 in animals A laboratorian or laboratory technician whose role it is to advise and assure proper collection, transportation, and storage of clinical samples; and as well to verify influenza laboratory diagnosis and oversea laboratory operations If additional resources are available, an expanded team should also include the following team members: A communications specialist whose role it is to provide expertise on risk communication during an outbreak investigation A logistician who role it is to provide logistical and administrative support A data manager who role it is to enter data, to manage the investigation database, and to ensure the security of the database. Each member of the team will likely have more than one of these skills but must have clearly defined roles and responsibilities to ensure that the team works cooperatively.

Question 2 Match who should be notified about the investigation on the left with the reason they should be notified on the right. Veterinary Health Authority Government officials (MOH and other gov’t offices or ministries) Healthcare personnel The community Non-governmental organizations The laboratory To give you advice and direction To satisfy their interest and offer education To be ready for samples that will be coming To conduct evaluation of diseased poultry So they know you are coming to investigate To serve as a resource for medical resources Match who should be notified about the investigation on the left with the reason they should be notified on the right. Veterinary Health Authority Government officials (MOH and other gov’t offices or ministries) Healthcare personnel The community Non-governmental organizations The laboratory To give you advice and direction To satisfy their interest and offer education To be ready for samples that will be coming To conduct evaluation of diseased poultry So they know you are coming to investigate To serve as a resource for medical resources

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 The Veterinary Health Authority should be notified to conduct an evaluation of diseased poultry or other animals in the area where suspect human H5N1 cases are being investigated. Government officials in the relevant ministries should be kept informed of the situation, and officials in the Ministry of Health may have advice and direction that will be useful in your investigation. Healthcare personnel caring for the affected patients should know that you will be arriving to investigate. You may want to remind them how to limit exposure to visitors and other hospital workers, and offer information or resources on case management as necessary. The community you will visit will likely be very interested in a case of avian influenza among them. Be prepared to answer questions, offer assurance that you and your RRT is handling the situation, and use the opportunity to educate them about how to prevent disease transmission. Non-governmental organizations in the area could be a resource for needed medical staff, antiviral medications, transportation, or other needed resources. If you inform them of the situation they may be able to offer help. The laboratory should know that clinical and possible environmental samples will be received from suspected H5N1 cases. If the hospital has already sent samples for testing, communicate with the laboratory on the progress of testing and results.

Question 3a Which of the following are NOT documents that you would need to bring with you to the field? Proof of employment Birth certificate Case information SOP’s (case management, lab specimen procedures Laboratory testing procedures WHO request for assistance: (PPE, antivirals, personnel) WHO guidelines for investigation Which of the following are NOT documents that you would need to bring with you to the field? Answer: b and d. In addition to the correct answers listed above, documents that you WOULD need include - Proof of employment Case information Case reporting forms Lists of known contacts Standardized questionnaires SOP’s (case management, lab specimen procedures WHO request for assistance: (PPE, antivirals, personnel) WHO guidelines for investigation Avian influenza references

Question 3b Below are 6 categories of supplies needed when you go to the field. Match the list of supplies to the general category. Categories: Epidemiological, Medical, Laboratory, Educational, PPE, Decontamination Case definitions Antiviral medication Goggles Gloves Graph paper Solution for decontaminating homes or hospital room Transportation containers Pens Gown and cap Reporting forms Specimen collection materials Ice Guidelines for contacts, family members, and healthcare workers Notebook/laptop Portable GIS unit Viral transport media Simple messages Respirators Match the supplies to the category in which they belong. The categories of supplies are epidemiological, medical, laboratory, educational, PPE, and decontamination. Answers on following slide.

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 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

Trigger Event #2 JULY 15 July 15th Dava Ghar hospital has admitted 2 patients with SARI Reported to District Health Office They suspect avian influenza due to poultry outbreaks in area Patients are related 65 year old grandmother (JAM) 10 year old grandson (AAJ) It is the morning of July 15, and you receive a call from a staff doctor at Dava Ghar hospital who notified the District Health Office that they have admitted 2 persons with severe respiratory illness. The doctor is concerned that his patients may have avian influenza, as a few confirmed poultry outbreaks have been reported in the neighboring province. Apparently, the two patients are related – a 65 year-old grandmother (JAM) and her ten-year old grandson (AAJ).

Setting: Small, mountain village in Pelu Jaghai province
Character Details JULY 15 65 year old grandmother = JAM Chronically ill Caretaker of grandson 10 year old grandson = AAJ Ill July 11 Uncle = JRO Grandfather = AWM Mother = NJC Caretaker of son (AAJ) The grandmother (JAM) resides in the same house as the child’s grandfather (AWM), and both live in a house near the grandson’s house in a small mountain village in the province. This village is almost 60 km away from the hospital. The child’s father was away in a nearby city during the week of illness onset. The child also has an uncle (JRO). The grandmother (JAM), who is chronically in ill-health, became a caretaker of the child on July 11th along with the mother (NJC) who lives with the child. The grandfather (AWM) also helped despite his elderly status and chronic heart illness. The child (AAJ) was brought to the hospital by his family two days ago and presented with the following symptoms: fever, cough, diarrhea and shortness of breath. Setting: Small, mountain village in Pelu Jaghai province

Exposure & Onset Details
JULY 15 Murg Market in Pelu Jaghai: Local market with live animals and location of A(H5N1) confirmed poultry outbreaks July 8th AAJ, NJC, & JRO attended live-market (“Murg Market”) Dava Ghar hospital: 60 km away from village July 13th AAJ becomes ill on July 10th The only pertinent history you are able to obtain regarding potential exposures is that the child visited a live-market (called the “Murg Market”) with his mother (NJC) and uncle (JRO) in Pelu Jaghai province (where his friends and relatives live) on July 8th. A Murg Market is an open market where local farmers and community folk come to buy and sell produce, meat, live poultry, and other (often live) animals, seafood, etc. The Director of Epidemiology of the MOH, following communication with the Ministry of Agriculture has determined that the Murg market was the location where the poultry that tested positive for A(H5N1) were discovered during the previous month. You obtain the history that the boy may have played with chickens at the live-market event. Further clinical history obtained over the phone reveals that the child (AAJ) became ill on July 10 and was admitted to the hospital almost 4 days later. By the 2nd day of illness (July 11th) the grandmother (JAM), who is chronically in ill-health, became a caretaker of the child on along with the mother (NJC) who lives with the child. The grandfather (AWM) also helped despite his elderly status and chronic heart illness. The child’s father was away in a nearby city during the week of illness onset. The family was very distressed and kept a close bedside vigil, taking care of the child for almost 48 hours in the village starting on July 11. By the 3rd day (13th), the child was deteriorating and also had a documented a fever of 38.7 °C (101.7° F). The family decided to bring him to the Dava Ghar hospital, despite the long distance. The child (AAJ) was brought to the hospital by his family presenting with the following symptoms: fever, cough, diarrhea and shortness of breath. 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
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 The child arrived in unstable (critical) condition late at night on the 13th (admitted on the 14th early morning). His chest X-ray on admission is shown. Shortly after admission yesterday (the 14th), the child rapidly deteriorated because of worsening respiratory distress - requiring endotracheal intubation and ventilatory support. He was started on Ceftriaxone. 10 year old child (AAJ) CXR on Admission

Caretaker Health Status at Hospital
JULY 15 Mother (NJC) and grandfather (AWM) are asymptomatic or deny symptoms Grandmother (JAM) reports respiratory condition suddenly worsened on July 9th Symptoms: fever, cough and dyspnea = SARI Admitted to hospital on July 14th Denied contact with Murg Market or poultry At admission of AAJ, the mother (NJC) is asymptomatic. The grandfather also denies any symptoms. HOWEVER, the grandmother reports that her ongoing respiratory condition suddenly worsened on about July 9th. The grandmother (JAM) has similar symptoms of fever, cough and dyspnea that began on July 9th. Her working diagnosis was that of a severe acute respiratory infection (SARI) and as her condition was not improving, she also was admitted to the hospital on July 14th. The grandmother repeatedly denied any visits to the Murg market or contact with poultry.

Rumor Surveillance JULY 15 May be additional sick persons with respiratory symptoms in Pelu Jaghai May continue to be wide-spread chicken deaths There are rumors that there are additional sick persons with similar symptoms in a village in the adjacent nearby province, Pelu Jaghai, where the Murg market is located, as well as continuing rumors of widespread chicken deaths on local farms in Pelu Jaghai.

Question 4a How would you classify AAJ into the WHO influenza A(H5N1) case definition? Information on AAJ is given for your reference. Under investigation Suspected Probable Confirmed Answer: The Chest X-ray and clinical deterioration extend the ‘suspected A(H5N1) status’ to C, a probable case designation. Clinical: Fever, cough, diarrhea and shortness of breath Epidemiological: Exposure to live-market on July 8th where influenza A(H5N1) infections in animals were confirmed in the last month. Laboratory: No lab specimens available. Note to instructor: Be sure to distribute the WHO case definitions handout Lectora: Link to WHO Case Definitions (or pdf of the handout): How would you classify AAJ, the 10-year old boy, into the WHO influenza A(H5N1) case definition? Information on AAJ is given for your reference. 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. Facilitator Answer: Whenever a suspected case of human infection with avian influenza A(H5N1) virus is being investigated, evidence for A(H5N1) infection is based on three important elements: CLINICAL findings, EPIDEMIOLOGICAL findings and LABORATORY testing. The initial symptoms and the epidemiological link to influenza A(H5N1) positive chickens would be sufficient to classify AAJ as a suspected case. The CXR and clinical deterioration extend the suspected A(H5N1) status to a “probable case” designation.

Question 4b How does patient JAM fit into the WHO influenza A(H5N1) case definition? Under investigation Suspected Probable Confirmed Answer: The above information is supportive of a designation of a. person under investigation Clinical: Fever, cough, and shortness of breath Epidemiological: Close contact (within 1 meter) with a person who is a suspected, probable, or confirmed H5N1 case. Close contact with probable case occurred 2 days after “onset of symptoms”. Laboratory: No lab specimens collected at time of questioning. How does patient JAM, the 65-year-old grandmother, fit into the WHO influenza A(H5N1) case definition? 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. The above information is supportive of a designation of “person under investigation.” NOTE: It should be noted that the grandmother 1) did not attend the live market and 2) was in fact symptomatic with respiratory complaints on July 9, prior to when her grandchild had onset of illness for the first time. However, the grandmother remains a source of concern since she is a contact of a probable case, is symptomatic, and has not provided any information about possible independent exposures to influenza A(H5N1).

Question 5 Create a line list: What variables should be included? ID #
Age Gender 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) Now let’s make a line list. NOTE TO INSTRUCTOR : Have the class brainstorm as many useful variables that they think should be captured in this kind of respiratory outbreak investigation. Keep in mind that additional variables may be collected as part of a case investigation and only a critical subset of these may be included on a line list. The recommended variables will appear with a left-click. Suggested for Lectora: Drag-and-drop to prioritize the entire list given in the notes on the next slide. Make a blank line list with categories selected by the class on the white board. Remind the group that for purposes of this case study and time constraints there will be a finite small number of specific fields for which information on the line lists will be provided to them as the case investigation storyline unfolds. After they fill out the line list for the second time on July 16th am (below), subsequent line list updates will be provided to them

Suggested Line List Format
ID # Initials Loc Age Sex EPI relation Occ Syx Onset - July Poss. Exp. Lab Status Case vs. Contact Outcome Answer: A fairly complete list is given below, but it is recommended that only those in bold be included in the line list, since the number of variables that can reasonably be included is limited. WHO has posted a suggested template for an A (H5N1) human case line listing, and also a template for a broader case report form on its web site. Identification # (arbitrary) Demographics and contact information Gender Age Patient contact information Possible exposure to infected animals or animal products in 7 days before symptom onset Possible contacts with suspect or confirmed human H5N1 cases in 7 days before symptom onset Occupation Clinical data Symptoms on day of onset Date of initial symptom onset Days of illness before initial presentation Illness onset during antiviral prophylaxis Date of report Hospital test results white blood cell count and differential hemoglobin/platelets Aspartate amino transferase (AST) /Amino alanine transferase (ALT) and creatinine − chest radiograph results H5 Laboratory diagnoses Date of sampling Type of specimens collected Laboratory specimens sent to Test results Antiviral treatment and date initiated Status – case (based on case definition) vs. contact Final disposition

Question 6 Update the line list with the cases as of July 15th mid-day
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 Live Mkt: July 8th Grandmother: July9th 2 JAM 65 F Grandmother of #1 (AAJ) Retired 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 Now let’s put in the information we currently have. Instructor: Have the class work through the contents of the line list on the board. Have each student also create their own line list using pen and paper, for their own reference. When complete, the answers can be shown by clicking on this slide. F: Fever; C: Cough; D: Diarrhea; S: Shortness of breath; M: Myalgias; URI – upper respiratory syx DG: Dava Ghar PJ: Pelu Jaghai

Question 7a When should you begin assessing contacts of this probable case? As soon as you become aware of the case Once you have determined the case status as being “suspect” or highter Once you have determined the case status as being “probable” or higher Once you have a confirmed diagnosis Answer: a. When should you begin assessing contacts of this probable case? As soon as you become aware of the case Once you have determined the case status as being “suspect” or highter Once you have determined the case status as being “probable” or higher Once you have a confirmed diagnosis Answer: a. You should begin to assess contacts as soon as possible after the case patient presents for treatment.

Question 7b Note whether the following statements used to define who is a close contact of this probable case are true or false. Answers: False True 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 Note whether the following statements used to define who is a close contact of this probable case are true or false. Instructor: Have the students go through all 6 statements before clicking to reveal all 6 answers. Because some of the statements are similar, they may want to revise a previous answer as they go through the list. Discussion points: Close contacts are defined in the WHO guidelines for investigation of human cases of avian influenza A(H5N1)--January 2007 as people who came within 1 meter of shared space with a confirmed or suspect case patient beginning 1 day before onset of symptoms through 14 days after onset of symptoms. You may choose to reference or hand out the WHO guidelines for investigation of human cases of avian influenza A(H5N1)--January Lectora: Link to the above document as a resource for answering the question? The amount of time the potential contact was close to the patient is important to consider. Walking by the patient, without any direct conversation or contact may not be sufficient to classify someone as a contact. Persons the case has kissed, embraced or shared utensils with should definitely be considered contacts. Other examples of close contact (within 1 meter) with a person include providing care, speaking with, or touching. These contacts should be assessed for fever, and the presence of other symptoms compatible with influenza A (H5N1) in humans.

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 Household members, friends, health care providers, pharmacists, traditional healers, workplace contacts and others are all examples of potential contacts. Prioritization of contact tracing activities may be necessary if a large number of contacts are eligible for tracing or personnel resources are limited. In such situations it may be necessary to focus on those contacts with the highest risk of infection or exposure. Factors that can be used to prioritize among contacts include 1) the probability of A(H5N1) infection in the case patient (e.g. contacts of confirmed or probable cases) and 2) the duration, spatial proximity, and intensity of exposure to the case patient (e.g. unprotected health-care workers, household contacts sharing the same sleeping or eating space, persons providing bedside care).

Question 8a Assuming that neuraminidase inhibitors are available:
Should AAJ be given anti-viral treatment? Should JAM be given anti-viral treatment? Answer: Yes No Hint: If antiviral drugs are available, treatment doses should be provided to suspected, probable and confirmed cases as classified according to the WHO case definition. Assuming that neuraminidase inhibitors are available, should AAJ and JAM be given anti-viral treatment? Instructor: Click to reveal this 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. Answer: By this classification 1. Yes, AAJ would meet the criteria to receive treatment with neuraminidase inhibitors. 2. No, JAM would not meet the criteria for treatment with neuraminidase inhibitors. Given her underlying condition and age, many clinicians would likely choose to empirically treat her as a case anyway.

Question 8b Should JAM receive anti-viral prophylaxis?
Should asympomatic close contacts of AAJ be given anti-viral prophylaxis? Should close contacts of JAM receive antiviral prophylaxis? Answer: Yes 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. Should JAM receive anti-viral prophylaxis? Should asymptomatic close contacts of AAJ be given anti-viral prophylaxis? Should close contacts of JAM receive antiviral prophylaxis? Instructor: After allowing the class to consider the answers to these 3 questions, click to reveal this hint. The WHO Rapid Advice Guidelines on pharmacological management of humans infected with avian influenza A (H5N1) virus also suggest 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. Answer: Yes, JAM is symptomatic, and should receive anti-viral prophylaxis (as discussed previously, some physicians may choose to give her treatment instead of prophylaxis, which is acceptable given her condition when antivirals are available and at this early stage of the cluster). Yes, asymptomatic contacts of AAJ would meet the criteria to receive prophylaxis with neuraminidase inhibitors. No, asymptomatic contacts of JAM would not meet the criteria to receive prophylaxis with neuraminidase inhibitors. Remember that the overall incubation period for influenza A(H5N1) is variable. You should also recognize that for current influenza A(H5N1) viruses, close and not casual contact is associated with person-to-person transmission. Individuals who are designated as contacts may in fact develop signs and symptoms of disease, leading to a change in their status to either suspected, probable or confirmed cases.

Question 9 If there are not enough antiviral resources for everyone, persons in the community should be prioritized for antiviral prophylaxis. Match the Risk Group on the left with the description on the right. High Risk Moderate Risk Low Risk Personnel culling likely non-infected animals Personnel handling sick animals or decontaminating environments using insufficient PPE Personnel handling sick animals or decontaminating environments using adequate PPE Unprotected close/direct exposure to H5N1 infected animals Healthcare or laboratory personnel in close contact with strongly suspected or confirmed patients or their samples with insufficient PPE Healthcare workers not in close contact Healthcare workers with close contact using adequate PPE Close household contact of strongly suspected or confirmed patients 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. Discussion points when considering these categories: The WHO Advice Guidelines on pharmacological management of humans infected with avian influenza A (H5N1) virus also classifies exposures into risk categories to assist with prioritization of chemo-prophylaxis. Prophylaxis should be given to each contact for 7 days (up to 10 days) after contact with case-patient. If neuraminidase inhibitors are available then high risk groups should be provided anti-viral prophylaxis, and moderate risk groups should be considered for prophylaxis depending on drug availability and strength of epidemiologic and clinical evidence. Answers: The risk categories are currently defined as follows. These answers are presented on the next slide. 1. High risk exposure groups are currently defined as: h. Household or close family contacts of a strongly suspected or confirmed H5N1 patient, because of potential exposure to a common environmental or poultry source as well as exposure to the index case. 2. Moderate risk exposure groups are currently defined as: b. Personnel involved in handling sick animals or decontaminating affected environments (including animal disposal) if personal protective equipment may not have been used properly. d. Individuals with unprotected and very close direct exposure to sick or dead animals infected with the H5N1 virus or to particular birds that have been directly implicated in human cases. e. Health care personnel in close contact with strongly suspected or confirmed H5N1 patients, for example during intubation or performing tracheal suctioning, or delivering nebulised drugs, or handling inadequately screened/sealed body fluids without any or with insufficient personal protective equipment. This group also includes laboratory personnel who might have an unprotected exposure to virus-containing samples. 3. Low risk exposure groups are currently defined as: f. Health care workers not in close contact (distance greater than 1 meter) with a strongly suspected or confirmed H5N1 patient and having no direct contact with infectious material from that patient. g. Health care workers who used appropriate personal protective equipment during exposure to H5N1 patients. a. Personnel involved in culling non-infected or likely non-infected animal populations as a control measure. c. Personnel involved in handling sick animals or decontaminating affected environments (including animal disposal), who used proper personal protective equipment

Question 9 Answers High 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 1. High risk exposure groups are currently defined as: h. Household or close family contacts of a strongly suspected or confirmed H5N1 patient, because of potential exposure to a common environmental or poultry source as well as exposure to the index case. 2. Moderate risk exposure groups are currently defined as: b. Personnel involved in handling sick animals or decontaminating affected environments (including animal disposal) if personal protective equipment may not have been used properly. d. Individuals with unprotected and very close direct exposure to sick or dead animals infected with the H5N1 virus or to particular birds that have been directly implicated in human cases. e. Health care personnel in close contact with strongly suspected or confirmed H5N1 patients, for example during intubation or performing tracheal suctioning, or delivering nebulised drugs, or handling inadequately screened/sealed body fluids without any or with insufficient personal protective equipment. This group also includes laboratory personnel who might have an unprotected exposure to virus-containing samples.

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 3. Low risk exposure groups are currently defined as: f. Health care workers not in close contact (distance greater than 1 meter) with a strongly suspected or confirmed H5N1 patient and having no direct contact with infectious material from that patient. g. Health care workers who used appropriate personal protective equipment during exposure to H5N1 patients. a. Personnel involved in culling non-infected or likely non-infected animal populations as a control measure. c. Personnel involved in handling sick animals or decontaminating affected environments (including animal disposal), who used proper personal protective equipment It should be tactfully explained to non-priority contacts that there is a scarcity of antiviral drugs and that they will be monitored carefully for the development of symptoms. To the extent possible plans regarding the distribution of scarce resources, such as access to prophylaxis treatment, should be specified in advance and government officials should engage stakeholders in determining what criteria should be used to make resource allocation decisions. Allocation plans should specify what goods are involved, who will make decisions about prioritization and distribution, who will be eligible to receive the scare resources, and what relevant criteria will be used to prioritize who will and will not receive resources. To the extent possible, there should be a commitment to transparency throughout the process and the reasoning behind choices should be fully articulated (in language appropriate for the intended audience).

Update: July 16th The RRT arrives at Dava Ghar
AAJ Update JAM Update Admission Fever 39 °C Heart rate 120 34 breaths/minute Blood pressure 90/60 O2 saturation 88% Outcome Intubated Jul 14 Hypotensive with renal failure Died on the 16th Respiratory and sputum samples of poor quality Admission Temperature 38.5 °C 28 breaths/minute Blood pressure 160/95 O2 saturation 90% Initial laboratory findings High lymphocyte count High leukocyte count Reminder: make sure the participants are taking notes. JULY 16: The hospital is a 5 hour car ride away and your rapid response team doesn’t arrive at the Dava Ghar hospital until the next day (July 16). You go directly to the hospital to begin investigation. You are told the following: The boy’s (AAJ) admission vital signs had been: a temperature of 39○C, heart rate of 120, and tachypnea at 34 breaths/minute with a blood pressure (BP) of 90/60. His oxygen saturation was 88%; he was subsequently intubated on July 14th and placed on mechanical ventilation. He became hypotensive and went into renal failure. Despite aggressive measures, he died on the 16th morning, prior to your arrival. You were told that respiratory sputum samples had been collected but subsequently discarded by the lab because they were considered of poor quality. Cultural practices and the family’s wishes precluded any further post-mortem evaluation. The grandmother was verified to be a caretaker of the child (AAJ) and presented to the hospital in moderate respiratory distress. CLICK to reveal JAM information: Her vital signs were as follows: temperature of 38.5○C, a respiratory rate of 28 breaths/minute; BP of 160/95 and an oxygen saturation of 90%. The grandmother’s initial laboratory findings included high lymphocyte / leukocyte counts.

Specimens Needed JULY 16 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. You and your team recognize that you will need to quickly determine whether you’re dealing with H5N1 or some other communicable pathogen. You are justifiably concerned that this may in fact represent an outbreak related to H5N1. You decide to send biological samples from the grandmother to the National laboratory for testing.

Question 10a What specimens need to be collected from the grandmother?
Endotracheal fluid Broncho-alveolar lavage Throat swab (oropharyngeal) Nasal swab (nasopharyngeal) Blood Acceptable answers: c. Throat swab, and/or e. Blood specimens Remember! It is vital to use proper safety equipment including goggles and PPE for the protection of the individual(s) carrying out the procedure(s). Treat all clinical samples as though they are potentially infected with avian influenza!!! What specimens need to be collected from the grandmother? Lower respiratory tract Endotracheal fluid Throat swab Nasal swab Answer: C. The throat swab If the patient is ambulatory (like the grandmother in this case), throat swabs are the priority specimen type to be collected. E. Blood specimens may be used to test for other infections or concurrent illnesses. If blood specimens are taken, then convalescent serum specimens need to be collected 14 or more days after first specimen is taken. Explanation/discussion points: Answer choice A: The specimens most likely to allow rapid confirmation of the presence of influenza A(H5N1) include lower respiratory tract specimens. This is because the influenza A (H5N1) virus preferentially binds to receptors in the lower respiratory tract of humans. If a patient has been intubated, then endotracheal fluid taken from the ET tube would provide an ideal specimen. However JAM is not intubated. Answer choice B. Similarly if the patient has undergone a broncho-alveolar lavage (BAL) procedure or has had a chest tube inserted for other reasons (these procedures should never be recommended for H5N1 diagnostic purposes alone), good quality specimens might also be obtained for influenza A (H5N1) testing. Answer choice D. Nasal swabs may also be diagnostically useful for human influenza virus subtypes that tend to bind to receptors in the upper respiratory tract (e.g., influenza A (H3N2), A(H1N1), and other non-A(H5N1) human influenza viruses). However nasopharyngeal specimens are technically often difficult to obtain and training is required to carry out the collection with appropriate technique. Remember that regardless of specimen type and collection method, it is important 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.The World Health Organization has posted more description of the Recommended laboratory tests to identify influenza A/H5 virus in specimens from patients with an influenza-like illness at .

Question 10b Which of the following statements about specimen collection is NOT true? It should begin as soon as possible after symptoms begin It should begin before antiviral medications are administered Sample should be collected even if symptoms began more than one week ago Multiple samples should be collected on multiple days if possible None of the above (all statements are true) Answer: e. Remember – it is better to collect too many specimens than not enough It is better to collect too many specimens than not enough. Influenza virus is most likely to be detected soon after symptoms begin. Ideally specimens are collected: •As soon as possible after symptoms begin – Although it may not always be logistically possible to collect respiratory specimens early in the clinical course of disease • Before antiviral medications are administered (but do not delay treatment to get laboratory specimens) • Even if symptoms began more than one week ago – It is still possible to detect virus in these specimens • On multiple days when you have access to patient – It is best to collect multiple types of specimens on multiple days to increase chances of virus detection/isolation

Specimen Collection Kit
JULY 15 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 Your team will collect the oropharyngeal swab from the grandmother (JAM). Because you are prepared, you have your supplies with you. Your specimen collection kit includes: Fiber-tipped applicators are used in collecting specimens from the oropharynx (throat), or the nasopharynx (nose). Although it may not always be possible, try not to use swabs made of cotton, that are treated with calcium alginate, or that have wooden handles or sticks since they inhibit PCR, a principle laboratory test used for influenza A (H5N1) confirmation. Individually wrapped applicators are preferable to ensure they are sterile. However if cotton-tipped swabs are the only type available, they should be used.

Question 11 Put the following steps for collecting an oropharyngeal specimens in the proper order Answers 1. 4. 3. 2. 5. Have the patient open his/her mouth wide open Slowly remove the swab while slightly rotating The patient should try to resist gagging and closing the mouth The swab touches the back of the throat near the tonsils Put tip of swab into vial containing VTM, breaking/cutting applicator’s stick Instructor: Ask the class if there is a clinician in the class willing to demonstrate the collection of an oropharyngeal specimen. If there is a volunteer, have a demonstration (or description if there is no one willing to offer a sample). If there is no response, continue with the question. Put the following steps for collecting an oropharyngeal specimens in the proper order 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 Answer: To collect the oropharyngeal specimen: 1. Have the patient open his/her mouth wide open. 2. While the swab touches the back of the throat near the tonsils… 3. the patient should try to resist gagging and closing the mouth. 4. Slowly remove the swab while slightly rotating it 5. Put tip of swab into vial containing VTM, breaking/cutting applicator’s stick

Question 12a Here is an image of a properly packed specimen. Label the packaging using the answer choices given. 1) 3 layers of _________ 2) Absorbent _________ 3) Labeling of the _________ as UN3373 diagnostic specimens Answer choices: contents packing material identification outer package packaging biohazard Here is an image of a properly packed specimen. Label the packaging using the answer choices given. Three layers of ________ Absorbent _________ Labeling of the __________ as UN 3373 diagnostic specimens Itemized list of ________ Specimen __________ ______label Answer choices: contents packing material identification outer package packaging biohazard 4) Itemized list of ______ 5) Specimen______ 6) _______ label

Question 12a Here is an image of a properly packed specimen. Label the packaging using the answer choices given. 1) 3 layers of e. packaging. 2) Absorbent b. packing material 3) Labeling of the d. outer package as UN3373 diagnostic specimens Here is an image of a properly packed specimen. Three layers of e. packaging Absorbent b. packing material Labeling of the d. outer package as UN 3373 diagnostic specimens Itemized list of a. contents Specimen c. ID f. Biohazard label Labeling of the d. outer package as UN 3373 diagnostic specimens If this material is not available to you, transport specimens with all appropriate labels and packaging in a cool box with ice. 4) Itemized list of a. contents 5) Specimen c. identification 6) f. Biohazard label

Question 12b Determine whether the following statements about storing specimens in VTM are true or false. Store specimens can be stored at 4 °C within 48 hours of collection both before and during transportation. Store specimens at -70 °C beyond 48 hours (if you will not be able to immediately transport specimen to laboratory) Never store specimens on dry ice Specimens may be stored in standard freezer Answers: True False Determine whether the following statements about storing specimens in VTM are true or false. Instructor: Walk students through all 4 statements, keeping track of their final response, and then click to show the answers. 1. This statement is true. Store specimens collected within 48 hours at 4 °C both before and during transportation. A cooler filled with ice packs can be used for this purpose. 2. This statement is true. Store specimens at -70 °C beyond 48 hours (if you will not be able to immediately transport specimen to laboratory). 3. This statement is false. Do not use dry ice unless the specimens are double-bagged and airtight; carbon dioxide from the dry ice can inactivate the virus. 4. This statement is false. Do not store in standard freezer – keep them on ice or in a refrigerator (standard freezers will damage specimen) A key point here is to 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. 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 12c When transporting specimens from potential cases of avian influenza from the field to the laboratory, you should follow which regulations? WHO guidelines for safe transport of infectious substances and diagnostic specimens Local regulations on the transportation of infectious material Neither a nor b Both a and b Answer: d. When transporting specimens from potential cases of avian influenza from the field to the laboratory, you should follow which regulations? WHO guidelines for safe transport of infectious substances and diagnostic specimens Local regulations on the transportation of infectious material Neither a nor b Both a and b Answer: d. When you send any specimens from potential cases of avian influenza from the field to a laboratory, we recommend that you follow WHO guidelines (outlined at the link below) for the safe transport of infectious substances and diagnostic specimens. In addition, you may need to follow local regulations on the transportation of infectious material.

Transportation Considerations
JULY 16 Documents to include Itemized list of specimens with identification numbers Instructions for the laboratory Information to maintain Identification numbers, linking to epidemiologic data forms Case demographics When and where a specimen was collected Type of specimen Coordinate shipment with the laboratory so they are prepared when the specimens arrive Remember: In all specimen shipments, include an itemized list of specimens, with specimen identification numbers that are linked to epidemiologic information and instructions for the laboratory. You will need to use a specimen tracking system to keep track of the specimens at all times. It is advisable to maintain a database that contains information about each specimen, including: Identification or tracking number on the specimen field data collection form that links to the tracking number on epidemiologic data collection forms Case demographics When and where a specimen was collected Type of specimen Be sure to coordinate the shipment with the laboratory. Arrangements should be made so that the laboratory is prepared to receive the specimens when they arrive. KEY POINTS: Whenever possible the field team should oversee the actual steps involved in packaging, transport and shipping, including labeling specimens, packing, courier handoff, etc.

Contact Identification
JULY 16 You have finished collecting patient specimens and have sent them off to the national laboratory You want to identify all potentially exposed individuals who have had contact with the probable case (AAJ) In a team meeting you determine that the contacts are Mother (NJC) Uncle (JRO), Grandparents (JAM & AWM) You have finished collecting patient specimens and have sent them off to the national laboratory. As part of contact tracing, you want to identify all of the potentially exposed individuals who have had contact with the probable case (AAJ). In a team meeting, you review available information and determine that the mother (NJC), uncle (JRO), who went with the child to the live bird market, and grandparents (JAM and AWM) qualify as contacts using the previously established criteria.

Question 13 Below is shown the line list from mid-day, July 15th. Update the line listing with all known contacts as of July 16th a.m. 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 Live Mkt: July 8th Grandmother: July9th No lab specimen Probable Case Hospitalized on ventilator, pneumonia,respiratory failure 2 JAM 65 F Grandmother of #1 (AAJ) Retired 9 Caretaker of #1 Timing - ? Pending Person under invest. Hospitalized On this slide is shown the line list from mid-day, July 15th. Update the line listing with all known contacts as of July 16th a.m. Instructor: Encourage the students to update the information in their own notes individually, as well as updating the class line list on the white board as a group.

Question 13 Answer Line list as of July 16th a.m.
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 Live-Mkt: July 8 No lab specimen Probable CASE Died (7/16) 2 JAM 65 F Grandmother (# 1) Retired F, C, S 9 Caretaker of # 1 Pending PUI/ Contact Hospitalized 3 AWM 70 Grandfather (# 1) Contact 4 NJC 36 Mother (# 1) Home-maker Caretaker of # 1; Live-Mkt: July 8 5 JRO 27 Uncle (# 1) Farmer The updated information on Case #1 is highlighted in red, as are the ID numbers of the 3 new contacts being investigated. As of July 16 a.m., this line list emphasizes that now there are at least 4 known contacts (AWM – the grandfather, JAM – the grandmother (and also a person under investigation), NJC – the mother and JRO – the uncle of the 10 year old index case (AAJ) at Dava Ghar. 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
Also think beyond the nuclear family Village health workers Traditional healers Taxi drivers Other people a case may have had close contact with while infectious While other contacts are not mentioned to keep the case study simple, it is important to think beyond the nuclear family. This could include village health workers, traditional healers, taxi drivers and other people a case may have had close contact with while infectious. Note to instructor: Future line list updates may be provided to the group without manual completion of each cell. This will facilitate the timely completion of the exercise.

Question 14a You want to know whether there are more contacts you should be concerned about. Which of the following places would NOT be one that you would visit at this point to determine if there are more cases and/or contacts? Health care facilities (hospitals, clinics, traditional healers) Patient (or family proxy) Patient’s village/neighborhood Patient’s school/workplace Answer: d. At this point in time, the appropriate information on close contacts can be gathered from the patient/proxy 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? Note: The specific questions to be asked about exposure will be addressed in the next question so keep this discussion focused on the general activities to be undertaken at each location. Health care facilities (hospitals, clinics, traditional healers) Patient (or family proxy) Patient’s village/neighborhood Patient’s school/workplace Answer: d. At this point in time, the appropriate information on close contacts can be gathered from the patient/proxy. Locations such as school or workplace can be followed up if the interview reveals that the patient may have had close contacts at these locations. Discussion points: You should identify all contacts the boy may have had going back to one day before symptom onset. The list therefore in this situation might include schoolmates, playmates, health care personnel (including traditional healers), and persons involved in transportation of the child. There are (at least) three key ways of obtaining information that may prove useful: Hospital/Other Health Care Facilities Talk to patient Go to home of case patients (village) to continue investigation

Question 14b In conducting contact tracing interviews, in which of these places would you need to wear personal protective equipment (PPE)? Health care facilities (hospitals, clinics, traditional healers) Patient (or family proxy) Patient’s village/neighborhood Answer: b. In conducting contact tracing interviews, in which of these places would you need to wear personal protective equipment (PPE)? Health care facilities (hospitals, clinics, traditional healers) Patient (or family proxy) Patient’s village/neighborhood Answer: b. The interviewer should wear full PPE (mask, gloves, gown, eye shield) if interviewing suspected cases. PPE does not need to be worn at the patient’s village or neighborhood unless in an environment known to be infected. It could create panic.

Question 14c Match the information source on the left with the contract tracing activities that should be conducted there on the right. Hospital or other medical facility Patient (or proxy) Patients home and village Administer case finding questionnaire to determine if the interviewee knows of anyone else who is sick, to ask about possible exposures, and to ask about possible contacts Retrace the steps of the patient and try to determine if there were any close contacts without adequate PPE. Find out more details about suspected exposures, conduct an environmental survey, and determine if there are any outbreaks among animals. Match the information source on the left with the contract tracing activities that should be conducted there on the right. Answer: 1. Hospital: b. Retrace the steps of the patient and try to determine if there were any close contacts without adequate PPE. 2. Patient/proxy: 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 3. Home/village/neighborhood: c. Find out more details about suspected exposures, conduct an environmental survey, and determine if there are any outbreaks among animals. Answer: 1. b a 3. c

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 cases Awareness of clusters of severe respiratory illness in family, friends and co-workers Awareness of H5N1 outbreaks occurring outside the country Exposure to animals and their environment Exposure to contaminated environments Exposure to cooked chicken products Inquire about illness or deaths in birds, cats, swine, or other animals in the household and neighboring area In countries or territories where influenza A(H5N1) viruses have been identified as a cause of illness in animals or people, the diagnosis of influenza A(H5N1) infection should be included in the differential diagnosis of all persons who have severe, unexplained acute febrile respiratory illness. In addition to symptoms, we want to consider the epidemiologic context of a patient that has acute respiratory disease. People who have touched ill poultry or have touched poultry that died of illness are at the greatest potential risk of infection. Situations with potential for H5N1 exposure include which of the following? Contact with confirmed or suspect human H5 cases Awareness of clusters of severe respiratory illness in family, friends and co-workers Awareness of H5N1 outbreaks occurring outside the country Exposure to animals and their environment Exposure to contaminated environments Exposure to cooked chicken products Inquire about illness or deaths in birds, cats, swine, or other animals in the household and neighboring area Answer: Instructor: Click for answers to appear (check-mark for correct, “x” for incorrect). All but Awareness of H5N1 outside the country and exposure to cooked chicken are exposure categories that will need to be explored with a case patient or his family. Further explanation and discussion points for correct answers are listed below. Contact with confirmed or suspect human H5 cases in the 7 days before symptom onset (including relationship with contact (first/last date of contact), type of contact (speaking distance, slept in same room, touched, provided bedside care, other). Awareness of clusters of severe respiratory illness in family, friends and co-workers. Exposure history to animals (chickens and other animals) and their environment in the 7 days before symptom onset (including setting, type of animal exposure, occupational exposure to animal and/or animal products, consumption of raw or undercooked animal products or traditional food preparations, or contact with an H5N1 outbreak in animals in the area Exposure to contaminated environments (e.g. exposure to poultry droppings including fertilizers or contaminated sewage, bathing in ponds/canals where domestic or wild birds can be found, etc.), and other animals regardless of their clinical status, especially those that may have consumed dead poultry (e.g. cats, dogs, and civets). Inquire about illness or deaths in birds, cats, swine, or other animals in the household and neighboring area.

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 house Number of people living in the home Construction material of the home Mapped location or photograph of house and surroundings Culture-specific risk factors Annual community festival days Live bird markets or other occupationally related exposures When interviewing at a patient’s home or in their village, which of the following are important contextual factors to observe and analyze? Number of people living in the home Construction material of the home Mapped location or photograph of house and surroundings Culture-specific risk factors Annual community festival days Live bird markets or other occupationally related exposures Instructor: Click for answers to appear (check-mark for correct, “x” for incorrect). Further explanation and discussion points for correct answers are listed below. Examine the house and its surroundings for evidence of domestic poultry (e.g. feathers, scratch marks on the floor or furniture, bird droppings, cages, poultry bones/carcasses). Note if poultry and other animals were allowed to enter the house, had access to household water and food storage areas, and if persons, especially children, were exposed to poultry or interior or exterior environmental surfaces potentially contaminated by poultry. Map or photograph the house and its surroundings. Indicate its location with respect to homes of other relatives or neighbors, farms (backyard and commercial), markets and nearby bodies of water that birds could inhabit. Every culture produces unique exposures and risk factors. These need to be understood and included in your investigation tools. For example culture and country-specific risk factors identified to date include: Consumption of duck blood pudding Cock fighting, mouth-to-beak exposure, and associated activities Swan defeathering Playing with dead chickens and chicken body parts Consumption of raw or undercooked poultry products Live bird market and other occupational exposures KEY POINTS: Unlike seasonal influenza or many other ‘routine’ respiratory pathogens, A(H5N1) infections have specific exposures (albeit often multiple and not clearly discernable) that need to be identified if at all possible. It is important to think of the local context when soliciting particular exposures. Review critical data collection elements and collect this information from all possible sources of information in these contexts.

Case Finding Results JULY 16 Child with unexplained respiratory illness reported in nearby province, Pelu Jaghai Director of Epidemiology recommends that your team meet the Ministry of Health field workers there and make site visits to hospitals and villages As a result of additional case finding activities undertaken by your team, a village health committee leader in nearby Pelu Jaghai has reported that there is also a child with unexplained respiratory illness there. The Director of Epidemiology recommends that you and part of your team go out to meet the MOH field workers in Pelu Jaghai and make site visits to the local hospital and villages. The Director of Epidemiology states that he will stay and manage the situation in Dava Ghar.

New Case and Contact 11-year-old boy, TMU
JULY 16 11-year-old boy, TMU Fever, cough shortness of breath starting July 12 Admitted July 15 Critically ill, not intubated You and your team don PPE, evaluate the patient, review medical chart, and interview available family members Mother (ACM) Reports boy visited Murg market on July 8 You visit the Pelu Jaghai hospital that day (July 16th). You are told by the staff doctor that yesterday they admitted a child of 11 years of age (TMU) for a severe respiratory illness characterized by fever, cough and shortness of breath that began on July 12. He is critically ill but not intubated and is available for clinical evaluation. He has been kept in relative isolation in a cleared-out hospital ward. You and your team members don your PPE, evaluate the patient, review the medical charts and interview some available family members. The mother (ACM) of this boy (TMU) isn’t a very good informant and cannot provide details about her son’s recent history except that the boy was well up until July 12th when he developed illness. She recalls that the boy also visited the Murg market on July 8th as this was within walking distance of their house. No one else from her family visited the Murg market.

Question 16 Update the line list with the current information as of the afternoon of July 16. Update the line list with the current information as of the afternoon of July 16. Instructor: Again encourage the class to participate in updating the class line list, but also encourage them to update their own notes.

Question 16 Answer Line list as of July 16th p.m.
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 Live-Mkt: July 8 No lab specimen Probable CASE Died (7/16) 2 JAM 65 F Grandmother (# 1) Retired F, C, S 9 Caretaker of # 1 Pending PUI/ Contact Hospitalized 3 AWM 70 Grandfather (# 1) Contact 4 NJC 36 Mother (# 1) Home-maker Caretaker of # 1; Live-Mkt: July 8 5 JRO 27 Uncle (# 1) Farmer 6 TMU PJ 11 Playmate (# 1) F, C, D, M 12 Suspect 7 AMC 29 Mother of # 6 Mother Caretaker of # 6 New case ID numbers for this update are highlighted in red. As of July 16 p.m. this line list shows there are two important individuals to follow in Pelu Jaghai – the 11 year old boy (TMU) who visited the Pelu Jaghai live-market on July 8th (SUSPECT CASE) and his mother (ACM - a CONTACT) who was a caregiver while he had his initial symptoms of respiratory illness. F: Fever; C: Cough; D: Diarrhea; S: Shortness of breath; M: Myalgias; URI – upper respiratory syx DG: Dava Ghar PJ: Pelu Jaghai

Differential Diagnoses
Human influenza Influenza A(H5N1) Upper respiratory infection Fever, headache, cough, sore throat Muscle ache, exhaustion Other respiratory symptoms Recovery: 2-7 days Can progress to pneumonia and respiratory failure in some cases Lower respiratory infection Fever, headache, cough, sore throat Muscle ache, exhaustion Difficulty breathing, respiratory distress Crackling on inhalation Increased respiratory rate Sputum production, possibly with blood Limited data: diarrhea Many illnesses can present with influenza-like symptoms. One might consider which clinical features distinguish Influenza A(H5N1) from seasonal influenza. Keep in mind that the underlying epidemiologic clues and laboratory testing must be sought, as seasonal influenza and influenza A (H5N1) in humans cannot be differentiated purely on clinical grounds. However, a description of the signs and symptoms commonly found in Human (seasonal) Influenza and Influenza A (H5N1) in humans can be useful. Human influenza: usually leads to an upper respiratory infection. Signs and symptoms include fever, headache, cough, sore throat, muscle ache, and exhaustion. Other respiratory symptoms may appear, varying from sore throat to difficulty breathing. People generally recover anywhere from 2 to 7 days after symptoms appear. However, cough and muscle ache may last more than 14 days. Although influenza generally causes an upper respiratory infection, it can progress to pneumonia and respiratory failure in some cases. Influenza A (H5N1) in humans: is different than seasonal human influenza infections. Avian influenza more often leads to a lower respiratory infection with variable upper respiratory involvement. Initial symptoms are similar to human influenza. These include fever, headache, cough, sore throat, muscle ache, and exhaustion. Symptoms of a lower respiratory infection appear early in course of the illness. Patients often begin to have difficulty breathing leading to progressive respiratory distress. A crackling sound may be heard during inhalation, and an increased respiratory rate may also be observed. By this time, sputum production may occur and may contain blood. Limited data also suggest that persons infected with Influenza A (H5N1) may be more likely to have diarrhea. They may also be more likely to demonstrate lymphopenia, thrombocytopenia, and increased liver function tests.

Non-Influenza Differential Diagnoses
Viral Bacterial Human influenza viruses Parainfluenza viruses Respiratory syncytial virus Adenovirus Rhinovirus Flaviviruses (e.g. Dengue) Coronaviruses (including SARS-CoV) Human metapneumovirus Hantavirus New / emerging viruses, such as bocavirus Mycobacteria tuberculosis Yersinia pestis (pneumonic plague) Streptococcus pneumoniae Staphylococcus aureus Hemophilus influenzae Burkholderia pseudomallei Legionella spp. Chlamydia pneumoniae Mycoplasma pneumoniae Coxiella burnetii (Q fever) Other differential diagnoses may present in a clinically similar fashion to influenza are viral and bacterial illnesses, including those listed here.

Do you think TMU has Influenza A(H5N1) infection?
Question 17 Do you think TMU has Influenza A(H5N1) infection? Do you think TMU has Influenza A(H5N1) infection? Instructor: Allow the class to discuss in the context of the differential diagnoses just presented. Any conclusion is acceptable at this point, since this is an opinion question.

Move on to Outbreak Investigation, Part 2

Influenza A(H5N1) in Humans: Outbreak Investigation in an International Setting Case Study 2 Welcome to the Outbreak Investigation portion of the Avian.

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Influenza A(H5N1) in Humans: Outbreak Investigation in an International Setting Case Study 2 Welcome to the Outbreak Investigation portion of the Avian.

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Presentation on theme: "Influenza A(H5N1) in Humans: Outbreak Investigation in an International Setting Case Study 2 Welcome to the Outbreak Investigation portion of the Avian."— Presentation transcript:

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