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Influenza A(H5N1) in Humans: Outbreak Investigation in an International Setting Case Study 2: Part 1 1 Learning Objectives • Describe key outbreak management issues that need to be addressed related to supplies, team composition, WHO policy and epidemiologic data management during an internationally located A(H5N1) outbreak investigation. • Identify critical coordination priorities involving the interface between animal and human health sectors, key stakeholders such as WHO, CDC and Ministries of Health and communication processes between CDC field staff, CDC Headquarters and relevant subject matter experts. 2 Learning Objectives (cont.) • List appropriate practices and procedures for: Specimen collection and transport Epidemiologic investigation Identification of transmission mechanisms Contact tracing Isolation/quarantine policy Treatment/control policy Risk communication priorities Recommended laboratory specimen protocols methods Ethical considerations 3 Outline • Review of the preparation for an outbreak investigation • Description of the situation and available details on the • case, surrounding events/history and environment Engage in outbreak investigation activities: Case definition Clinical / laboratory findings, samples, recommendations Line listing Contract Tracing Treatment options/ recommendations Principles are applicable to outbreaks from other known or newly emerging pathogens 4 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 6 Epidemiologic Setting • • • Mass deaths in chicken, geese, and waterfowl flocks Five months ago (March) Southeastern region Ministry of Agriculture (MOA) reported 3 test results “weakly positive” for avian influenza A(H5N1) Came from three dead chickens sent to national lab in Anawrahta (April) No systemic surveillance exists for H5N1 in poultry, wild bird or animal populations 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 8 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 a. So they can raise concerns and be aware of possible cases b. To be ready for samples that will be coming c. So they can undertake enhanced surveillance for sick or dying poultry d. So they know you are coming to investigate, can have medical records ready to review, and have appropriate staff available e. So they can leverage resources such as medical supplies or additional staff 2. Healthcare personnel 3. The community 4. Non-governmental organizations 5. The laboratory 9 Question 2 Answers Answer: 1. Veterinary health = c. Evaluate diseased poultry 2. Healthcare personnel = d. Knowledge that you will investigate 3. Community = a. Can raise concerns 4. NGOs = e. Medical personnel/supplies and resources 5. Laboratory = b. Prepare for incoming samples 10 Question 3 Below are 6 categories of supplies needed when you go to the field. Match the list of supplies to the general category. Categories: Epidemiological, Medical, Laboratory, Educational & Communications, PPE, Decontamination a. b. c. d. e. f. g. h. i. j. Case definitions Antiviral medication Goggles Gloves Graph paper Solution for decontaminating homes or hospital room Transportation containers Pens Gown and cap Reporting forms k. Specimen collection materials l. Ice m. Guidelines for contacts, family members, and healthcare workers n. Notebook/laptop o. Portable GIS unit p. Viral transport media q. Simple messages r. Respirators 11 Question 3 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 12 JULY 15 • • Trigger Event July 15th Dava Ghar hospital has admitted 2 patients with SARI Reported to District Health Office They suspect avian influenza due to poultry outbreaks in area Patients are related 65 year old grandmother (JAM) 10 year old grandson (AAJ) 13 JULY 15 Character Details • 65 year old grandmother • Grandfather = AWM = JAM • Mother = NJC Chronically ill Caretaker of grandson starting July 11 • 10 year old grandson = AAJ Onset July 10 • Uncle = JRO Caretaker of son (AAJ) Setting: Small, mountain village in Pelu Jaghai province 14 JULY 15 Exposure & Onset Details July 8th • AAJ, NJC, & JRO attended live-market (“Murg Market”) • AAJ becomes ill on July 10th Murg Market in Pelu Jaghai: Local market with live animals and location of A(H5N1) confirmed poultry outbreaks • JAM cares for him starting July 11th • July 13th AAJ brought to hospital with: fever (38.7), cough, diarrhea and shortness of breath Dava Ghar hospital: 60 km away from village 15 JULY 15 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 10 year old child (AAJ) CXR on Admission Cefriaxone treatment started 16 JULY 15 Caretaker Health Status at Hospital • Mother (NJC) and grandfather (AWM) are • asymptomatic or deny symptoms Grandmother (JAM) reports respiratory condition suddenly worsened on about July 9th JAM symptoms: fever, cough and dyspnea = SARI JAM admitted to hospital on July 14th JAM denied contact with Murg Market or poultry 17 JULY 15 Rumor Surveillance Update from Local Health Authorities • May be additional sick persons with respiratory symptoms in Pelu Jaghai • May continue to be wide-spread chicken deaths 18 Question 4 How would you classify AAJ into the WHO influenza A(H5N1) case definition? Information on AAJ is given for your reference. Clinical: Fever, cough, diarrhea and a. b. c. d. Under investigation Suspected Probable Confirmed shortness of breath, Chest x-ray positive for pneumonia Epidemiological: Exposure to livemarket on July 8th where influenza A(H5N1) infections in animals were confirmed in the last month. Laboratory: No lab specimens available. Answer: The Chest X-ray and clinical deterioration extend the ‘suspected A(H5N1) status’ to C, a probable case designation. 19 Question 5 How does patient JAM fit into the WHO influenza A(H5N1) case definition? a. Under investigation b. Suspected c. Probable d. Confirmed 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. Answer: The above information is supportive of a designation of a. person under investigation 20 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) 21 Suggested Line List Format ID # Initials Village Age Sex Possible exposures and date EPI relation Syx Onset Lab date- July Status Case status Outcome 22 Update the Line List JULY 15 Update the line list with the cases as of July 15th mid-day ID # Initials Village Age Sex 1 AAJ DG 10 M Live Mkt: July 8th Grandmother: July9th Child (exposed at live market) F,C,S 10 2 JAM DG 65 F Caretaker of #1 Timing unknown Grandmother of #1 (AAJ) F,C,S 9 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 Possible exposures and date EPI relation F: Fever; C: Cough; D: Diarrhea; S: Shortness of breath; M: Myalgias; URI – upper respiratory syx DG: Dava Ghar PJ: Pelu Jaghai Syx Onset date- July 23 Question 6 Which of the following would be considered contacts of AAJ? a. JAM b. A teacher who last spoke to him 2 weeks ago c. A tuk-tuk driver who drove him to a friends home on the 6th d. A neighbor who walked by AAJ but didn’t say anything to him on the 10th Answer: a. 24 Question 7 Note whether the following statements used to define who is a close contact of this probable case are true or false. Answers: 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 False True True False True True 25 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 26 Question 8 Assuming that neuraminidase inhibitors are available: 1.Should AAJ be given anti-viral treatment? 2.Should JAM be given anti-viral treatment? Answer: 1.Yes 2.Maybe Hint: If antiviral drugs are available, treatment doses should be provided to suspected, probable and confirmed cases as classified according to the WHO case definition. 27 Question 9 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. 28 Question 10 If there are not enough antiviral resources for everyone, persons in the community should be prioritized for antiviral prophylaxis. Match the Risk Group on the left with the description on the right. 1. High Risk 2. Moderate Risk 3. Low Risk a. Personnel culling likely non-infected animals b. 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 animals e. 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 contact g. Healthcare workers with close contact using adequate PPE h. Close household contact of strongly suspected or 29 confirmed patients Question 10 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 30 Question 10 Answers: Low Risk Groups Low risk exposure groups f. Health care workers not in close contact g. Health care workers using adequate PPE a. Personnel involved in culling non-infected or likely noninfected 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 31 advance Update: July 16th JULY 16 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 32 JULY 16 • • Specimens Needed You will need to quickly determine whether you’re dealing with H5N1 or some other communicable pathogen You send respiratory specimens from the grandmother to the National laboratory for testing. 33 Question 11 What specimen type is the top priority to be collected from JAM for laboratory testing for influenza? a.Endotracheal fluid b.Broncho-alveolar lavage c.Throat swab (oropharyngeal) d.Nasal swab (nasopharyngeal) e. Blood Remember! It is vital to use proper safety equipment including eye protection and PPE for the protection of the individual(s) carrying out the procedure(s). Treat all clinical samples as though they are potentially infected with avian influenza!!! Answer : c. Throat swab Comment: Nasal swabs should be collected to rule out seasonal influenza. In general, collect multiple samples on multiple days. 34 Question 12 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 (but treatment should not be delayed for specimen collection) 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 35 JULY 15 Collection vials with VTM Polyester fibertipped applicators Sterile saline which is 0.85% NaCl A sputum or mucus trap Specimen Collection Kit 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 36 Question 13 Answers Put the following steps for collecting an oropharyngeal specimens in the proper order 3. • • 4. • 2. • 5. • 1. Done appropriate PPE Slowly remove the swab while slightly rotating ; the patient should try to resist gagging and closing the mouth Swab oropharyngeal area behind tonsils Have the patient open his/her mouth wide open Put tip of swab into vial containing VTM, breaking/cutting applicator’s stick 37 Question 14 Here is an image of a properly packed specimen. Label the packaging using the answer choices given. 1) 3 layers of _________ 2) Absorbent _________ 3) Labeling of the _________ as UN3373 diagnostic specimens 4) Itemized list of ______ 5) Specimen______ 6) _______ label Answer choices: a. contents b. packing material c. identification d. outer package e. packaging f. biohazard 38 Question 15 Here is an image of a properly packed specimen. Label the packaging using the answer choices given. 1) 3 layers of e. packaging. 2) Absorbent b. packing material 3) Labeling of the d. outer package as UN3373 diagnostic specimens 4) Itemized list of a. contents 5) Specimen c. identification 6) f. Biohazard label 39 Question 16 Determine whether the following statements about storing specimens in VTM are true or false. Answers: 1.Specimens can be stored at 4 °C within 48 hours of collection both before and during transportation. True 2.Store specimens at -70 °C beyond 48 hours (if you will not be able to immediately transport specimen to laboratory) True 3.Never store specimens on dry ice False 4.Specimens may be stored in standard freezer False 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. 40 Question 17 When transporting specimens from potential human cases of influenza A(H5N1) infection from the field to the laboratory, you should follow which sets of regulations? 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. 41 JULY 16 • Epidemiologic and Specimen Tracking for Transportation 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 42 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) • You determine that close contacts are Mother (NJC) Uncle (JRO), Grandparents (JAM & AWM) 43 Update the Line List Below is shown the line list from mid-day, July 15th. Update the line listing with all known contacts as of July 16th a.m. ID Initials Vill- Age Sex Possible EPI relation Syx Onset Lab # age date Status exposures and date Case status Outcome 1 AAJ DG 10 M Live Mkt: July 8th Grandmothe r: July9th Index case F,C, S Jul 10 No lab specimen Probable Case Hospitalized on ventilator, pneumonia, respiratory failure 2 JAM DG 65 F Caretaker of #1 Timing - ? Grandmother of #1 (AAJ) F,C, S Jul 9 Pending Person under invest. Hospitalized 44 Line List as of July 16th a.m. ID Initials Vill- Age Sex # age Possible exposures and date Syx EPI relation Onset date 1 AAJ DG 10 M Live-Mkt: July 8 ‘index’ case F, C, D, S 10 2 JAM DG 65 F Caretaker of # 1 Grandm other (# 1) Grandfa ther (# 1) Mother (# 1) F, C, S 9 3 AWM DG 70 M Caretaker of # 1 4 NJC DG 36 F 5 JRO DG 27 M Caretaker of # 1; Live-Mkt: July 8 Live-Mkt: July 8 Uncle (# 1) Lab Status Case status Outcome No lab specime n Pending Probable CASE Died (7/16) PUI/ Hospitalized Contact Contact Contact Contact F: Fever; C: Cough; D: Diarrhea; S: Shortness of breath; M: Myalgias; URI – upper respiratory syx DG: Dava Ghar 45 PJ: Pelu Jaghai Beyond the Given Scenario Also think beyond the nuclear family Village health workers Traditional healers Taxi drivers Other people that may have had close contact with the case during the infectious period 46 Question 18 You want to know whether there are more contacts that you should be concerned about. Which of the following places would NOT be one that you would visit at this point to determine if there are more cases and/or contacts? a.Health care facilities (hospitals, clinics, traditional healers) b.Patient (or family proxy) c.Patient’s village/neighborhood d.Patient’s school/workplace e.None of the above Answer: e. Depending on the places visited by a case, any of these places could be important places to undertake additional contact tracing activities 47 Question 19 Which of the following scenarios does NOT list the appropriate PPE measure? 1. You will interview a symptomatic person that could be infected with influenza A(H5N1): Interview from more than 1-2 meters away and wear no PPE 2. You will be within 1-2 meters of a symptomatic person that could be infected with influenza A(H5N1) Wear a fit tested respirator and eye protection 3. You physically examine a person that could be infected with influenza A(H5N1) You need to wear droplet and contact precautions 4. You are entering an environment where poultry products or feces may be contaminated, Wear droplet and contact precautions including boots and undertake appropriate biosecurity/decontamination measures before leaving the premises Answer: Scenario 2. Respirators are used for aerosol-generating procedures. 48 Question 20 Match the information source on the left with the contract tracing activities that should be conducted there on the right. 1. Hospital or other medical facility 2. Patient (or proxy) 3. Patients home and village Answer: 1. b 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 in the facility 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. Look for additional cases 2. a 3. c 49 Question 21 Questions to ask the case patient/case patient’s family regarding potential H5N1 exposures should cover which of the following? Contact with confirmed , suspect, or probable human H5 cases Exposure to sick or dying animals, wild birds, other animals, or their environment Exposure to environments that may be contaminated with influenza A (H5N1) Exposure to cooked chicken products Handling/preparation of raw poultry and other animal products 50 Question 22 Questions to as the case patient/case patient’s family regarding additional case finding/H5N1 circulation in the community include which of the following? Awareness of additional cases of severe respiratory illness in family, friends and co-workers Awareness of H5N1 outbreaks occurring outside of the country Awareness of illness or deaths in birds, cats, swine, or other animals in the household and neighboring area 51 Question 23 When in a patient’s home or their village, what are important contextual factors to observe? Poultry in and around the house Construction material of the home Mapped location or photograph of house and surroundings Possible unique and culturally-specific mechanisms of exposure Annual community festival days Live bird markets or other occupationally related exposures 52 JULY 16 Case Finding Results • Child with unexplained respiratory illness reported in nearby province, Pelu Jaghai • Director of Epidemiology orders your team to meet the Ministry of Health field workers there and make site visits to hospitals and villages 53 JULY 16 • New Case and Contact 11-year-old boy, TMU Fever, cough shortness of breath , date of onset July 12 Admitted July 15 Critically ill, not intubated You and your team don PPE, evaluate the patient, review medical chart, and interview available family members • Mother (ACM) Reports boy visited Murg market on July 8 54 Update the line list with the current information as of the afternoon of July 16. 55 Line List as of July 16th p.m. ID Initials Vill- Age Sex # age 1 AAJ DG 10 M 2 JAM DG 65 F 3 AWM DG 70 M 4 NJC DG 36 F 5 JRO DG 27 M 6 TMU PJ 11 M 7 AMC PJ 29 F EPI relation Syx Onset Lab date Status Case status Outco me Live-Mkt: July 8 Caretaker of #1 Caretaker of #1 Caretaker of # 1; Live-Mkt: July 8 Live-Mkt: July 8 Live-Mkt: July 8 ‘index’ case Probable CASE PUI/ Contact Contact Died (7/16) Hospital ized Caretaker of #6 Mother of # 6 Possible exposures and date Grandmother (# 1) Grandfather (# 1) Mother (# 1) F, C, D, S F, C, S 10 9 No lab specimen Pending Contact Uncle (# 1) Playmate (# 1) Contact F, C, D, M 12 Pending Suspect CASE Hospital ized Contact F: Fever; C: Cough; D: Diarrhea; S: Shortness of breath; M: Myalgias; URI – upper respiratory syx DG: Dava Ghar 56 PJ: Pelu Jaghai Differential Diagnoses Human influenza • Commonly an upper respiratory infection • Fever, headache, cough, sore throat • Muscle ache, exhaustion • Other respiratory symptoms • Recovery: 2-7 days • Can progress to pneumonia and respiratory failure in some cases Influenza A(H5N1) • • • • • • • • • Commonly a lower respiratory infection Fever, headache, cough, sore throat Muscle ache, exhaustion Difficulty breathing, respiratory distress Crackling on inhalation Leukopenia, lymphopenia Increased respiratory rate Sputum production, possibly with blood Limited data: diarrhea An animal virus that is adapting to humans may have a mixed picture of clinical presentations. 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 Clinical signs and symptoms alone cannot distinguish the severe complications of seasonal influenza from influenza A (H5N1) infection in humans: Examine the epidemiology and collect specimens! 59 Move on to Outbreak Investigation, Part 2 60